20-F - RLFTY - Equibles

As filed with the Securities and Exchange Commission on May 1 2 , 2023

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 20-F

[Mark One]

☐	REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934

☒	ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2022

☐	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the period ended

☐	SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Date of event requiring this shell company report

Commission file number 001-41174

RELIEF THERAPEUTICS HOLDING SA

(Exact name of registrant as specified in its charter and translation of Registrant’s name into English)

Switzerland

(Jurisdiction of incorporation or organization)

Avenue de Sécheron 15

1202 Geneva

Switzerland

(Address of principal executive offices)

Jack Weinstein

Chief Executive Officer

RELIEF THERAPEUTICS Holding SA

Avenue de Sécheron 15

1202 Geneva

Switzerland

Tel: +41 22 545 11 16

Securities Registered or to be registered pursuant to Section 12(b) of the Act: None

Securities registered or to be registered pursuant to Section 12(g) of the Act:

Title of each class:	Name of exchange on which registered:
Ordinary Stock, par value CHF 0.01 per share	OTCBB<br><br>SIX Swiss Exchange (SIX)
American Depositary Shares, representing one share of Ordinary Stock, par value CHF 0.01 per share	OTCBB

Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act: None

Indicate the number of outstanding shares of each of the issuer’s classes of capital or ordinary stock as of the close of the period covered by the annual report: 5,616,334,617 (14,040,836 shares as adjusted for the reverse split which occurred on May 5, 2023)

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act: ☐ Yes ☒ No

If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934: ☐ Yes ☒ No

Note – Checking the box above will not relieve any registrant required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 from their obligations under those Sections.

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days: ☒ Yes ☐ No

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files): ☒ Yes ☐ No

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or an emerging growth company. See the definitions of “large accelerated filer”, “accelerated filer”, and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer	☐	Accelerated filer	☐	Non-accelerated filer	☒
				Emerging growth company	☒

If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards† provided pursuant to Section 13(a) of the Exchange Act. ☐

†	The term “new or revised financial accounting standard” refers to any update issued by the Financial Accounting Standards Board to its Accounting Standards Codification after April 5, 2012.

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:

U.S. GAAP ☐	International Financial Reporting Standards as issued		Other ☐
	by the International Accounting Standards Board	☒

If “Other” has been checked in response to the previous question, indicate by check mark which financial statement item the registrant has elected to follow. Item 17 ☐ Item 18 ☒

If this is an annual report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

TABLE OF CONTENTS


part i		3
ITEM 1	IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS	3
A.	DIRECTORS AND SENIOR MANAGEMENT	3
B.	ADVISERS	5
C.	AUDITORS	5
ITEM 2	OFFER STATISTICS AND EXPECTED TIMELINE	5
ITEM 3	KEY INFORMATION	5
A.	SELECTED FINANCIAL DATA	5
B.	CAPITALIZATION AND INDEBTEDNESS	6
C.	REASONS FOR THE OFFER AND USE OF PROCEEDS	6
D.	RISK FACTORS	7
ITEM 4	INFORMATION ON THE COMPANY	33
A.	HISTORY AND DEVELOPMENT OF THE COMPANY	33
B.	BUSINESS OVERVIEW	33
C.	ORGANIZATIONAL STRUCTURE	72
D.	PROPERTY, PLANT AND EQUIPMENT	72
ITEM 4A	UNRESOLVED STAFF COMMENTS	73
ITEM 5	OPERATING AND FINANCIAL REVIEW AND PROSPECTS	73
A.	OPERATING RESULTS	73
B.	LIQUIDITY AND CAPITAL RESOURCES	81
C.	RESEARCH AND DEVELOPMENT, PATENTS AND LICENSES, ETC.	84
D.	TREND INFORMATION	84
E.	OFF-BALANCE SHEET ARRANGEMENTS	85
F.	TABULAR DISCLOSURE OF CONTRACTUAL ARRANGEMENTS	85
G.	SAFE HARBOR	85
ITEM 6	DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES	85
A.	DIRECTORS AND SENIOR MANAGEMENT	85
B.	COMPENSATION	85
C.	BOARD PRACTICES	91
ITEM 7	MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS	93
A.	MAJOR SHAREHOLDERS [UPDATE]	93
B.	RELATED PARTY TRANSACTIONS	94
C.	INTERESTS OF EXPERTS AND COUNSEL	95
ITEM 8	FINANCIAL INFORMATION	95
A.	CONSOLIDATED STATEMENTS AND OTHER FINANCIAL INFORMATION	95
B.	SIGNIFICANT CHANGES	95
ITEM 9	THE OFFER AND LISTING	95
A.	OFFER AND LISTING DETAILS	95
B.	PLAN OF DISTRIBUTION	96

C.	MARKETS	96
D.	SELLING SHAREHOLDERS	96
E.	DILUTION	96
F.	EXPENSES OF THE ISSUE	96
ITEM 10	ADDITIONAL INFORMATION	96
A.	SHARE CAPITAL	96
B.	MEMORANDUM AND ARTICLES OF ASSOCIATION	96
C.	MATERIAL CONTRACTS	115
D.	EXCHANGE CONTROLS	115
E.	TAXATION	115
F.	DIVIDENDS AND PAYING AGENTS	121
G.	STATEMENT BY EXPERTS	121
H.	DOCUMENTS ON DISPLAY	121
I.	SUBSIDIARY INFORMATION	121
ITEM 11	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	121
ITEM 12	DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES	122
A.	DEBT SECURITIES	122
B.	WARRANTS AND RIGHTS	122
C.	OTHER SECURITIES	122
D.	AMERICAN DEPOSITARY RECEIPTS	122
ITEM 13	DEFAULTS, DIVIDEND ARREARAGES AND DELINQUENCIES	130
ITEM 14	MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS	130
ITEM 15	CONTROLS AND PROCEDURES	131
ITEM 16	RESERVED	131
ITEM 16A	AUDIT COMMITTEE FINANCIAL EXPERT	131
ITEM 16B.	CODE OF ETHICS	131
ITEM 16C.	PRINCIPAL ACCOUNTANT FEES AND SERVICES	131
ITEM 16D.	EXEMPTIONS FROM THE LISTING STANDARDS FOR AUDIT COMMITTEES	131
ITEM 16E.	PURCHASES OF EQUITY SECURITIES BY THE ISSUER AND AFFILIATED PURCHASERS	131
ITEM 16F.	CHANGE IN REGISTRANT’S CERTIFYING ACCOUNTANT	131
ITEM 16G.	CORPORATE GOVERNANCE	131
ITEM 16H.	MINE SAFETY DISCLOSURE	132
ITEM 17	FINANCIAL STATEMENTS	133
ITEM 18	FINANCIAL STATEMENTS	133
ITEM 19	EXHIBITS	133

INTRODUCTION

Unless otherwise indicated or the context otherwise requires, all references in this Annual Report on Form 20-F to the terms “Relief,” “Relief Therapeutics,” “the company,” “we,” “us” and “our” refer to RELIEF Therapeutics Holding SA together with its subsidiaries. Relief and its subsidiaries may also sometimes be referred to in this Form 20-F as the “Group.”

Our jurisdiction of incorporation is Switzerland, and our registered office is in Geneva, Canton of Geneva, Switzerland. A majority of our outstanding securities that are registered in our share register are owned by non-U.S. residents. Under the rules of the U.S. Securities and Exchange Commission, or the SEC, we are currently eligible for treatment as a foreign private issuer. As a foreign private issuer, we will not be required to file periodic reports and financial statements with the SEC as frequently or as promptly as U.S. domestic issuers whose securities are registered under the Securities Exchange Act of 1934, as amended, referred to herein as the Exchange Act.

We own trademarks for Relief Therapeutics in Switzerland. All other trade names, trademarks and service marks of other companies appearing in this prospectus are the property of their respective holders. Solely for convenience, the trademarks and trade names in this prospectus are referred to without the ^®^ and ^™^ symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend to use or display other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Our reporting currency is the Swiss franc. In this prospectus, unless otherwise specified, all monetary amounts are in Swiss francs, all references to “CHF” and “Swiss francs” mean Swiss francs and all references to “U.S. dollars,” “$,” “US$” and “USD” mean United States dollars. Throughout this prospectus, references to ADSs mean ADSs or ordinary shares represented by such ADSs, as the case may be.

We present our consolidated financial statements in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board, or IASB. Readers of this prospectus should note that there may be certain differences between the presentation of our financial position, results of operations and cash flows under IFRS and U.S. generally accepted accounting principles.

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This annual report on Form 20-F contains forward-looking statements that involve substantial risks and uncertainties. All statements contained in this annual report, other than statements of historical fact, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, projects, plans and objections of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend”, “may,” “plan,” “predict,” “project,” “target,” “potential,” “would,” “could,” “should,” “continue,” and other similar expressions are intended to identify forward-looking statements, though not all forward-looking statements contain these identifying words. The forward-looking statements in this annual report include, among other things, statements about:

•	the success, cost and development of our clinical programs, including the progress of, and results from, our (and our partners’) clinical trial and preclinical programs;
•	the ability of our collaboration partners to obtain authorizations to market products that are the subject of the respective collaborations;
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•	our ability or our collaboration partners’ abilities to obtain and maintain regulatory approval of our product candidates and any related restrictions, limitations or warnings on the label of any such product, if approved;
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•	our plans to pursue research and development of product candidates we may obtain in the future;
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•	our ability to compete with companies currently marketing or engaged in the development of treatments for indications that our product candidates are designed to target;
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•	the potential advantages or disadvantages of our product candidates;
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•	the rate and degree of market acceptance and clinical utility of our product candidates;
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•	the success of our collaborations and partnerships with third parties;
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•	our estimates regarding the potential market opportunities for our product candidates;
•	our sales, marketing, and distribution capabilities and strategy;
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•	our ability to establish and maintain arrangements for the manufacture of our product candidates;
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•	our ability to protect and defend our intellectual property;
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•	whether any of our product candidates (or our collaboration partners’ product candidates) will ever be approved for commercialization;
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•	whether we will ever achieve cash flow positive operations or profitability;
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•	whether we can obtain funding for our activities when required and on terms that are acceptable to us;
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•	our estimates regarding expenses, future revenues, capital requirements and requirements for additional financing;
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•	our expectations related to our use of our capital;
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•	the effect of the COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including, but not limited to our preclinical studies and clinical trials and our commercial activities;
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•	the impact of government laws and regulations; and
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•	our competitive position.
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You should read this annual report and the documents we have filed as exhibits to the annual report completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward- looking statements we make. You should refer to the sections of this annual report titled “Item 3. Key Information, D. Risk Factors,” “Item 4. Information on the Company.” and “Item 5. Operating and Financial Review and Prospects” for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments we may make.

This annual report on Form 20-F includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information.

PART I

ITEM 1	IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS
A.	DIRECTORS AND SENIOR MANAGEMENT
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The following table sets forth the names, dates of birth and positions of our directors and senior management as of the date of this annual report:

Directors

Name	Date of Birth	Position
Dr. Raghuram (Ram) Selvaraju	11/25/1978	Chairman
Dr. Tom Plitz	08/09/1968	Vice-Chairman
Dr. Patrice P. Jean	04/06/1971	Director
Paolo Galfetti	05/03/1965	Director
Michelle Lock	11/21/1968	Director
Senior Management<br> <br><br> <br>Name	Date of Birth	Position
Paolo Galfetti	05/03/1965	Chief Operating Officer
Jack Weinstein	01/19/1956	Chief Executive Officer
Jeremy Meinen	02/21/1989	Chief Financial Officer and Treasurer
Marco Marotta	06/20/1985	Chief Business Officer

Directors

Raghuram (Ram) Selvaraju, Ph.D., MBA, serves as Chairman of our Board of Directors. Dr. Selvaraju Managing Director of Equity Research at H.C. Wainwright & Co., LLC whose research focuses on the healthcare sector. Dr. Selvaraju has over 16 years of experience on Wall Street and previously was a pharmaceutical researcher at Serono in Switzerland. In addition, Dr. Selvaraju has appeared numerous times on Bloomberg, CNBC, Business News Network and BTV where he discussed drug development trends, healthcare reform policy, and pharma and biotech M&A. Prior to joining Wainwright, Dr. Selvaraju held Senior Research positions at MLV & Co., Aegis Capital Corp. – Head of Healthcare Equity Research and Director of Equity Research, Hapoalim Securities U.S.A. and Rodman & Renshaw LLC. Dr. Selvaraju became the youngest-ever recipient of the Serono Pharmaceutical Research Institute’s Inventorship Award for exceptional innovation and creativity in 2003. Dr. Selvaraju earned his Ph.D. in cellular immunology and molecular neuroscience and an M.S. in molecular biology from the University of Geneva in Switzerland on the basis of his drug development research. He also holds an M.B.A. from the Cornell University accelerated one-year program for scientists and engineers and a B.S. in biological sciences and technical writing from Carnegie Mellon University.

Tom Plitz serves as Vice Chairman of our Board of Directors and is chairperson of the Nomination and Compensation Committee of the Board. He most recently served as Chief Executive Officer of Chord Therapeutics SA, a privately held biopharmaceutical firm based in Geneva, Switzerland, which was acquired by Merck KGaA in January 2022, for an undisclosed amount. Prior to Chord, Dr. Plitz worked as Chief Scientific Officer of the rare disease company, Wilson Therapeutics, which was acquired for USD 855 million by Alexion Pharmaceuticals in April 2018. Dr. Plitz’s previous assignments include senior roles at Serono, Merck, and Shire Pharmaceuticals, where he worked across multiple therapeutic areas including neuroinflammatory, metabolic, and rare diseases, completing more than two decades of experience in pharmaceutical R&D. He holds a Ph.D. from Technical University of Munich, Germany

Patrice Jean is a member of our Board of Directors and is chairperson of the Audit and Finance Committee. She is the Chair of the Life Sciences Practice at Hughes Hubbard & Reed, an international law firm based in New York City. She has over a decade of experience counselling and leading startup pharmaceutical, chemical and biotechnology companies in all areas of intellectual property law including asserting and defending patent rights underlying core technologies and innovations. Dr. Jean serves as Vice-President of the New York Intellectual Property Law Education Foundation and is a board member of the New York Intellectual Property Law Association.. She holds a Ph.D. in molecular biology from Princeton University, a J.D. from Columbia University School of Law, and a B.A. in biochemistry from Xavier University.

Paolo Galfetti is a member of our Board of Directors, the chairperson of the Corporate Governance Committee, and the Chief Operating Officer of Relief. He has more than thirty years of management experience in the pharmaceutical sector including in the areas of business development and licensing, operational strategic management, clinical research and pharmaceutical discovery and development. Mr. Galfetti joined APR in 1995 as head of licensing and business development and was appointed Chief Executive Officer in 2002. Prior to joining APR, he was a founding partner, Chief Executive Officer and board member of the Institute for Pharmacokinetic and Analytical Studies AG (IPAS), a Swiss contract research organization focusing on Phase I and II clinical trials, as well as Chief Executive Officer and board member of Farma Resa s.r.l., an Italian contract research organization dedicated to Phase III and IV clinical trial on a contract basis. Mr. Galfetti is a Chartered Financial Analyst (CFA) and has a bachelor’s degree in economics from the Commercial University Bocconi, Milan, Italy.

Michelle Lock is a member of our Board of Directors. She is the Chief Operating Officer and Chief Commercial Officer of Covis Pharma Group, a Switzerland-based global specialty pharmaceutical company that markets therapeutic solutions for patients with life-threatening conditions and chronic illnesses. Ms. Lock’s broad biopharmaceutical industry experience spans nearly 30 years and includes leadership roles in commercialization across various therapeutic areas including oncology, hematology, cardiovascular and metabolic disease, liver disease, immunology, virology and neuroscience. Previously, Ms. Lock served as the Senior Vice President and Head of International organization at Acceleron Pharma Inc, a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. Before that, she was a consultant to biotechnology companies, providing leadership, guidance, and strategic support to managements seeking to establish or improve their international businesses based in Switzerland. Earlier, Ms. Lock was Senior Vice President & Head of International at Sage Therapeutics, a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel medicines to transform the lives of patients with life-altering central nervous system (CNS) disorders. During her career, Ms. Lock also spent 24 years with Bristol-Myers Squibb (BMS) in positions of increasing responsibility in sales, commercial, general management, regional leadership and business strategy. In her most recent role at BMS, she served as Vice President and General Manager for EU Country Clusters & Global Capabilities Hub leadership, Switzerland, driving the company’s leadership efforts in immuno-oncology. She has served as Honorary Ambassador between Switzerland and the U.S. since 2018, as well is a past member of the board of directors of the Swiss American Chamber of Commerce and the Interpharma Switzerland Pharmaceutical Industry. She earned a degree in Science/Nursing at Royal Melbourne University, Australia and studied General Management and Internal General Management at CEDEP, France.

Executive Officers

Paolo Galfetti. See biographical information above.

Jack Weinstein joined us in October 2020 and since December 2022 has served as our Chief Executive Officer. From October 2020 to December 2022, Mr. Weinstein served as our U.S. based Chief Financial Officer and Treasurer, and as the President of Relief U.S. Mr. Weinstein has nearly 40 years of wide-ranging executive management expertise, including as a CFO, investment banker and consultant in the biopharmaceutical and life sciences industries. Prior to joining Relief, Mr. Weinstein served as Managing Director and Head of Healthcare Investment Banking at Avalon NetWorth, an independent New York-based boutique investment bank. Prior to joining Avalon, Mr. Weinstein was CFO, Treasurer and Vice President of Business Development at Catalyst Pharmaceuticals, Inc.(Nasdaq: CPRX), a biopharmaceutical company developing therapies to treat rare diseases, where he led the Company through its Initial Public Offering. Prior to joining Catalyst, Mr. Weinstein was the President and founder of The Sterlington Group, Inc., a consulting firm providing strategic, business development, regulatory and “CFO” consulting services. Mr. Weinstein received his MBA from the Harvard Business School.

Jeremy Meinen became our Chief Financial Officer and Treasurer in December 2022. Previously Mr. Meinen had served as our Vice President Finance and Administration since October 2020 and our Chief Accounting Officer since December 2021. He joined Relief as ad-interim Chief Financial Officer in April 2020. Prior to joining Relief, Jeremy provided financial consulting, controlling and auditing services to companies in various industries. He began his career in an international audit firm, where he held positions of increasing responsibility and scope over more than six years. Mr. Meinen holds a Master of Science in finance from Bocconi University and a Bachelor of Arts degree in Business Administration from the University of Geneva. He is a Swiss certified public accountant and former licensed audit expert.

Marco Marotta became our Chief Business Officer in December 2021. Mr. Marotta joined us as part of our acquisition of APR, where he served as Corporate Director, Business Development and Licensing. Mr. Marotta joined APR in January 2015, where he was initially in charge to reshape and optimize APR’s end-to-end supply chain process, and afterwards, he joined the licensing and business development department, establishing and consolidating APR’s presence in emerging markets like the Asia-Pacific and Latin American regions. From 2019, Mr. Marotta led APR Business Development as a director, with responsibility of out-licensing proprietary products worldwide, divesting non-strategic assets and maximizing monetization as well as merging APR’s business with Relief. Mr. Marotta received a Master of Science in Engineering from the University Federico II in Napoli and an Executive MBA from Commercial University Bocconi in Milan.

B.	ADVISERS

Our principal Swiss legal advisor is VISCHER AG, located at Schuetzengasse 1, PO Box, CH-8021 Zurich, Switzerland and our principal United States (U.S.) legal adviser is Akerman LLP, located at 201 East Las Olas Boulevard, Suite 1800, Fort Lauderdale, Florida 33301

C.	AUDITORS

MAZARS SA has been our auditor since 2017. The address for MAZARS SA is Chemin de Blandonnet 2, 1214 Vernier-Geneva, Switzerland.

ITEM 2	OFFER STATISTICS AND EXPECTED TIMELINE

Not applicable.

ITEM 3	KEY INFORMATION
A.	SELECTED FINANCIAL DATA
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Summary Financial Information of Relief

We derived the selected consolidated financial data as of and for the years ended December 31, 2022 and 2021 from our audited consolidated financial statements included elsewhere in this annual report. We present our consolidated financial statements in accordance with International Financial Reporting Standards (IFRS), as promulgated by the International Accounting Standards Board (IASB). All amounts below are in Swiss Francs (CHF) and are in thousands.

The summary consolidated financial data below should be read together with those consolidated financial statements as well as the Item 5. “Operating and Financial Review and Prospects.” Our historical results for any prior period are not necessarily indicative of results to be expected in any future period, and our interim period results are not necessarily indicative of results to be expected for a full year or any other interim period.

	December 31,
Statement of Operations Data	2022			2021
Revenue		6,081			3,321
Other gains		9,921			1,171
Total Income		16,002			4,492
Raw materials and consumables expenses		(1,250	)		(750	)
External selling and distribution expenses		(3,307	)		(365	)
External research and development expenses		(12,393	)		(19,024	)
Personnel expenses		(12,998	)		(9,121	)
Other administrative expense		(7,747	)		(6,750	)
Other losses		(63	)		(752	)
EBITDA		(21,756	)		(32,270	)
Impairment losses on intangible assets		(26,424	)		—
Amortization and depreciation expense		(3,860	)		(2,036	)
Operating Loss		(52,040	)		(34,306	)
Financial income		18			97
Financial expense		(2,294	)		(1,316	)
Result before income taxes		(54,316	)		(35,525	)
Income taxes		3,526			820
Results for the period		(50,790	)		(34,705	)

Balance Sheet Data	December 31, 2022
Current Assets		22,583
Total Assets		188,798
Equity		145,417
Non-Current Liabilities		32,665
Current Liabilities		10,716
B.	CAPITALIZATION AND INDEBTEDNESS
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The table below sets forth our cash and cash equivalents and shows our capitalization as of December 31, 2022. You should read this table in conjunction with our unaudited condensed consolidated financial statements included in this annual report, together with the accompanying notes and the other information appearing under the heading “Item 5. Operating and Financial Review and Prospects.” All amounts below are in Swiss Francs (CHF) and are in thousands. Liabilities set forth below are unsecured and non-guaranteed.


Cash
Cash and Cash Equivalents	19,237
Total cash	19,237
Debt
Non-current liabilities	32,665
Current liabilities	10,716
Total debt	43,381
Shareholder’s equity:
Share capital	56,163
Treasury shares	(12,108	)
Reserves	220,961
Accumulated loss	(119,599	)
Total equity	145,417
Total liabilities and shareholder’s equity	188,798

As of April 30, 2023, we had cash and cash equivalents of approximately CHF 11.1 million. We will need to obtain additional funding to continue our operations beyond the third quarter of 2023.

On April 28, 2023, our stockholders approved a consolidation (or reverse split) of our ordinary shares at a 400 to 1 ratio. The consolidation occurred on May 5, 2023. Assuming we meet all listing requirements, we intend to seek a listing of our ordinary shares on the NASDAQ stock market. There can be no assurance that we will be successful in such listing.

C.	REASONS FOR THE OFFER AND USE OF PROCEEDS

Not applicable

D.	RISK FACTORS

Risk Factors Summary

We are providing the following summary of the risk factors contained in our Form 20-F to enhance the readability and accessibility of our risk factor disclosures. We encourage our stockholders to carefully review the full risk factors contained in this Form 20-F in their entirety for additional information regarding the risks and uncertainties that could cause our actual results to vary materially from our recent results or from our anticipated future results.

Risks Related to Our Business

•	We depend heavily on the success of our product candidates. If our clinical studies are unsuccessful, if we or our collaboration partners do not obtain regulatory approval or if we or our collaboration partners are unable to commercialize our product candidates, or if we experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected.
•	Our business is subject to significant regulation from governments and regulatory bodies, including marketing approval requirements, which could lengthen the development time, increase the cost of developing our drug product candidates or delay, prevent or limit the commercialization of our product candidates.
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•	We have a limited history of commercializing pharmaceutical products, which may make it difficult to evaluate our future viability.
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•	Results of early clinical studies may not be predictive of future study results.
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•	The successful commercialization of our product candidates will depend on the extent to which governmental authorities and health insurers establish adequate coverage and reimbursement levels and pricing policies.
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•	Our products may not gain market acceptance, in which case we or our collaboration partners may not be able to generate product revenues, which would materially adversely affect our business, financial condition and results of operations.
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•	We depend on enrollment of patients in our clinical studies for our product candidates. If we are unable to enroll patients in our clinical studies, our research and development efforts could be materially adversely affected.
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•	If serious adverse, undesirable or unacceptable side effects are identified during the development of our product candidates or following approval, if any, we may need to abandon our development of such product candidates, the commercial profile of any approved label may be limited, or we may be subject to other significant negative consequences following marketing approval, if any.
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•	We operate in highly competitive and rapidly changing industries, which may result in others discovering, developing or commercializing competing products before or more successfully than we do.
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•	Our business is subject to additional risks associated with international operations.
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•	The COVID-19 pandemic may impact our business.
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•	Our future growth and ability to compete depends on retaining our key personnel and recruiting additional qualified personnel.
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•	We may become exposed to costly and damaging liability claims, either when testing our product candidates or at the commercial stage or as a result of claims against our directors and officers, and our liability insurance may not cover all damages from such claims.
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•	Business disruptions could seriously harm our future revenue and financial condition and increase our costs.
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•	Pressure on drug product third-party payor coverage, reimbursement and pricing may impair our ability to be reimbursed at prices or on terms sufficient to provide a viable financial outcome.
•	We cannot give any assurance that any of our product candidates in development will receive regulatory approval, which is necessary before they can be commercialized.
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•	Clinical drug development involves a lengthy and expensive process with uncertain timelines and uncertain outcomes. If clinical studies of our product candidates are prolonged or delayed, we may be unable to obtain required regulatory approvals, and therefore be unable to commercialize our product candidates on a timely basis or at all.
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•	Even if we obtain and maintain approval for certain of our drug candidates from one jurisdiction, we may never obtain approval for our drug candidates in other jurisdictions, which would limit our market opportunities and adversely affect our business.
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•	We have conducted and may in the future conduct clinical studies for our drug candidates in the U.S., Europe and Switzerland, and the FDA, EMA and Swissmedic and applicable foreign regulatory authorities may not accept data from such studies.
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•	Even if certain of our product candidates obtain regulatory approval, we will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expenses. Additionally, our additional product candidates, if approved, could be subject to labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.
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•	Our business is subject to complex and evolving U.S. and international laws and regulations regarding clinical trials reimbursement and privacy and data protection. Many of these laws and regulations are subject to change and uncertain interpretation and could result in claims, changes to our business practices, penalties, increased cost of operations, or declines in user growth or engagement, or otherwise harm our business.
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•	We could be subject to liabilities under environmental, health and safety laws or regulations, or fines, penalties or other sanctions, if we fail to comply with such laws or regulations or otherwise incur costs that could have a material adverse effect on the success of our business.
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Risks Related to Our Relationships with Third Parties

•	If we fail to maintain our strategic relationships with any of our current or future collaboration or strategic partners, our business, commercialization prospects and financial condition may be materially adversely affected.
•	We may seek to form additional strategic alliances in the future with respect to our product candidates, and if we do not realize the benefits of such alliances, our business, financial condition, commercialization prospects and results of operations may be materially adversely affected.
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•	We rely on third parties to conduct our nonclinical and clinical studies and perform other tasks for us. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval for or commercialize our product candidates, and our business could be substantially harmed.
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•	We currently rely on third-party suppliers and other third parties for production of our product candidates and our dependence on these third parties may impair the advancement of our research and development programs and the development of our product candidates.
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Risks Related to Intellectual Property

•	We may not have sufficient patent terms to protect our products and business effectively.

•	We or our licensing or collaboration partners may become subject to intellectual property-related litigation or other proceedings to protect or enforce our patents or the patents of our licensors or licensees and collaborators, any of which could be expensive, time-consuming, and unsuccessful, and may ultimately result in our loss of ownership of intellectual property.
•	If we or our licensing or collaboration partners are unable to obtain and maintain effective patent rights for our technologies, product candidates or any future product candidates, or if the scope of the patent rights obtained is not sufficiently broad, our competitors could develop and commercialize products and technology similar or identical to ours, and our, or our collaboration partners’ ability to successfully commercialize our products and technology may be adversely affected.
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•	We may be subject to claims challenging the inventorship of our patents and other intellectual property.
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•	Patent policy and rule changes could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, thereby impairing our ability to protect our technologies and products.
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•	If we are unable to maintain effective proprietary rights for our technologies, product candidates or any future product candidates, we may not be able to compete effectively in our markets.
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•	Obtaining and maintaining our patent protection depends on compliance with various procedural, document-submission, fee-payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.
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•	The patent protection and patent prosecution for some of our product candidates could be dependent on third parties.
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•	Third-party claims of intellectual property infringement may expose us to substantial liability or may prevent or delay our or our collaboration partners’ development and commercialization efforts.
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•	We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
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•	We may not be able to protect our intellectual property rights throughout the world.
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•	We may be unable to protect our trade secrets, know-how and technologies.
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Risks Related to Our Financial Condition and Results of Operations

•	We are a commercial-stage biopharmaceutical company with a history of operating losses. Our recurring losses, negative cash flows and significant accumulated deficit have raised substantial doubt regarding our ability to continue as a going concern.
•	If we fail to obtain additional funding, we may delay, reduce or eliminate our product development programs or commercialization efforts.
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•	Raising additional capital will likely cause dilution to our shareholders, restrict our operations or require us to relinquish rights to our intellectual property or future revenue streams.
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•	Exchange rate fluctuations may materially affect our results of operations and financial condition.
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•	The SIX Exchange Regulation AG has launched an investigation into Relief, the results of which are uncertain.
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Risk Factors

You should carefully consider the risks and uncertainties described below and the other information in this Annual report before making an investment. Our business, financial condition or results of operations could be materially and adversely affected if any of these risks occur, and as a result, the market price of our shares could decline. This Annual report also contains forward-looking statements that involve risks and uncertainties. See “Forward-Looking Statements.” Our actual results could differ materially and adversely from those anticipated in these forward- looking statements as a result of certain factors.

Risks Related to Our Business

We depend heavily on the success of our product candidates. If our clinical studies are unsuccessful, if we or our collaboration partners do not obtain regulatory approval or if we or our collaboration partners are unable to commercialize our product candidates, or if we experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected.

We currently have a small number of products approved for sale, all of which were acquired in the business combination with APR, generating a limited volume of sales. We have licensed OLPRUVA^™^ (ACER-001), and have added additional products to our portfolio through our acquisitions of AdVita and APR. Our ability to generate significantly higher product revenues will depend heavily on successful clinical development, obtaining regulatory approval and eventual commercialization of these product candidates. The success of our current and future product candidates will depend on several factors, including the following:

•	completing preclinical studies and clinical studies that demonstrate the efficacy, safety and clinical utility of our product candidates;
•	receiving marketing approvals from applicable regulatory authorities;
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•	developing product formulations with sufficiently long-term stability and chemistry, manufacturing and controls that meet governmental regulatory standards;
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•	establishing commercial manufacturing capabilities;
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•	launching commercial sales, marketing and distribution operations;
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•	acceptance of our product candidates by patients, the medical community and third-party payors;
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•	a continued acceptable safety profile following approval;
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•	competing effectively with other therapies; and
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•	obtaining, maintaining, enforcing and defending our intellectual property rights and claims and not infringing on third parties’ intellectual property rights.
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If we or our collaborators do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to successfully commercialize our current or future product candidates, which would materially adversely affect our business, financial conditions and results of operations.

Our business is subject to significant regulation from governments and regulatory bodies, including marketing approval requirements, which could lengthen the development time, increase the cost of developing our drug product candidates or delay, prevent or limit the commercialization of our product candidates.

When a medicinal product candidate receives regulatory approval, the approval can nonetheless be subject to limitations, e.g., with regard to the indications for which it may be marketed. The approval may also be given subject to conditions, such as additional proof of the medicinal product’s effectiveness and safety. Even after approval is granted, manufacturing, safety, efficacy, recordkeeping, labeling, marketing, sales and distribution of its product candidates are regulated by government agencies in countries where we intend to market our products. All these activities are subject to recurring scrutiny and regular inspections by the relevant agencies. As a consequence, if previously unknown problems are discovered in connection with an approved product, its manufacturer or the manufacturing facilities, this can result in restrictions on the product, the manufacturer or the manufacturing facilities, up to the requirement to withdraw the product from the market. In any event, changes in existing regulations or adoption of new regulations could prevent the Company and/or its commercialization partners from obtaining or maintaining, or affect the timing of, future regulatory approvals.

These and other factors, alone or together, may have a material adverse effect on the Company’s business, financial condition, results of operations and growth prospects as well as the market price of our securities.

We have a limited history of commercializing pharmaceutical products, which may make it difficult to evaluate our future viability.

Our operations to date have mostly been limited to financing and staffing our company, developing our technology, and developing our product candidates. Until our acquisition of APR, we had not generated any revenue from product sales. While we began marketing commercial products with our acquisition of APR, our history of operating in the commercial market is short. Consequently, predictions about our future success or viability may not be as accurate as they could be if we had a longer history of successfully developing and commercializing pharmaceutical products. Factors that may affect our ability to commercialize our product candidates on our own include recruiting and retaining adequate numbers of effective sales and marketing personnel, obtaining access to or persuading adequate numbers of physicians to prescribe our drug candidates, and other unforeseen costs associated with creating an independent sales and marketing organization. Developing a sales and marketing organization requires significant investment, is time consuming and could delay the launch of our product candidates. Consequently, we may not be able to build an effective sales and marketing organization. Additionally, successful commercialization also requires an enhanced regulatory organization, which we currently do not have. If we are unable to build our own distribution and marketing capabilities, are unable to find suitable partners for the commercialization of our product candidates or do not successfully obtain the necessary regulatory capabilities, we may not generate sufficient revenues from them and as a result may not be able to reach or sustain profitability.

Results of early clinical studies may not be predictive of future study results.

Positive or timely results from preclinical or early-stage clinical studies do not ensure positive or timely results in late-stage clinical studies or product approval by the FDA, the EMA, or comparable foreign regulatory authorities. Products that show positive preclinical or early clinical results may not show sufficient safety or efficacy in later-stage clinical studies and therefore may fail to obtain regulatory approvals. In addition, preclinical and clinical data are often susceptible to varying interpretations and analyses. Many companies that believed their product candidates performed satisfactorily in preclinical and clinical studies have nonetheless failed to obtain marketing approval for the product candidates. The FDA, the EMA and comparable foreign regulatory authorities have substantial discretion in the approval process and in determining when or whether regulatory approval will be obtained for any of our product candidates. Even if we believe that the data collected from clinical studies of our product candidates are promising, such data may not be sufficient to support approval by the FDA, the EMA or any other regulatory authority.

In some instances, there can be significant variability in safety and/or efficacy results between different studies of the same product candidate due to numerous factors, including changes in study procedures set forth in protocols, differences in the size and type of the patient populations, adherence to the dosing regimen and other study protocols, and the rate of dropout among clinical study participants. In the case of our later-stage clinical product candidates, results may differ in general on the basis of the larger number of clinical study sites and the additional countries and languages involved in these clinical studies.

Clinical studies may include subject-reported outcomes, some of which may be captured with electronic diaries. We have no assurance and cannot rely on past experience that the high frequency of questioning is not influencing the measured outcome. In addition, low compliance with daily reporting requirements may impact the studies’ validity or statistical power. We cannot assure that any Phase 1, phase 2, phase 3 or other clinical studies that either we or our collaboration partners may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates.

If we or our collaboration partners are required to conduct additional clinical studies or other testing of any of our current or future product candidates that we or our collaboration partners develop, beyond the studies and testing that we or our collaboration partners contemplate, if we or our collaboration partners are unable to successfully complete clinical studies of our product candidates or other testing, if the results of these studies or tests are unfavorable or are only modestly favorable, or if there are safety concerns associated with our current or future product candidates, we may:

•	be delayed in obtaining marketing approval for our product candidates;
•	not obtain marketing approval;
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•	obtain approval for indications or patient populations that are not as broad as intended or desired;
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•	obtain approval with labeling that includes significant use or distribution restrictions or significant safety warnings, including boxed warnings;
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•	be subject to conditional approval or otherwise to additional post-marketing studies or other requirements; or
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•	remove the product from market after obtaining marketing approval.
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Our product development costs will also increase if we experience delays in testing or receiving marketing approvals and we may be required to obtain additional funds to complete clinical studies. We cannot assure that our clinical studies will begin as planned or be completed on schedule, if at all, or that we will not need to amend our studies after they have begun. Significant clinical study delays could also shorten any periods during which we or our collaboration partners may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which may harm our business and results of operations. In addition, some of the factors that cause, or lead to, clinical study delays may ultimately lead to the denial of regulatory approval of our product candidates.

The successful commercialization of our product candidates will depend on the extent to which governmental authorities and health insurers establish adequate coverage and reimbursement levels and pricing policies.

The successful commercialization of our product candidates will depend, in part, on the extent to which coverage and reimbursement for our products will be available from government and health administration authorities, private health insurers and other third-party payors. To manage healthcare costs, many governments and third-party payors increasingly scrutinize the pricing of new technologies and require greater levels of evidence of favorable clinical outcomes and cost-effectiveness before extending coverage. In light of such challenges to prices and the requirement for increasing levels of evidence of the benefits and clinical outcomes of new technologies, we cannot be sure that coverage will be available for any of our current or future product candidates that we or our collaboration partners will commercialize or, if available, that the reimbursement rates will be adequate in each respective region. If we are unable to obtain adequate levels of coverage and reimbursement for our product candidates, their marketability will be negatively and materially impacted.

Third-party payors may deny coverage and reimbursement status altogether for a given drug product or may cover the product but also establish prices at levels that are too low to enable us to realize an appropriate return on our investment in product development. Because the rules and regulations regarding coverage and reimbursement change frequently, in some cases at short notice, even when there is favorable coverage and reimbursement, future changes may occur that adversely impact the favorable status. Further, the net reimbursement for drug products may be subject to additional reductions in the future depending on policy changes enacted by the national regulatory bodies.

The unavailability or inadequacy and variability of third-party coverage and reimbursement could have a material adverse effect on the market acceptance of our product candidates and the future revenues we may expect to receive from those products. In addition, we are unable to predict what additional legislation or regulation relating to the healthcare industry or third-party coverage and reimbursement may be enacted in the future, or what effect such legislation or regulation would have on our business.

Our products may not gain market acceptance, in which case we or our collaboration partners may not be able to generate product revenues, which would materially adversely affect our business, financial condition and results of operations.

Even if the FDA, the EMA or any other regulatory authority approves the marketing of any product candidates that we develop, physicians, healthcare providers, patients or the medical community may not accept or use them. Efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources and may not be successful. If any of our current or future product candidates does not achieve an adequate level of acceptance, we or our collaboration partners may not generate significant product or royalty revenues or any profits from operations. The degree of market acceptance of our product candidates that are approved for commercial sale will depend on a variety of factors, including:

•	how clinicians and potential patients perceive our novel products;

•	the timing of market introduction;
•	the number and clinical profile of competing products;
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•	our ability to provide acceptable evidence of safety and efficacy;
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•	the prevalence and severity of any side effects;
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•	relative convenience and ease of administration;
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•	cost-effectiveness;
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•	patient diagnostics and screening infrastructure in each market;
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•	marketing and distribution support;
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•	availability of coverage, reimbursement and adequate payment from third party payors, both public and private; and
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•	other potential advantages over alternative treatment methods.
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If our product candidates fail to gain market acceptance, this will have a material adverse impact on our ability to generate revenues to provide a satisfactory, or any, return on our investments. Even if some products achieve market acceptance, the market may prove to not be large enough to allow us to generate significant revenues.

In addition, the potential market opportunity of our product candidates is difficult to estimate precisely. Our estimates of the potential market opportunity are predicated on several key assumptions such as industry knowledge and publications, third-party research reports and other surveys. These assumptions involve the exercise of significant judgment on the part of our management and are inherently uncertain, and the reasonableness of these assumptions could not have been assessed by an independent source in every detail. If any of the assumptions proves to be inaccurate, then the actual market for our product candidates could be smaller than our estimates of the potential market opportunity. If the actual market for our product candidates is smaller than we expect, or if any approved products fail to achieve an adequate level of acceptance by physicians, healthcare payors and patients, our product or royalty revenue may be limited, and it may be more difficult for us to achieve or maintain profitability.

We depend on enrollment of patients in our clinical studies for our product candidates. If we are unable to enroll patients in our clinical studies, our research and development efforts could be materially adversely affected.

If our product candidates are associated with serious adverse, undesirable or unacceptable side effects, we may need to abandon their development or limit development to certain uses or subpopulations in which such side effects are less prevalent, less severe or more acceptable from a risk–benefit perspective. Many compounds that initially showed promise in preclinical or early-stage testing were later found to cause side effects that restricted their use and prevented further development of the compound for larger indications.

Generally, the specific target population of patients and therapeutic time windows may make it difficult for us to enroll enough patients to complete clinical studies for our products in a timely and cost-effective manner. Delays in the completion of any clinical study of our product candidates will increase our costs, slow down our product candidate development and approval process, and delay or potentially jeopardize our or our collaboration partners’ ability to commence product sales and generate revenue. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical studies may also ultimately lead to the denial of regulatory approval of our product candidates.

If serious adverse, undesirable or unacceptable side effects are identified during the development of our product candidates or following approval, if any, we may need to abandon our development of such product candidates, the commercial profile of any approved label may be limited, or we may be subject to other significant negative consequences following marketing approval, if any.

Occurrence of serious side effects could impede clinical study enrollment and receipt of marketing approval from the U.S. FDA, the EMA and comparable other national regulatory authorities. Adverse events (AEs) and/or serious adverse events (SAEs) could also adversely affect physician or patient acceptance of our product candidates.

Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including the following:

•	regulatory authorities may withdraw approvals of such product and require us or our collaboration partners to take any approved products off the market;
•	regulatory authorities may require the addition of labeling statements, specific warnings, a contraindication or field alerts to physicians and pharmacies;
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•	we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;
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•	we may be required to change the way the product is administered, to conduct additional studies or to change the labeling of the product;
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•	we or our collaboration partners may be subject to limitations in how we promote the product;
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•	sales of the product may decrease significantly;
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•	we could be sued and held liable for harm caused to patients; and
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•	our reputation and physician or patient acceptance of our products may suffer.
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Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects.

We operate in highly competitive and rapidly changing industries, which may result in others discovering, developing or commercializing competing products before or more successfully than we do.

The biopharmaceutical and pharmaceutical industries are highly competitive and subject to significant and rapid technological change. Our success is highly dependent on our ability to discover, develop and obtain marketing approval for new and innovative products on a cost-effective basis and to market them successfully. In doing so, we face and will continue to face intense competition from a variety of businesses, including large, fully integrated pharmaceutical companies, specialty pharmaceutical companies and biopharmaceutical companies, academic institutions, government agencies and other private and public research institutions in Europe, the U.S. and other jurisdictions. Many of our potential competitors, alone or with their strategic partners, have substantially greater financial, technical and human resources than we do and significantly greater experience in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of treatments, and the commercialization of those treatments. Mergers and acquisitions in the pharmaceutical and biopharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors.

The highly competitive nature of and rapid technological changes in the pharmaceutical and biopharmaceutical industries could render our product candidates or our technology obsolete or noncompetitive. The commercial opportunity for our products could be reduced or eliminated if our competitors:

•	develop and commercialize products that are safer, more effective, less expensive, or more convenient or easier to administer;
•	obtain quicker FDA or other regulatory approval for their products;
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•	establish superior intellectual property and proprietary positions;
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•	have access to more manufacturing capacity;
•	implement more effective approaches to sales, marketing and distribution; or
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•	form more advantageous strategic alliances.
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Should any of these occur, our business, financial condition and results of operations could be materially adversely affected.

Our business is subject to additional risks associated with international operations.

Our business is subject to risks associated with conducting business internationally. Accordingly, our future results could be harmed by a variety of factors, including:

•	potentially reduced protection for intellectual property rights;
•	changes in a specific country’s or region’s political or economic environment;
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•	negative consequences from changes in tax laws;
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•	compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;
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•	difficulties associated with staffing and managing international operations, including differing labor relations;
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•	production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and
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•	business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.
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The COVID-19 pandemic may impact our business.

In December 2019, a novel strain of coronavirus, COVID-19, surfaced in Wuhan, Hubei Province, China. By March 2020, COVID-19 had spread to other countries, including Switzerland and the U.S., and was declared a pandemic by the World Health Organization on March 11, 2020. Since the beginning of the pandemic, governments, public institutions, and other organizations in countries and localities where COVID-19 cases have been identified have taken certain preventative or protective measures to combat the transmission of the virus, including implementation of travel restrictions or bans, closures of non-essential businesses, limitations of public gatherings, other social distancing and shelter-in-place measures, and delays or cancellations of elective surgeries. The COVID-19 pandemic continues to pose the risk that the Company, our employees, contractors, suppliers, and other partners may be prevented from conducting business activities for an indefinite period of time due to shutdowns that may be requested or mandated by state and federal governmental authorities.

As the COVID-19 pandemic continues, we may experience disruptions that could materially impact our business and planned clinical trials, including:

•	delays or difficulties in conducting preclinical and clinical trials;
•	interruption in global manufacturing and shipping that may affect the manufacturing and/or transport of clinical trial materials and other materials, including testing equipment; and
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•	changes in local regulations as a response to COVID-19 that may require us to change the way we perform our trials.
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Our future growth and ability to compete depends on retaining our key personnel and recruiting additional qualified personnel.

Our success depends upon the continued contributions of our key management, scientific and technical personnel, many of whom have substantial experience with or been instrumental for us and our projects. The loss of our key managers and senior scientists could delay our research and development activities. Laws and regulations on executive compensation, including legislation in Switzerland, may restrict our ability to attract, motivate and retain the required level of qualified personnel. In Switzerland, legislation affecting public companies has been passed that, among other things, imposes an annual binding shareholder “say on pay” vote with respect to the compensation of the executive management, including executive officers and the members of the board of directors. In addition, the competition for qualified personnel in the pharmaceutical and biopharmaceutical field is intense, and our future success depends upon our ability to attract, retain and motivate highly skilled scientific, technical and managerial employees. We face competition for personnel from other companies, universities, public and private research institutions and other organizations. If our recruitment and retention efforts are unsuccessful in the future, it may be difficult for us to implement our business strategy, which could have a material adverse effect on our business.

We may become exposed to costly and damaging liability claims, either when testing our product candidates or at the commercial stage or as a result of claims against our directors and officers, and our liability insurance may not cover all damages from such claims.

We are exposed to potential product liability and professional indemnity risks that are inherent in the research, development, manufacturing, marketing and use of pharmaceutical or biopharmaceutical products. Currently we have no products that have been approved for commercial sale; however, our current and future use of product candidates in clinical studies, and the sale of any approved products in the future, may expose us to liability claims. These claims might be made by patients that use the product, by healthcare providers, or by pharmaceutical or biopharmaceutical companies or others selling such products. Any claims against us, regardless of their merit, could be difficult and costly to defend and could materially adversely affect the market for our product candidates or any prospects for commercialization of our product candidates.

Although the clinical trial process is designed to identify and assess potential side effects, it is always possible that a drug, even after regulatory approval, may exhibit unforeseen side effects. If any of our product candidates were to cause adverse side effects during clinical studies or after approval of the product candidate, we may be exposed to substantial liabilities. Physicians and patients may not comply with any warnings that identify known potential adverse effects and patients who should not use our product candidates.

We continuously seek to maintain appropriate and cost-effective liability insurance coverage in connection with our products and for purposes of indemnifying our directors and officers for claims against them. It is, however, possible that our liabilities could exceed our insurance coverage. For example, we intend to expand our insurance coverage to include the sale of commercial products if we obtain marketing approval for any of our product candidates. However, we may not be able to maintain insurance coverage at a reasonable cost or obtain insurance coverage that will be adequate to satisfy any liability that may arise. If a successful liability claim or series of claims is brought against us for uninsured liabilities or in excess of insured liabilities, our assets may not be sufficient to cover such claims and our business operations could be impaired.

Should any of the events described above occur, this could have a material adverse effect on our business, financial condition and results of operations.

Business disruptions could seriously harm our future revenue and financial condition and increase our costs.

Our operations and those of our third-party collaborators and other contractors and consultants, could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics, and other natural or man-made disasters or business interruptions, for which we are partly uninsured. In addition, we rely on our third-party research institution collaborators for conducting research and development of our product candidates, and they may be affected by government shutdowns or withdrawn funding. The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses. We rely on third-party manufacturers to produce and process our product candidates. Our ability to obtain clinical supplies of our product candidates could be disrupted if the operations of these suppliers are affected by a man-made or natural disaster or by other business interruption.

Our operations are conducted internationally with employees, consultants and strategic vendors located in the U.S. and in Europe, including Switzerland, where the Company is headquartered. Damage or extended periods of interruption to our corporate, development or research facilities due to fire, natural disaster, power loss, communications failure, unauthorized entry or other events could cause us to cease or delay development of some or all of our product candidates. Although we maintain property damage and business interruption insurance coverage on these facilities, our insurance might not cover all losses under such circumstances and our business may be seriously harmed by such delays and interruption.

Pressure on drug product third-party payor coverage, reimbursement and pricing may impair our ability to be reimbursed at prices or on terms sufficient to provide a viable financial outcome.

The commercial success of our pharmaceutical products will depend substantially on the extent to which the cost of those products will be paid or reimbursed by government health administration authorities (such as Medicare and Medicaid in the U.S.), private health coverage providers and other third party payors. If reimbursement is not available, or is available only to limited levels, we may be unable to continue to successfully commercialize our products. Even if coverage is provided, the approved reimbursement amount may not be high enough to establish and maintain pricing sufficient to realize a meaningful return on our investment.

The healthcare industry is acutely focused on cost containment, both in the U.S. and elsewhere. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications, which could affect our ability to sell our products profitably. These payors may not view our products as cost-effective, and coverage and reimbursement may not be available to our customers, or may not be sufficient to allow our products, if any, to be marketed on a competitive basis. Cost-control initiatives could cause us to decrease the price we might establish for products, which could result in lower than anticipated product revenues. If the prices for our products decrease or if governmental and other third-party payors do not provide adequate coverage or reimbursement, our prospects for revenue and profitability will suffer.

We cannot give any assurance that any of our product candidates in development will receive regulatory approval, which is necessary before they can be commercialized.

We cannot be certain that any of our product candidates in development will be successful in clinical studies or receive regulatory approval. Applications for our product candidates could fail to receive regulatory approval for many reasons, including but not limited to the following:

•	the FDA, EMA, Swissmedic or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical studies;
•	the population studied in the clinical program may not be sufficiently broad or representative to assure safety in the full population for which we seek approval;
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•	the FDA, EMA, Swissmedic or comparable foreign regulatory authorities may disagree with our interpretation of data from nonclinical or clinical studies;
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•	the data collected from clinical studies of our product candidates may not be sufficient to support the submission of a new drug application (NDA) or other submission or to obtain regulatory approval in the U.S., Switzerland or elsewhere;
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•	we may be unable to demonstrate to the FDA, EMA, Swissmedic or comparable foreign regulatory authorities that a product candidate’s benefit-risk ratio for its proposed indication is acceptable;
•	the FDA, EMA, Swissmedic or other regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and
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•	the approval policies or regulations of the FDA, EMA, Swissmedic or comparable foreign regulatory authorities may change significantly in a manner rendering our clinical data insufficient for approval.
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We generally plan to seek regulatory approval to commercialize our product candidates in the U.S., the EU, Switzerland and in additional foreign countries where we have commercial and typically IP rights. To obtain regulatory approval in other countries, we must comply with numerous and varying regulatory requirements of such other countries regarding safety, efficacy, chemistry, manufacturing and controls, clinical studies, commercial sales, pricing, marketing and distribution of our product candidates. Even if we are successful in obtaining approval in one jurisdiction, we cannot ensure that we will obtain approval in any other jurisdictions. Failure to obtain marketing authorization for our product candidates will result in our being unable to market and sell such products, which would materially adversely affect our business, financial condition and results of operations. If we fail to obtain approval in any jurisdiction, the geographic market for our product candidates could be limited.

Similarly, regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of our product candidates.

Clinical drug development involves a lengthy and expensive process with uncertain timelines and uncertain outcomes. If clinical studies of our product candidates are prolonged or delayed, we may be unable to obtain required regulatory approvals, and therefore be unable to commercialize our product candidates on a timely basis or at all.

In order to commercialize any of our product candidates, we or our partners must obtain the necessary regulatory approvals to market and sell such product. To obtain that approval, we must demonstrate through extensive preclinical and clinical studies that our products are safe and effective in humans. Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the clinical study process. The results of preclinical and early clinical studies of our product candidates may not be predictive of the results of later-stage clinical studies. For example, the positive results generated to date in clinical studies for our product candidates do not ensure that later clinical studies will demonstrate similar results. Product candidates in later stages of clinical studies may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical studies. A number of companies in the pharmaceutical or biopharmaceutical industry, including us, have suffered significant setbacks in advanced clinical studies due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier studies. Our future clinical study results may not be successful.

Clinical studies must be conducted in accordance with the legal requirements, regulations or guidelines of the FDA, EMA, Swissmedic and comparable regulatory authorities, and are subject to oversight by these governmental agencies and institutional review boards (IRBs) at the medical institutions where the clinical studies are conducted. In addition, clinical studies must be conducted with supplies of our product candidates produced under cGMP and other requirements. We depend on medical institutions and CROs to conduct our clinical studies in compliance with cGCP standards. To the extent the CROs fail to enroll participants for our clinical studies, fail to conduct the study to cGCP standards or are delayed for a significant time in the execution of studies, including achieving full enrollment, we may be affected by increased costs, program delays or both, which may harm our business.

The completion of clinical studies for our clinical product candidates may be delayed, suspended or terminated as a result of many factors, including but not limited to:

•	the delay or refusal of regulators or IRBs to authorize us to commence or amend a clinical study at a prospective study site or changes in regulatory requirements, policies and guidelines;
•	delays or failure to reach agreement on acceptable terms with prospective CROs and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and study sites;
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•	delays in patient enrollment and variability in the number and types of patients available for clinical studies;
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•	the inability to enroll a sufficient number of patients in studies to ensure adequate statistical power to detect statistically significant treatment effects;
•	negative or inconclusive results, which may require us to conduct additional preclinical or clinical studies or to abandon projects that we expected to be promising;
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•	safety or tolerability concerns, which could cause us to suspend or terminate a study if we find that the participants are being exposed to unacceptable health risks;
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•	regulators or IRBs requiring that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or safety concerns, among others;
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•	lower than anticipated retention rates of patients and volunteers in clinical studies;
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•	our CROs or clinical study sites failing to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, deviating from the protocol or dropping out of a study;
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•	delays relating to adding new clinical study sites;
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•	difficulty in maintaining contact with patients after treatment, resulting in incomplete data;
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•	delays in establishing the appropriate dosage levels;
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•	the quality or stability of the product candidate falling below acceptable standards;
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•	the inability to produce or obtain sufficient quantities of the product candidate to complete clinical studies; and
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•	exceeding budgeted costs due to difficulty in accurately predicting costs associated with clinical studies.
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Any delays in completing our clinical studies will increase our costs, slow our product candidate development and approval process, and jeopardize our ability to commence product sales and generate sales revenues. Any of these occurrences may significantly harm our business, financial condition and prospects. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical studies may also ultimately lead to the denial of regulatory approval of certain of our product candidates.

Even if we obtain and maintain approval for certain of our drug candidates from one jurisdiction, we may never obtain approval for our drug candidates in other jurisdictions, which would limit our market opportunities and adversely affect our business.

If marketing authorization is obtained for certain of our product candidates, the products will remain subject to continual regulatory review and therefore authorization could be subsequently withdrawn or restricted. Any regulatory approvals that we receive for certain of our product candidates may also be subject to limitations on the approved indicated uses for which the products may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical studies, and surveillance to monitor the safety and efficacy of the product candidate. In addition, if the FDA or a comparable regulatory authority approves any of our product candidates in development, we will be subject to ongoing regulatory obligations and oversight by regulatory authorities, including with respect to the manufacturing processes, labeling, packing, distribution, adverse event reporting, storage, advertising and marketing restrictions, and record-keeping and, potentially, other post-marketing obligations, all of which may result in significant expense and limit our or our collaboration partners’ ability to commercialize such products. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and cGCP requirements for any clinical studies that we conduct post-approval. Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things:

•	restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls;
•	fines, warning letters or holds on clinical studies;
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•	refusal by the FDA to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of product license approvals;
•	regulatory constraints in promotion and distribution of drug products in various markets;
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•	product seizure or detention, or refusal to permit the import or export of products; and
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•	injunctions or the imposition of civil or criminal penalties.
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If any of these events occurs, our ability to sell such product may be impaired, and we may incur substantial additional expense to comply with regulatory requirements, which could materially adversely affect our business, financial condition and results of operations. Regulatory policies may be enacted that could prevent, limit or delay regulatory approval of our product candidates. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, which would adversely affect our business, prospects and ability to achieve or sustain profitability.

We have conducted and may in the future conduct clinical studies for our drug candidates outside the U.S., Europe and Switzerland, and the FDA, EMA and Swissmedic and applicable foreign regulatory authorities may not accept data from such studies.

We, or our collaboration partners, have conducted and may in the future choose to conduct one or more of our clinical studies outside the U.S., Europe and Switzerland. The acceptance of study data from clinical studies conducted outside the U.S., Europe and Switzerland or another jurisdiction by the FDA, EMA and Swissmedic or applicable foreign regulatory authority may be subject to certain conditions. In cases where data from foreign clinical studies are intended to serve as the basis for marketing approval, for instance in the U.S., the FDA will not approve the application on the basis of foreign data alone unless the following are true: the data are applicable to the U.S. population and U.S. medical practice; the studies were performed by clinical investigators of recognized competence; and the data are considered valid without the need for an on-site inspection by the FDA or, if the FDA considers such an inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. Additionally, the FDA’s clinical study requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory bodies have similar requirements. In addition, such foreign studies would be subject to the applicable local laws of the foreign jurisdictions in which the studies are conducted. There can be no assurance that the FDA, EMA, Swissmedic or any applicable foreign regulatory authority will accept data from studies conducted outside of the U.S. or the applicable jurisdiction. If the FDA, EMA, Swissmedic or any applicable foreign regulatory authority does not accept such data, it would result in the need for additional studies, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our drugs or drug candidates not receiving approval or clearance for commercialization in the applicable jurisdiction.

Even if certain of our product candidates obtain regulatory approval, we will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expenses. Additionally, our additional product candidates, if approved, could be subject to labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.

If marketing authorization is obtained for certain of our product candidates, the products will remain subject to continual regulatory review and therefore authorization could be subsequently withdrawn or restricted. Any regulatory approvals that we receive for certain of our product candidates may also be subject to limitations on the approved indicated uses for which the products may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including phase 4 clinical studies, and surveillance to monitor the safety and efficacy of the product candidate. In addition, if the FDA or a comparable regulatory authority approves any of our product candidates in development, we will be subject to ongoing regulatory obligations and oversight by regulatory authorities, including with respect to the manufacturing processes, labeling, packing, distribution, adverse event reporting, storage, advertising and marketing restrictions, and record-keeping and, potentially, other post-marketing obligations, all of which may result in significant expense and limit our or our collaboration partners’ ability to commercialize such products. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and cGCP requirements for any clinical studies that we conduct post-approval. Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things:

•	restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls;

•	fines, warning letters or holds on clinical studies;
•	refusal by the FDA to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of product license approvals;
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•	regulatory constraints in promotion and distribution of drug products in various markets;
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•	product seizure or detention, or refusal to permit the import or export of products; and
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•	injunctions or the imposition of civil or criminal penalties.
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Our business is subject to complex and evolving U.S. and international laws and regulations regarding clinical trials reimbursement and privacy and data protection. Many of these laws and regulations are subject to change and uncertain interpretation and could result in claims, changes to our business practices, penalties, increased cost of operations, or declines in user growth or engagement, or otherwise harm our business.

Regulatory authorities around the world have adopted laws and regulations and are continuing to consider a number of legislative and regulatory proposals, concerning privacy and data protection, including measures to ensure that encryption of users’ data does not hinder access of law enforcement agencies to that data. In addition, the interpretation and application of consumer and data protection laws in the U.S., Europe, Switzerland and elsewhere are often uncertain and in flux. It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our data practices. These laws and regulations, and legislative and regulatory proposals, if adopted, and such interpretations could, in addition to the possibility of fines, result in an order requiring that we change our data practices, which could have an adverse effect on our business and results of operations. Complying with these various laws could cause us to incur substantial costs or require us to change our business practices in a manner adverse to our business.

In the EU, new clinical trial regulations came into force on January 31, 2022. This new legislation enforces the centralization of clinical trial applications and approvals, New clinical trial sponsors must begin using the new system by January 31, 2023, and any previously approved trial sponsors must comply from January 31, 2025, but in some cases, this may extend timelines for clinical study approvals, due to potentially longer wait times enabling sponsors to apply for trial authorization in up to 30 European countries with a single online application. The General Data Protection Regulation (GDPR), which became effective in May 2018 in all EU member states, created a range of new compliance obligations for companies that process the personal data of EU residents. Although it is expected that the GDPR will provide consistency across the territory of the EU, it imposes more onerous requirements concerning consent and the obligations of sponsors of clinical trials (acting as data controllers), among other measures, which may increase the costs and extend the timelines of our product development efforts. Austerity measures in certain European nations may also affect the prices we are able to seek if our products are approved, as discussed below. Furthermore, the Brexit vote and the impact of the withdrawal of the UK may adversely affect business activity, political stability and economic conditions in the UK, the Eurozone, the EU and elsewhere. Specifically, Brexit and ongoing developments in the UK have created uncertainty with regard to data protection regulation in the UK. We may be required to comply with both the GDPR and the UK GDPR, exposing us to two parallel regimes with potentially divergent interpretations and enforcement actions for certain violations. The relationship between the UK and the EU in relation to certain aspects of data protection law remains unclear, for example, how data transfers between EU member states and the UK will be treated and the role of the UK’s Information Commissioner’s Office with respect to the EU following the end of the transitional period. Although we do not have material operations in the UK, we cannot rule out potential disruptions in relation to the clinical regulatory framework applicable to our clinical studies in the UK, and to data privacy and security rules with respect to personal data sharing with vendors and clinical investigators in the UK, and we cannot predict future implications.

Both in the U.S. and in the EU, legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical and biopharmaceutical products. We do not know whether additional legislative changes will be enacted, whether the regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be.

We could be subject to liabilities under environmental, health and safety laws or regulations, or fines, penalties or other sanctions, if we fail to comply with such laws or regulations or otherwise incur costs that could have a material adverse effect on the success of our business.

We are subject to numerous environmental, health and safety laws, regulations, and permitting requirements, including those governing laboratory procedures, decontamination activities, and the handling, transportation, use, remediation, storage, treatment and disposal of hazardous materials, human substances and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials that produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials or wastes either at our sites or at third-party disposal sites. In the event of such contamination or injury, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties. Although we maintain workers’ compensation insurance to cover us for costs and expenses, we may incur due to injuries to our employees resulting from the use of hazardous materials, human substances or other work-related injuries, this insurance may not provide adequate coverage against potential liabilities.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws, regulations or permitting requirements. Such laws, regulations and requirements are becoming increasingly more stringent and may impair our research, development or production efforts. Failure to comply with these laws, regulations and permitting requirements also may result in substantial fines, penalties or other sanctions.

Our relationships with clinical centers, customers and payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which, if violated, could expose us to criminal sanctions, civil penalties, exclusion from government healthcare programs, contractual damages, reputational harm and diminished profits and future earnings.

•	for instance, the U.S. healthcare Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under U.S. government healthcare programs such as Medicare and Medicaid;
•	for instance, the U.S. False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the U.S. government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
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•	for instance, the Health Insurance Portability and Accountability Act (HIPAA), imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
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•	HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
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•	for instance, the transparency requirements under the Health Care Reform Law require manufacturers of drugs, devices, biologics and medical supplies to report to the U.S. Department of Health and Human Services information related to payments and other transfers of value made by such manufacturers to physicians and teaching hospitals, and ownership and investment interests held by physicians or their immediate family members; and
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•	in various other jurisdictions, analogous laws and regulations, such as state anti-kickback and false claims laws, will apply to sales or marketing arrangements, consultancy and service agreements, and claims involving healthcare items or services reimbursed by nongovernmental third-party payors, including private insurers, and some state laws require pharmaceutical and biopharmaceutical companies to comply with the pharmaceutical and biopharmaceutical industries’ voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.
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Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available under the U.S. federal Anti-Kickback Statute, it is possible that some of our future business activities could be subject to challenge under one or more of such laws. In addition, recent healthcare-reform legislation has strengthened these laws. For example, the Health Care Reform Law, among other things, amends the intent requirement of the federal anti-kickback and criminal healthcare fraud statutes. A person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it. Moreover, the Health Care Reform Law provides that the government may assert that a claim including items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the False Claims Act.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, exclusion from U.S. government-funded healthcare programs, such as Medicare and Medicaid, other foreign healthcare reimbursement and procurement programs, and the curtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business with is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs.

Risks Related to Our Relationships with Third Parties

If we fail to maintain our strategic relationships with any of our current or future strategic partners, our business, commercialization prospects and financial condition may be materially adversely affected.

We rely, in part, on our strategic partners. Good relationships with our strategic partners are important for our business prospects. If our relationships with our current or future strategic partners were to challenge our use of their intellectual property or our calculations of the payments we are owed under our agreements, our business, financial condition, commercialization prospects and results of operations could be materially adversely affected.

We may seek to form additional strategic alliances in the future with respect to our product candidates, and if we do not realize the benefits of such alliances, our business, financial condition, commercialization prospects and results of operations may be materially adversely affected.

We face significant competition in seeking appropriate collaborators. Collaborations are complex and time-consuming to negotiate, document and manage. Any delays in entering into new strategic partnership agreements related to our product candidates could delay the development and commercialization of our product candidates and reduce their competitiveness even if they reach the market. We may also be restricted under existing and future collaboration agreements from entering into strategic partnerships or collaboration agreements on certain terms with other potential collaborators. We may not be able to negotiate collaborations on acceptable terms, or at all, for any of our existing or future product candidates and programs because the potential partner may consider that our research and development pipeline is insufficiently developed to justify a collaborative effort, or that our product candidates and programs do not have the requisite potential to demonstrate safety and efficacy in the target population. If we are unsuccessful in establishing and maintaining a collaboration with respect to a particular product candidate, we may have to curtail the development of that product candidate, reduce the scope of or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of our sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense, for which we have not budgeted. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we will not be able to bring our product candidates to market and generate product revenue. Even if we are successful in establishing a new strategic partnership or entering into a collaboration agreement, we cannot be certain that, following such a strategic transaction or license, we will be able to progress the development and commercialization of the applicable product candidates as envisaged, or that we will achieve the revenues that would justify such transaction, and we could be subject to the following risks, each of which may materially harm our business, commercialization prospects and financial condition:

•	we may not be able to control the amount and timing of resources that the collaboration partner devotes to the product development program;
•	the collaboration partner may experience financial difficulties;
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•	we may be required to grant or otherwise relinquish important rights such as marketing, distribution and intellectual property rights; or
•	business combinations or significant changes in a collaboration partner’s business strategy may adversely affect our willingness to continue any arrangement.
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We rely on third parties to conduct our nonclinical and clinical studies and perform other tasks for us. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval for or commercialize our product candidates, and our business could be substantially harmed.

We have relied upon and plan to continue to rely upon third-party clinical research organizations or contract research organizations (CROs), to monitor and manage data for our ongoing nonclinical and clinical programs, including the clinical studies of our product candidates. We rely on these parties for execution of our nonclinical and clinical studies and control only certain aspects of their activities. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory, and scientific standards and our reliance on the clinical CROs does not relieve us of our regulatory responsibilities. We and our clinical CROs and other vendors are required to comply with current Good Manufacturing Practice (cGMP), current Good Clinical Practice (cGCP), and current Good Laboratory Practice (cGLP), which are regulations and guidelines enforced by the FDA, the Competent Authorities of the Member States of the EU and comparable foreign regulatory authorities for our product candidates in nonclinical and clinical development (where applicable). Regulatory authorities enforce these regulations through periodic inspections of study sponsors, principal investigators, study sites and other contractors. If we or any of our clinical CROs or vendors fail to comply with applicable regulations, the data generated in our nonclinical and clinical studies may be deemed unreliable and the EMA, FDA, other regulatory authorities may require us to perform additional nonclinical and clinical studies before approving our marketing applications. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that all of our clinical studies comply with cGCP regulations. In addition, our clinical studies must be conducted with products produced under cGMP regulations. Our failure to comply with these regulations may require us to repeat clinical studies, which would delay the regulatory approval process.

If any of our relationships with these third-party clinical CROs terminates, we may not be able to enter into arrangements with alternative clinical CROs or do so on commercially reasonable terms. In addition, our clinical CROs are not our employees, and except for remedies available to us under our agreements with such clinical CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing nonclinical and clinical programs. If clinical CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the data they obtain is compromised due to their failure to adhere to our protocols, regulatory requirements, or for other reasons, our clinical studies may be extended, delayed, or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. Clinical CROs may also generate higher costs than anticipated. As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase, and our ability to generate revenue could be delayed.

Switching or adding additional clinical CROs involves additional cost and requires management time and focus. In addition, there is a natural transition period when a new clinical CROs commences work. As a result, delays occur, which could materially impact our ability to meet our desired clinical development timelines. Though we carefully manage our relationships with our clinical CROs, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.

We currently rely on third-party suppliers and other third parties for production of our product candidates and our dependence on these third parties may impair the advancement of our research and development programs and the development of our product candidates.

We currently rely on and expect to continue to rely on third parties for the manufacturing and supply of chemical and biological compounds and formulations for the clinical studies of our current and future product candidates. For the foreseeable future, we expect to continue to rely on such third parties for the manufacture of any of our product candidates on a clinical or commercial scale, if any of our product candidates receives regulatory approval. Reliance on third-party providers may expose us to different risks than if we were to manufacture product candidates ourselves. The facilities used by our contract manufacturers to manufacture our product candidates must be approved by the FDA or other regulatory authorities, pursuant to inspections that will be conducted after we submit our NDA or comparable marketing application to the FDA or other regulatory authority. We do not have control over a supplier’s or manufacturer’s compliance with these laws, regulations and applicable cGMP standards and other laws and regulations, such as those related to environmental health and safety matters. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or others, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities. In addition, we have no control over the ability of our contract manufacturers to maintain adequate quality control (QC), quality assurance (QA) and qualified personnel. If we are compelled or we wish to find alternative manufacturing facilities, this could significantly impact our ability to develop, obtain regulatory approval for or market our product candidates. Any failure to achieve and maintain compliance with these laws, regulations and standards could subject us to the risk that we may have to suspend the manufacturing of our product candidates or that obtained approvals could be revoked, which would adversely affect our business and reputation.

Third-party providers may breach agreements they have with us because of factors beyond our control. Contract manufacturers often encounter difficulties involving production yields, QC and QA, as well as shortages of qualified personnel. They may also terminate or refuse to renew their agreements because of their own financial difficulties or business priorities, potentially at a time that is costly or otherwise inconvenient for us. If we are unable to find adequate replacement or another acceptable solution in time, our clinical studies could be delayed, or our commercial activities could be harmed.

In addition, the fact that we are dependent on our suppliers and other third parties for the manufacture, storage and distribution of our product candidates means that we are subject to the risk that our product candidates and, if approved, commercial products may have manufacturing defects that we have limited ability to prevent or control. The sale of products containing such defects could result in recalls or regulatory enforcement action that could adversely affect our business, financial condition and results of operations.

Growth in the costs and expenses of components or raw materials may also adversely influence our business, financial condition and results of operations. Supply sources could be interrupted from time to time and, if interrupted, we cannot be certain that supplies could be resumed (whether in part or in whole) within a reasonable timeframe and at an acceptable cost or at all. Our current and anticipated future dependence upon others for the manufacturing of our current and future product candidates may adversely affect our future profit margins and our, or our collaboration partners’, ability to commercialize any products that receive marketing approval on a timely and competitive basis.

Risks Related to Intellectual Property

We may not have sufficient patent terms to protect our products and business effectively.

Patents have a limited lifespan. In the U.S. and Europe, the natural expiration of a patent is generally 20 years after it is filed. Although various extensions or adjustments may be available, such as adjustments based on certain delays caused by the U.S. Patent and Trademark Office (the USPTO) or the European Patent Office (EPO) to the life of a patent, and the protection it affords, is limited. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned, co-owned and licensed patent portfolios may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours or otherwise provide us with a competitive advantage. Even if patents covering our product candidates are obtained and unchallenged, once the patent life has expired for a product, we may be open to competition from generic medications.

Although patent term extensions under the Hatch-Waxman Act in the U.S. and under supplementary protection certificates (SPCs) in Europe may be available to extend the patent exclusivity term for our products, we cannot provide any assurances that any such patent term extension will be obtained and, if so, for how long. The Hatch-Waxman Act permits a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended, and only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended. However, we may not be granted any extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. It is not possible to base an SPC in Europe on a patent in a European Member State if that patent expires before the market approval of the clinical product, protected by the patent, is obtained. As the “product” (active ingredient(s)) must be “protected by a basic patent in force”, only a granted patent that is in force, and remains in force until it reaches the end of its full term, can serve as a “basic patent” upon which an SPC can be based. Therefore, expired patents and pending patent applications cannot serve as the basis for an SPC. Given the relatively long clinical development timelines of biologicals and new chemical entities for therapeutic purpose, we may not be granted any patent extensions as we might fail to apply for the extensions prior to expiration of relevant patents. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or if the term of any such extension is less than we request, such result could have a material adverse effect on our business.

We or our licensing or collaboration partners may become subject to intellectual property-related litigation or other proceedings to protect or enforce our patents or the patents of our licensors or licensees and collaborators, any of which could be expensive, time-consuming, and unsuccessful, and may ultimately result in our loss of ownership of intellectual property.

Competitors may infringe our patents or the patents of our licensors or collaborators. To counter such infringement, we may be required to file infringement claims against those competitors, which can be expensive and time-consuming. If we or one of our licensing or collaboration partners were to initiate legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid or unenforceable or that the defendant’s products do not infringe our or our licensing collaborators’ patents or that we or our licensing collaborators infringe the defendant’s patents. In patent litigation in the U.S., defendant counterclaims alleging invalidity, unenforceability and non-infringement are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, obviousness-type double patenting, lack of written description, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO or the EPO, or made a misleading statement, during prosecution. In addition, third parties may raise similar claims before administrative bodies in the U.S., in Europe or elsewhere, even outside the context of litigation. Such mechanisms include re-examination, post-grant review, inter partes review, interference and derivation proceedings as well as equivalent proceedings in foreign jurisdictions, such as opposition proceedings in Europe. The outcome following legal assertions of invalidity and unenforceability is unpredictable. Such proceedings or patent litigations could result in the revocation or cancellation of or amendment to our patents in such a way that they no longer cover our product candidates or otherwise provide any competitive advantage. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which the patent examiner and we or our licensing or collaboration partners were unaware during prosecution. A court may also refuse to stop a third party from using the technology in question on the grounds that our patents do not cover that technology. An adverse result in any proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly, which could have a material adverse effect on our business and financial condition.

Interference proceedings provoked by third parties or brought by us or declared by the USPTO or the EPO may be necessary to determine the priority of inventions with respect to our patents or patent applications or those of our licensors, licensees or collaborators. An unfavorable outcome could require us or our licensing or collaboration partners to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be materially harmed if the prevailing party does not offer us or our licensing or collaboration partners a license on commercially reasonable terms or at all. If we or our licensing or collaboration partners are unsuccessful in any interference proceedings, we may lose our ownership of intellectual property, or our patents may be narrowed or invalidated. There can be no assurance as to the outcome of the interference and opposition proceedings, and any of the foregoing could result in a material adverse effect on our business, financial condition, results of operations or prospects.

Our defense of litigation, interference proceedings or other intellectual property-related proceedings may fail and, even if successful, may result in substantial costs and distract our management and other employees from their normal responsibilities. Such litigation or proceedings could substantially increase our operating losses and could substantially reduce the funds necessary to continue our clinical studies and research programs or force us to license necessary technology from third parties or enter into development partnerships that would help us bring our product candidates to market. We may not be able to prevent, alone or with our licensing or collaboration partners, misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the U.S.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions, decisions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our Shares.

If we or our licensing or collaboration partners are unable to obtain and maintain effective patent rights for our technologies, product candidates or any future product candidates, or if the scope of the patent rights obtained is not sufficiently broad, our competitors could develop and commercialize products and technology similar or identical to ours, and our, or our collaboration partners’ ability to successfully commercialize our products and technology may be adversely affected.

We rely upon a combination of patents, trade secret protection and confidentiality agreements to protect the intellectual property related to our technologies and product candidates. Our success depends in large part on our and our licensing or collaboration partners’ ability to obtain and maintain patent and other intellectual property protection in the U.S., the EU and other countries with respect to our proprietary technologies and product candidates. If such license is not granted or terminated, our licensing or collaboration partners may be required to cease development and commercialization of our product candidates, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.

We have sought to protect our proprietary position by filing patent applications in the U.S. and other countries related to any of our novel technologies and products that are important to our business. This process is expensive, time-consuming, and complex, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost, in a timely manner or in all jurisdictions. It is also possible that we will fail to identify patentable aspects of our or our licensing or collaboration partners’ research and development output before it is too late to obtain patent protection. Moreover, in some circumstances, we do not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we license to or from third parties. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.

The patent position of pharmaceutical and biopharmaceutical companies generally is highly uncertain and involves complex legal and factual questions for which legal principles remain unsolved. As a result, the inventorship, issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain. The pending or future patent applications that we own, co-own or in-license may fail to issue, fail to result in issued patents with claims that cover our product candidates in the U.S. or in other countries, or fail to effectively prevent others from commercializing competitive technologies and product candidates. Changes in either the patent laws or interpretation of the patent laws in the U.S. and other countries may diminish the value of our patents or narrow the scope of our patent protection.

We may not be aware of all third-party intellectual property rights potentially relating to our technologies or product candidates. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions remain confidential for a period of time after filing, and some remain so until issued. Therefore, we cannot be certain that we were the first to file any patent application related to our product candidates or technologies, or whether we were the first to make the inventions claimed in our owned or co-owned patents or pending patent applications, nor can we know whether those from whom we license patents were the first to make the inventions claimed or were the first to file.

There is no assurance that all potentially relevant prior art relating to our patents and patent applications has been found, which can invalidate a patent or prevent a patent from issuing from a pending patent application. Even if patents do successfully issue, and even if such patents cover our product candidates, third parties may challenge their validity, enforceability, or scope, which may result in such patents being narrowed, found unenforceable or invalidated, which could allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our or our collaboration partners’ inability to manufacture or commercialize products without infringing third-party patent rights. Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property, provide exclusivity for our product candidates, prevent others from designing around our claims or provide us with a competitive advantage. Any of these outcomes could impair our ability to prevent competition from third parties, which may have a material adverse effect on our business.

We may be subject to claims challenging the inventorship of our patents and other intellectual property.

We may be subject to claims that former employees, collaborators or other third parties have an interest or title in our patents or other intellectual property as an inventor or co-inventor. For example, we may have inventorship disputes arise from conflicting obligations of consultants, CROs, contract manufacturing organizations (CMOs), academic institutions or others who are involved in developing our product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or our ownership of our patents or other intellectual property. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or the right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Patent policy and rule changes could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, thereby impairing our ability to protect our technologies and products.

Changes in either the patent laws or interpretation of the patent laws in the U.S., EU or elsewhere could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents. Assuming the other requirements for patentability are met, in the U.S. prior to March 15, 2013, the first to make the claimed invention is entitled to the patent, whereas outside the U.S., the first to file a patent application was entitled to the patent. After March 15, 2013, under the Leahy-Smith America Invents Act (the Leahy-Smith Act), which was enacted on September 16, 2011, the U.S. moved to a first-to-file system. Under a first-to-file system, assuming the other requirements for patentability are met, the first inventor to file a patent application generally will be entitled to the patent on an invention regardless of whether a third party was the first to invent the invention. The Leahy-Smith Act also includes a number of significant changes that affect the way patent applications are prosecuted and may also affect patent litigation. These include allowing third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent by the USPTO administered during post grant proceedings, including re-examination proceedings, inter partes review, post-grant review and derivation proceedings. Therefore, the Leahy-Smith Act and its implementation increases the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and prospects. In addition, future actions by the U.S. Congress, the federal courts and the USPTO could cause the laws and regulations governing patents to change in unpredictable ways. Any of the foregoing could harm our business, financial condition and results of operations.

In addition, the patent positions of companies in the development and commercialization of biologics and pharmaceuticals are particularly uncertain. U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. This combination of events has created uncertainty with respect to the validity and enforceability of patents, once obtained. Depending on future actions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on our existing patent portfolio and our ability to protect and enforce our intellectual property in the future in the U.S.

If we are unable to maintain effective proprietary rights for our technologies, product candidates or any future product candidates, we may not be able to compete effectively in our markets.

In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce, and any other elements of our product candidate discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents. However, trade secrets can be difficult to protect and some courts inside and outside the U.S. are less willing or unwilling to protect trade secrets. For instance, the EU has introduced a new Directive on trade secrets increasing the standards for protection. Because we rely on our advisors, employees and third-party contractors and consultants to research and develop and to manufacture our product candidates, we must, at times, share our intellectual property with them. We seek to protect our intellectual property and other proprietary technology in part by entering into confidentiality agreements and master service agreements, if applicable, material transfer agreements, consulting agreements or other similar agreements with our advisors, employees, contractors, consultants, licensing and collaboration partners, and other third parties with confidentiality provisions. These agreements typically limit the rights of these third parties to use or disclose our confidential information, including our intellectual property and trade secrets. These agreements also typically restrict the ability of third parties to publish data potentially relating to our intellectual property, although our agreements may contain certain limited publication rights. For example, any academic institution that we may collaborate with in the future may expect to be granted rights to publish data arising out of such collaboration, provided that we may have the right to be notified in advance and given the opportunity to delay publication for a limited time period in order for us to secure patent protection of intellectual property rights arising from the collaboration, in addition to the opportunity to remove confidential or trade secret information from any such publication. We also conduct joint research and development programs that may require us to share intellectual property under the terms of our research and development or similar agreements. However, we cannot guarantee that we have entered into such agreements with each party that may have or have had access to our trade secrets or other confidential information or proprietary technology and processes, or that such agreements will not be breached or that our trade secrets or other confidential information will not otherwise be disclosed. Despite the contractual provisions employed when working with these advisors, employees and third-party contractors and consultants, the need to share intellectual property and other confidential information increases the risk that such confidential information becomes known by our competitors, is inadvertently incorporated into the product development of others or is disclosed or used in violation of these agreements. Additionally, our grant agreements typically provide for dissemination of results to academic institutions and to the general public. As a result, our information may be disseminated with the loss of protection status.

We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining the physical security of our premises and the physical and electronic security of our information technology systems. Despite our efforts to protect our intellectual property, our competitors may discover our trade secrets through breach of our agreements by third parties, for which we may not have adequate remedies for any breach, or publication of information by any of our CROs, academic partners, funding organizations or our licensing or collaboration partners. Additionally, if the steps taken to maintain our trade secrets are deemed inadequate by law, we may have insufficient recourse against third parties for misappropriating such trade secrets. Misappropriation or unauthorized disclosure of our trade secrets could impair our competitive position and may have a material adverse effect on our business. Moreover, if any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent such competitor or other third party from using that technology or information to compete with us. A competitor’s or other third party’s discovery of our intellectual property would impair our competitive position and have a material adverse effect on our business.

Further, the laws of different countries protect proprietary rights to a different extent or in a different manner. As a result, we may encounter significant problems in protecting and defending our intellectual property in different countries both in the U.S. and abroad. If we are unable to prevent material disclosure of the intellectual property related to our technologies to third parties, we will not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, financial condition and results of operations.

Despite confidentiality clauses within our employment agreements, we cannot ensure that departing employees will not breach any post-termination commitments in such agreements by allowing others to access our trade secrets.

Obtaining and maintaining our patent protection depends on compliance with various procedural, document-submission, fee-payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.

Periodic maintenance fees, renewal fees, annuity fees and various other government fees on a patent and patent application are due to be paid to the USPTO and other national patent agencies in several stages over the lifetime of the patent and patent application. The USPTO, the EPO and various other governmental patent agencies require compliance with a number of procedural, documentary, fee-payment and other similar provisions during the patent application process. We employ reputable law firms and other professionals to help us comply with these requirements and we are also dependent on our licensors or collaboration partners to take the necessary action to comply with these requirements with respect to certain of our intellectual property. Although an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Noncompliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, nonpayment of fees and failure to properly legalize and submit formal documents. In such an event, our competitors might be able to enter the market, which would have a material adverse effect on our business.

The patent protection and patent prosecution for some of our product candidates could be dependent on third parties.

Although we normally seek to obtain the right to control prosecution, maintenance and enforcement of the patents relating to our product candidates, there may be times when the filing and prosecution activities for patents relating to our product candidates are controlled by our licensors or collaboration partners. If any of our current or future licensing or collaboration partners fail to prosecute, maintain and enforce such patents and patent applications in a manner consistent with the best interests of our business, including by payment of all applicable fees for patents covering our product candidates, we could lose our rights to the intellectual property or our exclusivity with respect to those rights, our or our collaboration partners’ ability to develop and commercialize those product candidates may be adversely affected and we may not be able to prevent competitors from making, using, and selling competing products. In addition, even where we have the right to control patent prosecution of patents and patent applications we have licensed to and from third parties, we may still be adversely affected or prejudiced by actions or inactions of our licensees, our licensors and their counsel that took place prior to the date upon which we assumed control over patent prosecution.

Additionally, we may be adversely affected or prejudiced by actions or inactions of our external and internal patent counsels working solely on our projects or our joint patent counsels representing us and our collaboration partners.

Third-party claims of intellectual property infringement may expose us to substantial liability or may prevent or delay our or our collaboration partners’ development and commercialization efforts.

Numerous EU- and foreign-issued patents and pending patent applications, which are owned by third parties, exist in the fields in which we are developing product candidates. For example, we are aware of third-party patents or patent applications that may be construed to cover one or more of our product candidates. If these patents are asserted against us or our licensing or collaboration partners and either we or our licensing or collaboration partners are found to infringe any of these patents, and are unsuccessful in demonstrating that such patents are invalid or unenforceable, then we and our licensing or collaboration partners could be required to pay substantial monetary damages or cease further development or commercialization of one or more of our product candidates or be compelled to enter into onerous licenses with such third parties. There may also be other third-party patents or patent applications with claims to materials, formulations, methods of manufacture or methods of treatment related to the use or manufacture of our product candidates and technology. Although we generally conduct a freedom-to-operate search and review with respect to our product candidates, we cannot guarantee that our search and review is complete and thorough, nor can we be sure that we have identified each and every patent and pending application in the U.S. and abroad that is relevant or necessary to the manufacturing or commercialization of our product candidates or use of our technology. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our product candidates may infringe. In addition, third parties may file and obtain additional patents in the future and claim that use of our technologies infringes upon these patents.

Third parties may assert infringement claims against us based on existing patents or on patents that may be granted in the future, regardless of merit. Even if we believe such claims are without merit, a court of competent jurisdiction could hold that these third-party patents are valid, enforceable and infringed, which could materially and adversely affect our or our collaboration partners’ ability to commercialize our product candidates or technologies covered by the asserted third-party patents.

Parties making claims against us may also obtain injunctive or other equitable relief, which could effectively block our or our collaboration partners’ ability to further develop and commercialize one or more of our product candidates. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of management and employee resources from our business. In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties, redesign our infringing products or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure. Any of the foregoing could have a material and adverse effect on our business, financial conditions, results of operations and prospects.

In addition, claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business, financial condition, results of operations and prospects.

There could also be public announcements of the results of hearings, motions, decisions, or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our Shares.

Some of our competitors may have substantially greater resources and more mature and developed intellectual property portfolios than we do and may be able to sustain the costs of complex intellectual property litigation to a greater degree and for longer periods of time than we could. In addition, patent-holding companies that focus solely on extracting royalties and settlements by enforcing patent rights may target us. As the pharmaceutical and biopharmaceutical industries expand and more patents are issued, the risk increases that our product candidates may be subject to claims of infringement of the patent rights of third parties. The uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace.

We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

We employ and utilize the services of individuals who were previously employed or provided services to universities or other pharmaceutical or biopharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants, and independent contractors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of any of our employees’, consultants’ or independent contractors’ former employers or of other third parties. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, which could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

In addition, although it is our policy to require our employees, consultants and independent contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own. The assignment of intellectual property rights may not be self-executing or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries may be less extensive than those in the U.S. or Europe. In addition, the laws of different countries do not protect intellectual property rights to the same extent as the laws in the U.S. or Europe. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the U.S. or Europe, or from selling or importing products made using our inventions in and into the U.S., Europe or other jurisdictions. In the ordinary course of prosecution and maintenance activities, we determine whether to seek patent protection outside the U.S. and Europe and in which countries. This also applies to patents we have acquired or in-licensed from third parties. In some cases, we, or our predecessors in interest or licensors of patents within our portfolio, have sought patent protection in a limited number of countries for patents covering our product candidates. Competitors may use our technologies and products in jurisdictions where we have not obtained or are unable to adequately enforce patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection but enforcement is not as strong as that in the U.S. or Europe. These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing, which would have a material adverse effect on our business and financial positions.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets, and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement, misappropriation or other violations of our intellectual property and proprietary rights. Proceedings to enforce our patent rights in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

We may be unable to protect our trade secrets, know-how and technologies.

We also rely on trade secrets and non-patentable know-how and technologies it seeks to protect, in part, by confidentiality agreements with our employees, consultants, suppliers, licensees and other contractual parties. Trade secrets and non-patentable know-how and technologies are difficult to protect. There can be no assurance that these agreements represent effective protection or that they will not be breached, that we would have adequate remedies for any breach, or that our trade secrets or non-patentable know-how and technologies will not otherwise become known or be independently developed by competitors and other third parties.

These and other factors, alone or together, may have a material adverse effect on our business, financial condition, results of operations and growth prospects as well as the price of our shares.

Risks Related to Our Financial Condition and Results of Operations

We are a commercial-stage biopharmaceutical company with a history of operating losses. Our recurring losses, negative cash flows and significant accumulated deficit raise substantial doubt regarding our ability to continue as a going concern.

We incurred a net loss (defined as net loss attributable to owners of the Company) of approximately CHF 50.8 million for the year ended December 31, 2022 and had accumulated losses at consolidation level of approximately CHF 119.6 million as of December 31, 2022. We may continue to incur losses in the foreseeable future as development expenses and other operating expenses may exceed future revenue.

Our losses have resulted principally from research and development expenses and from general business and administrative expenses. We expect to continue to incur significant operating losses in the future as we continue our research and development efforts for our current and future product candidates and seek to obtain regulatory approval and commercialization of such product candidates. The amount of future losses is uncertain and our ability to achieve profitability, if ever, will depend on, among other things, us or partners successfully developing drug candidates, obtaining regulatory approval to market and commercialize drug candidates, manufacturing any approved products on commercially reasonable terms, growing our sales and marketing organization for any additional approved product and raising sufficient funds to finance our activities. We cannot guarantee that we will have sufficient funds available in the future to develop and commercialize our current or future drug candidates.

To date, we have financed our liquidity requirements primarily from equity financings and loans from our largest shareholder. Biopharmaceutical and pharmaceutical product development are highly speculative undertakings and involve a substantial degree of risk.

As of April 30, 2023, we have cash and cash equivalents of approximately CHF 11.1 million. We believe that our current cash and cash equivalents are sufficient to fund our operating expenses into the third quarter of 2023 and this raises substantial doubt about our ability to continue as a going concern. These factors individually and collectively indicate that a material uncertainty exists that may cast significant doubt about our ability to continue as a going concern. Our future viability is dependent on our ability to raise additional capital to finance our future operations. We may seek additional funding through public or private financings, debt financing or collaboration agreements. The inability to obtain funding, as and when needed, would have a negative impact on our financial condition and ability to pursue our business strategies. If we are unable to obtain the required funding to run our operations and to develop and commercialize our candidates, we could be forced to delay, reduce or eliminate some or all of our research and development programs, drug portfolio expansion or commercialization efforts, which could adversely affect our business prospects, or we may be unable to continue operations. Management continues to explore options to obtain additional funding. However, there is no assurance that we will be successful in raising funds, closing a collaboration agreement, obtaining sufficient funding on terms acceptable to us, or if at all, which could have a material adverse effect on our business, results of operations and financial conditions.

If we fail to obtain additional funding, we may delay, reduce or eliminate our product development programs or commercialization efforts.

We are currently advancing our product candidates through clinical development, either together with a collaboration partner or independently. We expect our research and development expenses to continue to increase in connection with our ongoing activities, particularly as we and/or our collaboration partners continue our ongoing studies and initiate new studies and initiate preclinical and clinical development of our product candidates.

We will require additional capital to develop and commercialize certain of our product candidates. If we receive regulatory approval for our current and future product candidates, and if we have not already licensed such product candidate to a collaboration partner and choose to commercialize such product candidate independently, we expect to incur significant commercialization expenses related to product manufacturing, sales, marketing, distribution and establishing a regulatory structure, depending on where we choose to commercialize. Additional funds may not be available on a timely basis, on favorable terms, or at all, and such funds, if raised, may not be sufficient to enable us to continue to implement our long-term business strategy. Additionally, we may be dependent on the status of the capital markets at the time such capital is sought. If we are not able to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

Raising additional capital may cause dilution to our shareholders, restrict our operations or require us to relinquish rights to our intellectual property or future revenue streams.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our liquidity needs through a combination of equity offerings, debt financings, grants, and license and development agreements in connection with collaborations. We do not have any material committed external source of funds. In the event we need to seek additional funds, we may raise additional capital through the sale of equity, convertible debt or other securities, and through drawdowns from our Share Subscription Facility in place with GEM Global Yield LLC SCS (GEM). In such an event, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a holder of our Shares. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or proposing dividends to our shareholders.

If we raise additional funds through collaborations, strategic alliances, or marketing, distribution or licensing arrangements with third parties, we may have to grant or otherwise relinquish valuable rights to our intellectual property or future revenue streams.

Exchange rate fluctuations may materially affect our results of operations and financial condition.

As our reporting currency is the Swiss franc, transactions and balance sheet items denominated in foreign currencies are converted into Swiss francs at the applicable exchange rates. Our current expenses are denominated in Swiss francs, U.S. Dollars and Euros. In the future, we expect that the majority of our revenue and expenses will be in U.S. Dollars and Euros. Therefore, unfavorable developments in the value of the Swiss franc as compared to the U.S. Dollar and Euro could have a material adverse effect on our business, financial condition and results of operations.

The SIX Exchange Regulation AG has launched an investigation into Relief, the results of which are uncertain.

The SIX Exchange Regulation AG – the self-regulatory supervisory body for issuers listed on the SIX Swiss Exchange – has launched a formal investigation into Relief due to potential violations of the rules on ad-hoc publicity. While we do not believe that this investigation will have a material adverse effect on our business, there can be no assurance of that conclusion.

ITEM 4	INFORMATION ON THE COMPANY
A.	HISTORY AND DEVELOPMENT OF THE COMPANY
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Relief was formed in 2013 and became public in 2016 following a reverse merger with THERAMETRICS holding AG. The latter was formed in 2007 under the company name i-Mondo AG, which later in 2007 was changed to mondoRPHAN AG, in 2008 to mondoBIOTECH holding AG, in 2013 to THERAMETRICS holding AG, and to RELIEF THERAPEUTICS Holding SA in 2016. RELIEF THERAPEUTICS Holding SA and its predecessors have been listed on the SIX Swiss Exchange since 2009.

Our legal seat is located in Geneva, Switzerland. Our registered office is located at Avenue de Sécheron 15, 1202 Genève, Switzerland, and our telephone number is +41 22 545 11 16. Our website address is http://www.relieftherapeutics.com. The reference to our website is for textual reference only and information contained in, or that can be accessed through, our website or any other website cited in this annual report is not a part thereof.

B.	BUSINESS OVERVIEW

We are a Swiss, commercial-stage biopharmaceutical company committed to delivering innovative treatment options with the potential for transformative outcomes to benefit those suffering from rare debilitating conditions that have no or limited treatment options. Our cost-effective, capital-efficient approach to drug development and commercialization is focused on rare metabolic disorders, rare skin diseases, rare respiratory diseases and rare monogenetic diseases.

Our portfolio offers a balanced mix of marketed, revenue-generating products, our proprietary, globally patented drug delivery platform technologies that have utility for development in other specialty or rare disease therapeutic areas and a highly targeted clinical development pipeline consisting of risk-mitigated assets that have been engineered for improvements in efficacy, safety or convenience to benefit the lives of patients. In addition, the Company is commercializing several legacy products via licensing and distribution partners.

We are actively pursuing a strategy to diversify our portfolio through the ongoing evaluation of potential in-licensing opportunities. To bring treatments to patients as quickly as possible, we are seeking partnerships with, or acquisitions of, companies that have late-stage clinical molecules with a strong human safety profile, allowing for relatively short, capital-efficient clinical trials with clear endpoints. We are also evaluating prospective opportunities that fit within our genetic medicine initiative for devastating, as-yet-unaddressed, rare monogenetic diseases.

We are led by a proven and seasoned management team of business leaders with significant experience in discovering, developing and commercializing important new medicines, delivering them to market and maximizing shareholder value. Collectively, the members of our management team have overseen research and development of products supporting regulatory approvals as well as commercial launches of marketed products.

In March 2021, we signed a Collaboration and License Agreement with Acer Therapeutics, Inc. (Acer) for the worldwide development and commercialization of ACER-001 (now OLPRUVA™) for the treatment of urea cycle disorders (UCDs) and maple syrup urine disease (MSUD). OLPRUVA™ is a proprietary powder formulation of sodium phenylbutyrate (NaPB) designed to be both taste-masked and immediate release. In August 2021, Acer submitted an NDA for ACER-001 to the FDA for use as a treatment of UCD, which submission was accepted for filing in November 2021 with a PDUFA decision date of June 5, 2022. However, on or about the PDUFA decision date, Acer received a complete response letter stating that a satisfactory inspection of Acer’s third-party contract manufacturer would be required before its NDA for ACER-001 could be approved. On December 27, 2022, Relief and Acer announced that, after resubmission, the FDA had approved ACER-001, under the trade name OLPRUVA™, for the treatment of UCDs. In addition, Acer has filed an IND to investigate OLPRUVA™ for the treatment of MSUD.

In June 2021, we signed and closed a definitive agreement to acquire all outstanding shares of APR Applied Pharma Research SA (APR), a privately held Swiss pharmaceutical company with over 25 years’ experience in identifying, developing and globally commercializing known molecules engineered with drug delivery systems in niche and rare diseases.

In July 2021, Relief acquired AdVita Lifescience GmbH (AdVita), a Germany-based privately held pharmaceutical company developing products for the treatment and diagnosis of rare lung diseases. AdVita’s capabilities helped the Company to further progress the development of RLF-100^®^ for a range of lung diseases.

In July 2022, we executed a definitive agreement with Meta Healthcare Ltd. (Meta), acquiring the worldwide rights, except for the UK, for a novel dosage form of a prescription drug already approved by the FDA and intended for the treatment of patients with PKU. This improved product is expected to increase patient acceptance and compliance as well as enable easier, self or caregiver administered metered dosing and dispensing. According to the terms of the agreement, Meta shall transfer to Relief all data, know-how, as well as any intellectual property as developed or generated so far by Meta. Relief shall only be responsible for funding the remaining development work as well as for filing and prosecuting a NDA in all countries worldwide except for the UK where Relief Therapeutics shall grant a license back to Meta, enabling Meta to directly promote and commercialize the product in such country. Other than the initial acquisition payment and low double-digit royalty payments on net profit of the product in the various countries, Relief shall be under no obligation to fund or pay any other amount to Meta.

Previously, Relief partnered with NeuroRx, Inc. (NeuroRx) to seek to develop RLF-100^®^ as a treatment of COVID-19. In September 2020, Relief entered into a binding collaboration agreement with NeuroRx (the Collaboration Agreement). The Collaboration Agreement established the terms under which we and NeuroRx collaborate and assist each other to maximize the revenues in our respective territories from the sale of aviptadil for intravenous and inhale use primarily for the treatment of COVID-19 related conditions.

Based on numerous breaches of the Collaboration Agreement by NeuroRx, in October 2021, we filed a lawsuit against NeuroRx and its then CEO, Dr. Jonathan Javitt, for multiple breaches of the Collaboration Agreement. The complaint was filed in the Supreme Court of the State of New York in Manhattan. On January 10, 2022, NeuroRx filed a complaint against Relief alleging that we were in breach of the Collaboration Agreement and have thus repudiated and cancelled the Collaboration Agreement. Additionally, NeuroRx’s claims included a count for defamation.

On November 14, 2022, Relief and NRx issued a press release announcing that the parties had entered into a definitive settlement agreement to resolve all matters relating to the pending litigation. At the closing of this settlement, held on December 19, 2022, (i) NRx transferred to Relief all of the assets that it previously used in its aviptadil development program, including its regulatory filings, patent applications, clinical data, and the formulation of the aviptadil product it was previously developing, (ii) Relief has the exclusive right and control going forward to develop and commercialize an aviptadil product, (iii) Relief has agreed to use commercially reasonable efforts to continue the existing Right to Try Program for aviptadil in the U.S. for at least two years, (iv) Relief will pay NRx milestone payments if it can successfully obtain commercial approval of an aviptadil product (whether for COVID-19 or any other indication), (v) Relief will pay NRx royalties based on a percentage of future sales of an aviptadil product (whether for COVID-19 or any other indication), up to a maximum of $30 million in the aggregate, (vi) NRx Pharmaceuticals has agreed not to compete in the development of an aviptadil product in the future, and (vii) at the closing, Relief and NRx Pharmaceuticals have dismissed their pending litigation. Further, the parties, as part of the settlement, the parties cancelled the collaboration agreement and exchanged mutual releases with respect to matters that were the subject of the litigation.

On November 24, 2021, we announced that we had entered into a collaboration agreement with InveniAI LLC (InveniAI), a U.S. based company that has pioneered the application of artificial intelligence and machine learning across biopharma and other industries, in order to identify promising drug candidates to treat rare and specialty diseases (the InveniAI Collaboration Agreement). Under the terms of the InveniAI Collaboration Agreement, InveniAI will use its proprietary platform for the identification of potential pharmaceutical product opportunities using its Pharma Big Innovation Data Lab, consisting of (i) its proprietary AlphaMeld platform, a cloud-based artificial intelligence platform that uses its proprietary machine learning and deep learning based neural networks to identify product opportunities in therapeutic areas, (ii) its cross-functional teams at its Integrated Center of Excellence, and (iii) domain expertise, to generate novel pharmaceutical opportunities and the related development pathway for the development of such concepts.

Under the terms of the InveniAI Collaboration Agreement, we paid InveniAI an initial up-front fee of $500,000. We will be required to pay success milestones for any products brought to us in connection with the InveniAI Collaboration Agreement ranging from $200,000 per product candidate for which we exercise our option to acquire IP rights to $50 million for any required product reaching $1 billion per year in net sales. We will also be required to pay royalties on any such commercialized product in certain countries a royalty of approximately three percent. We are not currently developing any product brought to us by InveniAI, and there can be no assurance that our collaboration with InveniAI will result in the development of new product candidates or product concepts.

Capital Resources

As of December 31, 2022, we had cash and cash equivalents of approximately CHF 19.2 million. As of April 30, 2023, we had cash and cash equivalents of approximately CHF 11.1 million. Based on current financial current projections, we expect that we have sufficient resources to fund operations into the third quarter of 2023.

Our Strategy

Our mission is to provide therapeutic relief to those suffering from debilitating rare diseases that have limited or no treatment options to help them live their best possible lives and achieve their full potential. We target established products with a proven history of safety and efficacy and either initial human therapeutic activity, proof-of-concept or a strong scientific rationale, allowing for relatively short, capital-efficient clinical trials with clear endpoints. Our global skills and internal research and development (R&D) resources are directed toward optimizing the therapeutic potential of these assets to deliver improvements in efficacy, safety and convenience through the application of our proprietary platform technologies, drug delivery systems or novel dosage forms.

Our risk-mitigated, cost-effective approach to drug development and commercialization is being advanced by an international team of well-established biopharma industry leaders with extensive research, development and rare disease expertise. Focusing on rare diseases with significant unmet medical need allows us to maintain a lean and capital efficient organization where all key strategic functions are internalized, combined with an optimized network of outsourced service providers for various development activities. We have a direct commercial footprint in the U.S. and in Europe, coupled with a strong network of commercial partners in the other major territories.

Our strategic plans are specifically centered around the therapeutic areas we know best, including:

•	Rare Metabolic Disorders:
•	PKU GOLIKE^®^ in phenylketonuria (PKU). We intend to maximize the commercial potential of the PKU GOLIKE^®^ family of products in all major territories either directly or through distribution partners in order to create a steady and growing positive cash flow; PKU GOLIKE^®^ is an approved, and fully reimbursed line of patented and differentiated medical food products for the dietary management of PKU.
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•	OLPRUVA^™^ in urea cycle disorders (UCDs). Pursuant to the FDA approval granted in December 2022, we are expecting OLPRUVA^™^ to become commercially available in the U.S. from mid-June 2023 as a new prescription option for the treatment of UCDs; in parallel, together with our collaboration partner Acer Therapeutics Inc. (Acer), we are currently pursuing approval for use of OLPRUVA^™^ in Europe.
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•	OLPRUVA^™^ in maple syrup urine disease (MSUD). Together with our collaboration partner Acer, we intend to pursue the development of OLPRUVA^™^ for the treatment of MSUD in the U.S. and Europe, especially considering this disease currently has no approved treatments available.
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•	RLF-OD032 in PKU. We intend to complete the development of this prescription drug candidate intended as a new, patented and highly differentiated treatment option for PKU; we anticipate the completion of the development and the filing of a 505(b)(2) NDA before the FDA in 2024 and anticipate an expected approval sometime in Q3/2025.
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•	Rare Skin Diseases:
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•	RLF-TD011 in epidermolysis bullosa (EB). We intend to advance the development of this drug candidate and to complete the ongoing proof of concept, investigator initiated clinical trial sometime before the end of 2023 subject to patient enrolment pace.
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•	RLF-TD011 in cutaneous T-cell lymphoma (CTCL). Subject to additional financing, we intend to conduct a proof of concept, investigator initiated clinical trial on CTCL patients at Northwestern University in the U.S. where clinical protocol has been already approved.
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•	Rare Respiratory Diseases:
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In 2023, we completed the development of a shelf stable formulation of RLF-100^®^ (aviptadil acetate) for both injectable intravenous (IV) and inhaled use.

The IV RLF-100^®^ formulation is specifically designed and indicated for all COVID or non-COVID related acute respiratory distress syndromes (ARDSs) because (i) it allows a prompt and efficient delivery of the drug in patients with severe conditions (e.g., patients in ICUs) while (ii) keeping under control the possible side effects because administered in a hospital setting.

The Inhaled RLF-100^®^ formulation is specifically designed and indicated for all the rare chronic lung diseases (CLDs) we are targeting because (i) it can maximize the clinical efficacy directly in the target organs (the lungs), (ii) while reducing the side effects of the drug (vasodilator and hypotension) because not systemically absorbed.

•	RLF-100^®^ in ARDSs. Subject to additional financing, we intend to advance the development of this drug candidate in ARDSs by entering into Phase 2 development.
•	RLF^®^ in CLDs. Subject to additional financing, we intend to advance the development of this drug candidate in the targeted CLDs, namely sarcoidosis, berylliosis and checkpoint inhibitor-induced pneumonitis (CIP) by entering into Phase 2 development.
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•	Expansion of our pipeline:

We intend to leverage our strength and experience to identify, acquire and bring to market drug candidates for therapeutic areas that align with our areas of focus.

Product Portfolio and Development Timeline

Relief Therapeutics’ portfolio offers a balanced mix of marketed, revenue-generating products, our proprietary, globally patented Physiomimic^™^ and TEHCLO^™^ drug delivery platform technologies and a highly targeted clinical development pipeline consisting of risk-mitigated assets focused in three core therapeutic areas: rare metabolic disorders, rare skin diseases and rare respiratory diseases where the company can best leverage its internal research and development (R&D) capabilities and track record.

In addition, Relief Therapeutics is commercializing several legacy products via licensing and distribution partners.

LOGO

DRUG DELIVERY PLATFORM TECHNOLOGIES

Our drug delivery platform technologies enable us to optimize the therapeutic potential of established products with proven efficacy, known safety profiles or where proof-of-concept exists. These platforms have utility for development in other specialty or rare disease therapeutic areas, partnerships and out-licensing.

TEHCLO NANOTECHNOLOGY^™^

Our TEHCLO Nanotechnology™ platform (TEHCLO™) consists of our proprietary, globally patent-protected electrode with nanocoating, the method for preparing and making highly stable aqueous solutions and our device for the electrolytic treatment of a fluid. TEHCLO™ was used to develop RLF-TD011, Nexodyn and some of our legacy products.

Our TEHCLO^™^ intellectual property portfolio consists of four patent families. The first three families include 107 granted patents world-wide directed to systems and methods for generating APR’s hypochlorous acid solution, compositions comprising APR’s hypochlorous acid solution and methods for treating ocular disorders. These patents expire between October 2026 and June 2030, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity. If granted, additional patents would expire no earlier than July 2040.

PHYSIOMIMIC TECHNOLOGY^™^

Our Physiomimic Technology^™^, used in the PKU GOLIKE^®^ product line, is our globally patented, proprietary method to engineer amino acids to modify their release and absorption to mimic the physiological absorption of natural dietary proteins. This technology provides extended-release, taste and odor masking and increased absorption.

Our PKU GOLIKE^®^ intellectual property portfolio consists of two patent families including 34 pending applications and 50 granted patents world-wide. Patents resulting from these families, if granted, will expire no earlier than 2036 and 2038, respectively, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity.

RARE METABOLIC DISORDERS

Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare metabolic disorder that hinders the body’s ability to break down the amino acid phenylalanine (Phe), resulting in a dangerous build-up of Phe when patients eat foods containing protein or aspartame. High levels of the Phe can lead to severe symptoms, including:

•	permanent cognitive disorders and intellectual disability;
•	delays in development;
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•	behavioral, emotional and social problems, and psychiatric disorders;
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•	a musty odor in the breath, skin or urine, caused by too much Phe in the body;
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•	neurological problems, which may include seizures;
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•	skin rashes (eczema);
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•	fair skin and blue eyes, because phenylalanine can’t transform into melanin, the pigment responsible for hair and skin tone;
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•	abnormally small head (microcephaly); and
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•	hyperactivity,
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In PKU patients, the enzyme needed to convert Phe is missing or severely reduced, which can result in high build-up of Phe and severe systemic damage, mainly in the brain. Treatment guidelines for these patients require a life-long strict and very limited, low protein diet combined with a Phe-free mix of amino acid (AA) supplementation (which can represent up to 75 percent of the total daily protein intake).

A further reduction of Phe levels is important before conception: pregnant women with PKU, including those with less severe forms of the disease, may place their unborn children at risk by not following the PKU diet. Children of woman with untreated PKU may have an unusually small head (microcephaly), congenital heart disease, developmental abnormalities or facial abnormalities. There is a strong relationship between the severity of these symptoms and high Phe levels in the mother.

Diagnosis and Incidence

Diagnosis of PKU in Europe and the U.S. is conducted on each and every newborn through the new-born screening (NBS) programs which are mandatory in those countries. When diagnosed, newborns are to specialized referral centers/hospitals trained to deal with such rare metabolic disorders. According to a study published in August 2020 in the American Journal of Human Genetics, approximately 450,000 people suffer from PKU worldwide.

Current Treatment Options for PKU

While PKU is not curable, if diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling Phe levels through a strict diet combined with AA supplementation or with available medications. Diet is composed by few amounts of natural food (based on severity of the disease) supplemented with AA mix with absence or low Phe content plus low protein foods. Diet is recommended for the entire life since it has been demonstrated that high Phe levels has an impact not only during growing but also in adulthood. In 2018, the FDA approved an enzyme substitute called pegvaliase, sold by BioMarin Pharmaceuticals under the brand name PALYNZIQ^®^^^(pegvaliase-pqpz). PALYNZIQ^®^^^is a derivative of the enzyme Phe ammonia-lyase that metabolizes Phe to reduce its blood levels (but it is not able to produce tyrosine as the natural enzyme, which still needs to be supplemented). Tetrahydrobiopterin (BH4), a cofactor for the oxidation of Phe, when taken by mouth, is also thought to reduce blood levels of Phe in some people. Along with PALYNZIQ^®^, BioMarin Pharmaceuticals also markets KUVAN^®^ (sapropterin dihydrochloride) for the treatment of PKU. There are also other amino acid products, sold both by prescription and over the counter, that are marketed toward PKU patients.

PKU GOLIKE^®^ for the Dietary Management of PKU

Patients with PKU require supplementation of amino acid (AA)-based foods for special medical purposes (FSMPs or medical formula) to prevent protein deficiency and optimize metabolic control. Many of these FSMPs can result in poor dietary compliance due to their taste and odor. Further, the unpleasant odor and aftertaste of current AA supplements can become a barrier to social interaction for PKU patients.

In addition, proteins needed for normal growth and coming from natural food sources are broken down during the digestion process and are gradually absorbed, keeping blood AA levels sufficient stable over time. However, free-AA mix administered to PKU patients in the form of FSMPs are not comparable to natural proteins because they do not need to be broken down before they are absorbed, resulting in a rapid peak of absorption and rapid decrease of their concentration into the bloodstream.

This rapid peak in blood amino acids following ingestion of FSMPs impairs the ability of the body to process them properly and incorporate them into the body’s own tissue, through a process known as anabolism, resulting in a portion of unprocessed amino acids which are then oxidated and eliminated. This rapid elimination of unprocessed AAs that is associated with traditional FSMPs represents a fundamental unmet need for PKU patients especially during any prolonged fasting period.

In order to compensate for the low levels of AAs during fasting periods, the body is forced to initiate a process called catabolism, where the body will break down lean muscle mass to obtain the AAs or energy it requires.

PKU GOLIKE^®^ products are Phe-free FSMPs for both children and adults. Developed with the Relief Therapeutics proprietary, patent-protected Physiomimic Technology^™^ drug delivery platform, PKU GOLIKE^®^ products are the first prolonged-release AA FSMPs, characterized by a special coating that ensures physiological absorption of the AAs mirroring that of natural proteins. The special coating also masks the unpleasant taste, odor and aftertaste of the AAs. PKU GOLIKE^®^ granules are flavorless and can be mixed with many foods. PKU GOLIKE^®^ products contain all 19 amino acids that people with PKU need to maintain neurological and muscular health and is fortified with 27 essential vitamins and minerals, including ones normally found in protein-rich foods like iron, calcium and vitamin B12.

The PKU GOLIKE^®^ line of products are available in convenient packets (PKU GOLIKE Plus^®^ for ages 3-16 and ages 16+), medical food bars (PKU GOLIKE BAR^®^) and tablets to be chewed (PKU GOLIKE KRUNCH^®^). Relief Therapeutics plans to expand the PKU GOLIKE^®^ commercial infrastructure beyond the current countries and aims to strengthen the commercial activities to increase and accelerate future growth. PKU GOLIKE^®^ is currently promoted and marketed by a direct sales and marketing infrastructure in U.S., Germany, Italy, Switzerland and Austria; in addition, the product is marketed in the UK, Spain, Israel and Ecuador by local distributors under contract with APR.

PKU GOLIKE^®^ products have been commercially available in Europe since 2018. Relief Therapeutics launched the PKU GOLIKE^®^ family of products in the U.S. in late October 2022, with its recently assembled commercial infrastructure and team. In early 2023, the company announced the U.S. and EU availability of the new red fruit and tropical fruit flavored PKU GOLIKE BAR^®^, which contain real fruit flavors, from natural ingredients. More flavors of the bars and other forms of PKU GOLIKE^®^ are currently in development.

On August 23, 2022, APR was issued U.S. patent number 11,419,837, which covers certain formulations of PKU GOLIKE^®^ and supplements the PKU GOLIKE^®^ intellectual property portfolio, which includes U.S. patent number 10,500,180, which was issued on December 10, 2019. The patents will expire no earlier than September 27, 2036, with the payment of all prescribed maintenance fees.

In March 2023, Relief Therapeutics presented the findings from pre-clinical research evaluating the metabolic impact of PKU GOLIKE^®^ on nitrogen balance, muscle strength and glucose in a poster session at the Society for Inherited Metabolic Disorders (SIMD) 44^th^ Annual Meeting. The poster summarized the acute and long-term metabolic effects of PKU GOLIKE^®^ supplementation on the utilization of AAs and glucose metabolism in a pre-clinical rat model using biomarkers for muscle metabolism, functional muscle performance and a glucose tolerance test. Due to the prolonged release of the AAs, beneficial effects were observed on AA oxidation, muscle metabolism, grip strength and glucose tolerance in healthy rats. BUN (blood urine nitrogen test) was significantly lower in the acute treatment with PKU GOLIKE^®^ indicating the potential to improve AA utilization in PKU patients resulting in a reduction of catabolic episodes. The results from this pre-clinical research demonstrate the important body composition benefits of the physiological absorption of our prolonged-release AA supplement PKU GOLIKE^®^. Detailed results from this study are available on the Relief Therapeutics website.

Relief Therapeutics plans to expand the PKU GOLIKE^®^ commercial infrastructure beyond the current countries to increase and accelerate future growth. This will be supported by newer formulations of PKU GOLIKE^®^.

In the U.S., PKU GOLIKE^®^ was granted ODD by the FDA for its development as a prescription drug. We have decided not to pursue this program and will continue to market our PKU GOLIKE^®^ line of products solely as FSMPs.

RLF-OD032 (formerly known as APR-OD32) for the Treatment of PKU

Through a definitive agreement with Meta Healthcare Ltd. (Meta), Relief Therapeutics has acquired the worldwide rights, title and interest, except in the UK, for a novel dosage form of a prescription drug already approved by the FDA and intended for the treatment of patients with PKU. This improved product is expected to increase patient acceptance and compliance as well as provide easy metered dosing and dispensing. Meta will provide the technology transfer package, while Relief Therapeutics will conduct clinical studies, manufacturing, regulatory submission and commercialization in the U.S. and EU.

According to the terms of the purchase agreement, Meta will transfer to Relief Therapeutics all data, know-how, as well as any intellectual property as developed or generated so far by Meta. Relief Therapeutics will only be responsible for funding the remaining development work as well as for filing and prosecuting NDA (or equivalent thereof) in all countries worldwide except for the UK, where we will grant a license back to Meta, enabling Meta to market the product in that country. Other than the initial acquisition payment and low double-digit royalty payments on net profits of the product in the various countries, we will be under no obligation to fund or pay any other amount to Meta.

Relief Therapeutics anticipates filing for registration approval in the U.S. and Europe through a 505(b)(2) NDA sometime in the second half of 2024.

ACER-001 / OLPRUVA™ (SODIUM PHENYLBUTYRATE) FOR ORAL SUSPENSION

In March 2021, Relief Therapeutics signed a collaboration and license agreement with Acer Therapeutics Inc. (Acer) for the worldwide development and commercialization of ACER-001 (sodium phenylbutyrate) for the treatment of various inborn errors of metabolism, urea cycle disorders (UCDs) and maple syrup urine disease (MSUD).

ACER-001 is a proprietary, coated powder formulation of sodium phenylbutyrate (NaPB) designed to be both taste-masked and immediate release. ACER-001 was developed using a multiple coating process, and the microparticles consist of an inert core center, a coated layer of active drug and a final taste-masking coating that quickly dissolves in the stomach to avoid a bitter taste while still allowing for rapid systemic absorption. ACER-001’s taste-masked formulation is designed to improve the palatability of NaPB and could make it a compelling alternative to existing NaPB-based treatments, as the unpleasant taste associated with NaPB is cited as a major impediment to patient compliance with those treatments. Additionally, bioequivalence trials have shown ACER-001 to have similar relative bioavailability to BUPHENYL^®^ under both fasted and fed conditions, along with significantly lower projected pricing compared to RAVICTI^®^.

On December 22, 2022, the FDA approved ACER-001 under the brand name OLPRUVA™ (sodium phenylbutyrate) for oral suspension as a prescription medicine as an adjunctive treatment for use in certain patients with UCDs.

Urea Cycle Disorders (UCDs)

The urea cycle is a series of biochemical reactions that occur primarily in the liver, which converts toxic ammonia produced by the breakdown of protein and other nitrogen-containing molecules in the human body into urea for excretion. Primary hyperammonemia is a term to describe an elevation of ammonia in blood or plasma due to a defect within the urea cycle, which is the pathway responsible for ammonia detoxification and arginine biosynthesis. Urea cycle disorders (UCDs) are rare diseases caused by genetic defects affecting any of the six enzymes or two transporters that are directly involved in the urea cycle function. The clinical situation is variable and largely depends on the time of onset. Newborns who are often affected by hyper-ammonaemic encephalopathy carry a potential risk of severe brain damage, which may lead to death. Outside the neonatal period, symptoms are very unspecific but most often neurological (with wide variability), psychiatric and/or gastrointestinal. Early identification of patients is extremely important to start effective treatment modalities immediately. The acute management includes detoxification of ammonia, which often requires extracorporeal means such as hemodialysis, and the use of intravenous drugs that work as nitrogen scavengers. Long-term management of patients with UCDs consists of a low-protein diet, which needs to be balanced and supplemented to avoid deficiencies of essential amino acids, trace elements or vitamins and the use of nitrogen scavengers. In cases where dietary management or medication is not effective, patients with UCD may require a liver transplant.

Diagnosis and Incidence

The diagnosis of UCDs is based on clinical observations, confirmed by biochemical and molecular genetic testing. A plasma ammonia concentration of 150 µmol/L or higher associated with a normal anion gap and a normal plasma glucose concentration is an indication for the presence of UCDs. Plasma quantitative amino acid analysis and measurement of urinary orotic acid can distinguish between the various types of UCDs. A definitive diagnosis of UCDs depends on either molecular genetic testing or measurement of enzyme activity. Molecular genetic testing is possible for all urea cycle defects. Studies suggest the incidence of UCDs in the U.S. and Europe is 1 in 35,000 live births. Approximately 2,100 patients suffer from UCDs in the U.S.

Current Treatment Options for UCDs

The current treatment of UCDs consists of dietary management to limit ammonia production in conjunction with medications that provide alternative pathways for the removal of ammonia from the bloodstream. Dietary protein must be carefully monitored, and some restriction is necessary; too much dietary protein causes excessive ammonia production. However, if protein intake is too restrictive or insufficient calories are consumed, the body will break down lean muscle mass to obtain the amino acids or energy it requires, which can also lead to excessive ammonia in the bloodstream. Dietary management may also include supplementation with special AA formulas developed specifically for UCDs, which can be prescribed to provide approximately 50 percent of the daily dietary protein allowance. Some patients may also require individual branched-chain amino acid supplementation.

Medications for UCDs primarily comprise nitrogen scavenger drugs, which are substances that provide alternative metabolic excretion pathways for nitrogen, thereby bypassing the urea cycle. The use of these alternative pathways for nitrogen removal is important for the management of acute episodes of hyperammonemia and are also included as part of a long-term treatment regime for UCD patients. Current nitrogen scavenger treatments for UCDs are based on sodium benzoate or phenylbutyrate, which conjugate with glycine and glutamine, respectively, allowing for urinary excretion of nitrogen as hippurate and phenylacetylglutamine, respectively.

According to a 2016 study by Shchelochkov et al., published in Molecular Genetics and Metabolism Reports, while nitrogen scavenging medications are effective in helping to manage UCD, non-compliance with treatment is common. Reasons given for non-compliance include the unpleasant taste associated with available medications, the frequency with which medication must be taken and the high cost of the medication.

Sodium phenylbutyrate (NaPB) is currently approved in the U.S. and the EU to treat patients with UCDs, which is marketed as BUPHENYL^®^ (sodium phenylbutyrate) Tablets, BUPHENYL^®^ (sodium phenylbutyrate) Powder and RAVICTI^®^ (glycerol phenylbutyrate) Oral Liquid. While a study provided by Horizon Therapeutics, Inc. in the RAVICTI^®^ package insert involving 46 adults with UCD demonstrated that BUPHENYL^®^ and RAVICTI^®^ were similarly effective in controlling the blood level of ammonia over a 24-hour period, many patients who take their medicine orally prefer RAVICTI^®^, as it is significantly more palatable than BUPHENYL^®^. However, the very high annual treatment cost of RAVICTI^®^, based on patient weight, is often prohibitive. RAVICTI^®^ and BUPHENYL^®^ are registered trademarks owned by or licensed to Horizon Therapeutics plc. Phenylburate is also marketed in the U.S., Europe, Australia and New Zealand under the trade name PHEBURANE^®^ (sodium phenylbutyrate) Oral Pellets. AMMONAPS (sodium phenylbutyrate) Tablets, another formulation of NaPB that claims to be tasteless and odor free is approved and marketed in Europe.

Rationale for OLPRUVA™ (formerly ACER-001) Treatment in UCDs

Two Phase 1 bridging studies that evaluated the bioavailability and bioequivalence of OLPRUVA^™^ (sodium phenylbutyrate) compared to sodium phenylbutyrate (BUPHENYL^®^) powder showed the bioequivalence of OLPRUVA^™^ administered as a suspension with sodium phenylbutyrate (BUPHENYL^®^) powder administered as a solution in healthy adult volunteers after a single dose under fasting and fed conditions (Steiner 2022).

Additionally, two Phase 1, open-label, repeated measures, taste assessment studies of polymer-coated sodium phenylbutyrate (OLPRUVA^™^) and sodium phenylbutyrate (BUPHENYL^®^) powder, conducted on healthy panelists who were required to complete a training program for a minimum of six months that educated panelists on the identification, description and quantification of sensory attributes of products, concluded that OLPRUVA^™^ had overall lower flavor intensity scores than sodium phenylbutyrate (BUPHENYL^®^) powder when administered within five minutes of preparation (Cedarbaum 2022).

Currently approved therapies for UCDs, including BUPHENYL^®^ and RAVICTI^®^, are required to be administered with food. BUPHENYL is required to be administered in a fed state due to its aversive odor and taste, with side effects including nausea, vomiting and headaches, which can lead to discontinuation of treatment. Additionally, prescribing information states that the BUPHENYL food effect is unknown. RAVICTI PK and pharmacodynamic (PD) properties were determined to be indistinguishable in fed or fasted states. OLPRUVA^™^ is uniquely formulated with its multi-particulate, taste-masked coating to allow for administration in a fasted state, while still allowing for rapid systemic release.

Based on the results from the food effect study within the first OLPRUVA^™^ BE trial, Acer commissioned Rosa & Co. LLC to create a PhysioPD PK model to evaluate the potential food effect on exposure, tolerability and efficacy of OLPRUVA^™^ in UCDs patients. Results from this in silico model suggested that administration of OLPRUVA^™^ in a fasted state required approximately 30 percent less PBA to achieve comparable therapeutic benefit to that in a fed state. In addition, the model predicted that administration of OLPRUVA ^™^ in a fasted state compared to administration of BUPHENYL^®^ or RAVICTI^®^ (same amounts of PBA) in their required fed states would be expected to result in higher peak blood PBA, PAA and PAGN concentrations, which should achieve a 43 percent increase in urinary PAGN levels (a negative correlation between blood ammonia area under the curve and 24-hour urinary PAGN amount has been demonstrated).

LOGO

In February 2021, Acer announced topline results from its bioequivalence trial in which OLPRUVA^™^ (formerly ACER-001) showed similar relative bioavailability to BUPHENYL^®^ (sodium phenylbutyrate) under fed conditions. The single-center, single-blind, randomized, single-dose crossover trial evaluated BE of OLPRUVA^™^ compared to BUPHENYL^®^ when administered under fed conditions in 36 healthy adults. The topline data from this trial showed OLPRUVA^™^ to have similar PK profiles for both PBA and PAA compared to BUPHENYL^®^ under fed conditions.

Registration Plan and FDA Approval of OLPRUVA^™^ (Sodium Phenylbutyrate) for Oral Suspension for UCDs

On December 22, 2022, the FDA approved ACER-001 under the brand name OLPRUVA™ (sodium phenylbutyrate) for oral suspension as a prescription medicine for use with certain therapy, including changes in diet, for the long-term management of adults and children weighing 44 pounds (20 kg) or greater and with a body surface area (BSA) of 1.2 m2 or greater, with UCDs, involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS). OLPRUVA™ is not used to treat rapid increase of ammonia in the blood (acute hyperammonemia), which can be life-threatening and requires emergency medical treatment. Please see Important Safety Information and full Prescribing Information, including Patient Information.

On March 15, 2023, Acer and Relief Therapeutics announced that, in support of a planned launch for commercial OLPRUVA^™^ in the third quarter of 2023, that Acer is actively adding resources to establish its commercial and medical affairs presence in the U.S. Acer has recently introduced its patient support service, OLPRUVA^™^ Navigator by Acer Therapeutics, designed to support UCD patients with support, access, education and patient adherence to treatment. Representatives are expected to begin accepting prescriptions late in the second quarter of 2023. Acer also reported that it is actively engaged in negotiations regarding access for OLPRUVA^™^ with the major commercial payers and state Medicaid organizations.

According to Acer, it has established a pricing strategy reflecting its commitment to deliver innovative treatments that are responsibly priced and accessible to those in need. Acer intends to price OLPRUVA^™^ competitively, at a significant discount to the currently available commercial product RAVICTI^®^, while implementing predictable pricing that will not increase beyond the rate of inflation. Acer indicated that it also plans to invest a portion of OLPRUVA^™^ revenue back into additional solutions aimed at improving outcomes for UCD patients.

We intend to seek approval from the European Medicines Agency (EMA) in the EU and potentially other territories outside the U.S. Because the FDA has approved an NDA for BUPHENYL^®^, which is referred to as the reference listed drug (RLD), we intend to rely on the RLD’s preclinical and clinical safety and efficacy data, while supplementing the data with a bridging study that shows similar relative bioavailability of OLPRUVA^™^ to BUPHENYL^®^. In parallel or after initial potential FDA approval for administration under fed conditions, and subject to additional capital, we also plan to evaluate potential development of OLPRUVA^™^ for administration under fasted (pre-meal) conditions, which will likely require additional nonclinical and clinical studies to provide the necessary evidence of safety and efficacy of OLPRUVA^™^ to be considered for FDA approval for administration under fasted (pre-meal) conditions.

Maple Syrup Urine Disease (MSUD)

Maple syrup urine disease (MSUD) is a rare inherited disorder caused by defects in the mitochondrial branched-chain ketoacid dehydrogenase complex, which results in elevated blood levels of the branched-chain amino acids (BCAA), leucine, valine and isoleucine, as well as the associated branched-chain ketoacids (BCKA) in a patient’s blood. Left untreated, this can result in neurological damage, mental disability, coma, or death. The most severe presentation of MSUD, known as “classic” MSUD, accounts for 80 percent of cases and can result in neonatal onset with encephalopathy and coma. Although metabolic management of the disease is possible via a highly restrictive diet, the outcome is unpredictable, and a significant portion of affected individuals are mentally impaired or experience neurological complications.

Diagnosis and Incidence of MSUD

MSUD is typically diagnosed at birth via newborn screening. Studies indicate that MSUD affects an estimated 1 in 185,000 infants worldwide. The disorder occurs more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns, and the Ashkenazi Jewish population, with an estimated incidence of 1 in 26,000. Approximately 3,000 patients suffer from MSUD worldwide, of whom approximately 1,000 are located in the U.S.

Current Treatment Options in MSUD

There are currently no approved pharmacologic therapies in the U.S. or the EU for MSUD. Treatment of MSUD consists primarily of a severely restricted diet to limit the intake of BCAA, with aggressive medical interventions when blood-levels of BCAA or BCKA become elevated.

Rationale for OLPRUVA^™^ Treatment in MSUD

Therapy with NaPB in UCD patients has been associated with a selective reduction in BCAA despite adequate dietary protein intake.

Based on this clinical observation, investigators at Baylor College of Medicine (BCM) explored the potential of NaPB treatment to lower BCAA and their corresponding BCKA in patients with MSUD. The investigators found that BCAA and BCKA were both significantly reduced following NaPB therapy in control subjects and in patients with MSUD, although there was no simple correlation between the patients’ levels of residual enzymatic activity with the response of plasma BCAA and their BCKA to NaPB. NaPB showed a statistically significant reduction of BCAA leucine, in all three healthy subjects and in three out of the five MSUD patients who participated in the trial. The reduction in leucine, the most toxic of the BCAAs, in the three responsive MSUD patients ranged between 28-34 percent, which is considered by clinicians to be a clinically meaningful response.

Investigators at BCM further explored the mechanistic rationale for NaPB lowering BCAA/BCKA levels. NaPB was found to be an allosteric inhibitor of the branched-chain keto acid dehydrogenase complex kinase (BCKD-kinase), and enzyme that regulates the activity of the branched-chain keto acid dehydrogenase complex (BCKDC) enzyme that is responsible for the normal metabolism of BCKAs. By inhibiting the BCKD-kinase, the BCKDC is constitutively activated, thus the increased activity results in a reduction in the plasma levels of BCAA and BCKA in all people, including those with MSUD, suggesting that NaPB may be an effective treatment for people with MSUD, who experience elevated BCAA levels.

In November 2020, study results evaluating the effect of NaPB in the management of acute MSUD attacks in pediatric patients (n=10) were published in the Journal of Pediatric Endocrinology and Metabolism showing a significant reduction in leucine levels in MSUD patients experiencing an acute attack. However, verifying this outcome would require additional validation in a controlled trial. If OLPRUVA™ is approved for the treatment of chronic MSUD, we believe patients will not be required to interrupt their therapy in the event of an acute crisis.

Registration Plan for MSUD

Acer has submitted an investigational new drug (IND) application to the FDA to evaluate the safety and efficacy of OLPRUVA^™^ for the treatment of MSUD, and although there can be no assurance, we expect that Acer will begin such study during the first quarter of 2023. Given its regulatory status with regard to UCDs, there is no requirement for Phase 1 studies in healthy volunteers. The timing of a Phase 2 clinical trial, if such a trial occurs, would be subject to completion of a commercial assessment of the opportunity, including, but not limited to, a possible pre-IND meeting with the FDA and/or the EMA, with an objective of validation and agreement on the primary and secondary clinical trial end-points, which remain important given that there are presently no approved treatment options for this disease nor are there guidelines to assess efficacy and safety of an investigational drug in this disease. If a successful clinical trial for OLPRUVA^™^ in MSUD is completed, along with our partner Acer, we plan to seek FDA approval to market OLPRUVA^™^ for the treatment of MSUD as an added indication in the U.S. by submitting a supplemental NDA (sNDA) incorporating the efficacy and safety data from the MSUD population, assuming OLPRUVA^™^ is approved for the treatment of UCDs prior to sNDA submission. We also intend to seek approval in the EU and other territories outside the U.S. after the sNDA for treatment of MSUD is filed, or simultaneously with the U.S. filing.

Royalty Sharing for OLPRUVA^™^

The companies will split net profits from OLPRUVA^™^ from Acer’s territories (consisting of the U.S., Canada, Turkey, Japan and Brazil) 60 percent to 40 percent in favor of Relief Therapeutics. In addition, Relief Therapeutics has licensed the rights for the rest of the world, where Acer will receive from Relief Therapeutics a 15 percent royalty on all net revenues received in the Relief Therapeutics territories.

RARE PULMONARY DISEASES

RLF-100® (AVIPTADIL ACETATE)

Aviptadil acetate is a synthetic form of vasoactive intestinal peptide (VIP) consisting of 28 amino acids which was first discovered in 1970. That same year, Nature published a short report entitled “Potent peripheral and splanchnic vasodilator peptide from normal gut,” authored by two young scientists working at the Karolinska Institute (Said, Mutt, 1970). Although named (or mis-named) for the intestinal tissue in which it was first isolated, human VIP is now known to be produced by neuroendocrine cells throughout the body by T-lymphocytes, B-lymphocytes and macrophages, primarily concentrated in the lungs. VIP is highly localized in the lung (Leys 1986, Virgolini 1995) but is a widely distributed that showed, in various models, effects in hemodynamics and coronary circulation (Feliciano 1998, Frase 1987, Henning 2001), kidney (Dimaline 1983, Calam 1983 and 1988), immune system (Gonzales-Rey 2007, Ganea 2015, Li 2013), intestinal tract (Iwasaki 2019) and reproduction (Fredericks 1983, Fraccaroli 2012).

VIP has a multimodal mechanism of action: decrease of inflammatory cytokines release leading to prevention of cytokine storm syndrome and viral replication, immunomodulating effect, vasodilating and bronchodilating effects and prevention of surfactant depletion. Seventy percent of VIP in the body is bound to a less common type of cell in the lung, the alveolar epithelial type II (AT2) cell, which is critical to the absorption of oxygen into the body. Five decades of subsequent research documented VIP’s role as a potent natural anti-cytokine that has unique capability to block pathways of cell death in ATII cells – the cell targeted by the SARS-CoV-2 virus.

Since RLF-100’s mechanism of action is not restricted to the protection of AT2 cells, we believe that its beneficial effects could extend to other types of acute lung injury (ALI) as supported by pre-clinical and preliminary clinical data in sepsis-induced ALI. It is our objective to establish our proprietary and patent-protected formulation of aviptadil, RLF-100^®^ as the standard of care for the prevention and treatment of respiratory failure and its complications in both the acute intensive care and chronic ambulatory settings.

In April 2023, Relief Therapeutics announced positive 12-month stability data for the liquid and lyophilized preparations of RLF-100^®^, intended for intravenous (IV) and inhaled administration. RLF-100^®^ is the company’s proprietary, patent protected investigational formulation of aviptadil acetate. The data from the stability study showed that both inhaled and IV RLF-100^®^ demonstrated high purity levels at 12 months at all temperatures tested, including refrigerated and room temperature environments. The results are consistent with prior data observed at three- and six-month intervals. The stability testing study will continue to determine the maximum shelf life of RLF-100^®^.

Based on the latest results, Relief Therapeutics intends to amend its previously filed provisional patent application for RLF-100® with the new findings. If granted, this patent could provide exclusivity for RLF-100® at least until 2042, without considering Hatch-Waxman extensions or other patent term adjustments. The Hatch-Waxman Act permits a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process.

Relief Therapeutics intends to develop the intravenous (IV) formulation of RLF-100^®^ for targeted COVID or non-COVID acute respiratory distress syndromes (ARDSs) because (i) it allows a prompt and efficient delivery of the drug in severe conditions (e.g., patients in intensive care units (ICUs)) while (ii) keeping under control the possible side effects because administered in a hospital setting and (iii) it remains a dosage form easy to handle by healthcare professionals (HPCs).

At the same time, Relief Therapeutics intends to develop the inhaled formulation of RLF-100® for targeted chronic lung diseases (CLDs) such as sarcoidosis, berylliosis and checkpoint inhibitor-induced pneumonitis (CIP) because (i) it can maximize the clinical efficacy directly in the target organs (the lungs), (ii) while reducing the side effects of the drug (vasodilator and hypotension) because it is not systemically absorbed and (iii) it is a patient friendly dosage form as those CLDs are primarily treated at home and drug administered directly by the patients.

COVID-19 ARDS

Acute respiratory failure is the primary cause of death in COVID-19. In some cases, the injury is attributed to cytokine storm – i.e., a massive release of inflammatory cytokines that then cause destruction of pulmonary epithelium cells. However, the cytokine storm is only produced after the SARS-CoV2 virus enters the ATII cell through binding of its spike protein to angiotensin converting enzyme 2 (ACE2) surface receptors (Mason 2020). ACE2 is not present on type I alveolar cells, which comprise 95 percent of the pulmonary epithelium hence those cells are not infected by the coronavirus. Similarly, only the ATII cell expresses the VPAC1 receptor to which VIP binds. VIP is shown to prevent their apoptosis in models of lung injury (Ao 2011, Pakbaz 1993). Hence, VIP represents a highly specific approach to rescuing the lung from the overwhelming failure of oxygenation seen in COVID-19.

Pulmonary drugs are difficult to develop, given regulatory requirements for long-term toxicology studies in multiple species, including primates (Tepper 2016). The FDA has asserted that these preclinical toxicology requirements must be observed in the case of candidate drugs to treat COVID-19. VIP, on the other hand, have successfully completed four species toxicology and safety pharmacology studies in both intravenous (IV) and inhaled dosages. Phase 2 trials in sarcoidosis (Prasse 2010), pulmonary hypertension (Petkov 2003, Leuchte 2008), pulmonary fibrosis (unpublished data) and asthma (Bundgaard 1983, Morice 1983 and 1986, Altiere 1984, Barnes 1984, Crimi 1988, Morice 1986) document that VIP has no major toxicities when inhaled at doses of 300µg/day or infused at dose of 6 pmol/kg/min. VIP was first proposed as a modulator of lung inflammation by Said (Said 1988, 1991). It has demonstrated positive effects in clinical trials of sepsis-related acute respiratory distress syndrome (ARDS) (Youssef 2020 preprint) and sarcoidosis (Prasse 2010).

In March 2020, at the beginning of the first wave of the pandemic in the U.S., our former collaboration partner, NeuroRx Inc. (NeuroRx), submitted an IND application to the FDA for a Phase 2b/3 trial of intravenous (IV)aviptadil for the treatment of patients with critical COVID-19 respiratory failure. Within 24 hours, the FDA issued a “Study May Proceed” letter and the first patients were treated in April 2020 at Thomas Jefferson University Hospital in Philadelphia.

In late 2020, a Phase 2b/3 clinical study with aviptadil acetate IV in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) was completed in the U.S. by NeuroRx. In its press release reporting those results, NeuroRx announced that across all patients and sites, the aviptadil acetate IV treated cohort met the primary endpoint for successful recovery from respiratory failure at days 28 (p=0.14) and 60 (p=0.13) and had a meaningful survival benefit after controlling for ventilation status and clinical site. However, they also reported that the trial did not demonstrate a statistically significant difference on the study’s primary endpoint without statistical adjustment for these pre- specified covariates. Based on these findings, NeuroRx announced on June 1, 2021, the company applied to the FDA for emergency use authorization (EUA) for aviptadil acetate IV for the treatment of acute respiratory failure due to critical COVID-19 and that it planned to submit an NDA with the FDA. On November 5, 2021, NeuroRx announced the FDA declined its application for EUA of aviptadil IV for the treatment of acute respiratory failure due to critical COVID-19. Subsequent applications filed by NeuroRx with the FDA seeking EUA for more limited use of the product for the treatment of COVID-19 and for breakthrough therapy designation for the product were also denied in the first half of 2022.

In March 2021, NeuroRx announced that aviptadil acetate IV was included in a National Institutes of Health (NIH)-sponsored Phase 3 ACTIV-3b/TESICO clinical trial in severely ill patients with COVID-19. In May 2022, Relief Therapeutics learned that the ACTIV-3b/TESICO trial was discontinued by its Data Safety Monitoring Board (DSMB) based on futility.

Relief Therapeutics intends to obtain and review all available clinical data, including data from the NIH-sponsored trial to better understand the results observed, up to and including the point at which the study was discontinued.

While regulatory approval for aviptadil acetate IV to treat COVID-19-induced ARDS has not been granted in the U.S., an unrelated pharmaceutical company received approval for this indication in India in early 2022 for their formulation of aviptadil, thereby substantiating Relief Therapeutics’ original hypothesis.

Inhaled RLF-100^®^ is being evaluated in an investigator-initiated trial at a site in Switzerland for the treatment of ARDS associated with COVID-19 (Leuppi/NCT04536350). While the study is in an advanced stage of recruitment, changing disease patterns have hindered the completion of patient recruitment. The lead investigator has reported that top-line data is now expected in the fourth quarter of 2023.

Non-COVID-19 ARDS

Infectious acute respiratory distress syndrome (ARDS) is a potentially life-threatening condition in which the lungs become severely inflamed, leading to buildup of fluid in the lungs, preventing oxygen from getting to the bloodstream and the rest of the body. Infectious ARDS results from an injury or an infection (such as pneumonia, severe flu, sepsis, etc.) of the air sacs in the lung. Plans for clinical trials of RLF-100 for the treatment of infectious ARDS are in development.

RLF-100® (AVIPTADIL ACETATE) IN CHRONIC LUNG DISEASES (CLDs)

Inhaled RLF-100® is under development for targeted CLDs, including pulmonary sarcoidosis, checkpoint inhibitor-induced pneumonitis (CIP) and chronic berylliosis.

Pulmonary sarcoidosis, chronic berylliosis and CIP are generally classified as granulomatous chronic lung diseases because they all have similar pathogenesis which lead to the formation of lung granulomas. It is a process driven by an exaggerated immune response where activation of CD4+ Th1 and Th17 cells causes the pro-inflammatory cytokine storms and lung granuloma formation.

Inhaled RLF-100^®^, which is the synthetic form of VIP, is supposed to bind its receptor VPAC1 on CD4+ Th1 and Th17 immune cells, thus inhibiting NfKB. Thanks to this specific mechanism of action, RLF-100^®^ is able to reduce the pro-inflammatory cytokines and increase anti-inflammatory cytokines, preventing granuloma formation and allowing disease resolution as detailed in the illustration below.

LOGO

Pulmonary Sarcoidosis

Sarcoidosis is an inflammatory disease characterized by the formation of granulomas—tiny clumps of inflammatory cells that can develop in any part of the body. When the disease occurs in the lungs, it is called pulmonary sarcoidosis and is a form of interstitial lung disease (ILD) which are a group of immune-mediated disorders that cause progressive fibrosis of the lung interstitium (the extravascular and extracellular space between cells in tissue).

The granulomas disrupt the intake of oxygen and can cause scarring on the lungs, preventing the lungs stretching fully, and therefore limiting their capacity. The prognosis for patients with pulmonary sarcoidosis ranges from benign and self-limiting to chronic, debilitating disease and death. Despite increasing advances in research, pulmonary sarcoidosis remains difficult to diagnose with limited treatment options to manage symptoms and no known cure. According to the Foundation for Sarcoidosis Research, approximately 200,000 Americans live with pulmonary sarcoidosis. Relief Therapeutics was granted ODD by the FDA for inhaled RLF-100® for the treatment of pulmonary sarcoidosis in August 2021.

Checkpoint Inhibitor-Induced Pneumonitis (CIP)

Checkpoint inhibitor-induced pneumonitis (CIP) is a rare, potentially fatal form of lung inflammation following treatment with immune checkpoint inhibitors (ICIs). ICIs are a type of immune therapy used to treat cancer. CIP can result in cough, dyspnea, fever, chest pain, and in severe cases, lack of oxygen in the lungs (hypoxia) and respiratory distress. The use of inhaled RLF-100^®^ for this indication will be further evaluated to explore whether such use could enhance compliance with chemotherapy and improve outcomes for cancer patients. Relief Therapeutics received a Swiss method-of-use patent protection related to the inhaled formulation of RLF-100^®^ for the potential treatment of CIP extending into at least 2039.

Berylliosis / Chronic Beryllium Disease (CBD)

Chronic beryllium disease (CBD) is an orphan lung disease caused by the inhalation of beryllium particles, dust or fumes in the workplace, resulting in severe inflammation of the lungs, coughing and increasing breathlessness (dyspnea). CBD is a clinical phenocopy of sarcoidosis. Currently there are no treatments approved for berylliosis. The ex-vivo effect of RLF-100^®^ on mononuclear cells in the setting of CBD is currently being evaluated. Together with the results from the Phase 2b sarcoidosis trial, these results would justify the therapeutic use of inhaled RLF-100^®^ in CBD, providing a rationale for the clinical trial design in this indication.

SENTINOX

Sentinox, is a novel, acid-oxidizing solution containing hypochlorous acid in a nasal spray formulation that was developed by APR. Sentinox was certified in Europe on February 16, 2021, as a Class III medical device (certificate number EPT 0477.MDD21/4200.1). Sentinox is intended for irrigation, cleansing and moistening of the nasal cavities and is indicated to reduce the risk of infections caused by bacteria and viruses, including SARS-CoV-2, by lowering the nasal microbial load; symptomatic nasal care; and nasal care in cases of minor lesions/alterations of the nasal mucosa.

On October 27, 2021, we reported positive interim results from our randomized, controlled clinical trial designed to evaluate the safety and efficacy of Sentinox in reducing viral load in the upper respiratory airways in recently SARS-CoV-2 infected patients. We also reported that data from the study suggest Sentinox could potentially be effective in reducing the SARS-CoV-2 viral load at the level of the nasal mucosa.

On March 17, 2022, Relief Therapeutics and APR reported the final data from APR’s clinical trial of nasal spray, Sentinox, in SARS-CoV-2 infected patients. The post-market, interventional, randomized, controlled clinical study (NCT04909996, clinicaltrials.gov) enrolled 57 patients who were randomized to receive Sentinox treatment 0.5 ml into each nostril, performed three times/day or five times/day for five days as add-on to the standard therapy, vs. no Sentinox treatment group. The study was designed to assess the efficacy and safety of Sentinox spray in terms of viral load reduction, negativization and infectivity in recently infected SARS-CoV-2 individuals. It was conducted by the Hygiene Unit of IRCCS Policlinico San Martino Hospital in Genoa, Italy, and coordinated by Professor Giancarlo Icardi.

Considering the small sample size and the high variability in the baseline viral load observed within study groups, the primary endpoint was not reached; however, the results of the study suggest the potential efficacy of Sentinox in the reduction of the nasal viral load, negativization and infectivity and confirmed its safety and tolerability.

Additional analyses have been conducted in patients stratified according to baseline value of RT-PCR cycles: in the subgroup with medium (Ct 20-30) viral load, the use of Sentinox significantly reduced the viral load of 1.9761 Log10 (p=0.0178) at day five compared to the control group, suggesting a positive trend in the treatment effect. Further efficacy analyses on the ITT population showed that negativization in the Sentinox three times/day group started at day four; at day six patients with negative swab were almost two-fold compared to the control group (47 percent in Sentinox group versus 22 percent in no treatment group) (p=0.0005). Similar results were obtained in the analysis conducted in the 20-30 RT PCR cycles subpopulation.

Analysis on infectivity data was also conducted in the ITT population: patients were considered “not infectious” (patient likely not be able to spread virus to others) when the cycle threshold value of >35 cycles was achieved (Carrouel et al. 2021; Jang et al. 2021; Iwanami et al. 2021; Choudhuri et al. 2020). In the three times/day Sentinox group, 71 percent of patients were non-infectious versus 44 percent in the control group at day six (p<0.0001). Overall safety data monitored through clinical examination showed a good safety profile for Sentinox. This has been confirmed also by VAS and LIKERT scale results.

Relief Therapeutics initiated a confirmatory, controlled clinical trial in the prevention of viral and bacterial airborne infections in the fourth quarter of 2022. Completion of the clinical trial is subject to availability of capital.

RARE CONNECTIVE TISSUE DISORDERS

NEXODYN^®^ Acid-Oxidizing Solution (AOS)

Nexodyn^®^ Acid-Oxidizing Solution (AOS) was developed using APR’s proprietary, patent protected TEHCLO Nanotechnology^®^ and is a solution of highly pure and stabilized hypochlorous acid (HClO >95% of free chlorine species), acidic pH (2.5 – 3.0) with high reduction-oxidation potential (ORP 1.000 – 1.200 mV). The product is a self-administered sprayable solution with ancillary antimicrobial properties intended for use in the debridement, irrigation, cleansing and moistening of acute and chronic wounds (e.g., diabetic foot ulcers, pressure ulcers and vascular ulcers), post-surgical wounds, burns and other lesions. The product is certified in the EU as a Class III medical device and is certified as a 510(k) medical device in the U.S.

Nexodyn^®^ AOS is proven to restart healing in chronic wounds by creating an ideal microenvironment to sustain the physiological healing process. A wealth of evidence and real-world experience has consistently shown accelerated wound closure with reduced infection rates and less wound-associated pain.

The anti-microbial and anti-inflammatory properties of Nexodyn^®^ AOS, along with its tolerability, could make this an attractive treatment candidate for the management of wounds in epidermolysis bullosa (EB), with the potential to be the only product approved for the control of wound infection in this disease, thereby reducing long term antibiotic use, while assisting wound healing and decreasing wound related pain, all of which would significantly benefit quality of life in patients with this genetic disorder.

RLF-TD011 (formerly referred to as APR-TD011 or APR-TM011)

RLF-TD011 is a differentiated acid oxidizing solution of hypochlorous acid (HCIO) that combines strong antimicrobial action with anti-inflammatory properties, thereby allowing for infection control, reduction of wound colonization, alleviation of pain and itching and improved wound healing.

Developed with APR’s proprietary, patent-protected TEHCLO Nanotechnology®, RLF-TD011 employs an exclusive combination of three physio-chemical properties—high-purity HCIO, hypotonic low pH and high oxidation-reduction potential (ORP), which is believed to support a faster physiological healing of wounds by creating a favorable wound microenvironment. HCIO is well known as a broad-spectrum, fast acting antimicrobial agent, which reinforced by low pH and high ORP contributes to the prevention and treatment of skin infections.

RLF-TD011 for the Potential Treatment of Epidermolysis Bullosa

RLF-TD011 is an investigational drug candidate with the potential to treat wounds in epidermolysis bullosa (EB) as it is a self-administered, sprayable solution enabling targeted application while avoiding skin contact and cross-contamination. EB, also known as “Butterfly Skin,” is a group of rare, genetic, life-threatening connective tissue disorders characterized by skin fragility and blistering, which may appear in response to minor injury, even from heat, rubbing or scratching. These widely distributed, painful, chronic wounds can easily become infected, resulting in an elevated risk of sepsis and death. A crucial element of patient management involves rigorous and timely wound care.

There are four main types of EB, which are classified based on the depth, or level, of blister formation: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. In severe cases, the blisters may develop into chronic wounds or occur inside the body, such as the lining of the mouth or stomach. Patients with JEB and DEB are at increased risk for serious complications, including aggressive squamous cell carcinoma. The National Epidermolysis Bullosa Registry (NEBR) reports, based on 16 years of data, that the incidence of EB in the U.S. is 19.57 per 1 million live births and the prevalence is 11.07 per 1 million population. Worldwide, EB impacts 500,000 lives.

Currently there is no cure or approved treatments for EB in the U.S. RLF-TD011 could represent the first product specifically indicated for EB patients that provides a comprehensive solution to prevent or reduce wound colonization and infection. This, along with its anti-inflammatory action, could provide symptom relief and wound healing. The Company estimates the global market opportunity for EB to exceed USD 1.0 billion.

Subject to clinical demonstration of efficacy and safety in clinical trials, RLF-TD011 could play an important role in the reduction of inflammation by inhibiting the NF-kB pro-inflammatory pathway and, at the same time, may offer a faster wound healing in EB patients and by reducing the itching and pain linked to infections and inflammation. In a preliminary clinical trial, EB patients who administered RLF-TD011 demonstrated improvement in skin blistering and tissue repair within just two weeks of treatment, and the product candidate was shown to be well tolerated with a favorable safety profile.

In late 2019, RLF-TD011 was granted ODD by the FDA for the treatment of EB, which qualifies the sponsor of the treatment for certain development incentives, including seven-year marketing exclusivity after FDA marketing approval is received. Relief Therapeutics intends to seek qualified infectious disease product (QIDP) designation status for RLF-TD011, which may confer up to an additional five years of market exclusivity regardless of patent protection status. Good Manufacturing Practice (GMP) grade product is being prepared for clinical development under an FDA-authorized IND.

In February 2023, Relief Therapeutics announced the first three patients were enrolled in a proof-of-concept, investigator-initiated study to evaluate RLF-TD011 as a treatment for EB (NCT05533866). The primary aim of this study will be to assess changes in the skin microbiome before, during and after treatment with RLF-TD011. Patients with dystrophic or junctional EB whose wounds are colonized by staphylococcus aureus, pseudomonas aeruginosa or commensal organisms will be treated with RLF-TD011 for eight weeks followed by discontinuation of treatment for four weeks with assessment of their wound microbiome at each stage. All study participants will have the option to continue treatment in a six-month open label study extension. Results of this study are expected sometime between the fourth quarter of 2023 and the first quarter of 2024 depending on the enrollment and treatment pace.

RLF-TD011 for Potential Treatment in Oncology Supportive Care

RLF-TD011 is currently approved in Europe as a Class III medical device for the treatment of skin lesions and toxicities induced by cancer treatments, including anti-epidermal growth factor receptors (anti-EGFR) monoclonal antibodies, such as Cetuximab. The use of anti-EGFR inhibitors causes papulopustular manifestations due to their interference of epidermal growth factor receptor (EGFR) signaling in the skin with a high risk of secondary infections.

Following commercial assessment, the company is planning to conduct a follow-on clinical study to renew product approval in Europe as a Class III medical device beyond 2024, when the new EU device regulations will apply. This clinical study will be a multi-center, post-market, double-blinded, placebo-controlled trial to evaluate the efficacy, safety and tolerability of RLF-TD011 in the management of skin lesions and reactions resulting from anti-EGFR monoclonal antibodies and/or radiotherapy treatments in oncology patients. This study would follow a preliminary, proof of concept study completed by the company on 15 patients with head and neck cancer treated for 8-12 weeks with Cetuximab and showing a mean reduction of 94 percent of the lesion area compared to the standard of care

In January 2023, Relief Therapeutics announced that an independent institutional review board (IRB) approved the protocol of an investigator-initiated trial to evaluate RLF-TD011 as an adjunctive treatment for patients diagnosed with cutaneous t-cell lymphoma (CTCL) (NCT05728879). The study will evaluate the effect of RLF-TD011, on the microbiome of CTCL skin lesions and determine tolerability, symptom improvement, and potential for reducing lesion size and skin disease activity.

Cutaneous t-cell lymphoma (CTCL) is a rare, heterogeneous group of non-Hodgkin’s lymphomas characterized by abnormal accumulation of malignant t-cells in the skin that can result in the development of rashes, plaques and tumors. Because CTCL is rare and often looks like eczema or another common skin disease, it can be difficult to diagnose. Advanced CTCL lesions harbor staphylococcus aureus, which release toxins that stimulate malignant cells and drive disease progression. This often leads to recurrent skin infections with a high risk for sepsis and death. Treatment of advanced CTCL remains a challenge, with five-year disease-specific survival rates ranging from 70 percent for early stage to 24 percent for advanced disease, with the greatest mortality stemming from bacterial infections.

While there are many types of CTCLs, the most common diagnoses are mycosis fungoides, primary CTCL and primary cutaneous anaplastic large cell lymphoma. The overall incidence rate of CTCL was 8.55 per 1 million with MF being the subtype with the highest incidence, at 5.42 per 1 million. The overall incidence of CTCL in the U.S. and Europe has increased, a reflection of better diagnostic tools and increased awareness among physicians and patients, which has led to improved disease detection.

According to Fortune Business Insights, the North American CTCL therapeutics market size is projected to reach an annual valuation of USD 587.4 million by 2028, registering a 13.6 percent compound annual growth rate (CAGR) in the 2021-2028 period. The market value was estimated to be worth USD 225.9 million in 2020 and reached USD 240.9 million in 2021. The increasing burden of CTCL in the region is slated to increase the demand for novel CTCL therapeutics solutions. Cleveland Clinic reports that more than 3,000 new CTCL patients are diagnosed in the U.S. each year and about 16,000-20,000 individuals suffer from mycosis fungoides, the most common form of CTCL that is linked to skin-localized immune cell stimulation.

LEGACY PRODUCTS

Our legacy products are revenue-generating, approved products marketed in various countries and regions of the world including the U.S. and Europe, originally developed and patented by APR and subsequently licensed to third parties for commercialization in the different territories. The rights on the legacy products were acquired by Relief Therapeutics as part of the 2021 acquisition of APR.

SETOFILM / ONDISSOLVE

SETOFILM is the first prescription-only medicine approved in Europe and Canada, developed as an orodispersible film (ODF) formulation. The product is available in 4 mg and 8 mg doses. Once placed on the tongue, it dissolves in a few seconds and is swallowed with saliva without the need for water. The innovative ODF form may reduce the patient pill burden and enable patients to take their medication virtually anywhere.

The product is indicated for radiotherapy induced nausea and vomiting (RINV), chemotherapy induced nausea and vomiting (CINV) as well as postoperative induced nausea and vomiting (PONV) in both adults and children 6 months of age or older. The product has been formulated and developed using the RapidFilm drug delivery technology and is the form of a soluble film to be placed on the tongue where it dissolves in few seconds thus greatly improving patient compliance and avoiding possible risks of suffocation in kids.

The product is approved in Europe and Canada as prescription drug and it is marketed by Norgine B.V. and Takeda Pharmaceuticals respectively under license from APR.

CAMBIA^™^

Diclofenac potassium is an off-patent, potent non-steroidal anti-inflammatory drug (NSAID) widely used for treating inflammatory conditions and pain management. By applying its patented Dynamic Buffering Technology (DBT), APR developed the first and only NSAID approved by the FDA for the treatment of acute migraine attacks with or without aura in adults. The product is currently marketed as CAMBIA^TM^ by Assertio Therapeutics Inc. (Nasdaq: ASRT) in the U.S. and Miravo Healthcare (formerly Nuvo Pharmaceuticals Inc.) in Canada, under an exclusive, royalty-bearing license agreement with APR.

In January 2022, APR received a notice of allowance from the U.S. Patent and Trademark Office (USPTO) for patent application number 16/713,052 entitled, “Ready to Use Diclofenac Packs” with an expiration date in 2039.

On February 28, 2022, Unimedica Laboratories Pvt. Ltd., India, sent APR a Notice of Certification under the Federal Food, Drug, and Cosmetic Act (FFDCA) related to the filing of an abbreviated new drug application (ANDA) for CAMBIA. While there can be no assurance, it is unlikely that Unimedica will get accelerated approval, and we reserve the right to seek to enforce our patents.

DBT and CAMBIA are currently protected by a family of four patents listed in the FDA Orange Book, all expiring in 2026. In 2023, based on litigation settlements between Assertio and specific generic filers, generic versions at Cambia may become available. CAMBIA is currently available in the form of a dry powder packed into a single dose envelope to be poured and dissolved in water before administration.

VOLTADOL

Developed by APR using a patented matrix patch technology, Voltadol is a topical, locally applied and locally acting patch delivering diclofenac sodium, an off-patent, potent non-steroidal anti-inflammatory drug (NSAID) for the local treatment of painful, acute conditions such as muscle and joint strains. Unlike heat plaster, the patch contains an anti-inflammatory. It penetrates deep to the source of pain to provide powerful pain relief. The medicated patch provides up to two times more powerful deep pain relief, compared to a non-medicated, non-heated placebo patch. The patch also provides 12 hours continuous release of the active ingredient (diclofenac) to the site of pain. This means the patch only needs to be applied once in the morning and once in the evening to provide effective pain relief. The product is marketed in various countries as an over-the-counter medicine by GlaxoSmithKline (GSK) which recently spun-off the rights to Haleon.

NeuroRx Collaboration Agreement

On September 18, 2020, we entered into a binding collaboration agreement (the Collaboration Agreement) with NeuroRx. The Collaboration Agreement established the terms under which we will collaborate and assist with NeuroRx in order to maximize revenues in our respective territories from the sale of RLF-100® for intravenous and inhaled use primarily in the treatment of COVID-19 related conditions. The NeuroRx territory included the U.S., Canada, and Israel. The Relief territory comprised the rest of the world and includes the EU, Switzerland, Iceland, Norway, the UK, the Channel Islands, Liechtenstein, Monaco, Andorra, San Marino and Vatican City.

The Collaboration Agreement provided that we would fund the costs associated with the clinical trials and development of RLF-100® (aviptadil acetate) in the U.S., which development would be conducted and managed by NeuroRx. NeuroRx was responsible for ensuring that the costs of the clinical trials and development activities for RLF-100 IV did not exceed the budget contemplated by the parties by more than 30 percent. The Collaboration Agreement also provided options for the parties to treat health conditions outside COVID-19 and for the commercialization of RLF-100® outside of the above-described territories.

Dispute and Litigation with NeuroRx

On October 7, 2021, because of breaches of the Collaboration Agreement by NeuroRx, among others, we filed a lawsuit against NeuroRx and its Chief Executive Officer, Dr. Jonathan Javitt, for multiple breaches of the Collaboration Agreement (Complaint). The Complaint was filed in the Supreme Court in the State of New York in Manhattan. The suit alleged, among other matters, breaches of the covenant of good faith and fair dealing and tortious interference with prospective economic advantage. The Complaint, among other remedies, sought damages, an order compelling NeuroRx to comply with multiple provisions of the Collaboration Agreement, and a declaration directing NeuroRx to deliver the entire data set from the Phase 2b/3 clinical trial of intravenously administering aviptadil to Relief.

On January 10, 2022, NeuroRx, through its parent, NRx, filed a complaint against Relief. In the complaint, NeuroRx claimed damages in excess of $185 million and sought a ruling that the Collaboration Agreement is void. It also included a count for defamation.

On November 14, 2022, Relief and NRx issued a press release announcing that the parties had entered into a definitive settlement agreement to resolve all matters relating to the pending litigation. At the closing of this settlement, which was held on December 19, 2022, (i) NRx transferred to Relief all of the assets that it previously used in its aviptadil development program, including its regulatory filings, patent applications, clinical data, and the formulation of the aviptadil product it was previously developing, (ii) Relief has the exclusive right and control going forward to develop and commercialize an aviptadil product, (iii) Relief has agreed to use commercially reasonable efforts to continue the existing Right to Try Program for aviptadil in the U.S. for at least two years, (iv) Relief will pay NRx milestone payments if it can successfully obtain commercial approval of an aviptadil product (whether for COVID-19 or any other indication), (v) Relief will pay NRx royalties based on a percentage of future sales of an aviptadil product (whether for COVID-19 or any other indication), up to a maximum of $30 million in the aggregate, (vi) NRx Pharmaceuticals has agreed not to compete in the development of an aviptadil product in the future, and (vii) at the closing, Relief and NRx Pharmaceuticals dismissed their pending litigation. Further, the Collaboration Agreement was cancelled. Finally, as part of the settlement, the parties exchanged releases of all claims that could have been brought in the lawsuits between the parties.

Patents and Licenses

Our success depends significantly on our ability to develop, obtain and maintain intellectual property rights for our product candidates, technology and know-how, to operate without infringing intellectual property rights of others and to prevent others from infringing our intellectual property rights. We seek to protect our proprietary position by, among other methods, filing patent applications in Europe, the U.S. and other relevant jurisdictions related to our proprietary technology, inventions and improvements that are vital to the development of our business, where patent protection is available. We also rely on trade secrets, know-how and in licensing opportunities to develop and maintain our proprietary position.

OLPRUVA^™^ License

We in-licensed from Acer the rights to commercialize OLPRUVA^™^ for the treatment of UCD and MSUD. Under the terms of our collaboration agreement, Acer received approximately $10 million cash payment (originally $14 million, offset by repayment of the $4 million outstanding balance of the prior loan, plus interest, from Relief to Acer). Relief will also pay Acer up to $20 million ($15 million which has been paid to-date) in U.S. development and commercial launch costs for the UCDs and MSUD indications. Acer will retain development and commercialization rights in the U.S., Canada, Brazil, Turkey, and Japan. The companies will split net profits from Acer’s territories 60 percent to 40 percent favor of Relief. In addition, Relief has licensed the rights for the rest of the world, where Acer will receive from Relief a 15 percent royalty on all revenues received in Relief’s territories. Acer may also receive a total of $6 million in development milestone payments following the first EU marketing approvals for UCDs and MSUD. Acer intends to submit the patent for listing by the FDA in the Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book.

In parallel with Acer’s actions, Relief and Acer are pursuing similar claims in the European Patent Office to cover OLPRUVA^™^ as Relief continues to execute on its plan to submit a Marketing Authorization Application (MAA) for OLPRUVA^™^ for the treatment of patients with UCDs in Europe. There can be no assurance that Relief and Acer will be successful in those endeavors.

Acer maintains its own intellectual property portfolio. In August 2014, Acer was granted ODD by the FDA to sodium phenylbutyrate (OLPRUVA^™^) for the treatment of Maple Syrup Urine Disease.

As of the date of this annual report, Acer’s patent portfolio for ACER-001(OLPRUVA™) consists of three patent families. The first family includes 41 granted patents world-wide directed towards novel sodium phenylbutyrate particle formulations and methods of use. These patents have an expiration date of October 2036, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity. If granted, additional patents, would expire no earlier than October 2036. Acer’s patent portfolio further includes PCT/US2021/040760 and PCT/US2022/040082. Patents granting from applications claiming priority to PCT/US2021/040760 will expire in July 2041, excluding any patent term adjustments or extensions, or any form of potential exclusivity. Patents granted from applications claiming priority to PCT/US2022/040082 will expire in April 2042, excluding any patent term adjustments or extensions, or any form of potential exclusivity.

OLPRUVA^™^’s patent applications worldwide are as follows:

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Palatable Compositions Including Sodium Phenylbutyrate and Uses Thereof	Granted: United States (Patent Nos. 11,154,521, 11,202,767, and 11,433,041), Albania, Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, European Patent Convention, Spain, Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco, North Macedonia, Malta, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San Marino<br> <br><br> <br>Pending: Bahrain, Brazil, Canada, European Patent Convention, Israel, Japan, Republic of Korea, Kuwait, Mexico, New Zealand, Oman, Qatar, Saudi Arabia, United Arab Emirates	October 17, 2036. Expiration of pending patents to be determined upon grant.
Administration of Sodium Phenylbutyrate in a Fasted State to Treat Urea Cycle Disorders	Pending: Patent Cooperation Treaty	Applications claiming priority to this PCT application, if granted, will expire no earlier than July 7, 2041.
Dosage Form for Improving Palatability of Drug Substance	Granted: China<br> <br><br> <br>Pending: China, Patent Cooperation Treaty	August 24, 2031 (China). Applications claiming priority to the PCT application, if granted, will expire no earlier than April 12, 2042.
*	Two Patent Applications
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Aviptadil Acetate/RLF-100^®^ Patents

As of the date of this annual report, Relief has two patent families covering formulations of aviptadil acetate. The first family includes a patent in the U.S. valid until at least July 2029, with extension opportunities up to five years, as well as patents in several countries in Europe and the rest of the world valid until at least 2026, excluding extension opportunities comparable to the U.S. The first family applications were filed in 2006 and granted between 2011 and 2012. The second family includes an unpublished provisional application. Relief’s aviptadil patents and patent applications worldwide are as follows:

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Formulation for Aviptadil	United States (No. 8,178,489), China, European Patent Convention, Mexico, India, Austria, Denmark, Switzerland/Lichtenstein, Germany, Spain, United Kingdom, Ireland, Netherlands, Turkey	July 3, 2029 (United States), March 7, 2026 (all other jurisdictions)
Unpublished	United States (provisional)	Expiration of any potential applications claiming priority to this provisional application to be determined upon grant.

AdVita

As of the date of this annual report, AdVita has three patent families in various stages of prosecution. The first family includes 1 granted patent and 15 applications world-wide claiming priority to PCT/EP2020/062420. Patents granting from applications claiming priority to PCT/EP2020/062420 will expire in May 2040, excluding any patent term adjustments or extensions, or any form of potential exclusivity. The second family includes 15 applications world-wide claiming priority to PCT/EP2021/052151. Patents granted from applications claiming priority to PCT/EP2021/052151 will expire in January 2041, excluding any patent term adjustments or extensions, or any form of potential exclusivity. The last family includes an a PCT application , PCT/IB2022/053709. Each family of applications is directed to novel uses and/or formulations of Aviptadil for treating various conditions such as drug-induced pneumonitis. AdVita’s patents and patent applications worldwide are as follows:

Summary Description of Patent Application	United States or Foreign Jurisdiction	Expiration Date
Patent Family 1
Vasoactive Intestinal Peptide (VIP) for Use in the Treatment of Drug-Induced Pneumonitis	United States (Application No. 17/595,025), Australia, Brazil, Canada, Switzerland, China, European Patent Convention, Hong Kong, Israel, Japan, Republic of Korea, Mexico, New Zealand, Russian Federation, Singapore, South Africa	May 5, 2040 (Switzerland) Applications, if granted, will expire no earlier than May 5, 2040.
Patent Family 2
Human Anti-Inflammatory Peptides for the Inhalatory Treatment of Inflammatory Pulmonary Diseases	United States (Application No. 17/759,559), Australia, Brazil, Canada, China, European Patent Convention, Hong Kong, Israel, India, Japan, Republic of Korea, Mexico, New Zealand, Singapore, South Africa	Applications claiming priority to this PCT application, if granted, will expire no earlier than Jan 29, 2041.
Patent Family 3
Use of Aviptadil Alone or in Combination with Alpha Lipoic Acid as a Therapeutic Medicament for Post-Viral Infection Syndrome	Patent Cooperation Treaty	Expiration of any potential applications claiming priority to this PCT application to be determined upon grant.

Partner Patents and Licenses

TECHLO Technology^™^

As of the date of this annual report, our TEHCLO^TM^ portfolio consists of four patent families. The first three families include 107 granted patents world-wide directed to systems and methods for generating hypochlorous acid solution, compositions comprising Relief’s hypochlorous acid solution, and methods for treating ocular disorders. These patents expire between October 2026 and June 2030, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity. If granted, additional patents would expire no earlier than July 2040.

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Patent Family 1
Electrolytic Water Treatment Device Having Sintered Nanoparticle Coated Electrode and Method for Making Acid or Basic Water Therewith	United States (Patent No. 8,277,634)	August 23, 2029
Device Comprising an Electrode with Nanocoating for Preparing a Highly Stable Aqueous Solution and Method for Making this Aqueous Solution	Austria, Belgium, Bulgaria, Switzerland, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, European Patent Convention, Spain, Finland, France, United Kingdom, Greece, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco, Netherlands, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, Turkey	October 24, 2026 (Luxembourg), October 23, 2026 (all other jurisdictions)
New Highly Stable Aqueous Solution, Electrode with Nanocoating for Preparing the Solution and Method for Making this Electrode	Australia, Canada, China, Israel, Mexico, New Zealand, Republic of Korea, Russian Federation, Singapore, South Africa	October 22, 2026 (China), October 23, 2026 (all other jurisdictions)
A Device for the Electrolytic Treatment of a Fluid	India	October 23, 2026
Patent Family 2
Highly Stable Electrolytic Water with Reduced NMR Half Line Width	United States (Patent Nos. 8,709,495, 9,402,192, and 9,889,153), Austria, Australia, Belgium, Bulgaria, Brazil, Canada, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, European Patent Convention, Spain, Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Japan, Republic of Korea, Lithuania, Luxembourg, Latvia, Monaco, Malta, Mexico, Netherlands, Norway, New Zealand, Poland, Portugal, Romania, Russian Federation, Sweden, Singapore, Slovenia, Slovakia, Turkey, South Africa<br> <br><br> <br>* Two patents	February 7, 2030 (United States Patent No. 8,709,495), April 24, 2028 (one United Kingdom patent), April 26, 2028 (Greece), April 25, 2028 (all other patents and jurisdictions)
Electrolytic Acid Water	India	April 25, 2028
Patent Family 3
Methods of Treating Outer Eye Disorders Using High ORP Acid Water and Compositions Thereof	United States (Patent No. 8,691,289), Germany, European Patent Convention, Spain, France, United Kingdom, Italy, South Africa	June 15, 2030 (United Kingdom), March 13, 2032 (United States), June 16, 2030 (all other jurisdictions)
Patent Family 4
Therapeutic Uses of Oxidising Hypotonic Acid Solutions	United States (Application No. 17/597,220), United Arab Emirates, Australia, Brazil, Canada, China, Colombia, Egypt, European Patent Convention, Israel, Japan, Korea, Kuwait, Qatar, Russian Federation	Applications, if granted, will expire no earlier than July 2040.

We were granted worldwide licenses for TECHLO^TM^ to numerous regional and national pharmaceutical firms. None of the licenses, either individually or as a whole, currently represent a material amount of the revenues of the consolidated company.

Physiomimic Technology^™^ - PKU GOLIKE^®^

As of the date of this annual report, the PKU GOLIKE^®^ portfolio consists of two patent families including 34 pending applications and 50 granted patents world-wide. Patents resulting from these families, if granted, will expire no earlier than 2036 and 2038, respectively, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity.

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Patent Family 1
Modified Release Orally Administered Amino Acid Formulations	Granted: United States (Nos. 10,500,180 and 11,419,837), Armenia, Austria, Australia, Azerbaijan, Belgium, Bulgaria, Belarus, Switzerland, China, Colombia, Czechia, Germany, Denmark, Eurasian Patent Convention, European Patent Convention, Spain, Finland, France, United Kingdom, Greece, Croatia, Hungary, Indonesia, Ireland, Israel, Italy, Jordan, Kyrgyzstan, Kazakhstan, Lebanon, Lithuania, Macao, Malta, Mexico, Malaysia, Norway, Netherlands, Poland, Portugal, Romania, Russian Federation, Sweden, Slovenia, Slovakia, Tajikistan, Turkmenistan, Turkey, Taiwan, South Africa<br> <br><br> <br>Pending: United States (Application No. 17/660,999), Argentina, Australia, Brazil, Canada, Chile, China, Egypt, European Patent Convention, Gulf Cooperation Council, Hong Kong, Israel, Iraq, Malaysia, Philippines, Pakistan, Saudi Arabia, Uruguay, Venezuela, Vietnam<br> <br><br> <br> Two Applications	September 25, 2036 (Jordan), September 28, 2036 (Taiwan), September 27, 2036 (all other jurisdictions).<br> <br><br> <br>Applications, if granted, will expire no earlier than September 27, 2036.
Patent Family 2
Methods of Normalizing Markers of Amino Acid Metabolism	Granted: Iraq	August 29, 2039 (Iraq)
	Pending: United States (Application No. 16/543,437), Australia, Brazil, Canada, Chile, China, Colombia, European Patent Convention, Hong Kong, Israel, Pakistan, Saudi Arabia, Taiwan	Expiration of pending patents to be determined upon grant.

We were granted licenses for PKU GOLIKE^®^ in Spain, Portugal, the UK, Ireland, Brazil, Israel, Gaza territories and West Bank, Ecuador, Greece and Cyprus.. None of the licenses, either individually or as a whole, currently represent a material amount of the revenues of the consolidated company.

Dynamic Buffer Technology - Diclofenac

As of the date of this annual report, our diclofenac patent portfolio consists of multiple patent families comprising 49 granted patents world- wide, with expiration dates in either between 2026 and 2040, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity. The portfolio further includes 14 pending applications directed to new diclofenac formulations and methods of use. If granted, patents resulting from these pending applications will expire between 2026 and 2041, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity.

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Patent Family 1
Diclofenac Formulations and Methods of Use	Granted: United States (Nos. 7,759,394, 8,097,651, 8,927,604 and 9,827,197), Australia, Canada, Switzerland, Germany, European Patent Convention, Spain, France, United Kingdom, Greece, Indonesia, Italy, Jordan, Republic of Korea, Lebanon, Malta, Mexico, Norway, New Zealand, Pakistan, Poland, Portugal, Russian Federation, Turkey, South Africa<br> <br><br> <br>Pending: United States (Application No. 16/716,511), China, Egypt, Gulf Cooperation Council, Hong Kong, Thailand<br> <br><br> <br>* Two Patents<br> <br> Three Patents<br> <br>* Four Patents	June 16, 2026 (all United States Patents), June 8, 2026 (Lebanon), June 14, 2026 (Malta), June 15, 2026 (United Kingdom), June 16, 2026 (all other jurisdictions). Expiration of pending applications to be determined upon grant.
Diclofenac Formulations	Granted: Germany, Spain, France, United Kingdom, Italy,	June 15, 2026 (United Kingdom), June 16, 2026 (All other jurisdictions)
Patent Family 2
Moisture Resistant Container Systems for Rapidly Bioavailable Dosage Forms	Granted: United States (Nos. 7,700,125 and 8,097,267)	February 7, 2026 (No. 8,097,267), October 11, 2026 (No. 7,700,125)
Patent Family 3
Substantially Sodium Free Diclofenac Potassium Oral Solutions	Granted: United States (No. 11,127,318)<br> <br><br> <br>Pending: United States (Application No. 17/463,154), European Patent Convention	January 27, 2038 (United States Patent No. 11,127,318). Expiration of pending patents to be determined upon grant.
Patent Family 4
Ready to Use Diclofenac Stick Packs	Granted: United States (No. 11,260,026)<br> <br><br> <br>Pending: United States (Application No. 17/584,212), European Patent Convention, Hong Kong	February 22, 2040 (United States Patent No. 11,260,026). Expiration of pending applications to be determined upon grant.
Patent Family 5
Bioavailable Sugar-Based Diclofenac Formulations	Patent Cooperation Treaty	Expiration of pending application to be determined upon grant.

We licensed Diclofenac to Assertio Therapeutics for its Cambia^®^ product and to Novartis for its Voltaren^®^/Voltfast^®^ product. We entered into a partnership agreement with Fidia Farmaceutici S.p.A. for diclofenac patches. We also entered into license and supply agreements with Actavis Group PTC ehf (MerckleGmbH) and Zentiva k.s..

We sold the IT Patent for Diclofenac to the Neilos s.r.l. (an affiliate of Shedir Pharma Group S.p.A) but retained a non-exclusive and perpetual license right on such patent for the production in the country of Italy of drops solution for oral administration containing Diclofenac Potassium as sole active ingredient in a concentration of 5 percent. The sale of this patent does not have an effect on the license and supply agreements described in this section.

We received a sublicense right in the territory of U.S. and China from Fidia Farmaceutici in relation to the following patents owned by IBSA Farmaceutici on Diclofenac transdermal patch:

•	Chinese Patent No. CN101001616B;
•	U.S. Patent No. 10,328,034.
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We do not believe that this license agreement our material to its business.

Oral Disposable Film—Ondansetron

As of the date of this annual report, our Ondansetron patent portfolio consists of two patent families comprising two pending applications and six granted patents with expiration dates ranging from 2027 to 2031, exclusive of any patent term adjustments or extensions, or any form of potential exclusivity.

Summary Description of Patent or Patent Application	United States or Foreign Jurisdiction	Expiration Date
Patent Family 1
Non-Mucoadhesive Film Dosage Forms	United States (Patent Nos. 8,580,830 and 9,682,037), Canada, Republic of Korea	November 22, 2029 (United States Patent No. 8,580,830), October 2, 2027 (All other patents)
Patent Family 2
Fast Dissolving Drug Delivery Systems	Granted: Russian Federation, South Africa<br> <br><br> <br>Pending: Brazil, Egypt	March 23, 2031. Expiration of pending patents to be determined upon grant.

APR has granted a license right on the abovementioned patents and patent applications to Takeda in Canada. This license does not represent a material amount of our revenues.

Other APR IP

In addition to the patents and applications described above, APR has several other pending applications and granted patents:

•	U.S. Patent No. 8,039,024, entitled “Device and composition for the delivery of a preservative-free balsamic cream” and patents in Canada, Russia and Ukraine entitled “Adhesive Label with Bittering Agent and Fluidifying Agents for Natural Airway Secretions” claim and cover a preservative-free, OTC decongestant stick pack which is no longer marketed.
•	I.T. patent 102020000021223 and pending unpublished applications in the U.S. and Canada related to dermal compositions, entitled “Dermal Compositions Replicating the Vernix Caseosa”, cover and claim OTC formulations targeting atopic dermatitis as well as other moderate skin disorders.
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Manufacturing and Supply

We do not own or operate facilities for the manufacture, packaging, labeling, storage or distribution of preclinical or clinical supplies of any of our drug candidates. We instead contract with and rely on third-party CMOs to manufacture, package, label, store test and distribute all preclinical development and clinical supplies of our drug candidates, and we plan to continue to do so for the foreseeable future. APR maintains laboratories for the testing of its products. Such laboratories are also used to develop new formulations.

Compliance with governing rules and quality requirements

The facilities used by our collaboration partners and CMOs to manufacture our product candidates are systematically audited by local authorities and occasionally inspected by competent authorities where the clinical studies are ongoing. The facilities where the commercial productions are performed must be approved by the FDA or other relevant regulatory authorities, pursuant to inspections that are conducted after we submit our NDA or comparable marketing applications. We perform periodic quality audits of the manufacturing facilities and CMOs to monitor their compliance with the regional laws, regulations and applicable cGMP standards and other laws and regulations, such as those related to environmental health and safety matters. The scope of our audits also involves monitoring the ability of our providers to maintain adequate QCs and QA systems including personnel qualification.

After manufacturing, our products are submitted to extensive characterization and QC testing plans performed by using properly developed analytical methods that are qualified or validated; this ensures the accuracy of the results generated and provides evidence of the quality of our products. In addition, our products are submitted to detailed and standardized stability programs aimed at demonstrating product stability during the storage period; this, in addition to guaranteeing the safety of the products, supports the definition of a suitable supply chain that may encompass the distribution of the products in different continents.

Contractual framework

We have established, with CMOs supplying drug substances or drug products under cGMP, quality agreements and master service agreements. Quality agreements define the quality standards required to develop, produce and supply the product, and also define the responsibilities related to the collaboration with regards to the quality related aspects. Manufacturing service agreements define the commercial and financial framework under which product manufacturing under cGMP is performed. Any failure to achieve and maintain compliance with the laws, regulations and standards, suspension of the manufacturing of our product candidates or revoke of cGMP permissions, which would adversely affect our business and reputation, are defined in the master service agreements and quality agreements. The risk that any third-party providers may breach the agreements they have with us because of factors beyond our control and the possibility that they may also terminate or refuse to renew their agreements because of their own financial difficulties or business priorities, potentially at a time that is costly or otherwise inconvenient for us, is managed by us with constant investments toward maintaining reserve stocks and in-depth process know-how.

Interaction with collaboration partners and CMOs

Finally, our partnership with CMOs is managed through an efficient project management platform in which teams are formed with the representatives of each key function from both parties. Meetings occur either through telephone conferences aimed at updating short-term actions or face-to-face conferences when mid- to long-term development plans are discussed.

Acquisition of APR Applied Pharma Research SA

On April 30, 2021, we entered into a binding term sheet with the then current shareholders of APR Applied Pharma Research SA, a privately held Swiss company with over 25 years of experience in identifying developing and commercializing known molecules engineered with drug delivery systems in niche and rare diseases, to acquire all of the outstanding shares of APR. On June 28, 2021, the former shareholders of APR and Relief signed and closed a definitive agreement for Relief to acquire all outstanding shares of APR. Under the terms of the agreement APR’s shareholders have received from Relief CHF 21.5 million in cash and 206,786,784 Consideration Shares at a value of CHF 45 million when the Consideration Shares were issued and listed. The APR shareholders were also eligible to receive possible future contingent milestone payments in the aggregate maximum amount of up to CHF 35 million, upon achievement of pre-agreed objectives involving (i) the execution of a definitive agreement for the commercialization of Sentinox (as such product is defined below), (ii) the launch of Sentinox in the first of France, Germany, Spain, Italy, and the UK, (iii) the launch of PKU GOLIKE^®^ in the U.S., and (iv) the launch of RLF-TD011 (as such product is described below) in the first of France, Germany, Spain, Italy and the UK. The launch of PKU GOLIKE^®^ in the U.S. on October 10, 2022 marked the completion of the third milestone, for which Relief issued a cash payment of CHF 2.8 million as well as 150,200,120 shares.

Acquisition of AdVita Lifescience GmbH

On July 28, 2021, we announced the closing of a definitive agreement to acquire all of the outstanding shares of AdVita Lifescience GmbH. Under the agreement, the stockholders of AdVita received 135,741,063 of our ordinary shares, representing EUR 25 million (approximately CHF 27.4 million) in value based on a 60-day volume weighted average price (VWAP) of our ordinary shares and were also eligible to receive additional contingent payments in cash. In April 2022, we made an initial milestone payment of EUR 5 million (approximately CHF 5 million) upon completion of the first milestone.

As of the date of this annual report, the former shareholders of AdVita may receive up to EUR 10 million (approximately CHF 10 million) upon achievement of pre-agreed milestones involving (i) the approval in the U.S. or Europe of the inhaled form of aviptadil for the treatment of sarcoidosis or berylliosis, and (ii) the conduct of a phase II clinical study for the inhaled form of aviptadil in the treatment of checkpoint inhibitor-induced pneumonitis.

AdVita was founded in 2019 for the purpose of developing products and strategies to improve the therapy and diagnosis of rare lung diseases. Among AdVita’s assets are intellection property rights that may cover RLF-100 inhaled formulation specifications and the potential application of inhaled Aviptadil in the treatment of Acute Respiratory Distress Syndrome, Checkpoint Inhibitor-induced Pneumonitis and Sarcoidosis.

Collaboration Agreement with InveniAI LLC

Under the terms of the InveniAI Collaboration Agreement, InveniAI will use its proprietary platform for the identification of potential pharmaceutical product opportunities using its Pharma Big Innovation Data Lab, consisting of (i) its proprietary AlphaMeld platform, a cloud-based artificial intelligence platform that uses its proprietary machine learning and deep learning based neural networks to identify product opportunities in therapeutic areas, (ii) its cross-functional teams at its Integrated Center of Excellence, and (iii) domain expertise, to generate novel pharmaceutical opportunities and the related development pathway for the development of such concepts.

In the collaboration it is expected that InveniAI will use its platform to navigate the volume of data for all regulatory agency approved drugs and their associated active ingredients to identify potential rate and specialty disease indications for development and commercialization by us (product concepts). InveniAI will seek to prioritize top product concepts, associated diseases, scientific packages and evidence to support the potential drug development opportunities by us. We anticipate that InveniAI’s platform will complement APR’s existing capabilities in research and development and in drug reformulation. Based on product leads developed by InveniAI, we hope to develop proprietary versions of existing drugs, and to protect those drugs with long-lived intellectual property and defensible product claims.

We are not currently developing any product brought to us by InveniAI, and there can be no assurance that our collaboration with InveniAI will result in the development of new product candidates or product concepts.

Regulation in the United States

The Company assumes that some of its product candidates will be submitted under an NDA and that approval of not only the products but also their manufacture is required before starting to market them. According to the definition of the U.S. Code of Federal Regulations, a drug product is approved only after demonstrating that it meets standards that assure the product’s safety, purity, effectiveness and potency.

The design, pre-clinical and clinical study, manufacture, labeling, packaging, storage, holding, sale, distribution, marketing, and promotion of pharmaceutical products – including biologic products – are subject to extensive and rigorous government regulation. The Federal Food, Drug, and Cosmetic Act (FFDCA) and other federal and state statutes and regulations govern or influence these activities. Non-compliance with applicable requirements can result in fines, recall or seizure of products, total or partial suspension of production and/or distribution, refusal of the government to enter into supply contracts or to approve NDAs, civil penalties and criminal prosecution.

Product Approval Process

Pharmaceutical products are subject to extensive regulation by the FDA. The FFDCA, and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending NDAs, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Pharmaceutical product development for a new product or certain changes to an approved product in the U.S. typically involves preclinical laboratory and animal tests, the submission to the FDA of an IND, which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought. Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially based upon the type, complexity and novelty of the product or disease.

Preclinical tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as animal trials to assess the characteristics and potential safety and efficacy of the product. The conduct of the preclinical tests must comply with federal regulations and requirements, including good laboratory practices. The results of preclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. Long term preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted.

The FDA’s Center for Drug Evaluation and Research fosters early communications between sponsors and new drug review divisions to provide guidance on the data necessary to warrant IND submission, and a 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin.

Clinical trials involve the administration of the IND to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with good clinical practice, or GCP, an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors; as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The study protocol and informed consent information for patients in clinical trials must also be submitted to an institutional review board, or IRB, for approval. An IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions.

Clinical trials to support NDAs for marketing approval are typically conducted in three sequential phases, but the phases may overlap. In Phase 1, after the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence on effectiveness. Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication, dosage tolerance, and optimum dosage, and to identify common adverse effects and safety risks. If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug. In most cases the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the drug. A single Phase 3 trial with other confirmatory evidence may be sufficient in instances where the study is a large multicenter trial demonstrating internal consistency and a statistically persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible.

In addition, the manufacturer of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanded access.

After completion of the required clinical testing, an NDA is prepared and submitted to the FDA. FDA approval of the NDA is required before marketing of the product may begin in the U.S.. The NDA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls. The cost of preparing and submitting an NDA exceeds USD 3,000,000.

The FDA has 60 days from its receipt of an NDA to determine whether the application will be filed based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. If the NDA submission is filed, the FDA reviews the NDA to determine, among other things, whether the proposed product is safe and effective for its intended use. The FDA has agreed to certain performance goals in the review of NDAs. Most such applications for standard review drug products are reviewed within ten to twelve months; most applications for priority review drugs are reviewed in six to eight months. Priority review can be applied to drugs that the FDA determines offer major advances in treatment or provide a treatment where no adequate therapy exists. The review process for both standard and priority review may be extended by the FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA may also refer applications for novel drug products, or drug products that present difficult questions of safety or efficacy, to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. As a condition of NDA approval, the FDA may require a risk evaluation and mitigation strategy, or REMS, to help ensure that the benefits of the drug outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe use, or ETASU. ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug. Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.

Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing NDAs.

Quality Assurance

The FDA regulates the facilities, processes and procedures used to manufacture and market pharmaceutical products in the U.S. Manufacturing facilities, including those located outside the U.S., must be registered with the FDA and all products made in such facilities must be manufactured in accordance with cGMP regulations enforced by the FDA. Compliance with cGMP regulations requires the dedication of substantial resources and requires significant expenditures. These cGMP standards are particularly stringent for biologic products. The FDA periodically inspects manufacturing facilities and procedures to assure compliance. The FDA may cause a suspension or withdrawal of product approvals if regulatory standards are not maintained. In the event an approved manufacturing facility is required by the FDA to curtail or cease operations, or otherwise becomes inoperable, or a third party contract manufacturing facility faces manufacturing problems, obtaining the required FDA authorization to manufacture at the same or a different manufacturing site could result in production delays, which could adversely affect the Company’s business, results of operations, financial condition and cash flow.

The FDA conducts pre-approval inspections of facilities engaged in the development, manufacture, processing, packing, testing and holding of the products subject to INDs. If the FDA concludes that the facilities to be used do not or did not meet cGMP, GLP or GCP requirements, it will not approve an IND application. Corrective actions to remedy the deficiencies must be performed and are usually verified in a sub-sequent inspection. In addition, manufacturers of both pharmaceutical products and active pharmaceutical ingredients (APIs) used to formulate the product also ordinarily undergo a pre-approval inspection, although the inspection can be waived when the manufacturer has had a passing cGMP inspection in the immediate past. Failure of any facility to pass a pre-approval inspection will result in delayed approval and would have a material adverse effect on the Company’s business, results of operations, financial condition and cash flows.

The FDA also conducts periodic inspections of facilities to assess their cGMP status. If the FDA were to find serious cGMP non-compliance during such an inspection, it could take regulatory actions that could adversely affect the Company’s business, results of operations, financial condition and cash flows. Imported API and other components needed to manufacture products could be rejected by U.S. Customs, usually after conferring with the FDA. In respect to domestic establishments, the FDA could initiate product seizures or request product recalls and seek to enjoin a product’s manufacture and distribution. In certain circumstances, violations could support civil penalties and criminal prosecutions. In addition, if the FDA concludes that a company is not in compliance with cGMP requirements, sanctions may be imposed that include classifying that company as an “unacceptable supplier”, thereby disqualifying that company from selling products to federal agencies.

Marketing

Companies that market pharmaceutical products in the U.S. are subject to various federal and state laws pertaining to healthcare fraud and abuse, including prohibitions on the offer of payment or acceptance of kickbacks or other remuneration for the purchase of products, such as inducements to potential patients to request the company’s products. Specifically, the federal Anti-Kickback Statute prohibits persons or entities from knowingly and willfully soliciting, receiving, offering or providing remuneration, directly or indirectly, to induce either the referral of an individual, or the furnishing, recommending, or arranging for a good or service, for which payment may be made under a federal healthcare program, such as the Medicare and Medicaid pro-grams. Due to legislative changes, violations of the Anti-Kickback Statute also carry potential federal False Claims Act liability. Because of the sweeping language of the federal Anti-Kickback Statute, many potentially beneficial business arrangements would be prohibited if the statute were strictly applied. To avoid this outcome, the U.S. Department of Health and Human Services’ Office of Inspector General has published regulations—known as “safe harbors”—that identify exceptions or exemptions to the statute’s prohibitions. Arrangements that do not fit within the safe harbors are not automatically deemed to be illegal but must be evaluated on a case-by-case basis for compliance with the statute. Additionally, many states have adopted laws similar to the federal Anti-Kickback Statute. Some of these state prohibitions apply to referral of patients for healthcare items or services reimbursed by any third party payer, not only the Medicare and Medicaid programs, and do not contain identical safe harbors.

The Company is unaware of any violations of these laws. However, due to the breadth of the statutory provisions and the absence of uniform guidance in the form of regulations or court decisions, there can be no assurance that its practices will not be challenged under anti-kickback or similar laws. Violations of such restrictions may be punishable by civil and/or criminal sanctions, including fines and civil monetary penalties, as well as the possibility of exclusion from participation in U.S. federal and state healthcare programs (including Medicaid and Medicare). Any liability from such a violation could have a material adverse effect on our business, financial condition, results of operations and cash flows.

In addition, the FDA has the authority to regulate the claims made by a manufacturer in marketing its products to ensure that such claims are true, not misleading, supported by scientific evidence and consistent with the products approved or cleared labeling. Failure to comply with FDA requirements in this regard could result in, among other things, suspensions or withdrawal of approvals, product seizures, injunctions against the manufacture, holding, distribution, marketing and sale of a product, civil and criminal sanctions.

Also, the federal False Claims Act prohibits persons from knowingly filing, or causing to be filed, a false claim to, knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay or transmit money or property to, or the knowing use of false statements to obtain payment from, the government. When an entity is determined to have violated the False Claims Act, it may be required to pay up to three times the actual damages sustained by the government, plus civil penalties for each separate false claim. Various states have also enacted laws modeled after the federal False Claims Act. Federal and state authorities and private whistleblower plaintiffs have brought actions against pharmaceutical product manufacturers alleging that the manufacturers’ activities constituted causing healthcare providers to submit false claims, alleging that the manufacturers themselves made false or misleading statements to the federal government, or alleging that the manufacturers improperly promoted their products for “off-label” uses not approved by the FDA, or offered inducements to referral sources that are prohibited by the federal Anti-Kickback Statute. To the extent the Company becomes the subject of any such investigations or litigation, it could be time-consuming and costly to the Company and could have a material adverse effect on its business. In addition, if its activities are found to violate federal or state False Claims Act statutes, it could have a material adverse effect on its business, financial conditions, results of operations and cash flows.

Product Liability

There are potential liability risks that arise from the testing, manufacturing, marketing and sale of pharmaceutical products. In addition to direct expenditures for damages, settlement and defense costs, there is a possibility of adverse publicity as a result of product liability claims. Some plaintiffs have received substantial damage awards in some jurisdictions against pharmaceutical companies based upon claims for injuries allegedly caused by the use of their products. In addition, it may be necessary for the Company to voluntarily or mandatorily recall or withdraw products that do not meet approved specifications, or which subsequent data demonstrate may be unsafe or ineffective, which would also result in adverse publicity as well as in costs connected to the recall and loss of revenue.

Health Information Privacy and Security

There are potential liability risks that arise from the testing, manufacturing, marketing and sale of pharmaceutical products. In addition to direct expenditures for damages, settlement and defense costs, there is a possibility of adverse publicity as a result of product liability claims. Some plaintiffs have received substantial damage awards in some jurisdictions against pharmaceutical companies based upon claims for injuries allegedly caused by the use of their products. In addition, it may be necessary for the Company to voluntarily or mandatorily recall or withdraw products that do not meet approved specifications or which subsequent data demonstrate may be unsafe or ineffective, which would also result in adverse publicity as well as in costs connected to the recall and loss of revenue.

Legislative and regulatory initiatives at the state and federal levels address concerns about the privacy and security of health information. HITECH expands the health information privacy and security protections under HIPAA and imposes new obligations to notify individuals and the U.S. Department of Health and Human Services Office for Civil Rights (OCR), of breaches of certain unsecured health information. Compliance with these laws and regulations may require the Company to spend substantial sums, including, but not limited to, purchasing new information technology, which could negatively impact financial results. Additionally, if the Company fails to comply with the HIPAA privacy, security and breach notification standards, it could suffer civil penalties of up to USD 1,500,000 per calendar year for violations of an identical standard and criminal penalties of up to USD 250,000 and 10 years in prison for offenses committed with the intent to sell, transfer, or use individually identifiable health information for commercial advantage, personal gain or malicious harm. In addition, healthcare providers will continue to remain subject to any state laws that are more restrictive than the federal privacy regulations. These privacy laws vary by state and could impose additional penalties.

The provisions of HIPAA criminalize situations that previously were handled exclusively civilly through repayments of overpayments, offsets and fines by creating new federal healthcare fraud crimes. Further, as with the federal laws, general state criminal laws may be used to prosecute healthcare fraud and abuse. A violation could subject the Company to penalties, fines and/or possible exclusion from Medicare or Medicaid. Such sanctions could significantly reduce its financial results. Future healthcare legislation and regulation or other changes in the administration of or interpretation of existing legislation or regulations regarding governmental healthcare pro-grams could have an adverse effect on the Company’s business the results of its operations.

Regulation in the European Union

Product development, the regulatory approval process, and safety monitoring of medicinal products and their manufacturers in the EU proceed in much the same manner as they do in the U.S.. Therefore, many of the issues discussed above apply similarly in the context of the EU. In addition, drugs are subject to the extensive price and reimbursement regulations of the various EU Member States.

In the EEA, which is comprised of the 27 Member States of the EU plus Norway, Iceland and Liechtenstein, medicinal products can only be commercialized after obtaining a marketing authorization. There are two types of marketing authorization: the Community Marketing Authorization, which is issued by the EC through the Centralized Procedure based on the opinion of the Committee for Medicinal Products for Human Use (CHMP), a body of the EMA, and which is valid throughout the entire territory of the EEA; and the National Marketing Authorization, which is issued by the competent authorities of the Member States of the EEA and authorizes marketing only in that Member State’s national territory and not the EEA as a whole.

The Centralized Procedure is compulsory for human medicines for the treatment of human immunodeficiency virus or acquired immune deficiency syndrome (AIDS), cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions, and viral diseases; for veterinary medicines for use as growth or yield enhancers; for medicines derived from biotechnology processes, such as genetic engineering; for advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines; and for officially designated ‘orphan medicines’ (medicines used for rare human diseases). The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation, or for products that are in the interest of public health in the EU. The National Marketing Authorization is for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for marketing in a Member State of the EEA, this National Marketing Authorization can be recognized in another Member State through the Mutual Recognition Procedure. If the product has not received a National Marketing Authorization in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure. Under the Decentralized Procedure, an identical dossier is submitted to the competent authorities of each of the Member States in which the marketing authorization is sought, one of which is selected by the applicant as the Reference Member State (RMS). If the RMS proposes to authorize the product, and the other Member States do not raise objections, the product is granted a National Marketing Authorization in all the Member States in which the authorization was sought. Before granting the marketing authorization, the EMA or the competent authorities of the Member States of the EEA assesses the risk–benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

Clinical Studies

As is the case in the U.S., the various phases of preclinical and clinical research in the EU are subject to significant regulatory controls. The EU Clinical Trial Regulation (EU) No. 536/2014 (Clinical Trials Relation) on clinical trials and medicinal products for human use, repealed Directive 2001/20/EC. The Clinical Trials Regulation entered into application on January 31, 2022 and is intended to simplify the current rules for clinical trial authorization and standards of performance. For instance, there will be a streamlined application procedure via a single entry point, a EU portal and database. The new clinical trial portal and database will be maintained by the EMA in collaboration with the European Commission and the EU Member States. The objectives of the Clinical Trials Regulation include consistent rules for conducting trials throughout the EU, consistent data standards and adverse events listing, and consistent information on authorization status. Additionally, information on the conduct and results of each clinical trial carried out in the EU will be made publicly available.

Marketing Approval

Marketing approvals under the EU regulatory system may be obtained through a centralized or decentralized procedure. The centralized procedure results in the grant of a single marketing authorization, which is valid for all (currently 27) EU Member States and the three European Free Trade Association (EFTA) members (Norway, Iceland and Liechtenstein).

Pursuant to Regulation (EC) No. 726/2004, as amended, the centralized procedure is mandatory for drugs developed by means of specified biotechnological processes, advanced-therapy medicinal products, drugs for human use containing a new active substance for which the therapeutic indication is the treatment of specified diseases, including but not limited to AIDS, neurodegenerative disorders, auto-immune diseases and other immune dysfunctions, as well as drugs designated as orphan drugs. The CHMP also has the discretion to permit other products to use the centralized procedure if it considers them sufficiently innovative or they contain a new active substance.

In the marketing authorization application, the applicant has to properly and sufficiently demonstrate the quality, safety and efficacy of the drug. Under the centralized approval procedure, the CHMP, possibly in conjunction with other committees, is responsible for drawing up the opinion of the EMA on any matter concerning the admissibility of the files submitted in accordance with the centralized procedure, such as an opinion on the granting, variation, suspension or revocation of a marketing authorization, and pharmacovigilance.

The CHMP and other committees are also responsible for providing guidelines and have published numerous guidelines that may apply to our product candidates. These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of drug products and may include, among other things, the preclinical studies required in specific cases, the manufacturing and control information that should be submitted in a marketing authorization application, and the post-approval measures required to monitor patients and evaluate the long-term efficacy and potential adverse reactions. Although these guidelines are not legally binding, we believe that our compliance with them is likely to be necessary to gain approval for any of our product candidates.

The maximum timeframe for the evaluation of a marketing authorization application by the CHMP under the centralized procedure is 210 days after receipt of a valid application. This period will be suspended until such time as the supplementary information requested by the CHMP has been provided by the applicant. Likewise, this time limit will be suspended for the time allowed for the applicant to prepare oral or written explanations. When an application is submitted for a marketing authorization in respect of a drug that is of major interest from the viewpoint of public health and in particular therapeutic innovation, the applicant may request an accelerated assessment procedure. If the CHMP accepts such a request, the time limit of 210 days will be reduced to 150 days, but it is possible that the CHMP can revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

If the CHMP concludes that the quality, safety and efficacy of the product are sufficiently proven, it adopts a positive opinion. This is sent to the EC, which drafts a decision within approximately 67 days following the CHMP opinion. After consulting with the Member States, the EC adopts a decision and grants a marketing authorization, which is valid for the whole of the EEA. The marketing authorization may be subject to certain conditions, which may include, without limitation, the performance of post-authorization safety and/or efficacy studies.

The EMA has various programs, including accelerated assessment, conditional approval and Priority Medicines (PRIME), which are intended to increase agency interactions, expedite or facilitate the process for reviewing drug candidates, and/or provide for initial approval on the basis of surrogate endpoints. One or more of our product candidates may qualify for some of these expedited development and review programs. However, even if a drug candidate qualifies for one or more of these programs, the EMA may later decide that the drug candidate no longer meets the conditions for qualification. Eligibility to the PRIME scheme is limited to products considered to offer a major therapeutic advantage in populations with high unmet need. PRIME is a voluntary scheme aimed at enhancing interaction and early dialogue with developers of promising medicines through achieving the early appointment of the Rapporteur for the product, optimizing development plans and speeding up evaluation so these medicines can reach patients earlier. Products benefiting from PRIME can expect to be eligible for accelerated assessment at the time of application for a marketing authorization application.

EU legislation also provides for a system of regulatory data and market exclusivity. According to Article 14(11) of Regulation (EC) No. 726/2004, as amended, and Article 10(1) of Directive 2001/83/EC, as amended, upon receiving marketing authorization, new chemical entities approved on the basis of a complete independent data package benefit from 8 years of data exclusivity and an additional 2 years of market exclusivity. Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic (abbreviated) application. During the additional 2-year period of market exclusivity, a generic marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic medicinal product can be marketed until the expiration of the market exclusivity. The overall 10-year period will be extended to a maximum of 11 years if, during the first 8 years of those 10 years, the marketing authorization holder (MAH) obtains an authorization for one or more new therapeutic indications that, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. Even if a compound is considered to be a new chemical entity and the innovator can gain the period of data exclusivity, another company nevertheless could also market another version of the drug if such company obtained marketing authorization based on a marketing authorization application with a completely independent data package of pharmaceutical test, preclinical tests and clinical studies. However, products designated as orphan medicinal products enjoy, upon receiving marketing authorization, a period of 10 years of orphan market exclusivity. See also “Orphan drug regulation” below. Depending upon the timing and duration of the EU marketing authorization process, products may be eligible for an SPC of up to five years, pursuant to Regulation (EC) No. 469/2009. Such SPCs extend the rights under the basic patent for the drug.

In the EU, the pediatric regulation (Regulation (EC) No 1901/2006, as amended) requires sponsors to submit a pediatric investigation plan at the end of Phase 1. This plan will provide the details of the quality, non-clinical and clinical studies required to support the authorization of a pediatric indication. Additional rules apply to medicinal products for pediatric use under Regulation (EC) No. 1901/2006. Potential incentives include a six-month extension of any supplementary protection certificate granted pursuant to Regulation (EC) No. 469/2009, but not in cases in which the relevant product is designated as an orphan medicinal product pursuant to Regulation (EC) No. 141/2000, as amended. Instead, a medicinal product designated as an orphan medicinal product may enjoy an extension of the 10-year market exclusivity period granted under Regulation (EC) No. 141/2000 to 12 years subject to the conditions applicable to orphan drugs.

Orphan Drug Regulation

In the EU, Regulation (EC) No. 141/2000, as amended, states that a drug will be designated as an orphan drug if its sponsor can establish:

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that it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 persons in the EU when the application is made, or that it is intended for the diagnosis, prevention or treatment of a life- threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment; and

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that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if such method exists, that the drug will be of significant benefit to those affected by that condition.

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Regulation (EC) No. 847/2000 sets out further provisions for implementation of the criteria for designation of a drug as an orphan drug. An application for the designation of a drug as an orphan drug must be submitted at any stage of development of the drug before filing of a marketing authorization application.

If a EU-wide community marketing authorization in respect of an orphan drug is granted or if all the EU Member States have granted marketing authorizations in accordance with the procedures for mutual recognition, the EU and the Member States will not, for a period of 10 years, accept another application for a marketing authorization, or grant a marketing authorization or accept an application to extend an existing marketing authorization, for the same therapeutic indication, in respect of a similar drug. This period may, however, be reduced to 6 years if, at the end of the fifth year, it is established, with respect to the drug concerned, that the criteria for orphan-drug designation are no longer met; in other words, when it is shown on the basis of available evidence that the product is sufficiently profitable not to justify maintenance of market exclusivity. Notwithstanding the foregoing, a marketing authorization may be granted, for the same therapeutic indication, to a similar drug if:

•	the holder of the marketing authorization for the original orphan drug has given its consent to the second applicant;
•	the holder of the marketing authorization for the original orphan drug is unable to supply sufficient quantities of the drug; or
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•	the second applicant can establish in the application that the second drug, although similar to the orphan drug already authorized, is safer, more effective or otherwise clinically superior.

Other incentives available to orphan drugs in the EU include financial incentives such as a reduction of fees or fee waivers and protocol assistance. ODD does not shorten the duration of the regulatory review and approval process.

Manufacturing and Manufacturers’ License

Pursuant to Directive 2003/94/EC, as transposed into the national laws of the Member States, the manufacturing of investigational medicinal products and approved drugs is subject to a separate manufacturer’s license and must be conducted in strict compliance with cGMP requirements, which mandate the methods, facilities and controls used in manufacturing, processing and packing of drugs to assure their safety and identity. Manufacturers must have at least one qualified person permanently and continuously at their disposal. The qualified person is ultimately responsible for certifying that each batch of finished product released onto the market has been manufactured in accordance with cGMP and the specifications set out in the marketing authorization or investigational medicinal product dossier. cGMP requirements are enforced through mandatory registration of facilities and inspections of those facilities. Failure to comply with these requirements could interrupt supply and result in delays, unanticipated costs and lost revenues, and subject the applicant to potential legal or regulatory action, including but not limited to warning letters, suspension of manufacturing, seizure of product, injunctive action, or possible civil and criminal penalties.

Wholesale Distribution and License

Pursuant to Directive 2001/83/EC, the wholesale distribution of medicinal products is subject to the possession of an authorization to engage in activity as a wholesaler in medicinal products. Possession of a manufacturing authorization includes authorization to distribute by wholesale the medicinal products covered by that authorization. The distribution of medicinal products must comply with the principles and guidelines of cGDP.

Advertising

In the EU, the promotion of prescription medicines is subject to intense regulation and control, including EU and national legislation as well as self- regulatory codes (industry codes). Advertising legislation inter alia includes a prohibition on direct-to-consumer advertising. All advertising of prescription medicines must be consistent with the product’s approved Summary of Product Characteristics, and must be factual, accurate, balanced and not misleading. Advertising of prescription medicines pre-approval or off-label is not allowed. Some jurisdictions require that all promotional materials for prescription medicines be subjected to prior review and approval, either internal or regulatory.

Other Regulatory Requirements

A Marketing Authorization Holder (MAH) for a medicinal product is legally obliged to fulfill a number of obligations by virtue of its status as an MAH. The MAH can delegate the performance of related tasks to third parties, such as distributors or marketing partners, provided that this delegation is appropriately documented and the MAH maintains legal responsibility and liability.

An MAH for a medicinal product is legally obliged to fulfill a number of obligations by virtue of its status as an MAH. The MAH can delegate the performance of related tasks to third parties, such as distributors or marketing partners, provided that this delegation is appropriately documented and the MAH maintains legal responsibility and liability.

The obligations of an MAH include the following:

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Manufacturing and batch release. MAHs should guarantee that all manufacturing operations comply with relevant laws and regulations, applicable GMPs, and the product specifications and manufacturing conditions set out in the marketing authorization, and that each batch of product is subject to appropriate release formalities.

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Availability and continuous supply. Pursuant to Directive 2001/83/EC, as transposed into the national laws of the Member States, the MAH for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medical product to pharmacies and persons authorized to supply medicinal products so that the needs of patients in the Member State in question are covered.

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•	Advertising and promotion. MAHs remain responsible for all advertising and promotion of their products, including promotional activities by other companies or individuals on their behalf, and in some cases must conduct internal or regulatory pre-approval of promotional materials. Regulation in this area also covers interactions with healthcare practitioners and/or patient groups, and in some jurisdictions legal or self-regulatory obligations to disclose such interactions exist.
•	Medical affairs/scientific service. MAHs are required to disseminate scientific and medical information on their medicinal products to healthcare professionals, regulators and patients.
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•	Legal representation and distributor issues. MAHs are responsible for regulatory actions or inactions of their distributors and agents.
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•	Preparation, filing and maintenance of the application and subsequent marketing authorization. MAHs must maintain appropriate records, comply with the marketing authorization’s terms and conditions, fulfill reporting obligations to regulators, submit renewal applications and pay all appropriate fees to the authorities. We may hold any future marketing authorizations granted for our product candidates in our own name or appoint an affiliate or a collaboration partner to hold marketing authorizations on our behalf. Any failure by an MAH to comply with these obligations may result in regulatory action against an MAH and ultimately threaten our ability to commercialize our products.
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International Regulation

In addition to regulations in the U.S. and Europe, a variety of foreign regulations govern clinical trials, commercial sales and distribution of product candidates. The approval process varies from country to country and the time to approval may be longer or shorter than that required for FDA or EMA approval.

Pharmaceutical Coverage, Pricing and Reimbursement

In both domestic and foreign markets, our or our collaboration partners’ sales of any approved products will depend in part on the availability of coverage and adequate reimbursement from third-party payors. Third-party payors include government authorities, managed care providers, private health insurers and other organizations. Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our products, if approved, unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our products. Sales of our products will therefore depend substantially, both domestically and abroad, on the extent to which the costs of our products will be paid by third-party payors. These third-party payors are increasingly focused on containing healthcare costs by challenging the price and examining the cost-effectiveness of medical products and services.

In addition, significant uncertainty exists as to the coverage and reimbursement status of newly approved healthcare product candidates. The market for our product candidates for which we may receive regulatory approval will depend significantly on access to third-party payors’ drug formularies or lists of medications for which third-party payors provide coverage and reimbursement. The industry competition to be included in such formularies often lead to downward pricing pressures on pharmaceutical or biopharmaceutical companies. Additionally, third-party payors may refuse to include a particular branded drug in their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or another alternative is available. Because each third-party payor individually approves coverage and reimbursement levels, obtaining coverage and adequate reimbursement is a time-consuming, costly and sometimes unpredictable process. We may be required to provide scientific and clinical support for the use of any product to each third-party payor separately with no assurance that approval would be obtained, and we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. This process could delay the market acceptance of any product and could have a negative effect on our future revenues and operating results. We cannot be certain that our product candidates will be considered cost-effective. Because coverage and reimbursement determinations are made on a payor-by-payor basis, obtaining acceptable coverage and reimbursement from one payor does not guarantee we will obtain similar acceptable coverage or reimbursement from another payor. If we are unable to obtain coverage of, and adequate reimbursement and payment levels for, our product candidates from third-party payors, physicians may limit how much or under what circumstances they will prescribe or administer them and patients may decline to purchase them. This in turn could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition and future success.

In the EU, the pricing and reimbursement mechanisms by private and public health insurers vary largely by country and even within countries. The public systems reimbursement for standard drugs is determined by guidelines established by the legislator or responsible national authority. The approach taken varies by Member State. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed. Other Member States allow companies to fix their own prices for medicines but monitor and control company profits and may limit or restrict reimbursement. The downward pressure on healthcare costs in general, particularly prescription drugs, has become very intense. As a result, increasingly high barriers to the entry of new products are being erected and some EU countries require the completion of studies that compare the cost-effectiveness of a particular product candidate with that of currently available therapies in order to obtain reimbursement or pricing approval. Special pricing and reimbursement rules may apply to orphan drugs. Inclusion of orphan drugs in reimbursement systems tend to focus on the medical usefulness, need, quality and economic benefits to patients and the healthcare system as for any drug. Acceptance of any medicinal product for reimbursement may come with cost, use and often volume restrictions, which again can vary by country. In addition, results based rules of reimbursement may apply.

Environmental, Health, and Safety Laws and Regulations

We are subject to numerous environmental, health and safety laws and regulations and permitting requirements, including those governing laboratory procedures, decontamination activities, and the handling, transportation, use, remediation, storage, treatment, and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, and the risk of injury, contamination or noncompliance with environmental, health and safety requirements cannot be eliminated. Although compliance with such laws and regulations and permitting requirements has not had a material effect on our capital expenditures, earnings or competitive position, environmental, health and safety laws, and regulations and permitting requirements have tended to become increasingly stringent and, to the extent that legal or regulatory changes may occur in the future, they could result in, among other things, increased costs to us or the impairment of our research, development or production efforts.

C.	ORGANIZATIONAL STRUCTURE

We are a Swiss stock corporation (société anonyme). We were originally formed in 2013, with our registered office and domicile in Geneva, Switzerland. Our Swiss enterprise identification number is CHE-113.516.874. We are located in the Canton of Geneva, City of Geneva, at Avenue de Sécheron 15, 1202 Genève, Switzerland.

As of the date of this annual report we have the following direct subsidiaries:

Name	Domicile	Percent<br>Owned
Relief Therapeutics International SA	Switzerland	100
Relief Therapeutics US, Inc.	Connecticut (U.S.)	100
Relief Therapeutics, Inc.	Delaware (U.S.)	100
APR Applied Pharma Research SA	Switzerland	100
APR Applied Pharma Research Holding SA	Switzerland	100
APR Applied Pharma Research – Italy s.r.l.	Italy	100
APR Applied Pharma Research Deutschland GmbH	Germany	100
AdVita Lifescience GmbH	Germany	100
AdVita Lifescience AG	Switzerland	100
AdVita Lifescience, Inc.	New York (U.S.)	100
D.	PROPERTY, PLANT AND EQUIPMENT
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The Group leases approximately 1,800 square feet of office, lab space and representative offices located in Geneva and Balerna (Switzerland), Freiburg im Breisgau and Offenbach am Main (Germany), and Rome (Italy). Our headquarters are at Avenue de Sécheron 15, Geneva, Switzerland. We are not aware of any environmental issues or other constraints that would materially impact the intended use of our facilities. While we may require additional space and facilities our business expands, we believe that our current facilities are suitable and adequate to meet our current needs.

ITEM 4A	UNRESOLVED STAFF COMMENTS

None.

ITEM 5	OPERATING AND FINANCIAL REVIEW AND PROSPECTS

We are a company developing drugs via participation in active entities that have obtained intellectual properties through their own research activities, or via in-licensing, or via internal research and development activities. Historically, our development has focused primarily on clinical-stage projects based on molecules of natural origin (peptides and proteins) with a history of clinical testing and use in human patients or a strong scientific rationale.

The following discussion contains references to the financial statements of Relief Therapeutics Holding SA and its consolidated subsidiaries (also referred to as the Company). These financial statements consolidate the Company’s subsidiaries and include the Company’s interest in investments held at fair value. Subsidiaries are those entities over which the Company retains control. Where we have neither control nor significant influence for financial accounting purposes, we recognize our holding in such entity at fair value. For additional information regarding the accounting treatment of these entities, see Note 1 of our consolidated financial statements included in this annual report. For additional information regarding our operating structure, see “Basis of Presentation and Consolidation” below.

A.	OPERATING RESULTS

Overview

In March 2021, we signed a Collaboration and License Agreement with Acer Therapeutics, Inc. (Acer) for the worldwide development and commercialization of ACER-001 (now OLPRUVA™) for the treatment of urea cycle disorders (UCDs) and maple syrup urine disease (MSUD). OLPRUVA™ is a proprietary powder formulation of sodium phenylbutyrate (NaPB) designed to be both taste-masked and immediate release. In August 2021, Acer submitted an NDA for ACER-001 to the FDA for use as a treatment of UCD, which submission was accepted for filing in November 2021 with a PDUFA decision date of June 5, 2022. However, on or about the PDUFA decision date, Acer received a complete response letter stating that a satisfactory inspection of Acer’s third-party contract manufacturer would be required before its NDA for ACER-001 could be approved. On December 27, 2022, Relief and Acer announced that, after resubmission, the FDA had approved ACER-001, under the trade name OLPRUVA™, for the treatment of UCDs. In addition, Acer has filed an IND to investigate OLPRUVA™ for the treatment of MSUD.

In July 2022, we executed a definitive agreement with Meta Healthcare Ltd. (Meta), acquiring the worldwide rights, except for the UK, for a novel dosage form of a prescription drug already approved by the FDA and intended for the treatment of patients with PKU. This improved product is expected to increase patient acceptance and compliance as well as enable easier, self or caregiver administered metered dosing and dispensing. According to the terms of the agreement, Meta shall transfer to Relief all data, know-how, as well as any intellectual property as developed or generated so far by Meta. Relief shall only be responsible for funding the remaining development work as well as for filing and prosecuting an NDA in all countries worldwide except for the UK where Relief Therapeutics shall grant a license back to Meta, enabling Meta to directly promote and commercialize the product in such country. Other than the initial acquisition payment and low double-digit royalty payments on net profit of the product in the various countries, Relief shall be under no obligation to fund or pay any other amount to Meta.

On November 14, 2022, Relief and NRx issued a press release announcing that the parties had entered into a definitive settlement agreement to resolve all matters relating to the pending litigation. At the closing of this settlement, held on December 19, 2022, (i) NRx transferred to Relief all of the assets that it previously used in its aviptadil development program, including its regulatory filings, patent applications, clinical data, and the formulation of the aviptadil product it was previously developing, (ii) Relief has the exclusive right and control going forward to develop and commercialize an aviptadil product, (iii) Relief has agreed to use commercially reasonable efforts to continue the existing Right to Try Program for aviptadil in the U.S. for at least two years, (iv) Relief will pay NRx milestone payments if it can successfully obtain commercial approval of an aviptadil product (whether for COVID-19 or any other indication), (v) Relief will pay NRx royalties based on a percentage of future sales of an aviptadil product (whether for COVID-19 or any other indication), up to a maximum of $30 million in the aggregate, (vi) NRx Pharmaceuticals has agreed not to compete in the development of an aviptadil product in the future, and (vii) at the closing, Relief and NRx Pharmaceuticals have dismissed their pending litigation. Further, as part of the settlement, the parties cancelled the Collaboration Agreement and exchanged mutual releases with respect to matters that were the subject of the litigation.

Material Agreements

We are party to certain agreements with third parties relating to licensing, collaboration, or other matters that are material to our business and performance.

NeuroRx

In September 2020, we entered into a collaboration agreement with NeuroRx for the global commercialization of RLF-100® (aviptadil acetate) and the selection of commercial partners. This partnership was designed to rapidly advance RLF-100® through clinical development so that it reaches COVID-19 patients worldwide as soon as possible. Under the agreement, NeuroRx was to lead commercialization in the U.S., Canada, and Israel, while we were to lead commercialization in Europe and the rest of the world.

On December 19, 2022, we finalized a settlement with NeuroRx by which the collaboration agreement was cancelled. For additional information, “Item 4. Information on the Company – B. Business Overview.”

Acer Therapeutics

On January 25, 2021, we entered into an option agreement with Acer Therapeutics Inc providing exclusivity for the right to negotiate a potential collaboration and license agreement (CLA) for worldwide development and commercialization for ACER-001 (now OLPRUVA™).

Under the terms of the option agreement, we paid Acer a $1 million USD non-refundable payment in return for exclusivity until June 30, 2021 to negotiate and enter into a definitive collaboration and license agreement for the development of ACER-001. Further, in connection with entering into the option agreement, we made a $4 million USD secured loan to Acer.

On March 22, 2021, both companies announced the execution of the CLA. Acer since received a $10 million USD cash payment (originally $14 million USD, offset by repayment of the $4 million USD outstanding balance of the prior loan, plus interest, to Acer). We also committed to pay Acer up to $20 million USD ($15 million which has been paid to-date) in U.S. development and commercial launch costs of the molecule for the treatment of the UCD and MSUD indications. Acer will retain development and commercialization rights in the U.S., Canada, Brazil, Turkey and Japan. The companies will split net profits from Acer’s territories 60 percent to 40 percent in our favor. In addition, we have licensed the rights for the rest of the world, where Acer will receive from us a 15 percent royalty on all revenues received in our territories. Acer may also receive a total of $6 million USD in development milestone payments following the first EU marketing approvals for UCDs and MSUD.

GEM Global Yield LLC SCS

On January 20, 2021, we signed a binding agreement with our largest shareholder, GEM Global Yield LLC SCS (GEM) for the implementation of a new share subscription facility (SSF) in the amount of up to CHF 50 million.

Under the terms of the SSF, we have the right to periodically, during a timeframe of up to three years, issue and sell shares to GEM. Under the facility, GEM undertakes to subscribe to or acquire our ordinary registered shares upon our exercise of a drawdown notice. In accordance with the customary terms of the SSF agreement, we control the timing and maximum amount of any drawdown and retains the right, not the obligation, to draw down on the full commitment amount. Future subscription prices under the SSF will correspond to 90 percent of the average of the closing bid prices on the SIX Swiss Exchange during the reference period, which corresponds to fifteen trading days following Relief’s drawdown notice.

Under the terms of the SSF, we are required to pay GEM a commitment fee of CHF 1.25 million, which is currently outstanding as an interest bearing loan pursuant to the SSF. As of the date of this annual report, no amounts have been drawn on this facility.

APR Applied Pharma Research SA

On April 30, 2021, we entered into a binding term sheet with the then current shareholders of APR Applied Pharma Research SA, a privately held Swiss company with over 25 years of experience in identifying developing and commercializing known molecules engineered with drug delivery systems in niche and rare diseases, to acquire all of the outstanding shares of APR. On June 28, 2021, the former shareholders of APR and Relief signed and closed a definitive agreement for Relief to acquire all outstanding shares of APR. Under the terms of the agreement APR’s shareholders have received from Relief CHF 21.5 million in cash and 206,786,784 Consideration Shares at a value of CHF 45 million when the Consideration Shares were issued and listed. The APR shareholders were also eligible to receive possible future contingent milestone payments in the aggregate maximum amount of up to CHF 35 million, upon achievement of pre-agreed objectives involving (i) the execution of a definitive agreement for the commercialization of Sentinox (as such product is defined below), (ii) the launch of Sentinox in the first of France, Germany, Spain, Italy, and the UK, (iii) the launch of GOLIKE in the U.S., and (iv) the launch of RLF-TD011 (as such product is described below) in the first of France, Germany, Spain, Italy and the UK. The launch of PKU GOLIKE^®^ in the U.S. on October 10, 2022 marked the completion of the third milestone, for which Relief issued a cash payment of CHF 2.8 million as well as 150,200,120 shares.

AdVita Lifescience GmbH

On July 28, 2021, we announced the closing of a definitive agreement to acquire all of the outstanding shares of AdVita Lifescience GmbH. Under the agreement, the stockholders of AdVita received 135,741,063 of our ordinary shares, representing EUR 25 million (approximately CHF 27.4 million) in value based on a 60-day Volume Weighted Average Price of our ordinary shares and were also eligible to receive additional contingent payments in cash. In April 2022, we made an initial milestone payment of EUR 5 million (approximately CHF 5 million) upon completion of the first milestone.

AdVita was founded in 2019 for the purpose of developing products and strategies to improve the therapy and diagnosis of rare lung diseases. Among AdVita’s assets are intellection property rights that may cover RLF-100® inhaled formulation specifications and the potential application of inhaled aviptadil in the treatment of acute respiratory distress syndrome, checkpoint inhibitor-induced pneumonitis and sarcoidosis.

InveniAI LLC Collaboration Agreement

In the collaboration it is expected that InveniAI will use its platform to navigate the volume of data for all regulatory agency approved drugs and their associated active ingredients to identify potential rate and specialty disease indications for development and commercialization by us (“product concepts”) . InveniAI will seek to prioritize top product concepts, associated diseases, scientific packages and evidence to support the potential drug development opportunities by us. We anticipate that InveniAI’s platform will complement APR’s existing capabilities in research and development and in drug reformulation. Based on product leads developed by InveniAI, we hope to develop proprietary versions of existing drugs, and to protect those drugs with long-lived intellectual property and defensible product claims.

Basis of Preparation and Consolidation

Our consolidated financial statements have been prepared in accordance with IFRS, as issued by the IASB, and comply with Swiss law. They have been prepared under the historical cost convention, as modified by the revaluation of financial instruments at fair value, are presented in Swiss Francs (CHF), and all values are rounded to the nearest thousand (TCHF), except when otherwise indicated.

The consolidated financial statements comprise the financial statements of us and our subsidiaries as of December 31, 2022. Control is achieved when we are exposed, or have rights, to variable returns from our involvement with the investee and have the ability to affect those returns through our power over the investee.

Specifically, we control an investee if and only if we have:

•	power over the investee (i.e., existing rights that give us the current ability to direct the relevant activities of the investee);
•	exposure, or rights, to variable returns from our involvement with the investee; and
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•	the ability to use our power over the investee to affect our returns.

When we have less than a majority of the voting or similar rights over an investee, we consider all relevant facts and circumstances in assessing whether we have power over an investee, including:

•	any contractual arrangement over the other vote holders of the investee;
•	rights arising from other contractual arrangements; and
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•	our voting rights and potential voting rights.
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We reassess whether or not we control an investee if facts and circumstances indicate that there are changes to one or more of the three elements of control. Consolidation of a subsidiary begins when we obtain control over the subsidiary and ceases when we lose control of the subsidiary. Assets, liabilities, income and expenses of a subsidiary acquired or disposed of during the year are included in the statement of comprehensive income from the date we gain control until the date we cease to control the subsidiary.

Profit or loss and each component of other comprehensive income are attributed to the equity holders of RELIEF THERAPEUTICS Holding SA and to the non-controlling interests, even if this results in the non-controlling interests having a deficit balance. When necessary, adjustments are made to the financial statements of subsidiaries to bring their accounting policies into line with our accounting policies. Inter-company transactions, balances and unrealized gains/losses on transactions between us and our subsidiaries are eliminated. The accounting policies of subsidiaries are consistent with the policies adopted by RELIEF THERAPEUTICS Holding SA.

Components of Our Results of Operations

Revenue and Other Gains

Revenue is primarily derived from our portfolio of marketed products and the provision of R&D services to third parties. We generate revenue from product sales, licensing fees, and royalties since the date of acquisition of APR in June 2021. Prior to the acquisition, Relief did not generate any revenue from commercial activities.

To date, our revenue has been substantially less than our operating expenses and does not significantly contribute to our cash needs. Accordingly, we rely on external funding to continue operations and fund our clinical and commercial development plan. We expect the expansion of our PKU GOLIKE^®^ franchise as a medical food in the U.S. and other territories, as well as the commercialization of OLPRUVA^™^ by Acer (for which we may receive royalty repayments in the amount of 60 percent of net profits) will contribute to increases in future revenues. We do not expect to generate revenue from product candidates unless and until we complete their development and obtain regulatory approvals.

Other gains generally consist of gains on disposal of intangible assets, write-offs of liabilities and adjustments in fair value of certain assets and liabilities.

Raw Materials and Consumables Expenses

Raw materials and consumables expenses are comprised of expenditures incurred with third parties in relation to the purchase and manufacturing of drug products for sale, as well as laboratory supplies in connection with R&D services provided to customers.

External Selling and Distribution Expenses

External selling and distribution expenses are comprised of expenditures incurred with third parties in relation to advertising, marketing, sales promotion, shipping, distribution, and commission on sales, for the sale of products and R&D services.

External Research and Development Expenses

External research and development expenses include costs associated with outsourced clinical research organization activities, sponsored research studies, clinical trial costs, process development, drug candidate manufacturing expenses, license fees, and investigator-sponsored trials, including licensing fees and milestone payments charged by licensors or collaboration partners, as well as expenses related to laboratory supplies and materials.

Costs for certain development activities, such as clinical trials, are recognized based on an evaluation of the progress to completion of specific tasks using information from the clinical sites and our vendors. Costs associated with the development activity under collaboration agreements are recognized based on actual expenses reported by our collaboration partners.

Personnel Expenses

Personnel expenses consist of employee-related expenses, including salaries, benefits, share-based compensation, and other related costs.

Our benefits under our defined benefit (pension) plan are determined using the projected unit credit method, pursuant to which costs are recognized immediately in the statement of financial position with a corresponding debit or credit to retained earnings through other comprehensive income in the period in which they occur.

Past service costs are recognized in profit or loss on the earlier of: the date of the plan amendment or curtailment, or the date that the restructuring- related costs are recognized.

The following changes in the net defined benefit obligation are recognized under ‘personnel expense’ in the consolidated statement of comprehensive income:

•	service costs comprising of current service costs, past-service costs, gains and losses on curtailments and non-routine settlements; and
•	net interest expense or income.
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The cost of share-based compensation is recognized over the period in which the performance and/or service conditions are fulfilled. The cumulative expense recognized for such transactions at each reporting date reflects the extent to which the performance and/or service conditions underlying the share award are earned. The financial statements in any period represent the movement in cumulative expense recognized at the beginning and the end of such period. No expense is recognized for awards that do not ultimately vest, except in certain cases.

Other Administrative Expenses

Other administrative expenses consist primarily of corporate facility costs, fees for legal and audit services, and consulting fees not otherwise included in research and development expenses.

Financial Income

Financial income consists mainly of foreign exchange net result, when positive. Foreign exchange net result is allocated to financial expense when negative.

Financial Expense

Financial expense consists mainly of interest expense associated with the discounting over time of provisions for contingent payments measured at fair value. The commitment fee that became due upon execution of our current share subscription facility agreement with GEM in January 2021 is expensed over the period of effectiveness of the instrument. In addition, we incurred negative interest charge on our Swiss franc and Euro cash deposits until year-end 2022.

Income Taxes

We are subject to corporate income taxation in Switzerland, the U.S., Italy, and Germany. We are also subject to corporate capital tax for our parent company and subsidiaries located in Switzerland. Unless and until the Group becomes profitable in certain tax jurisdictions, we expect income tax losses and gains will primarily arise from variations of deferred tax assets and liabilities.

Relief Results of Operations

The following table, which has been derived from our audited financial statements for the years ended December 31, 2022 and 2021, together with changes from year to year.

	December 31,						Change
Statement of Operations Data	2022			2021			(2022 to 2021)
Revenue		6,081			3,321			2,760
Other gains		9,921			1,171			8,750
Total Income		16,002			4,492			11,510
Raw materials and consumables expenses		(1,250	)		(750	)		(500	)
External selling and distribution expenses		(3,307	)		(365	)		(2,942	)
External research and development expenses		(12,393	)		(19,024	)		6,631
Personnel expenses		(12,998	)		(9,121	)		(3,877	)
Other administrative expenses		(7,747	)		(6,750	)		(997	)
Other losses		(63	)		(752	)		689
EBITDA		(21,756	)		(32,270	)		10,514
Reversal of impairment losses on intangible assets		(26,424	)		—			(26,424	)
Amortization and depreciation expense		(3,860	)		(2,036	)		(1,824	)
Operating loss		(52,040	)		(34,306	)		(17,734	)
Financial income		18			97			(79	)
Financial expenses		(2,294	)		(1,316	)		(978	)
Result before income taxes		(54,316	)		(35,525	)		(18,791	)
Income taxes		3,526			820			2,706
Results for the period		(50,790	)		(34,705	)		(16,085	)

Comparison of the Years Ended December 31, 2022 and 2021

Revenue and other gains

In 2022, we generated CHF 6.1 million in revenue from product sales, licensing fees, royalties and contract services, compared to CHF 3.3 million in 2021. Relief began generating revenue following the acquisition of APR at the end of June 2021, which generated net sales of CHF 3.2 million in the six-month period from July 1, 2021 to December 31, 2021. On an annualized basis, revenue decreased by 8.4 percent mainly due to a decrease in non-recurring license fees and in contract services revenue.

Other gains were CHF 9.9 million in 2022, compared to CHF 1.2 million in 2021. In the current period, other gains consisted mainly of a change in the fair value of provisions for contingent liabilities (CHF 8.9 million) and an impairment reversal (CHF 0.5 million) following the repayment of a loan issued to NeuroRx in 2020 and for which we had recorded a complete impairment allowance. In the comparative period, other gains were mainly related to write-offs of liabilities.

The 2022 one-off gain of CHF 8.9 million resulted from unfavorable changes in the estimated market potential and development programs for certain clinical stage assets acquired in the APR and AdVita business combinations. Under the acquisition agreements, Relief agreed to pay additional consideration upon completion of specific milestones. The fair value of the contingent consideration is recorded as a liability on our balance sheet and adjusted at the end of each reporting period based on the estimated probability of occurrence and the time factor. Any changes in fair value of the contingent liability due to assumption adjustments are recorded as ‘Other gains’ or ‘Other losses’. Refer to notes 7 and 18 of our consolidated financial statements for further information.

Raw materials and consumables expenses, and external selling and distribution expenses

Raw materials and consumables expenses, and external selling and distribution expenses, were, respectively, CHF 1.3 million and CHF 3.3 million in 2022. We did not incur any such expenses prior to the acquisition of APR and its marketing activities. In addition, premarketing and marketing activities in relation to the launch of PKU GOLIKE^®^ in the U.S. in October 2022 accounted for CHF 2.5 million in 2022.

External Research and Development Expenses

External research and development expenses were primarily driven by development activities for RLF-100^®^ and expenses incurred by Acer for the development and intended commercialization of ACER-001. The decrease of CHF 6.6 million, to CHF 12.4 million in 2022 from CHF 19.0 million in 2021, was primarily due to a reduction of CHF 6.7 million in development expenses associated with RLF-100^®^. Expenditures associated with other in-process programs did not vary materially.

Contingent upon availability of funds, we plan to further increase our research and development expenses for the foreseeable future as we commence additional clinical trials and pursue discovery and development of new product candidates.

Personnel Expenses

Personnel expenses increased to CHF 13.0 million in 2022, compared to CHF 9.1 million in 2021, an increase of CHF 3.9 million mainly due to an increase in employee headcount resulting from the acquisitions of APR and AdVita and the establishment of our U.S. sales force. Non-cash remuneration in the form of stock options amounted to CHF 2.2 million and CHF 1.1 million in 2022 and 2021, respectively. As of December 31, 2022, Relief had 69 full-time equivalents on its payroll.

Other Administrative Expenses

Other administrative expenses increased to CHF 7.7 million in 2022, compared to CHF 6.7 million in 2021, an increase of CHF 1.0 million. The main drivers of this increase were higher expenses related to the maintenance and prosecution of intellectual property, travel of Company’s staff, and IT infrastructure and software primarily due to the addition of APR and AdVita. Legal fees remain flat as non-recurring costs incurred as part of Relief’s effort to list its securities on Nasdaq were offset by a reduction in costs incurred for other legal and regulatory matters.

Other Losses

Other losses were not material in 2022, compared to CHF 0.8 million in 2021. Other losses for the comparative period were mainly constituted by an impairment loss of CHF 0.4 million on the loan issued to NeuroRx in 2020.

Impairment Expense

We conducted impairment tests of intangible assets as of June 30 and December 31, 2022, and concluded that the carrying amount of certain assets, mainly intangible assets associated with PKU GOLIKE^®^ and Sentinox^™^, exceeded their recoverable amount. As a result, we recognized a non-cash impairment charge on intangible assets of CHF 26.4 million in the current period. The impairment charge reflects a reduction of estimated future net cash flows from PKU GOLIKE^®^ following changes in market assumptions, and, for Sentinox^™^, a one-year delay in the estimated launch date.

Amortization and Depreciation Expense

Amortization and depreciation expenses were CHF 3.9 million in 2022, compared to CHF 2.0 million in 2021. These expenses are mainly related to the amortization of our intangible assets. Prior to the acquisition of APR in June 2021, we did not have amortizable intangible assets nor material property, plant, and equipment assets on our balance sheet.

Financial Income

Financial income was not material in 2022, compared to CHF 0.1 million in 2021. Financial income for the comparative period was mainly constituted by a net foreign exchange gain on monetary assets and liabilities and transactions denominated in U.S. dollars and Euros. In 2022, the net foreign exchange result was a loss recorded in financial expense.

Financial Expenses

Financial expenses increased to CHF 2.3 million in 2022, compared to CHF 1.3 million in 2021, an increase of CHF 1.0 million. The cost of unwinding of the time discount of provisions for contingent consideration for the acquisition of APR and AdVita increased to CHF 1.3 million in 2022 from CHF 0.7 million in 2021 as the period that elapsed was 12 months in 2022, compared to 6 months in 2021. Financial expenses also increased as the Company incurred a net foreign exchange loss of CHF 0.4 million in 2022, compared to a net foreign exchange gain in 2021.

Income Taxes

Income taxes were a gain of CHF 3.5 million in 2022, compared to a gain of CHF 0.8 million in 2021. The income tax gain resulted mainly from the amortization and impairment of intangible assets and a corresponding reduction in the temporary difference between the carrying amount of these assets and their tax base. In 2022, the Company also wrote off deferred tax assets for a total amount of CHF 1.5 million as the criteria for the recognition of these assets were not met as of December 31, 2022. The write-off charge was offset by a reduction in deferred tax liabilities of CHF 5.0 million.

Summary of critical accounting judgements and key sources of estimation uncertainty

Our operating and financial review and prospects were derived from our consolidated financial statements in conformity with IFRS as issued by the IASB. The preparation of the consolidated financial statements in conformity with IFRS requires management to make estimates and assumptions that affect the application of policies and reported amounts of assets, liabilities, income, expenses and related disclosures. The estimates and underlying assumptions are based on historical experience and various other factors that are believed to be reasonable under the circumstances, the results of which form the basis for making the judgments about carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates. The estimates and assumptions that have a significant risk of causing a material adjustment to the carrying amounts of assets and liabilities within the next financial year are described below.

Critical accounting judgements and key sources of estimation uncertainty are described in note 4 of our 2022 consolidated financial statements included in this annual report.

B.	LIQUIDITY AND CAPITAL RESOURCES

Sources of Liquidity

To date, we have funded our operations primarily through private placements, at-the-market sales of treasury shares, and equity offerings and loans from our largest shareholder, GEM. We have never been profitable and have incurred operating losses in each year since inception. We have an accumulated deficit of CHF 119.6 million as of December 31, 2022 and expect to incur further losses over the foreseeable future as we develop our business. We have spent, and expect to continue to spend, a substantial amount of funds in connection with implementing our business strategy, including our planned product development and commercialization efforts.

As Relief continues to incur significant operating losses, our ability to pursue and finance our operations and our intended development plans depends on our ability to continue to raise additional financing. Our primary uses of capital are R&D expenses, personnel compensation expenses, and administrative expenses. We expect to continue to incur substantial expenses in connection with our product candidates at various stages of development and for working capital requirements. We expect to continue to raise financing through the sale of equity and debt financing. We intend to use future expected proceeds, together with cash on hand, to finance our development and commercial activities and the diversification of our pipeline, as well as to fund our outstanding liabilities and other commitments. We expect our expenses to increase in connection with our ongoing activities, particularly as we continue to advance our portfolio of product candidates, initiate further clinical trials, and seek marketing approval for our product candidates. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur additional commercialization expenses related to program sales, marketing, manufacturing, and distribution to the extent that such sales, marketing and distribution are not the responsibility of potential partners. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations.

Going Concern

As of December 31, 2022, we had cash and cash equivalents of CHF 19.2 million. Based on current operating plans, we expect that we have sufficient resources to fund operations into the third quarter of 2023. This raises substantial doubt about our ability to continue as a going concern. Please refer to note 4.1 ‘going concern’ of our consolidated financial statements included in this annual report. Our consolidated financial statements do not include any adjustments or classifications that may result from our possible inability to continue as a going concern.

Our future capital requirements will depend on many factors, including:

•	the scope, progress, results and costs of our ongoing and planned preclinical studies and clinical trials;
•	the number and development requirements of other product candidates that we may pursue;
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•	the costs, timing and outcome of regulatory review of our product candidates;
---	---
•	the timing amount of milestone payments we may have to pay in relation to the acquisitions of APR and AdVita;
---	---
•	the extent to which we in-license or acquire other product candidates and technologies;
---	---
•	the costs and timing of future commercialization activities, including drug manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive or have received marketing approval;
---	---
•	the timing of repayment of the Relief’s borrowings; and
---	---
•	the funding necessary to sustain our commercial operations until we attain the breakeven point.
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We will need to raise additional capital to fund continued operations beyond the third quarter of 2023. We may not be successful in our efforts to raise additional funds or achieve profitable operations. We continue to explore potential opportunities and alternatives to obtain the additional resources that will be necessary to support our ongoing operations beyond the third quarter of 2023, including raising additional capital through either private or public equity or debt financing, or additional program collaborations or non-dilutive funding, as well as using our treasury share sales program or our shares subscription facility with GEM.

If we are unable to obtain additional funding to support our current or proposed activities and operations, we may not be able to continue our operations as proposed, which may require us to suspend or terminate any ongoing development activities, modify our business plan, curtail various aspects of our operations, cease operations, or seek relief under applicable bankruptcy laws. In such event, our stockholders may lose a substantial portion or even all of their investment.

Cash Flows

The following table summarizes our cash flows for each of the periods presented.

	December 31,
In thousands	2022			2021
Cash flow from operating activities		(24,126	)		(35,718	)
Cash flow from investing activities		(7,999	)		(30,262	)
Cash flow from financing activities		6,417			67,689
Net (decrease) increase in cash and cash equivalents		(25,708	)		1,709
Cash and cash equivalents at end of period		19,237			44,761

Operating Activities

Net cash used in operating activities consist of the net operating loss adjusted for changes in net working capital and for non-cash items such as impairment and depreciation, fair value adjustments, the value of share-based services and changes in post-employment benefits.

Net cash used in operating activities was CHF 24.1 million in 2022, compared to CHF 35.7 million in 2021. The decrease in cash used in operating activities of CHF 11.6 million was due to an increase in net loss of CHF 16.1 million, before adjustments for non-operating transactions, offset by an increase in non-cash items of CHF 19.0 million and an increase in change in net working capital of CHF 10.8 million.

Investing Activities

Net cash used in investing activities was CHF 8.0 million in 2022, compared to CHF 30.3 million in 2021.

In 2022, net cash used in investing activities consisted primarily of payments to the former shareholders of APR and AdVita in relation to the completion of contractual milestones.

In 2021, net cash used in investing activities consisted primarily in payments for the acquisition of APR and ACER 001 license.

Financing Activities

Net cash from financing activities was CHF 6.4 million in 2022, compared to CHF 67.7 million in 2021.

In 2022, net cash from financing activities consisted primarily of CHF 7.1 million gross proceeds from the offer of treasury shares into the trading market, partially offset by issuance costs of CHF 0.2 million and by debt repayments of CHF 0.5 million.

In 2021, net cash from financing activities consisted primarily of CHF 50.9 million gross proceeds from the offer of treasury shares into the trading market and private placements of CHF 25 million, partially offset by issuance costs of CHF 2.8 million and by debt repayments of CHF 5.6 million.

Quantitative and Qualitative Disclosure about Financial Risks

We are exposed to various financial risks such as credit risk, liquidity risk and market risk (including interest rate and currency risk). The following is an overview of the extent of such risks and our processes employed to handle those risks.

Credit Risk

Credit risk refers to the risk that a party will default on its contractual obligations to us, resulting in financial losses. We do not currently have any revenue and as a result we do not have credit risk with relation to our customers. Our financial assets consist of mainly cash, for which the risk is minimal as such deposits are at well-known banks in Switzerland with an “A” rating as per Standard & Poors.

Liquidity Risk

Liquidity risk implicates our ability to maintain sufficient cash and cash equivalents to meet our financial obligations. Our management monitors our net liquidity through rolling forecasts of projected cash flows.

Interest Rate Risk

We are exposed to interest risk in respect of the Company’s cash deposits, bank loans and other interest-bearing liabilities. We deem the interest rate risk as low on its performance and its equity.

Currency Risk

We operate internationally and are exposed to currency risk arising from various exposures, primarily with respect to the Swiss francs, Euros and U.S. dollars. Currency risk arises from future transactions, recognized assets and liabilities and net investments in foreign operations. To manage such risk, we monitor our exposure by periodically assessing future spending needs in foreign currencies and maintain foreign currency cash balances to cover anticipated future requirements. We do not enter into any forward currency transactions.

While we consider our current exposure to foreign currency risk to be low, adverse changes in the value of the Swiss franc could still have a significant negative impact on our financial condition, results of operations, and future prospects.

JOBS Act Exemptions and Foreign Private Issuer Status

We qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act of 2012 (JOBS Act) in the U.S. An emerging growth company may take advantage of specified reduced reporting and other requirements that are otherwise applicable generally to public companies. This includes an exemption from the auditor attestation requirement in the assessment of our internal control over financial reporting pursuant to the Sarbanes-Oxley Act of 2002. We may take advantage of this exemption for up to five years or such earlier time that we are no longer an emerging growth company. We will cease to be an emerging growth company if we have more than $1.07 billion in total annual gross revenue, have more than $700 million in market value of our ordinary shares held by non-affiliates or issue more than $1 billion of nonconvertible debt over a three- year period. We may choose to take advantage of some but not all of these provisions that allow for reduced reporting and other requirements.

Upon completion of the U.S. listing to which this annual report relates, we will report under the Securities Exchange Act of 1934, as amended, or the Exchange Act, as a non-U.S. company with foreign private issuer status. Even after we no longer qualify as an emerging growth company, as long as we qualify as a foreign private issuer under the Exchange Act, we will be exempt from certain provisions of the Exchange Act that are applicable to U.S. domestic public companies, including:

•	the sections of the Exchange Act regulating the solicitation of proxies, consents or authorizations in respect of a security registered under the Exchange Act;
•	sections of the Exchange Act requiring insiders to file public reports of their stock ownership and trading activities and liability for insiders who profit from trades made in a short period of time;
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•	the rules under the Exchange Act requiring the filing with the SEC of quarterly reports on Form 10-Q containing unaudited financial and other specified information, or current reports on Form 8-K, upon the occurrence of specified significant events; and
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•	Regulation FD, which regulates selective disclosures of material information by issuers.
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C.	RESEARCH AND DEVELOPMENT, PATENTS AND LICENSES, ETC.
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See “Item 4. Information on the Company – B. Business Overview” and “Item 5. Operating and Financial Review and Prospects – A. Operating Results”.

D.	TREND INFORMATION

See “Item 5. Operating and Financial Review and Prospects – A. Operating Results and B. Liquidity and Capital Resources”.

E.	OFF-BALANCE SHEET ARRANGEMENTS

As of the date of this annual report, the Company had the contingent liabilities listed in note 36 of the 2022 consolidated financial statements included in this annual report. There were no other material off-balance sheet arrangements.

F.	TABULAR DISCLOSURE OF CONTRACTUAL ARRANGEMENTS

The following table summarizes our contractual commitments as of December 31, 2022:

(TCHF)	Less than<br>1 year
Lease liabilities (1)		340	309	140	—	789
Financial borrowings (2)		1’652	12	3	—	1’667
Total
(1)	Represents the minimum lease payments due under our operating leases for offices, laboratory space, company cars, and office and labs material.
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(2)	Bank loans are classified as short term due to the absence of contractual repayment date that renders their repayment date uncertain and dependent on the creditor’s demand.
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Further, as described elsewhere in this document, we have committed to pay royalties on any revenue derived from the sale of aviptadil and OLPRUVA™, to NeuroRx and Acer Therapeutics, respectively, as well as royalties on net commercialization profit of a low double-digit percentage to Meta if we commercialize or license RLF-OD32. We currently do not generate any revenue from these three compounds and therefore have no current payment obligations.

We enter into contracts in the normal course of business with CROs, contract manufacturing organizations and other third parties for clinical trials, preclinical studies, manufacturing and other services and products for operating purposes. These contracts generally provide for termination upon notice, and therefore we believe that our non-cancelable obligations under these agreements are not material.

G.	SAFE HARBOR

This annual report contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act, and as defined in the Private Securities Litigation Reform Act of 1995. See “Special Note with Respect to Forward Looking Statements” included elsewhere in this annual report.

ITEM 6	DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES
A.	DIRECTORS AND SENIOR MANAGEMENT
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For information about our directors and senior management, see “Item 1. Identity of Directors, Senior Management and Advisers – A. Directors and Senior Management”.

B.	COMPENSATION

Compensation in General

We are subject to the Directive on Information Relating to Corporate Governance of the SIX Swiss Exchange (Corporate Governance Directive) and the Swiss Ordinance Against Excessive Compensation in Public Companies of November 20, 2013, as amended from time to time (Compensation Ordinance), and the Swiss Code of Obligations.

In line with the requirements of the Compensation Ordinance, the Company’s Articles of Association and the Organizational Regulation include provisions on the following governance and compensation-related matters:

•	number of permissible mandates in the supreme governing bodies of other legal entities;
•	maximum terms of employment contracts and maximum notice period for members of the Executive Committee;
---	---

•	principles of compensation applicable to the Board of Directors and Executive Committee;
•	shareholders’ binding vote on compensation of the Board of Directors and Executive Committee;
---	---
•	additional amount for members of the Executive Committee hired after the vote on compensation by the Annual General Meeting; and
---	---
•	loans, credit facilities and post-employment benefits for members of the Board of Directors and of the Executive Committee.
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Role of the Compensation Committee

The Nomination and Compensation Committee (NCC) assists the Board of Directors in all nomination and compensation matters. As detailed in the Organizational Rules of the Company, the NCC is responsible for ensuring the best possible leadership and management talent for the company and an appropriate compensation policy. In particular, the NCC is responsible for the following activities:

•	identification of suitable candidates for positions on the Board of Directors and on the Executive Committee;
•	recommendation and proposal of compensation principles and programs, including share-based compensation plans;
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•	recommendation and proposal of the compensation for the members of the Board of Directors and Executive Committee; and
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•	recommendation and proposal of specific compensation packages for other members of management.
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The decision-making authorities in compensation matters are summarized in the table below:

Level of Authority CEO*	CEO	Nomination<br>and<br>Compensation<br>Committee	Board of<br>Directors	Annual<br>General<br>Meeting
Compensation policy including share-based plans		proposes	approves
Aggregate compensation of the Board of Directors		proposes	reviews	approves
Individual remuneration of the Board of Directors members		proposes	approves
Aggregate compensation of the Executive Committee		proposes	reviews	approves
Individual compensation of the CEO		proposes	approves
Individual compensation of Executive Committee members	proposes	reviews	approves
Compensation report		proposes	approves

The NCC consists of a minimum of one member of the Board. The members of the NCC are elected individually and annually by the Annual General Meeting (AGM) for the period until the following AGM. At the AGM 2022, Thomas Plitz (NCC Chairman) and Raghuram Selvaraju were elected members of the NCC.

The NCC meets as often as the business requires, but at least once a year. The NCC Chairman may invite the Chairman of the Board, the CEO or other members of the Executive Committee to join the meeting in an advisory capacity. However, the executives do not take part in the meeting, or parts of meeting, during which their own compensation is discussed. The NCC Chairman reports to the Board on the activities of the committee after each meeting. The NCC may retain external advisors to obtain support in fulfilling its duties.

Role of Shareholders and Say-On-Pay Vote

At the AGM to be held by the end of June 2023, a binding vote on the compensation amount of the Board and Executive Committee will be conducted. The AGM will vote on the maximum compensation amount of the Board for the period of office until the following AGM and on the maximum compensation amount of the Executive Committee for the next financial year. The prospective voting structure provides the Company and its management with the necessary level of planning certainty to operate efficiently.

The AGM held on May 31, 2022, approved a maximum compensation amount of CHF 2’500’000 for the Board for the period from the AGM 2022 to the AGM 2023 and a maximum compensation amount of CHF 5’000’000 for the Executive Committee for the financial year 2023.

Method of Determination of Compensation

Based on the recommendation of the NCC, the Board of Directors decides upon the compensation of the Board of Directors and Executive Committee at its own discretion, which is ultimately approved by the AGM. When preparing the compensation proposals, the NCC takes the following factors into consideration:

•	affordability and overall situation of the Company;
•	business financial results and individual performance; and
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•	level of compensation paid by other companies that are deemed to be comparable in terms of industry (where they compete for talent) and complexity (defined by their size and geographic scope).
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The compensation of the Board of Directors and Executive Committee is reviewed annually on the basis of those factors; however, the review does not necessarily lead to any adjustment.

Based on the recommendation of the NCC, the Board decides on the compensation of the Board and Executive Committee at its own discretion, which is prospectively approved by the AGM. When preparing the compensation proposals, the NCC takes the following factors into consideration:

•	Affordability and overall situation of the Company;
•	Achievement of corporate goals and individual objectives; and
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•	Level of compensation paid by comparable companies in the biotech and pharmaceutical industry (where they compete for talent) and complexity (defined by their size and geographic scope).
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The compensation of the Board and Executive Committee is reviewed annually on the basis of those factors. However, the review does not necessarily lead to adjustments.

Executive Compensation

In accordance with the laws of Switzerland, we do not report executive compensation on an individualized basis. The disclosure below includes all forms of compensation given by us in exchange for services rendered in 2022 and 2021 by members of the Executive Committee.

In 2022 and 2021, members of the Executive Committee received total remuneration as follows:

Compensation of the Executive Committee for the 2022 Calendar Year, in CHF

	Fixed<br>Compensation
Total Executive Committee (1)		1,635,477	160,130	89,087	35,068	—	1,919,762
(1)	The highest paid member of the Executive Committee in 2022 was our former Chief Financial Officer and later Chief Executive Officer, Jack Weinstein, who received CHF 481,521 of fixed compensation, CHF 50,130 of variable cash compensation, and CHF 10,929 in other benefits.
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(2)	Does not include the Company’s mandatory contribution to social security (AHV) of CHF 128,696.
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Compensation of the Executive Committee for the 2021 Calendar Year, in CHF

	Fixed<br>Compensation
Total Executive Committee (1)		1,763,451	231,340	30,151	—	1,947,634	3,972,476
(1)	The highest paid member of the Executive Committee in 2021 was our then Chief Financial Officer, Jack Weinstein, who received CHF 460,614 of fixed compensation, CHF 175,000 of variable cash compensation and CHF 1,096,799 of options.
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(2)	Reflects the value of share-based payments in accordance with IFRS 2 at grant date independently of the vesting schedule. Such stock option values are theoretical values at grant date and do not reflect taxable income nor realized income.
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(3)	Does not include the Company’s mandatory contribution to social security (AHV) of CHF 82,953
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During the 2022 fiscal year, remuneration to the executive committee amounted to CHF 1,919,762. This was within the limit of CHF 5,000,000 approved by the AGM 2022.

Employment Arrangements

We have entered into employment letters with each of our executive officers. These agreements provide for a base salary and annual incentive cash and option bonus opportunities as well as payments upon termination. Agreements with our executive officers may be terminated upon two to twelve months’ advance notice.

Principles and Compensation Architecture

Our compensation principles are aligned with the Company’s strategy of becoming profitable by growing its business and increasing revenue. The compensation principles are as follows:

•	Balance between competitiveness and affordability: within the Company’s financial ability, compensation levels are competitive and aligned with market practice for similar functions in comparable companies in the biotech and pharmaceutical industry;
•	Pay for performance: part of compensation is directly linked to the performance of the business and to the achievement of individual objectives; and
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•	Alignment with shareholders’ interests: part of compensation is delivered in the form of stock options and thus is directly tied to the Company’s long-term share performance.
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The compensation of the members of the Executive Committee consists of fixed and variable remunerations. Fixed remuneration comprises the base salary and other benefits. Variable remuneration may comprise a performance-based cash bonus and equity grants.

Compensation Model for Executive Officers

	Vehicle	Purpose	Drivers	Performance
Fixed Base Salary	Monthly Cash	Attract & Retain	Market practice	—
Performance bonus	Cash bonus	Pay for performance	Business and individual performance	Company’s profitability, individual performance
Employee Participation Program	Share options	Align to shareholders’ interests	Level of the role	Share price
Benefits	Pension/insurance plans	Protect against risk	Market practice	—

Fixed Base Salary. The fixed base salary pays for the function and depends on our financial ability, the market value of the function and the profile of the individual in terms of qualifications and skill set.

Performance Bonus. The performance bonus rewards the effective and successful conduct of the business and the achievement of individual objectives. The target performance bonus is generally expressed as a percentage of the fixed base salary. At the discretion of the Board and the NCC, decision to grant a bonus may be taken. The bonus amount effectively paid out is then determined by the Board, based upon the proposal of the NCC. The performance bonus is usually paid in cash or options, usually at the end of the financial year.

Employee Participation Program. The Employee Participation Program provides an incentive for management to make significant contributions towards our long-term success and aligns their interests to those of our shareholders. The Board of Directors determines the individual allocation of stock options at its own discretion, taking into account the level of the role and economic considerations. The value of the options for financial reporting purpose is calculated according to the Black-Scholes valuation model.

Benefits. Executive Officers participate in the regular pension and retirement plans applicable to all employees in their country of employment. The provisions of those pension and retirement plans are in line with local regulations and prevailing market practice. Further, executive officers may be entitled to benefits in kind, in line with local market practice, such as a company car or other benefits.

Contractual Provisions. The employment contracts of our executive officers are concluded for an indefinite period and without a notice period. They do not contain any agreement on severance provisions.

NON-EMPLOYEE DIRECTOR COMPENSATION

The disclosure of compensation below includes all forms of compensation given by us in exchange for services rendered by members of our Board of Directors in 2022 and 2021, in CHF.

Board of Directors	Cash Fee<br>2022
Raghuram Selvaraju<br> <br>Chairman since May 25, 2016		500,000	475,000	—	248,470	500,000	723,470
Thomas Plitz<br> <br>Member since December 17, 2020		150,000	125,000	—	266,103	150,000	391,103
Patrice Jean<br> <br>Member since June 18, 2021		150,000	76,998	—	16,330	150,000	93,329
Paolo Galfetti (3)<br> <br>Member since June 18, 2021		150,000	79,722	—	—	150,000	79,722
Michelle Lock<br> <br>Member since January 28, 2022		92,473	—	—	—	92,473	—
Thomaz Burckhardt<br> <br>Member until 8 February 2021		—	7,500	—	—	—	7,500
Total		1,042,473	764,220	—	530,903	1,042,473	1,295,123
(1)	Reflects value of share-based payments in accordance with IFRS 2 at grant date independently of the vesting schedule. Such stock option values are theoretical values at grant date and do not reflect taxable income nor realized income.
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(2)	Does not include the Company’s mandatory contribution to social security of CHF 35,515 (2021: 18,628).
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(3)	For his executive role, Mr. Galfetti received an additional remuneration of CHF 442’990 in cash and CHF 64’636 in the form of pension contribution for the 2022 calendar year. His executive compensation is reported as part of the compensation of the Executive Committee.
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The figures in the table above cover the 2022 calendar year, as required by Swiss law. They differ from the period authorized by the AGM, which runs from AGM to AGM (the Authorization Period). Differences between calendar years and Authorization periods are shown in the tables below.

During the current Authorization Period, members of the Board of Directors are expected to earn a total compensation of CHF 1,141,667. This is within the limit of CHF 2,500,000 approved at the EGM 2022.

	Calendar Year 2022			Authorization period 2023/2022
Compensation (CHF)		Period	Amount		Period	Amount	(1)	Approved
Cash Fee		January 2022-<br>December 2022	1,042,473		July 2022-June<br>2023	1,141,667
Options		January 2022-<br>December 2022	—		July 2022-June<br>2023	—
Total			1,042,473			1,141,667		2,500,000
(1) As this period is not yet ended as of the date of this report, the amount includes actual to date and an estimate of the compensation to be earned over the remaining period to the AGM 2023.
	Calendar Year 2021			Authorization period 2022/2021
---	---	---	---	---	---	---	---	---
Compensation (CHF)		Period	Amount		Period	Amount	(1)	Approved
Cash Fee		January 2021-<br>December 2021	764,220		July 2021-<br>June 2022	922,110
Options		January 2021-<br>December 2021	530,903		July 2021-<br>June 2022	264,800
Total			1,295,123			1,186,911		2,500,000

In 2022 and 2021, no compensation was granted to former members of the Board of Directors or related parties.

Option Grants to Members of the Board of Directors and Executive Committee

During 2022 and 2021, the following options to purchase shares of the Company’s ordinary stock as listed on the SIX Swiss Exchange were granted to members of the Board of Directors and Executive Committee:

Date of Grant	Options Granted			Expiration Date
January 1, 2021		100,000	0.2690	December 31, 2025
May 30, 2021		8,500,000	0.0100	1/2 on each of May 29, 2027 and 2028
September 12, 2021		1,900,000<br> <br>3,200,000	0.0100<br> <br>0.1540	1/3 on each of September 12, 2027, 2028 and 2029
December 20, 2021		3,000,000	0.0100	December 27, 2027
December 30, 2021		15,500,000<br> <br>11,000,000	0.0610<br> <br>0.0100	1/3 on each of December 27, 2027, 2028 and 2029
C.	BOARD PRACTICES
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Our Board of Directors currently consists of five members. As a foreign private issuer, we are not required to have independent directors on our Board of Directors, except that our audit committee is required to consist fully of independent directors, subject to certain phase-in schedules.

Overview

The Board of Directors is self-constituting and determines our internal organization. The Chairman convenes the Board as often as our affairs require and presides (or in his absence, another Board member specifically designated by the majority of the other members present at the meeting) over the Board meetings. Each Board member is entitled to request to the Chairman, in writing, a meeting of the Board by indicating the grounds for such a request. The Chairman decides on the agenda items and motions. Every Director is entitled to request to the Chairman, in writing, the inclusion of a specific agenda item by indicating the grounds for such a request.

To pass a valid resolution, the majority of the Board members has to attend the meeting. Meetings may also be held by telephone or video conference, to which all the Board members are invited. No quorum is required for confirmatory resolutions and adaptations of the Articles in connection with capital increases. The Board of Directors passes its resolutions by way of simple majority. The members of the Board may only vote in person, not in proxy. In the event of a tie vote, the Chairman has the deciding vote. Minutes of deliberations and resolutions are kept and signed by the Chairman and the designated Secretary.

The Board has established the following permanent committees to further strengthen our corporate governance structure.

Audit and Finance Committee

The Audit and Finance Committee (AFC) advises the Board of Directors in the performance of its supervisory duties. In particular, the AFC reviews the financial reporting to shareholders and the general public as well as the relationship with the external auditors; satisfies itself that our financial risk management and our internal controls are of an appropriate standard; ensures that its activities are consistent and compliant with the Organizational Regulations; assesses adherence to the relevant ‘best practice’ corporate governance provisions, to the extent such practice has effect on the activities and the functions of the AFC; satisfies itself that our overall fraud prevention procedures are of an appropriate standard and ensures that appropriate procedures to enable employees to confidentially and anonymously submit their concerns regarding accounting, internal controls or auditing matters are in place.

As of the date of this annual report, the AFC is composed of Patrice Jean (Chair), Michelle Lock and Thomas Plitz.

Nomination and Compensation Committee

The Nominating and Compensation Committee (NCC) advises the Board of Directors in the performance of its supervisory duties related to nomination and compensation matters. It is responsible for ensuring the best possible leadership and management of the Company and for determining compensation policies, including share-based incentive programs, for the Company’s top management and Board of Directors.

As of the date of this annual report, the NCC is composed of Thomas Plitz (Chair) and Raghuram Selvaraju.

Corporate Governance Committee

The Corporate Governance Committee (CGC) advises the Board on all matters of corporate governance. It is responsible for carrying out in-depth analysis of specific corporate governance-related matters and monitors compliance with corporate governance principles and policies.

As of the date of this annual report, the CGC is composed of Paolo Galfetti (Chair) and Patrice Jean.

Other Corporate Governance Matters

The Sarbanes-Oxley Act of 2002, as well as related rules subsequently implemented by the SEC, requires foreign private issuers, including our company, to comply with various corporate governance practices. In addition, Nasdaq rules provide that foreign private issuers may follow home country practice in lieu of the Nasdaq corporate governance standards, subject to certain exceptions and except to the extent that such exemptions would be contrary to U.S. federal securities laws.

We intend to take all actions necessary for us to maintain compliance as a foreign private issuer under the applicable corporate governance requirements of the Sarbanes-Oxley Act of 2002, the rules adopted by the SEC and Nasdaq’s listing standards.

Because we are a foreign private issuer, our directors and senior management are not subject to short-swing profit and insider trading reporting obligations under Section 16 of the U.S. Securities Exchange Act of 1934, as amended, or the Exchange Act. They will, however, be subject to the obligations to report changes in share ownership under Section 13 of the Exchange Act and related SEC rules.

Indemnification of Officers and Directors

Under Swiss law, a corporation may indemnify its officers and directors against losses and expenses, except for such losses and expenses arising from willful misconduct or negligence (although some legal scholars advocate that at least gross negligence be required), including attorney’s fees, judgments, fines, and settlement amounts actually and reasonably incurred in a civil or criminal action, suit or proceeding by reason of having been the representative of, or serving at the request of, the corporation.

Subject to Swiss law, our articles of association provide for indemnification of the exiting and former members of our board of directors, executive management, and the heirs, executors and administrators, against liabilities arising in connection with the performance of their duties in such capacity, and permits us to advance the expenses of defending any act, suit or proceeding to members of our board of directors and executive management. In addition, under general principles of Swiss employment law, an employer may be required to indemnify an employee against losses and expenses incurred by such employee in the proper execution of their duties under their employment agreement with the company.

We have entered into indemnification agreements with each of the members of our board of directors and with our executive officers.

D.	EMPLOYEES

At December 31, 2022, we had a total of 69 employees. Our relationship with our employees is good and no employees are covered by a labor union. We did not employ any temporary employees during 2022.

E.	SHARE OWNERSHIP

For information about share ownership by our directors and senior management, see “Item 7. Major Shareholders and Related Party Transactions – A. Major Shareholders”.

ITEM 7	MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS
A.	MAJOR SHAREHOLDERS
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The following table sets forth information with respect to the beneficial ownership of our ordinary shares as of April 30, 2023 by:

•	each of our executive officers;
•	each of our directors; and
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•	each person, or group of affiliated persons, who is known by us to beneficially own more than 3 percent of our outstanding ordinary shares.
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These share holding numbers have not been adjusted for the 400:1 reverse split which occurred on May 5, 2023.

Beneficial ownership is determined in accordance with the rules and regulations of the SEC and includes voting or investment power with respect to our ordinary shares. Ordinary shares subject to options that are currently exercisable or exercisable within 60 days after calculation date are considered outstanding and beneficially owned by the person holding the options for the purpose of calculating the percentage ownership of that person but not for the purpose of calculating the percentage ownership of any other person. Except as otherwise noted, the persons and entities in this table have sole voting and investment power with respect to all of the ordinary shares beneficially owned by them, subject to community property laws, where applicable. Except as otherwise set forth below, the address of the beneficial owner is c/o the Company. The information in the table below is based on information known to us or ascertained by us from public filings made by the shareholders. We have also set forth below information known to us regarding any significant change in the percentage ownership of our ordinary shares by any major shareholders during the past three years. The major shareholders listed below do not have voting rights with respect to their ordinary shares that are different from the voting rights of other holders of our ordinary shares.

Name	Shares
5 Percent Stockholders
GEM Global Yield LLC SCS†		1,155,899,126	0	20.58	%*
Executive Officers and Directors
Jack Weinstein		185,000	18,600,000	*	*
Jeremy Meinen		140,655	1,100,000	*	*
Marco Marotta		0	1,500,000	*	*
Raghuram Selvaraju		0	8,963,197	*	*
Thomas Plitz		500,000	1,500,000	*	*
Patrice Jean		140,000	200,000	*	*
Paolo Galfetti		31,237,437	12,500,000	*	*
Michelle Lock		0	0	*	*
†	As set forth in a filing with the SIX Swiss Exchange on April 7, 2023. Pursuant to such filing, Christopher Brown, a resident of the State of New York, is the person who can exercise the voting rights at his own discretion.
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*	Calculated at the date of notification based on the number of outstanding shares registered at the Commercial Register of Geneva.
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**	Less than one percent.
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We are not aware of any arrangement, the operation of which may result in a change of control of the Company.

B.	RELATED PARTY TRANSACTIONS

The following is a description of related party transactions we have entered into with the beneficial owners of 10 percent or more of our ordinary shares, which are our only voting securities, senior management and members of our Board of Directors, from January 1, 2021, to December 31, 2022.

GEM Global Yield LLC SCS

Under the terms of the SSF, we have the right to periodically, during a timeframe of up to three years, issue and sell shares to GEM. Under the facility, GEM undertakes to subscribe to or acquire ordinary registered shares of the Company upon the Company’s exercise of a drawdown notice. In accordance with the customary terms of the SSF agreement, the Company controls the timing and maximum amount of any drawdown and retains the right, not the obligation, to draw down on the full commitment amount. Future subscription prices under the SSF will correspond to 90 percent of the average of the closing bid prices on the SIX Swiss Exchange during the reference period, which corresponds to fifteen trading days following Relief’s drawdown notice.

Management and Board of Directors

The following additional transactions were carried out with our executive officers and members of our board of directors

Key Management Compensation, in TCHF	2022
Fees, salaries and other short-term employee benefits		2,873	2,759
Post-employment benefits		89	30
Share-based compensation		—	814
Total compensation for key management		2,962	3,603
C.	INTERESTS OF EXPERTS AND COUNSEL
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None.

ITEM 8	FINANCIAL INFORMATION
A.	CONSOLIDATED STATEMENTS AND OTHER FINANCIAL INFORMATION
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Consolidated Financial Statements

Our audited financial statements for the fiscal years ended December 31, 2022 and 2021 are included in Item 18 of this annual report.

Legal Proceedings

From time to time, we may become involved in legal, governmental or arbitration proceedings or be subject to claims arising in the ordinary course of our business. Except as set forth therein or elsewhere in this Annual Report, we are not presently a party to any legal, governmental or arbitration proceeding. Regardless of the outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors.

Dividend Distribution Policy

We have not paid any dividends since our incorporation. Even if future operations lead to significant levels of distributable profits, we currently intend that any earnings will be reinvested in our business and that dividends will not be paid until we have an established revenue stream to support continuing dividends. Under our articles of association, the declaration of dividends requires a resolution passed by a simple majority of the votes cast at a shareholders’ meeting regardless of abstentions and empty or invalid votes. The proposal to pay future dividends to shareholders will in addition effectively be at the discretion of our board of directors after considering various factors including our business prospects, liquidity requirements, financial performance and new product development. In addition, payment of future dividends is subject to certain limitation pursuant to Swiss law or by our articles of association. Accordingly, investors cannot rely on dividend income from our ordinary shares and any returns on an investment in our ordinary shares will likely depend entirely upon any future appreciation in the price of our ordinary shares.

B.	SIGNIFICANT CHANGES

Except as otherwise disclosed above or elsewhere in this annual report, there has been no significant change since the date of the most recent financial statements included in this annual report.

ITEM 9	THE OFFER AND LISTING
A.	OFFER AND LISTING DETAILS
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Not applicable.

B.	PLAN OF DISTRIBUTION

Not applicable.

C.	MARKETS

Our ordinary shares trade on the SIX Swiss Exchange (SIX) under the symbol “RLF” and over the counter in the U.S. under the symbol “RLFTF”. Our ADRs trade in the over-the-counter market under the symbol “RLFTY.”

D.	SELLING SHAREHOLDERS

Not applicable.

E.	DILUTION

Not applicable.

F.	EXPENSES OF THE ISSUE

Not applicable.

ITEM 10	ADDITIONAL INFORMATION
A.	SHARE CAPITAL
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Issued Share Capital

Our issued share capital as of December 31, 2022 was 5,616,334,617 shares with a par value of CHF 0.01 per share, including 1,210,809,431 shares held in treasury.

On April 28, 2023, the extraordinary general meeting of shareholders approved the consolidation (reverse split) of the Company’s ordinary shares at a 400 to 1 ratio. On May 5, 2023, the reverse split was implemented in accordance with the resolution of the extraordinary general meeting. Following the consolidation, our issued share capital was 14,040,837 shares with a par value of CHF 4.00 per share, including 3,022,336 shares held in treasury.

Unless stated otherwise, all numbers of shares throughout this annual report are pre-reverse split and shall be divided by 400 to obtain the equivalent in post-reverse split shares. The same applies to disclosures related to stock options and derivative instruments.

Each issued ordinary share is fully paid. We currently have no deferred shares in our issued share capital.

Ordinary Shares

To the extent dividends are paid, holders of ordinary shares are entitled to receive dividends in proportion to the number of ordinary shares held by them and according to the amount paid up on such ordinary shares during any portion or portions of the period in respect of which the dividend is paid. Holders of ordinary shares are entitled, in proportion to the number of ordinary shares held by them and to the amounts paid up thereon, to share in any surplus in the event of our winding up. The holders of ordinary shares are entitled to receive notice of, attend either in person or by proxy or, being a corporation, by a duly authorized representative, and vote at general meetings of shareholders.

B.	MEMORANDUM AND ARTICLES OF ASSOCIATION

Please read this section in conjunction with our Articles of Association, which are attached to this annual report as Exhibit 3.1.

Increase of Share Capital

Under Swiss law, we may increase our share capital (capital-actions) with a resolution of the general meeting of shareholders (ordinary capital increase) that must be carried out by the board of directors within three months of the respective general meeting in order to become effective. Under our articles of association and Swiss law, in the case of subscription and increase against payment of contributions in cash, a resolution passed by an absolute majority of the shares represented at the general meeting of shareholders is required. In the case of subscription and increase against contributions in kind or to fund acquisitions in kind, when shareholders’ statutory pre-emptive subscription rights or advance subscription rights are limited or withdrawn or where transformation of freely disposable equity into share capital is involved, a resolution passed by two-thirds of the shares represented at a general meeting of shareholders and the absolute majority of the par value of the shares represented is required.

Furthermore, under the Swiss Code of Obligations (CO), our shareholders, by a resolution passed by two-thirds of the shares represented at a general meeting of shareholders and the absolute majority of the par value of the shares represented, may empower our board of directors to issue shares of a specific aggregate par value up to a maximum of 50 percent of the share capital in the form of:

•

conditional share capital (capital-actions conditional) for the purpose of issuing shares in connection with, among other things, (i) option and conversion rights granted in connection with bonds and similar debt instruments of the Company or one of our subsidiaries or (ii) grants of rights to employees, members of our board of directors or consultants or to our subsidiaries or other persons providing services to the Company or a subsidiary to subscribe for new shares (conversion or option rights); or

•

authorized share capital (capital-actions autorisé) to be utilized by the board of directors within a period determined by the shareholders but not exceeding two years from the date of the shareholder approval.

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Pre-Emptive and Advance Subscription Rights and Pre-Emptive Rights

Pursuant to the CO (but subject to the articles of association), shareholders have subscription rights (droits de souscription) to subscribe for new issuances of shares in connection with ordinary and authorized capital increases. With respect to conditional capital in connection with the issuance of bonds or similar debt instruments, shareholders have pre-emptive rights (droit de souscrire préalablement) for the subscription of such bonds or similar debt instruments.

A resolution passed at a general meeting of shareholders by two-thirds of the shares represented and the absolute majority of the par value of the shares represented may authorize our board of directors to withdraw or limit subscription rights or pre-emptive rights in certain circumstances.

If preemptive rights are granted, but not exercised, the board of directors may allocate the unexercised preemptive rights at its discretion.

Our Authorized Share Capital

As of December 31, 2022, our board of directors was authorized under our articles of association to increase at any time our ordinary share capital, until May 30, 2024, by a maximum amount of CHF 10,000,000.00 by issuing up to 1,000,000,000 registered shares to be fully paid up with a par value of CHF 0.01 each.

Increases in partial amounts are permitted. The board of directors has the power to determine the type of contributions, the issue price and the date on which the dividend entitlement starts.

With respect to our authorized share capital, the board of directors is authorized by our articles of association to withdraw restrict or to exclude limit the pre-emptive subscription rights of shareholders, and to allocate them to third parties or to us, in the event that the newly issued shares are issued under the following circumstances:

•	for the acquisition of companies, parts of companies or participations, for the acquisition of products, intellectual property or licenses, or for investment projects or for the financing or refinancing of such transactions through a placement of shares;
•	for the purpose of broadening the shareholder constituency or in connection with a listing of shares on domestic or foreign stock exchanges;
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•	for the participation of employees, members of the Board of Directors and consultants of the Company or its subsidiaries in accordance with one or more regulations adopted by the Board of Directors;
---	---
•	for investment projects and/or financial instruments which are used in national or international capital markets, or for raising capital in a fast and flexible manner, which would hardly be achieved without the exclusion of the statutory subscription rights of the existing shareholders; or
---	---
•	for other valid grounds pursuant to Article 652b, paragraph 2 of the Swiss Code of Obligations.
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This authorization is exclusively linked to the particular available authorized share capital set out in the respective article. If the period to increase our share capital out of authorized share capital lapses without having been used by the board of directors, the authorization to withdraw or to limit the pre-emptive subscription rights lapses simultaneously with such capital.

Our Conditional Share Capital

As of December 31, 2022, we had available conditional capital of 1,668,769,814 shares with a nominal value of CHF 0.01 each in the aggregate nominal value of CHF 16,687,698.14, as follows:

•

1,563,000,000 registered shares to be fully paid up, each with a nominal value of CHF 0.01 to the nominal value of CHF 15,630,000.00 through the exercise of conversion or option rights granted to entitled parties in connection with bonds and similar financial instruments or loans of the Company or its subsidiaries that allow for conversion into shares of the Company, or option rights granted to existing and/or new shareholders in connection with capital increases.

•

105,769,814 registered shares to be fully paid up, each with a nominal value of CHF 0.01 to a nominal value of CHF 1,057,689.14 through the exercise of options granted to employees, members of the Board of Directors and consultants of the Company or its subsidiaries.

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As to the conditional share capital described in the first bullet point above, the subscription rights of shareholders are excluded. The Board of Directors determines the conversion and option terms, the issue price and the date of dividend entitlement. The Board of Directors is authorized to limit or exclude the preemptive rights of existing shareholders in the event: (1) of the financing or refinancing of the acquisition of enterprises, parts of enterprises, participations or investments, (2) of the financing or refinancing of the Company or its subsidiaries, (3) of the issuance of convertibles and/or option bonds for the purpose of placement on national or international capital markets (including private placements), (4) for purposes of the underwriting of such bonds and other financial instruments by one or more banks with subsequent public offer; or if the issuance occurs in national or international capital markets, or (5) through a private placement.

As to the conditional share capital described in the second bullet point above, the rights of pre-emption and subscription rights of shareholders are excluded in connection with the issuance of any shares, options or subscription rights thereof.

To the extent that the advance subscription rights are withdrawn or limited, (i) the convertible bonds, warrants or similar instruments are to be issued at market conditions; (ii) the term to exercise the convertible bonds, warrants or similar instruments may not exceed ten years from the date of issue of the respective instrument and (iii) the conversion, exchange or exercise price of the convertible bonds, warrants or similar instruments has to be set with reference to or be subject to change based upon the valuation of the Company’s equity or market conditions.

The extraordinary general meeting of shareholders held on April 28, 2023 approved a revision of the terms of the conditional and authorized capitals under the articles of association for consistency with the consolidation of our ordinary share capital at a ratio of 400 to 1.

Uncertificated Securities

Our shares are in the form of uncertificated securities (droits-valeurs, within the meaning of Article 973c of the CO) and are established as book-entry securities within the meaning of the Swiss Federal Act on Securities held with an Intermediary of 2008, as amended. In accordance with Article 973c of the CO, we will maintain a non-public register of uncertificated securities (registre des droits-valeurs). We may at any time convert uncertificated securities into share certificates (including global certificates), one kind of certificate into another, or share certificates (including global certificates) into uncertificated securities. Following entry in the share register, a shareholder may at any time request from us a written confirmation in respect of his or her shares. Shareholders are not entitled, however, to request the conversion and/or printing and delivery of share certificates. We may print and deliver certificates for shares at any time.

General Meeting of Shareholders

Ordinary/Extraordinary Meetings, Powers

The general meeting of shareholders is our supreme corporate body. Under Swiss law, an annual general meeting of shareholders must be held annually within six months after the end of a corporation’s financial year. In our case, this generally means on or before June 30. In addition, extraordinary general meetings of shareholders may be held.

The following powers are vested exclusively in the general meeting of shareholders:

•	adopting and amending the articles of association, including the change of a company’s purpose or domicile;
•	electing the members of the board of directors, the chairman of the board of directors, the members of the compensation committee, the auditors and the independent proxy;
---	---
•	approving the business report, the annual statutory and consolidated financial statements, and deciding on the allocation of profits as shown on the balance sheet, in particular with regard to dividends;
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•	approving the aggregate amount of compensation of members of the board of directors and the executive committee;
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•	discharging the members of the board of directors and the executive committee from liability with respect to their conduct of business;
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•	dissolving a company with or without liquidation; and
---	---
•	deciding matters reserved to the general meeting of shareholders by law or the articles of association or submitted to it by the board of directors.
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An extraordinary general meeting of shareholders may be called by a resolution of the board of directors or the general meeting of shareholders or, under certain circumstances, by a company’s auditor, liquidator or the representatives of bondholders, if any. In addition, the board of directors is required to convene an extraordinary general meeting of shareholders if shareholders representing at least 10 percent of our share capital request such general meeting of shareholders in writing. Such request must set forth the items to be discussed and the proposals to be acted upon. The board of directors must convene an extraordinary general meeting of shareholders and propose financial restructuring measures if, based on our stand-alone annual statutory balance sheet, half of our share capital and statutory reserves are not covered by our assets.

Voting and Quorum Requirements

Shareholder resolutions and elections (including elections of members of the board of directors) require the affirmative vote of the absolute majority of shares represented at the general meeting of shareholders, unless otherwise stipulated by law or our articles of association.

Under Swiss law and our articles of association, a resolution of the general meeting of the shareholders passed by two-thirds of the shares represented at the meeting, and the absolute majority of the par value of the shares represented is required for:

•	a change in our corporate purpose;
•	the introduction and abolition of voting shares;
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•	restrictions on the transferability of registered shares;
---	---
•	authorized or conditional capital increase;
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•	capital increase from equity for investment in kind or for the purpose of acquisition of assets and the granting of special privileges;
---	---
•	the restriction or abolition of subscription rights;
---	---
•	the transfer of our headquarters;
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•	facilitating or waiving restrictions on transferability of registered shares; or
•	the dissolution of the company.
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The same voting requirements apply to resolutions regarding transactions among corporations based on Switzerland’s Federal Act on Mergers, Demergers, Transformations and the Transfer of Assets of 2003, as amended (Swiss Merger Act).

In accordance with Swiss law and generally accepted business practices, our articles of Nasdaq do not provide quorum requirements generally applicable to general meetings of shareholders. To this extent, our practice varies from NASDAQ listing standards, which require an issuer to provide in its bylaws for a generally applicable quorum, and that such quorum may not be less than one-third of the outstanding voting shares.

Notice

General meetings of shareholders must be convened by the board of directors at least 20 days before the date of the meeting. The general meeting of shareholders is convened by way of a notice appearing in our official publication medium, currently the Swiss Official Gazette of Commerce. Registered shareholders may also be informed by ordinary mail or e-mail. The notice of a general meeting of shareholders must state the items on the agenda, the motions to the shareholders and, in case of elections, the names of the nominated candidates. A resolution on a matter which is not on the agenda may not be passed at a general meeting of shareholders, except for motions to convene an extraordinary general meeting of shareholders or to initiate a special investigation, on which the general meeting of shareholders may vote at any time. No previous notification is required for motions concerning items included in the agenda or for debates that do not result in a vote.

All of the owners or representatives of our shares may, if no objection is raised, hold a general meeting of shareholders without complying with the formal requirements for convening general meetings of shareholders (a universal meeting). This universal meeting of shareholders may discuss and pass binding resolutions on all matters within the purview of the general meeting of shareholders, provided that the owners or representatives of all the shares are present at the meeting.

Agenda Requests

Pursuant to Swiss law and our articles of association, one or more shareholders, whose combined shareholdings represent the lower of (i) one tenth of our share capital and (ii) an aggregate par value of at least CHF 1,000,000 may request that an item be included in the agenda for a general meeting of shareholders. To be timely, the shareholder’s request must be received by us generally at least 45 calendar days in advance of the meeting. The request must be made in writing and shall specify the agenda item and the shareholders’ proposals.

In addition, if the shareholder intends to solicit proxies from the shareholders of a company, such shareholder shall notify the company of this intent in accordance with SEC Rule 14a-4 and/or Rule 14a-8.

Our business report, the compensation report and the auditor’s report must be made available for inspection by the shareholders at our registered office no later than 20 days prior to the general meeting of shareholders. Shareholders of record must be notified of this in writing.

Voting Rights

Each of our ordinary shares entitles a holder to one vote. The ordinary shares are not divisible. The right to vote and the other rights of share ownership may only be exercised by shareholders (including any nominees) who are entered in the share register at a cut-off date determined by the board of directors. Those entitled to vote in the general meeting of shareholders may be represented by the independent proxy holder (annually elected by the general meeting of shareholders), by its legal representative, who does not have to be a shareholder, or by another shareholder with voting rights. The chairman has the power to decide whether to recognize a power of attorney.

Dividends and Other Distributions

Our board of directors may propose to shareholders that a dividend or other distribution be paid but cannot itself authorize the distribution. Dividend payments require a resolution passed by an absolute majority of the shares represented at a general meeting of shareholders. In addition, our auditors must confirm that the dividend proposal of our board of directors conforms to Swiss statutory law and our articles of association.

100

Under Swiss law, we may pay dividends only if we have sufficient distributable profits from the previous business year (bénéfice de l’exercice) or brought forward from the previous business years (report des bénéfices), or if we have distributable reserves (réserves à libre disposition), each as evidenced by the Company’s audited stand-alone statutory balance sheet prepared pursuant to Swiss law, and after allocations to reserves required by Swiss law and by the articles of association have been deducted. We are not permitted to pay interim dividends out of profit of the current business year.

Distributable reserves are generally booked either as “free reserves” (réserves libres) or as “reserve from capital contributions” (apports de capital). Under the CO, if our general reserves (réserve générale) amount to less than 20 percent of our share capital recorded in the Commercial Register (i.e., 20 percent of the aggregate par value of our issued capital), then at least five percent of our annual profit must be retained as general reserves. In addition, if our general reserves amount to less than 50 percent of our share capital recorded in the Commercial Register, 10 percent of the amounts distributed beyond payment of a dividend of five percent must be retained as general reserves. The CO permits us to accrue additional general reserves. Further, a purchase of our own shares (whether by us or a subsidiary) reduces the distributable reserves in an amount corresponding to the purchase price of such own shares. Finally, the CO under certain circumstances requires the creation of revaluation reserves which are not distributable.

Distributions out of issued share capital (i.e., the aggregate par value of our issued shares) are not allowed and may be made only by way of a share capital reduction. Such a capital reduction requires a resolution passed by an absolute majority of the shares represented at a general meeting of shareholders. The resolution of the shareholders must be recorded in a public deed and a special audit report must confirm that claims of our creditors remain fully covered despite the reduction in our share capital recorded in the Commercial Register. Our share capital may be reduced below CHF 100,000 only if and to the extent that at the same time the statutory minimum share capital of CHF 100,000 is reestablished by sufficient new fully paid-up capital. Upon approval by the general meeting of shareholders of the capital reduction, the board of directors must give public notice of the capital reduction resolution in the Swiss Official Gazette of Commerce three times and notify creditors that they may request, within two months of the third publication, satisfaction of or security for their claims. The reduction of our share capital may be implemented only after expiration of this time limit.

Our board of directors determines the date on which the dividend entitlement starts. Dividends are usually due and payable shortly after the shareholders have passed the resolution approving the payment, but shareholders may also resolve at the annual general meeting of shareholders to pay dividends in quarterly or other installments.

Transfer of Shares

For as long as the shares are in uncertificated form (droits-valeurs) and registered as book-entry securities, any transfer of the shares has to be made in accordance with the FISA. The transfer of book-entry securities by way of assignment is excluded. The company maintains, through Computershare, a share register, in which the full name, address and nationality (in the case of legal entities, the company name and registered office) of the shareholders and usufructuaries are recorded.

Voting rights may be exercised only after a shareholder has been entered in the share register (registre des actions) with his or her name and address (in the case of legal entities, the registered office) as a shareholder with voting rights.

Inspection of Books and Records

Under the CO, a shareholder has a right to inspect the share register with respect to his or her own shares and otherwise to the extent necessary to exercise his or her shareholder rights. No other person has a right to inspect the share register. Our books and correspondence may be inspected with the express authorization of the general meeting of shareholders or by resolution of the board of directors and subject to the safeguarding of our business secrets and other legitimate interests.

Special Investigation

If the shareholders’ inspection rights as outlined above prove to be insufficient in the judgment of the shareholder, any shareholder may propose to the general meeting of shareholders that specific facts be examined by a special examiner in a special investigation. If the general meeting of shareholders approves the proposal, we or any shareholder may, within 30 calendar days after the general meeting of shareholders, request a court at our registered office in Geneva, Switzerland to appoint a special examiner. If the general meeting of shareholders rejects the request, one or more shareholders representing at least 10 percent of our share capital or holders of shares in an aggregate par value of at least CHF 2,000,000 may request that the court appoint a special examiner. The court will issue such an order if the petitioners can demonstrate that the board of directors, any member of the board of directors or our executive committee infringed the law or our articles of association and thereby caused damages to the Company or the shareholders. The costs of the investigation would generally be allocated to us and only in exceptional cases to the petitioners.

101

Compulsory Acquisitions; Appraisal Rights

Business combinations and other transactions that are governed by the Swiss Merger Act (i.e., mergers, demergers, transformations and certain asset transfers) are binding on all shareholders. A statutory merger or demerger requires approval of two-thirds of the shares represented at a general meeting of shareholders and the absolute majority of the par value of the shares represented.

If a transaction under the Swiss Merger Act receives all of the necessary consents, all shareholders are compelled to participate in such transaction.

Swiss corporations may be acquired by an acquirer through the direct acquisition of the shares of the Swiss corporation. The Swiss Merger Act provides for the possibility of a so-called “cash-out” or “squeeze-out” merger with the approval of holders of 90 percent of the issued shares. In these limited circumstances, minority shareholders of the corporation being acquired may be compensated in a form other than through shares of the acquiring corporation (for instance, through cash or securities of a parent corporation of the acquiring corporation or of another corporation). For business combinations effected in the form of a statutory merger or demerger and subject to Swiss law, the Swiss Merger Act provides that if equity rights have not been adequately preserved or compensation payments in the transaction are unreasonable, a shareholder may request the competent court to determine a reasonable amount of compensation.

In addition, under Swiss law, the sale of “all or substantially all of our assets” by us may require the approval of two-thirds of the number of shares represented at a general meeting of shareholders and the absolute majority of the par value of the shares represented. Whether a shareholder resolution is required depends on the particular transaction, including whether the following test is satisfied:

•	a core part of our business is sold without which it is economically impracticable or unreasonable to continue to operate the remaining business;
•	our assets, after the divestment, are not invested in accordance with our corporate purpose as set forth in the articles of association; and
---	---
•	the proceeds of the divestment are not earmarked for reinvestment in accordance with our corporate purpose but, instead, are intended for distribution to our shareholders or for financial investments unrelated to our corporate purpose.
---	---

A shareholder of a Swiss corporation participating in certain major corporate transactions may, under certain circumstances, be entitled to appraisal rights. As a result, such shareholder may, in addition to the consideration (be it in shares or in cash) receive an additional amount to ensure that the shareholder receives the fair value of the shares held by the shareholder. Following a statutory merger or demerger, pursuant to the Swiss Merger Act, shareholders can file an appraisal action against the surviving company. If the consideration is deemed inadequate, the court will determine an adequate compensation payment.

Board of Directors

Pursuant to Swiss law and according to our articles of association, the board of directors shall consist of at least one member. Swiss law requires that any listed company exceeding two of the three thresholds specified in art. 727 para.1 no. 2 of the CO in two successive financial years shall have each gender represented by at least 30 percent on the board of directors and 20 percent on the executive management team. If a company fails to comply, it must be disclosed in the remuneration report, including an explanation and a designation of measures to be taken to reconcile the failed compliance. For our board of directors, this rule will apply, subject to meeting the thresholds required under the CO, from the business year 2026, whereas for the executive management from the business year 2031. The triggering thresholds are (i) a balance sheet total of 20 million CHF, (ii) sales revenue of 40 million CHF and (iii) an average of 250 full-time employees per year.

The members of our board of directors are elected by the general meeting of shareholders for a term of one year. A year within the meaning of this provision is the period between two ordinary general meetings of shareholders. If a member of the board of directors retires or is replaced, his successor shall continue in office until the end of his predecessor’s term. Each member of our board of directors must be elected individually.

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Powers

The board of directors has the following non-delegable and inalienable powers and duties:

•	the ultimate direction of the business of the Company and issuing of the relevant directives;
•	laying down the organization of the Company;
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•	formulating accounting procedures, financial controls and financial planning;
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•	nominating and removing persons entrusted with the management and representation of the Company and regulating the power to sign for the Company;
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•	the ultimate supervision of those persons entrusted with management of the Company, with particular regard to adherence to law, our articles of association, and regulations and directives of the Company;
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•	issuing the business report and the compensation report, and preparing for the general meeting of shareholders and carrying out its resolutions; and
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•	informing the court in case of over-indebtedness.
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The board of directors may, while retaining such non-delegable and inalienable powers and duties, delegate some of its powers, in particular direct management, to a single or to several of its members, committees or to third parties (such as executive officers) who need be neither members of the board of directors nor shareholders. Pursuant to Swiss law and our articles of association, details of the delegation and other procedural rules such as quorum requirements have been set in the organizational rules established by the board of directors.

Indemnification of Executive Officers and Directors

We continuously seek to maintain appropriate and cost-effective liability insurance coverage in connection with our products and for purposes of indemnifying our directors and officers for claims against them. In addition, under general principles of Swiss employment law, an employer may be required to indemnify an employee against losses and expenses incurred by such employee in the proper execution of his or her duties under the employment agreement with the employer. See “Differences in Corporate Law—Indemnification of Directors and Executive Management and Limitation of Liability.”

Conflict of Interest

Swiss law does not have a general provision regarding conflicts of interest. However, the CO contains a provision that requires our directors and executive officers to safeguard the Company’s interests and imposes a duty of loyalty and duty of care on our directors and executive officers. This rule is generally understood to disqualify directors and executive officers from participation in decisions that directly affect them. Our directors and executive officers are personally liable to us for breaches of these obligations. In addition, Swiss law contains provisions under which directors and all persons engaged in the Company’s management are liable to the Company, each shareholder and the Company’s creditors for damages caused by an intentional or negligent violation of their duties. Furthermore, Swiss law contains a provision under which payments made to any of the Company’s shareholders or directors or any person related to any such shareholder or director, other than payments made at arm’s length, must be repaid to the Company if such shareholder or director acted in bad faith.

Our board of directors has adopted a Code of Business Conduct and Ethics and will adopt, upon the closing of this offering, other policies that will cover a broad range of matters, including the handling of conflicts of interest.

Principles of the Compensation of the Board of Directors

Pursuant to Swiss law, our shareholders must annually, upon becoming a public company whose shares are listed for trade by the public, approve the compensation of the board of directors and the persons whom the board of directors has, fully or partially, entrusted with the management of the Company. The board of directors must issue, on an annual basis, a written compensation report that must be reviewed together with a report on our business by our auditor. The compensation report must disclose all compensation, loans and other forms of indebtedness granted by the Company, directly or indirectly, to current or former members of the board of directors and executive management to the extent related to their former role within the Company or not on customary market terms.

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The disclosure concerning compensation, loans and other forms of indebtedness must include the aggregate amount for the board of directors and the executive management as well as the particular amount for each member of the board of directors and executive officer, specifying the name and function of each respective person.

Certain forms of compensation are prohibited for members of our board of directors and executive management, such as:

•	severance payments provided for either contractually or in the articles of association (compensation due until the termination of a contractual relationship does not qualify as severance payment);
•	advance compensation;
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•	incentive fees for the acquisition or transfer of corporations or parts thereof by the Company or by companies being, directly or indirectly, controlled by us;
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•	loans, other forms of indebtedness, pension benefits not based on occupational pension schemes and performance-based compensation not provided for in the articles of association; and
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•	equity securities and conversion and option rights awards not provided for in the articles of association.
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Compensation to members of the board of directors and executive management for activities in entities that are, directly or indirectly, controlled by the Company is prohibited if the compensation (i) would have been prohibited if it was paid directly by the Company, (ii) is not provided for in the articles of association or (iii) has not been approved by the general meeting of shareholders.

The general meeting of shareholders votes on the compensation received directly or indirectly by the board of directors, the executive management and the advisory board. The general meeting of shareholders must vote annually on the compensation of its board of directors, executive management and the advisory board, and accordingly, at such a meeting, the vote of the general meeting of shareholders shall have a binding effect.

In the event that the general meeting of shareholders votes prospectively on the compensation of the executive management, the articles of association may provide for an additional amount for the compensation of the members of the executive management appointed after the vote.

The additional amount may only be used if the total amount of the compensation of the executive management decided by the general meeting of shareholders is not sufficient for the compensation of the new members until the next vote of the general meeting of the shareholders.

The general meeting of shareholders shall not vote on the additional amount of compensation.

Borrowing Powers

Neither Swiss law nor our articles of association restrict in any way our power to borrow and raise funds. The decision to borrow funds is made by or under the direction of our board of directors, and no approval by the shareholders is required in relation to any such borrowing.

Repurchases of Shares and Purchases of Own Shares and Other Limitations on the Right to Own Shares

The CO limits our right to purchase and hold our own shares. We and our subsidiaries may purchase shares only if and to the extent that (i) freely disposable equity capital is available in the required amount; and (ii) the combined nominal value of all such shares does not exceed 10 percent of the share capital. Pursuant to Swiss law, where shares are acquired in connection with a transfer restriction set out in the articles of association, the foregoing upper limit is 20 percent. We currently do not have any transfer restriction in our articles of association. If we own shares that exceed the threshold of 10 percent of our share capital, the excess must be sold or cancelled by means of a capital reduction within a reasonable time.

Shares held by us or our subsidiaries are not entitled to vote at the general meeting of shareholders but are entitled to the economic benefits applicable to the shares generally, including dividends and pre-emptive rights in the case of share capital increases.

Swiss law and/or our articles of association do not impose any restrictions on the exercise of voting or any other shareholder rights by shareholders residing outside of Switzerland.

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Notification and Disclosure of Substantial Share Interests, Opting Out of Mandatory Tender Offer

The Swiss Federal Financial Market Infrastructure Act, as amended from time to time, (FMIA) requires persons who directly, indirectly or in concert with other parties acquire or dispose of listed shares of a Swiss company or purchase or sale rights or obligations relating to the listed shares, and, thereby, directly, indirectly or in concert with other parties reach, exceed or fall below a threshold of 3, 5, 10, 15, 20, 25, 33^1^/^3^, 50 or 66^2^/^3^ percent of the company’s voting rights (whether exercisable or not) to notify the company and SIX Exchange Regulation AG of such acquisition or disposal in writing within four trading days. Within two trading days after the receipt of such notification, the company must publish such information through SIX Exchange Regulation AG’s electronic reporting and publishing platform.

As of the date of this Prospectus, our articles of association contain an opting-out provision. Hence, a purchaser of shares in the Company is not obliged to make a public tender offer in accordance with the provisions of the FMIA.

Pursuant to Article 663c of the CO, Swiss corporations whose shares are listed on a stock exchange must specify the significant shareholders and their shareholdings in the notes to the balance sheet, where these are known or ought to be known. Significant shareholders are defined as shareholders and groups of shareholders linked through voting rights who own more than five percent of all voting rights.

Changes to Swiss Corporate Law

On January 1, 2023, new amendments to Swiss corporate law came into force. These changes were geared towards greater flexibility for share capital and equity distributions, enhancement of shareholders’ rights in terms of better corporate governance, and modernization of shareholders’ meetings. Companies have a two-year transition period in order to adapt these regulations.

Share Capital and Nominal Value

Under the new amendment, existing companies may state their share capital to a currency other than Swiss Francs at the end of a business year, provided that (i) the chosen currency is the most relevant currency to the company’s activities, (ii) the share capital in the foreign currency corresponds to an equivalent value of at least CHF 100,000, (iii) the accounting and financial reporting are done in the same currency, and (iv) the foreign currency is one in which the Swiss Federal Council has declared as suitable for the purpose (namely the Swiss Franc, U.S. Dollar, Euro, British Pound and Japanese Yen). Further, the nominal value of shares may be set below the current minimum of CHF 0.01 to any amount higher than zero.

Intended Acquisition of Assets and Repayment Obligations

Currently, in the case of an anticipated acquisition of assets (beabsichtigte Sachübernahme), where a company intends or undertakes to acquire certain assets soon after incorporation or a capital increase, current Swiss law imposes a qualified majority for the shareholders’ meeting and strict transparency rules. This has led to questions regarding when an acquisition meets the thresholds of a relevant acquisition of assets. The amendments have removed these rules; however, transparency for acquisition of assets remain in place, and the new law provides for a repayment obligation in case of an unfair advantage or disadvantage.

Where an acquisition of assets is made in connection with a contribution in kind or another manner in which a shareholder contributes in kind where the value of the contributed asset exceeds the shareholder’s capital contribution obligation and, in consideration, the company grants another consideration in return to the shareholder on top of issuing shares. In such cases, the respective consideration must be disclosed in the articles of association and in the commercial register.

Participation Capital

The amendments will allow listed companies limited by shares to provide for participation capital (non-voting stock) up to ten times the amount of she share capital. Furthermore, the amendment distinguishes between shareholders and holders of participation capital when it comes to calculating the thresholds necessary to reach a quorum for certain decisions. By way of example, under the new amendments, shareholders of listed companies can initiate a special investigation if they hold at least five percent of the share capital or voting rights, even if the share capital does not exceed the participation capital.

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Arbitration

A company’s articles of association may contain an arbitration clause regarding corporate disputes, which is binding on all parties, including the company and its shareholders. The seat of the arbitration tribunal must be in Switzerland.

Virtual Shareholders Meetings

Swiss companies may now hold virtual shareholders meetings, provided that the possibility of virtual shareholders meetings is spelled out in the company’s articles of association.

Stock Exchange Listing

Our ordinary shares are listed on the SIX Swiss Exchange under the symbol “RLF” and over the counter in the U.S. under the symbol “RLFTF.” Our ADSs trade in the U.S. over-the-counter market under the symbol “RLFTY.”

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COMPARISON OF SHAREHOLDER RIGHTS

The Swiss laws applicable to Swiss corporations and their shareholders differ from laws applicable to U.S. corporations and their shareholders. The following table summarizes significant differences in shareholder rights between the applicable provisions of the CO and the Compensation Ordinance (as a company incorporated in Switzerland and listed on a stock exchange) and the Delaware General Corporation Law, applicable to companies incorporated in Delaware and their shareholders. Please note that this is only a general summary of certain provisions applicable to companies in Delaware. Certain Delaware companies may be permitted to exclude certain of the provisions summarized below in their charter documents.

DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Mergers and similar arrangements
Under the Delaware General Corporation Law, with certain exceptions, a merger, consolidation, sale, lease or transfer of all or substantially all of the assets of a corporation must be approved by the board of directors and a majority of the outstanding shares entitled to vote thereon. A shareholder of a Delaware corporation participating in certain major corporate transactions may, under certain circumstances, be entitled to appraisal rights pursuant to which such shareholder may receive cash in the amount of the fair value of the shares held by such shareholder (as determined by a court) in lieu of the consideration such shareholder would otherwise receive in the transaction. The Delaware General Corporation Law also provides that a parent corporation, by resolution of its board of directors, may merge with any subsidiary of which it owns at least 90.0% of each class of capital stock without a vote by the shareholders of such subsidiary. Upon any such merger, dissenting shareholders of the subsidiary would have appraisal rights.	Under Swiss law, with certain exceptions, a merger or a division of the corporation or a sale of all or substantially all of the assets of a corporation must be approved by two-thirds of the shares represented at the respective general meeting of shareholders as well as the absolute majority of the share capital represented at such shareholders’ meeting. The articles of association may increase the voting threshold. A shareholder of a Swiss corporation participating in a statutory merger or demerger pursuant to the Swiss Merger Act can file an appraisal right lawsuit against the surviving company. As a result, if the consideration is deemed “inadequate,” such shareholder may, in addition to the consideration (be it in shares or in cash) receive an additional amount to ensure that such shareholder receives the fair value of the shares held by such shareholder. Swiss law also provides that a parent corporation, by resolution of its board of directors, may merge with any subsidiary of which it owns at least 90.0% of the shares without a vote by shareholders of such subsidiary, if the shareholders of the subsidiary are offered the payment of the fair value in cash as an alternative to shares.
Shareholder Lawsuits
Class actions and derivative actions generally are available to shareholders of a Delaware corporation for, among other things, breach of fiduciary duty, corporate waste and actions not taken in accordance with applicable law. In such actions, the court has discretion to permit the winning party to recover attorneys’ fees incurred in connection with such action.	Class actions and derivative actions as such are not available under Swiss law. Nevertheless, certain actions may have a similar effect. A shareholder is entitled to bring suit against directors for breach of, among other things, their fiduciary duties and claim the payment of the company’s damages to the corporation. Likewise, an appraisal lawsuit won by a shareholder will indirectly compensate all shareholders. Under Swiss law, the winning party is generally entitled to recover attorneys’ fees incurred in connection with such action, provided, however, that the court has discretion to permit the shareholder whose claim has been dismissed to recover attorneys’ fees incurred to the extent he acted in good faith.

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DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Shareholder Vote on Board and Management Compensation
Under the Delaware General Corporation Law, the board of directors has the authority to fix the compensation of directors, unless otherwise restricted by the certificate of incorporation or bylaws.	Pursuant to the Compensation Ordinance, applicable to Swiss companies traded on exchanges, such as Nasdaq, the general meeting of shareholders has the non-transferable right, amongst others, to vote separately (in a binding vote) on the aggregate compensation due to the board of directors, executive management and advisory boards.
Annual vote on Board Renewal
Unless otherwise specified in the certificate of incorporation or bylaws, the annual meeting of shareholders elects annually (i.e., until the next annual meeting), by a plurality of votes, the shareholders on a date and at a time designated by or in the manner provided members of the board of directors (including the chairman) and the in the bylaws. Re-election is possible.	The general meeting of shareholders elects annually (i.e., until the following general meeting of shareholders), by a plurality of votes, the members of the board of directors (including the chairman) and the members of the compensation committee individually for a term of office of one year. Re-election is possible.
Indemnification of Directors and Executive Management and Limitation of Liability
The Delaware General Corporation Law provides that a certificate of incorporation may contain a provision eliminating or limiting the personal liability of directors, officers, employees or agents of the corporation for monetary damages for breach of a fiduciary duty as a director, except no provision in the certificate of incorporation may eliminate or limit the liability of a director for:<br> <br><br> <br>• any breach of a director’s duty of loyalty to the corporation or its shareholders;<br> <br><br> <br>• acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law;<br> <br><br> <br>• statutory liability for unlawful payment of dividends or unlawful share purchase or redemption; or<br> <br><br> <br>• any transaction from which the director derived an improper personal benefit.	Under Swiss corporate law, an indemnification of a director or member of the executive management in relation to potential personal liability is not effective to the extent the director or member of the executive management intentionally or negligently violated his or her corporate duties towards the corporation (certain views advocate that at least a grossly negligent violation is required to exclude the indemnification). Most violations of corporate law are regarded as violations of duties towards the corporation rather than towards the shareholders. In addition, indemnification of other controlling persons is not permitted under Swiss corporate law, including shareholders of the corporation.<br> <br><br> <br>Nevertheless, a corporation may obtain and pay for directors’ and officers’ liability insurance, which typically covers negligent acts as well.

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DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Indemnification of Directors and Executive Management and Limitation<br>of Liability (Continued)
A Delaware corporation may indemnify any person who was or is a party or is threatened to be made a party to any proceeding, other than an action by or on behalf of the corporation, because the person is or was a director or officer, against liability incurred in connection with the proceeding if the director or officer acted in good faith and in a manner reasonably believed to be in, or not opposed to, the best interests of the corporation; and the director or officer, with respect to any criminal action or proceeding, had no reasonable cause to believe his or her conduct was unlawful.<br> <br><br> <br>Unless ordered by a court, any foregoing indemnification is subject to a determination that the director or officer has met the applicable standard of conduct:<br> <br><br> <br>• by a majority vote of the directors who are not parties to the proceeding, even though less than a quorum;<br> <br><br> <br>• by a committee of directors designated by a majority vote of the eligible directors, even though less than a quorum;<br> <br><br> <br>• by independent legal counsel in a written opinion if there are no eligible directors, or if the eligible directors so direct; or by the shareholders.
Moreover, a Delaware corporation may not indemnify a director or officer in connection with any proceeding in which the director or officer has been adjudged to be liable to the corporation unless and only to the extent that the court determines that, despite the adjudication of liability but in view of all the circumstances of the case, the director or officer is fairly and reasonably entitled to indemnity for those expenses which the court deems proper.

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DELAWARE CORPORATE LAW

SWISS CORPORATE LAW

Directors’ Fiduciary Duties

A director of a Delaware corporation has a fiduciary duty to the corporation and its shareholders. This duty has two components: the duty of care and the duty of loyalty. The duty of care requires that a director act in good faith, with the care that an ordinarily prudent person would exercise under similar circumstances. Under this duty, a director must inform himself of, and disclose to shareholders, all material information reasonably available regarding a significant transaction. The duty of loyalty requires that a director act in a manner he reasonably believes to be in the best interests of the corporation. He must not use his corporate position for personal gain or advantage. This duty prohibits self-dealing by a director and mandates that the best interest of the corporation and its shareholders take precedence over any interest possessed by a director, officer or controlling shareholder and not shared by the shareholders generally. In general, actions of a director are presumed to have been made on an informed basis, in good faith and in the honest belief that the action taken was in the best interests of the corporation. However, this presumption may be rebutted by evidence of a breach of one of the fiduciary duties. Should such evidence be presented concerning a transaction by a director, a director must prove the procedural fairness of the transaction, and that the transaction was of fair value to the corporation.

A director of a Swiss corporation has a fiduciary duty to the corporation only. This duty has two components: the duty of care and the duty of loyalty. The duty of care requires that a director act in good faith, with the care that an ordinarily prudent director would exercise under similar circumstances. Under this duty, a director must inform himself of, and disclose, all material information reasonably available regarding a significant transaction. The duty of loyalty requires that a director act in a manner he reasonably believes to be in the best interest of the corporation. He must not use his corporate position for personal gain or advantage. This duty prohibits in principle self-dealing by a director and mandates that the best interest of the corporation take precedence over any interest possessed by a director or officer. The burden of proof for a violation of these duties is with the corporation or with the shareholder bringing a suit against the director. Directors also have an obligation to treat shareholders equally proportionate to their share ownership.

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DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Shareholder Action by Written Consent
A shareholder of a Delaware corporation has the right to put any proposal before the annual meeting of shareholders, provided it complies with the notice provisions in the governing documents. A special meeting may be called by the board of directors or any other person authorized to do so in the governing documents, but shareholders may be precluded from calling special meetings.	At any general meeting of shareholders any shareholder may put proposals to the meeting if the proposal is part of an agenda item. Unless the articles of association provide for a lower threshold or for additional shareholders’ rights:<br> <br><br> <br>• one or several shareholders representing 10.0% of the share capital may ask that a general meeting of shareholders be called for specific agenda items and specific proposals; and<br> <br><br> <br>• one or several shareholders representing 10.0% of the share capital or CHF 1.0 million of nominal share capital may ask that an agenda item including a specific proposal be put on the agenda for a regularly scheduled general meeting of shareholders, provided such request is made with appropriate notice.<br> <br><br> <br>Any shareholder can propose candidates for election as directors without prior written notice. In addition, any shareholder is entitled, at a general meeting of shareholders and without advance notice, to (i) request information from the Board on the affairs of the company (note, however, that the right to obtain such information is limited), (ii) request information from the auditors on the methods and results of their audit and (iii) request, under certain circumstances and subject to certain conditions, a special audit.
Cumulative Voting
Under the Delaware General Corporation Law, cumulative voting for elections of directors is not permitted unless the corporation’s certificate of incorporation provides for it.	A Swiss corporation may remove, with or without cause, any director at any time with a resolution passed by an absolute majority of the shares represented at a general meeting of shareholders. The articles of association may provide for a qualified majority for the removal of a director.

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DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Removal of Directors
Unless there is cumulative voting or there is a classified board, generally a director or the entire board of directors may be removed, with or without cause, by the holders of a majority of the shares then entitled to vote at an election of directors	A Swiss corporation may remove, with or without cause, any director at any time with a resolution passed by an absolute majority of the shares represented at a general meeting of shareholders. The articles of association may provide for a qualified majority for the removal of a director.
Transactions with Interested Shareholders
The Delaware General Corporation Law generally prohibits a Delaware corporation from engaging in certain business combinations with an “interested shareholder” for three years following the date that such person becomes an interested shareholder. An interested shareholder generally is a person or group who or which owns or owned 15.0% or more of the corporation’s outstanding voting shares within the past three years.	No such rule applies to a Swiss corporation.
Variation of Rights of Shares
A Delaware corporation may vary the rights of a class of shares with the approval of a majority of the outstanding shares of such class, unless the certificate of incorporation provides otherwise.	The general meeting of shareholders of a Swiss corporation may resolve that preference shares be issued or that existing shares be converted into preference shares with a resolution passed by a majority of the shares represented at the general meeting of shareholders. Where a company has issued preference shares, further preference shares conferring preferential rights over the existing preference shares may be issued only with the consent of both a special meeting of the adversely affected holders of the existing preference shares and of a general meeting of all shareholders, unless otherwise provided in the articles of association.<br> <br><br> <br>Shares that are granted more voting power are not regarded as a special class for these purposes.

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DELAWARE CORPORATE LAW	SWISS CORPORATE LAW
Amendment of Governing Documents
A Delaware corporation’s governing documents may be amended with the approval of a majority of the outstanding shares entitled to vote, unless the certificate of incorporation provides otherwise.	By way of a public deed, the articles of association of a Swiss corporation may be amended with a resolution passed by an absolute majority of the shares represented at such meeting, unless otherwise provided in the articles of association. There are a number of resolutions, such as an amendment of the stated purpose of the corporation and the introduction of authorized and conditional capital, that require the approval by two-thirds of the votes and an absolute majority of the nominal value of the shares represented at a shareholders’ meeting. The articles of association may increase the voting thresholds.
Inspection of Books and Records
Shareholders of a Delaware corporation, upon written demand under oath stating the purpose thereof, have the right during the usual hours for business to inspect for any proper purpose, and to obtain copies of list(s) of shareholders and other books and records of the corporation and its subsidiaries, if any, to the extent the books and records of such subsidiaries are available to the corporation.	Shareholders of a Swiss corporation may only inspect books and records if the general meeting of shareholders or the board of directors approved such inspection. The inspection right is limited in scope and only extends to information required for the exercise of shareholder rights and does not extend to confidential information. The right to inspect the share register is limited to the right to inspect that shareholder’s own entry in the share register.
Payment of Dividends
The board of directors may approve a dividend without shareholder approval. Subject to any restrictions contained in its certificate of incorporation, the board may declare and pay dividends upon the shares of its capital stock either:<br> <br><br> <br>• out of its surplus, or<br> <br><br> <br>• in case there is no such surplus, out of its net profits for the fiscal year in which the dividend is declared and/or the preceding fiscal year.	Dividend payments are subject to the approval of the general meeting of shareholders. The board of directors may propose to shareholders that a dividend shall be paid but cannot itself authorize the distribution.<br> <br><br> <br>Payments out of the Company’s share capital (in other words, the aggregate nominal value of the Company’s registered share capital) in the form of dividends are not allowed and may be made by way of a capital reduction only. Dividends may be paid only from the profits brought forward from the previous business years or if the Company has distributable reserves, each as will be presented on the Company’s audited annual stand-alone balance sheet. The dividend may be determined only after the allocations to reserves required by the law and the articles of association have been deducted.

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DELAWARE CORPORATE LAW

SWISS CORPORATE LAW

Creation and Issuance of New Shares

Shareholder approval is required to authorize capital stock in excess of that provided in the charter. The corporation must file a certificate of amendment to its certificate of incorporation before the creation of additional authorized shares may become effective. The board of directors may, without shareholder consent, authorize capital stock to be issued for consideration consisting of cash, any tangible or intangible property or any benefit to the corporation, or any combination thereof.

All creation of shares requires a shareholders’ resolution documented by way of a public deed. The creation of authorized or conditional share capital requires at least two-thirds of the voting rights represented at the general meeting of shareholders and an absolute majority of the nominal value of shares represented at such meeting. The board of directors may issue shares out of the authorized share capital during a period of up to two years. Shares are created and issued out of conditional share capital through the exercise of options or of conversion rights that the board of directors may grant in relation to, e.g., debt instruments or to employees.

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C.	MATERIAL CONTRACTS

Except as otherwise disclosed in this annual report on Form 20-F (including the exhibits hereto), we are not currently, and have not been in the past two years, party to any material contract, other than contracts entered into in the ordinary course of business.

D.	EXCHANGE CONTROLS

There are no Swiss governmental laws, decrees or regulations that restrict, in a manner material to us, the export or import of capital, including any foreign exchange controls, or that generally affect the remittance of dividends or other payments to non-residents or non-citizens of Switzerland who hold our ordinary shares.

E.	TAXATION

The following summary contains a description of the material Swiss and U.S. federal income tax consequences of the acquisition, ownership and disposition of ordinary shares, but it does not purport to be a comprehensive description of all the tax considerations that may be relevant to a decision to purchase ordinary shares. The summary is based upon the tax laws of Switzerland and regulations thereunder and on the tax laws of the U.S. and regulations thereunder as of the date hereof, which are subject to change.

Swiss tax considerations

This summary of material Swiss tax consequences is based on Swiss law and regulations and the practice of the Swiss tax administration as in effect on the date hereof, all of which are subject to change (or subject to changes in interpretation), possibly with retroactive effect. The summary does not purport to consider the specific circumstances of any particular shareholder or potential investor and does not relate to persons in the business of buying and selling ordinary shares or other securities. The summary is not intended to be, and should not be interpreted as, legal or tax advice to any particular potential shareholder, and no representation with respect to the tax consequences to any particular shareholder is made.

Current and prospective shareholders are advised to consult their own tax advisors in light of their particular circumstances as to the Swiss tax laws, regulations and regulatory practices that could be relevant to them in connection with the acquiring, owning and selling or otherwise disposing of ordinary shares and receiving dividends and similar cash or in-kind distributions on ordinary shares (including dividends on liquidation proceeds and stock dividends) or distributions on ordinary shares based upon a capital reduction (remboursements de la valeur nominale) or reserves paid out of capital contributions (réserves issues d’apports en capital) and the consequences thereof under the tax laws, regulations and regulatory practices of Switzerland.

Taxation

We are, through Relief, subject to corporate Swiss federal, cantonal and communal taxation in Switzerland, Canton of Geneva, City of Geneva, respectively, and through APR, we are subject to corporate Swiss federal, cantonal and communal taxation in Switzerland, Canton of Ticino, City of Balerna.

We are entitled under Swiss laws to carry forward any losses incurred for a period of seven years and can offset our losses carried forward against future taxable profit. As of December 31, 2022, we had consolidated tax loss carry-forwards totaling CHF 145 million. There is no certainty that we will make sufficient profits to be able to utilize these tax loss carry-forwards in full.

The effective corporate income tax rate (federal, cantonal and communal) where we are domiciled in the Canton of Geneva is currently 13.99 percent and is 18.47 percent in the Canton of Ticino.

Federal, cantonal and communal individual income tax and corporate income tax

Non-resident shareholders

Shareholders who are not resident in Switzerland for tax purposes, and who, during the relevant taxation year, have not engaged in a trade or business carried on through a permanent establishment or fixed place of business situated in Switzerland for tax purposes (all such shareholders for purposes of this section termed, “Non-resident shareholders”), will not be subject to any Swiss federal, cantonal and communal income tax on dividends and similar cash or in-kind distributions on Shares (including liquidation proceeds and stock dividends) (for the purposes of this section, “dividends”), distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions), and distributions paid out of reserves from capital contributions (réserves issues d’apports en capital) on shares, or capital gains realized on the sale or other disposition of shares (see, however, “Swiss federal withholding tax” below for a summary of Swiss federal withholding tax on dividends.)

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Resident private shareholders

Swiss-resident individuals who hold their shares as private assets are required to include dividends, but not distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions), and distributions paid out of reserves from capital contributions (réserves issues d’apports en capital), in their personal income tax return and are subject to Swiss federal, cantonal and communal income tax on any net taxable income for the relevant taxation period, including the dividends, but not the distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions), and distributions paid out of reserves from capital contributions (réserves issues d’apports en capital). Shareholders holding at least 10 percent of the share capital of the Company may be able to deduct their taxable dividends at 30 percent at the federal level and up to 50 percent at the cantonal level, depending on their respective cantonal rates, as partial relief from economic double taxation. Capital gains resulting from the sale or other disposition of shares are, subject to a few exceptions, not subject to Swiss federal, cantonal and communal income tax, and conversely, capital losses are not tax-deductible for resident private shareholders (the shareholders referred to in this paragraph for the purposes of this section, “Resident private shareholders”). See “Domestic commercial shareholders” below for a summary of the taxation treatment applicable to Swiss-resident individuals, who, for income tax purposes, are classified as “professional securities dealers” or are otherwise deemed to hold Company shares in their commercial wealth.

Domestic commercial shareholders

Corporate and individual shareholders who are resident in Switzerland for tax purposes, and corporate and individual shareholders who are not resident in Switzerland, and who, in each case, hold their shares as part of a trade or business carried on in Switzerland, in the case of corporate and individual shareholders not resident in Switzerland, through a permanent establishment or fixed place of business situated, for tax purposes, in Switzerland, are required to recognize dividends, distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions) and distributions paid out of reserves from capital contributions (réserves issues d’apports en capital) received on shares and capital gains or losses realized on the sale or other disposition of shares in their income statement for the relevant taxation period and are subject to Swiss federal, cantonal and communal individual or corporate income tax, as the case may be, on any net taxable earnings for such taxation period. The same taxation treatment also applies to Swiss-resident private individuals who, for income tax purposes, are classified as “professional securities dealers” for reasons of, inter alia, frequent dealing, or leveraged investments, in shares and other securities (the shareholders referred to in this paragraph for purposes of this section, “Domestic commercial shareholders”). Domestic commercial shareholders who are corporate taxpayers may be eligible for tax relief (réduction pour participations) in respect of dividends and distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions), and distributions paid out of reserves from capital contributions (réserves issues d’apports en capital), as well as capital gains on sales of shares, if the shares held by them as part of a Swiss business have an aggregate market value of at least CHF 1 million or represent 10 percent or more of the outstanding share capital of the Company (in the case of capital gains, if the shares have been held for at least one year).

Swiss cantonal and communal private wealth tax and capital tax

Non-resident shareholders

Non-resident shareholders are not subject to Swiss cantonal and communal private wealth tax or capital tax.

Resident private shareholders and domestic commercial shareholders

Resident private shareholders and domestic commercial shareholders who are individuals are required to report their shares as part of their private wealth or their Swiss business assets, as the case may be, and will be subject to Swiss cantonal and communal private wealth tax on any net taxable wealth (including shares), in the case of domestic commercial shareholders to the extent the aggregate taxable wealth is allocable to Switzerland. Domestic commercial shareholders who are corporate taxpayers are subject to Swiss cantonal and communal capital tax on taxable capital to the extent the aggregate taxable capital is allocable to Switzerland.

Swiss federal withholding tax

Dividends that the Company pays on the shares are subject to Swiss Federal withholding tax (impôt anticipé) at a rate of 35 percent on the gross amount of the dividend. The Company is required to withhold the Swiss federal withholding tax from the dividend and remit it to the Swiss Federal Tax Administration. Distributions based upon a capital reduction capped to the nominal value (e.g. réduction de la valeur nominale des actions) and distributions paid out of reserves from contributions (réserves issues d’apports en capital) are not subject to Swiss federal withholding tax.

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The Swiss federal withholding tax on a dividend will be refundable in full to a resident private shareholder and to a domestic commercial shareholder, who, in each case, inter alia, as a condition to a refund, duly reports the dividend in his individual income tax return as income or recognizes the dividend in his income statement as earnings, as applicable.

A Non-resident shareholder may be entitled to a partial or full refund, as the case may be, of the Swiss federal withholding tax on a dividend if the country of his or her residence for tax purposes has entered into an international treaty for the avoidance of double taxation with Switzerland and the conditions of such treaty are met. Such shareholders should be aware that the procedures for claiming treaty benefits (and the time required for obtaining a refund) might differ from country to country. For example, a shareholder who is a resident of the U.S. for the purposes of the bilateral tax treaty between the U.S. and Switzerland is eligible for a partial refund of the amount of the withholding tax in excess of the 15 percent treaty rate, provided such shareholder: (i) qualifies for benefits under this treaty and qualifies as beneficial owner of the dividends; (ii) holds, directly or indirectly, less than 10 percent of the voting stock of the Company; (iii) does not qualify as a pension scheme or retirement arrangement for the purpose of the bilateral treaty; and (iv) does not conduct business through a permanent establishment or fixed base in Switzerland to which the shares are attributable. Such an eligible U.S. shareholder may apply for a refund of the amount of the withholding tax in excess of the 15 percent treaty rate. The applicable refund request form may be filed with the Swiss Federal Tax Administration following receipt of the dividend and the relevant deduction certificate, however no later than 31 December of the third year following the calendar year in which the dividend was payable.

Swiss federal stamp taxes

The Company will be subject to and pay to the Swiss Federal Tax Administration a one percent Swiss federal issuance stamp duty (droit de timbre d’émissions) on the consideration received for the issuance of the shares less certain costs incurred in connection with the issuance, where the share capital increase exceeds the nominal value of the shares. The issuance and delivery of the shares to the initial shareholders at the offering price is not subject to Swiss federal securities transfer stamp duty (droit de timbre de négociation).

Any subsequent dealings in the shares, for which a bank or another securities dealer in Switzerland, as defined in the Swiss Federal Stamp Tax Act, acts as an intermediary, or is a party, to the transaction, are, subject to certain exemptions provided for in the Swiss Federal Stamp Tax Act, subject to Swiss securities transfer stamp duty tax at an aggregate tax rate of up to 0.15 percent of the consideration paid for such shares.

Material U.S. Federal Income Tax Considerations for U.S. Holders

The following summary of the material U.S. federal income tax consequences of the acquisition, ownership and disposition of our ordinary shares or ADRs is based upon current law and does not purport to be a comprehensive discussion of all the tax considerations that may be relevant to a decision to purchase our ordinary shares or ADRs. This summary is based on current provisions of the Internal Revenue Code of 1986, as amended, or the Code, existing, final, temporary and proposed U.S. Treasury Regulations, administrative rulings and judicial decisions, in each case as available on the date of this annual report. All of the foregoing are subject to change, which change could apply retroactively and could affect the tax consequences described below.

This section summarizes the material U.S. federal income tax consequences to U.S. holders and certain non-U.S. holders, each as defined below, of our ordinary shares or ADRs. This summary addresses only the U.S. federal income tax considerations for holders that acquire our ordinary shares or ADRs at their original issuance and hold our ordinary shares or ADRs as capital assets. This summary does not address all U.S. federal income tax matters that may be relevant to a particular holder. Each prospective investor should consult a professional tax advisor with respect to the tax consequences of the acquisition, ownership or disposition of our ordinary shares or ADRs. This summary does not address tax considerations applicable to a holder of our ordinary shares or ADRs that may be subject to special tax rules including, without limitation, the following:

•	banks or other financial institutions;
•	insurance companies;
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•	dealers or traders in securities, currencies, or notional principal contracts;
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•	tax-exempt entities, including an “individual retirement account” or “Roth IRA” retirement plan;
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•	regulated investment companies or real estate investment trusts;
•	“qualified foreign pension funds,” or entities wholly owned by a “qualified foreign pension fund”;
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•	persons who have elected to mark securities to market;
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•	persons that hold the ordinary shares as part of a hedge, straddle, conversion, constructive sale or similar transaction involving more than one position;
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•	holders (whether individuals, corporations or partnerships) that are treated as expatriates for some or all U.S. federal income tax purposes;
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•	persons who acquired the ADRs as compensation for the performance of services;
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•	persons holding the ADRs in connection with a trade or business conducted outside of the U.S.;
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•	holders that own (or are deemed to own) 10 percent or more of our ordinary shares or ADRs, by vote or value; and
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•	holders that have a “functional currency” other than the U.S. dollar.
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Further, this summary does not address any aspects of any U.S. state, local or non-U.S. tax law, alternative minimum tax, gift or estate consequences, the rules regarding qualified small business stock within the meaning of Section 1202 of the Code, any election to apply Section 1400Z-2 of the Code to gains recognized with respect to our ordinary shares, any other U.S. federal tax other than the income tax or the indirect effects on the holders of equity interests in entities that own our ordinary shares or ADRs.

For the purposes of this summary, a “U.S. holder” is a beneficial owner of ordinary shares or ADRs that is (or is treated as), for U.S. federal income tax purposes:

•	an individual who is either a citizen or resident of the U.S.;
•	a corporation, or other entity that is treated as a corporation for U.S. federal income tax purposes, created or organized in or under the laws of the U.S. or any state thereof or of the District of Columbia;
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•	an estate, the income of which is subject to U.S. federal income taxation regardless of its source; or
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•	a trust, if a court in the U.S. is able to exercise primary supervision over its administration and one or more U.S. persons has the authority to control all of the substantial decisions of such trust or has a valid election in effect under applicable U.S. Treasury Regulations to be treated as a U.S. person.
---	---

If a partnership holds ordinary shares or ADRs, the tax treatment of a partner will generally depend upon the status of the partner and upon the activities of the partnership. This discussion does not address the tax treatment of partnerships or other entities that are pass-through entities for U.S. federal income tax purposes or persons that hold their ordinary shares or ADRs through partnerships or other pass-through entities. A partner in a partnership or other pass-through entity that will hold our ordinary shares or ADRs should consult his, her or its tax advisor regarding the tax consequences of acquiring, holding and disposing of our ordinary shares or ADRs through a partnership or other pass-through entity, as applicable.

We will not seek a ruling from the U.S. Internal Revenue Service, or IRS, with regard to the U.S. federal income tax treatment of an investment in our ordinary shares or ADRs, and we cannot assure you that the IRS will agree with the conclusions set forth below.

PERSONS CONSIDERING AN INVESTMENT IN OUR ORDINARY SHARES OR ADSs SHOULD CONSULT THEIR TAX ADVISORS AS TO THE PARTICULAR TAX CONSEQUENCES APPLICABLE TO THE ACQUISITION, OWNERSHIP AND DISPOSITION OF THE ORDINARY SHARES OR ADRs, INCLUDING THE APPLICABILITY OF U.S. FEDERAL, STATE AND LOCAL TAXES.

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Ownership of ADRs

For U.S. federal income tax purposes, a holder of ADRs will generally be treated as the owner of the ordinary shares represented by such ADRs. Gain or loss will generally not be recognized on account of exchanges of ordinary shares for ADRs, or of ADRs for ordinary shares. References to ordinary shares in this discussion are deemed to include ADRs, unless context otherwise required.

Taxation of distributions

As discussed above, we do not currently expect to make distributions on our ordinary shares. In the event that we do make distributions of cash or other property, subject to the PFIC rules described below, distributions paid on ordinary shares, other than certain pro rata distributions of ordinary shares, will generally be treated as dividends to the extent paid out of our current or accumulated earnings and profits (as determined under U.S. federal income tax principles). Because we do not maintain calculations of our earnings and profits under U.S. federal income tax principles, we expect that distributions generally will be reported to U.S. holders as dividends. For so long as our ordinary shares are listed on Nasdaq or we are eligible for benefits under the Treaty, dividends paid to certain non-corporate U.S. holders will be eligible for taxation as “qualified dividend income” and therefore, subject to applicable limitations, will be taxable at rates not in excess of the long-term capital gain rate applicable to such U.S. holder.

U.S. holders should consult their tax advisors regarding the availability of the reduced tax rate on dividends in their particular circumstances. The amount of a dividend will include any amounts withheld by us in respect of Swiss income taxes. The amount of the dividend will be treated as foreign-source dividend income to U.S. holders and will not be eligible for the dividends-received deduction generally available to U.S. corporations under the Code. Dividends will be included in a U.S. holder’s income on the date of the U.S. holder’s actual or constructive receipt of the dividend. The amount of any dividend income paid in Swiss Francs will be the U.S. dollar amount calculated by reference to the exchange rate in effect on the date of actual or constructive receipt, regardless of whether the payment is in fact converted into U.S. dollars at that time. If the dividend is converted into U.S. dollars on the date of actual or constructive receipt, a U.S. holder should not be required to recognize foreign currency gain or loss in respect of the dividend income. A U.S. holder may have foreign currency gain or loss if the dividend is converted into U.S. dollars after the date of actual or constructive receipt. Such gain or loss would generally be treated as U.S.-source ordinary income or loss.

Subject to certain significant conditions, some of which vary depending upon the U.S. holder’s particular circumstances, Swiss income taxes withheld from dividends on ordinary shares at a rate not exceeding the rate provided by the U.S.–Swiss Treaty and not refundable to a U.S. holder may be creditable against the U.S. holder’s U.S. federal income tax liability. Swiss taxes withheld in excess of the rate applicable under the U.S.-Swiss Treaty will not be eligible for credit against a U.S. holder’s federal income tax liability. The rules governing foreign tax credits are complex and U.S. holders should consult their tax advisors regarding the creditability of foreign taxes in their particular circumstances. In lieu of claiming a foreign tax credit, U.S. holders may, at their election, deduct foreign taxes, including any Swiss income tax, in computing their taxable income, subject to generally applicable limitations under U.S. law. An election to deduct foreign taxes instead of claiming foreign tax credits applies to all foreign taxes paid or accrued in the taxable year.

Sale or other disposition of ordinary shares

Subject to the PFIC rules described below, gain or loss realized on the sale or other disposition of ordinary shares will be capital gain or loss and will be long-term capital gain or loss if the U.S. holder held the ordinary shares for more than 1 year. The amount of the gain or loss will equal the difference between the U.S. holder’s tax basis in the ordinary shares disposed of and the amount realized on the disposition, in each case as determined in U.S. dollars. This gain or loss will generally be U.S.-source gain or loss for foreign tax credit purposes. The deductibility of capital losses is subject to various limitations.

Passive foreign investment company (PFIC) rules

Under the Code, we will be a PFIC for any taxable year in which, after the application of certain “look-through” rules with respect to subsidiaries, either (i) 75 percent or more of our gross income consists of “passive income,” or (ii) 50 percent or more of the average quarterly value of our assets consists of assets that produce, or are held for the production of, “passive income.” For purposes of the above calculations, we will be treated as if we hold our proportionate share of the assets of, and directly receive our proportionate share of the income of, any other corporation in which we directly or indirectly own at least 25 percent, by value, of the shares of such corporation. Passive income for this purpose generally includes, among other things, interest, dividends, rents, certain non-active royalties and capital gains.

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If we are classified as a PFIC, a U.S. holder will generally be treated as owning stock owned by us in any direct or indirect subsidiaries that are also PFICs and will be subject to similar adverse rules with respect to distributions to us by, and dispositions by us of, the stock of such subsidiaries. A mark-to market election is not permitted for shares of any subsidiary of ours that is also classified as a PFIC.

The determination of whether we are, or will be, a PFIC for a taxable year depends, in part, on the application of complex U.S. federal income tax rules, which are subject to various interpretations. The tests for determining PFIC status are subject to a number of uncertainties. These tests are applied annually, and it is difficult to accurately predict future income, assets and activities relevant to this determination. In addition, because the market price for the ordinary shares is likely to fluctuate, the market price may affect the determination of whether we will be considered a PFIC. There can be no assurance that we will not be considered a PFIC for any taxable year. Prospective investors should consult their tax advisors regarding our PFIC status.

If we were deemed to be a PFIC in any year during which a U.S. investor held or holds ordinary shares (assuming such U.S. holder has not made a timely mark-to-market election, as further described below), any gain recognized by a U.S. holder on a sale or other disposition (including certain pledges) of the ordinary shares would be allocated ratably over the U.S. holder’s holding period for the ordinary shares. The amounts allocated to the taxable year of the sale or other disposition and to any year before we became a PFIC would be taxed as ordinary income. The amount allocated to any other taxable year would be subject to tax at the highest rate in effect for individuals or corporations, as appropriate, for that taxable year, and an interest charge would be imposed on the amount allocated to that taxable year. Further, to the extent that any distribution received by a U.S. holder on its ordinary shares exceeds 125 percent of the average of the annual distributions on the ordinary shares received during the preceding three years or the U.S. holder’s holding period, whichever is shorter, that distribution would be subject to taxation in the same manner as gain, described immediately above.

If we are a PFIC for any year during which a U.S. holder holds common shares, we generally will continue to be treated as a PFIC with respect to the U.S. holder for all succeeding years during which the U.S. holder holds common shares, even if we cease to meet the threshold requirement for PFIC status.

A U.S. holder can avoid certain of the adverse rules described above by making a mark-to-market election with respect to its ordinary shares, provided that the ordinary shares are “marketable.” Ordinary shares will be marketable if they are “regularly traded” on a “qualified exchange” or other market within the meaning of applicable Treasury regulations. If a U.S. holder makes the mark-to-market election, it generally will recognize as ordinary income any excess of the fair market value of the ordinary shares at the end of each taxable year over their adjusted tax basis, and will recognize an ordinary loss in respect of any excess of the adjusted tax basis of the ordinary shares over their fair market value at the end of the taxable year (but only to the extent of the net amount of income previously included as a result of the mark-to-market election). If a U.S. holder makes this election, the holder’s tax basis in the ordinary shares will be adjusted to reflect the income or loss amounts recognized. Any gain recognized on the sale or other disposition of ordinary shares in a year when we are a PFIC will be treated as ordinary income and any loss will be treated as an ordinary loss (but only to the extent of the net amount of income previously included as a result of the mark-to-market election). Once made, the election cannot be revoked without the consent of the IRS unless the ordinary shares cease to be marketable.

In addition, in order to avoid the application of the foregoing rules, a U.S. person who owns stock in a PFIC for U.S. federal income tax purposes may make a “qualified electing fund” (QEF) election with respect to such PFIC if the PFIC provides the information necessary for such election to be made. If a U.S. person makes a QEF election with respect to a PFIC, the U.S. person will be currently taxable on their pro rata share of the PFIC’s ordinary earnings and net capital gain (at ordinary income and capital gain rates, respectively) for each taxable year that the entity is classified as a PFIC and will not be required to include such amounts in income when actually distributed by the PFIC. We do not intend to provide the information necessary for U.S. holders to make QEF elections.

Under proposed U.S. Treasury Regulations, if a U.S. holder has an option, warrant or other right to acquire stock of a PFIC (such as the Warrants), such option, warrant or right is considered to be PFIC stock also subject to the rules discussed above. However, a U.S. holder generally may not make a QEF election or mark-to-market election with respect to warrants. In addition, under proposed U.S. Treasury Regulations, if a U.S. holder holds an option, warrant or other right to the acquired stock of a PFIC, the holding period with respect to shares of stock of the PFIC acquired upon exercise of such option, warrant or other right will include the period that the option, warrant or other right was held. Thus, this will impact the availability of a timely QEF election and mark-to-market election with respect to such shares as discussed below. Because of the complexity and uncertainty of the treatment of the Warrants under the PFIC rules, each U.S. holder should consult his own tax advisor regarding the application of the PFIC rules to the common shares acquired upon an exercise of common warrants and the availability of, and procedure for making, a qualifying election with respect to common warrants.

If we were a PFIC or, with respect to particular U.S. holder, were treated as a PFIC for the taxable year in which we paid a dividend or for the prior taxable year, the preferential dividend rates discussed above with respect to dividends paid to certain non-corporate U.S. holders would not apply.

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If a U.S. holder owns ordinary shares or Warrants during any year in which we are a PFIC, the holder generally must file annual reports containing such information as the U.S. Treasury may require on IRS Form 8621 (Information Return by a Shareholder of a Passive Foreign Investment Company or Qualified Electing Fund) (or any successor form) with respect to us, generally with the holder’s federal income tax return for that year.

U.S. holders should consult their tax advisors concerning our potential PFIC status and the potential application of the PFIC rules.

Net investment income tax

Certain U.S. holders that are individuals, estates or trusts and whose income exceeds certain thresholds generally are subject to a 3.8 percent tax on all or a portion of their net investment income, which may include their gross dividend income and net gains from the disposition of the ordinary shares. If you are a U.S. holder that is an individual, estate or trust, you should consult your tax advisors regarding the applicability of this net investment income tax to your income and gains in respect of your investment in the common shares..

Information reporting and backup withholding

Payments of dividends and sales proceeds that are made within the U.S. or through certain U.S.-related financial intermediaries generally are subject to information reporting, and may be subject to backup withholding, unless (i) the U.S. holder is a corporation or other exempt recipient or (ii) in the case of backup withholding, the U.S. holder provides a correct taxpayer identification number and certifies that they are not subject to backup withholding.

The amount of any backup withholding from a payment to a U.S. holder will be allowed as a credit against the holder’s U.S. federal income tax liability and may entitle the U.S. holder to a refund, provided that the required information is furnished in a timely manner to the IRS.

Information with respect to foreign financial assets

Certain U.S. holders who are individuals (and, under proposed regulations, certain entities) may be required to report information relating to an interest in our ordinary shares, subject to certain exceptions (including an exception for ordinary shares held in accounts maintained by certain U.S. financial institutions). U.S. holders should consult their tax advisors regarding the effect, if any, of this legislation on their ownership and disposition of the ordinary shares.

F.	DIVIDENDS AND PAYING AGENTS

Not applicable.

G.	STATEMENT BY EXPERTS

The consolidated financial statements of RELIEF THERAPEUTICS Holding SA contained herein have been included in reliance on the report of MAZARS SA, independent registered public accounting firm, appearing elsewhere herein, and upon the authority of said firm as experts in accounting and auditing.

H.	DOCUMENTS ON DISPLAY

We are subject to the information reporting requirements of the Exchange Act applicable to foreign private issuers, and under those requirements file reports with the SEC. The SEC maintains a website at http://www.sec.gov from which filings may be accessed.

I.	SUBSIDIARY INFORMATION

For information about our subsidiaries, see “Item 4. Information on the Company – C. Organizational Structure.”

ITEM 11	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK

For information about our quantitative and qualitative disclosures about market risk, see “Item 5. Operating and Financial Review and Prospects – B. Liquidity and Capital Resources.”

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ITEM 12	DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES
A.	DEBT SECURITIES
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Not Applicable.

B.	WARRANTS AND RIGHTS

Not Applicable.

C.	OTHER SECURITIES

Not applicable.

D.	AMERICAN DEPOSITARY RECEIPTS

J.P. Morgan Chase Bank, N.A. (J.P. Morgan) is acting as the depositary bank for our American Depositary Receipts. J.P. Morgan’s depositary offices are located at 383 Madison Avenue, Floor 11, New York, New York 10179. American Depositary Shares are sometimes referred to as ADSs and represent ownership interests in securities that are on deposit with the depositary bank. ADSs may be represented by certificates that are commonly known as American Depositary Receipts or ADRs. The depositary bank typically appoints a custodian to safekeep the securities on deposit. In this case, the custodian is The Corporation Trust Company, located at 1209 Orange Street, Wilmington, Delaware 19801.

A copy of the deposit agreement, as amended, is on file with the SEC under cover of a Registration Statement on Form F-6. You may obtain a copy of the deposit receipt from the SEC’s Public Reference Room at 100 F Street, N.E., Washington, DC 20549 and from the SEC’s website at www.sec.gov. Please refer to Relief Therapeutics Holding SA and Registration Number 333-260712 when retrieving such copy.

We are providing you with a summary description of the material terms of the ADSs and of your material rights of a holder of ADSs. Please remember that summaries by their nature lack the precision of the information. summarized and that the rights and obligations of an owner of ADSs will be determined by reference to the terms of the deposit agreement and not by this summary. We urge you to review the deposit agreement in its entirety.

Each ADS represents the right to receive, and to exercise the beneficial ownership interests in, ordinary shares that are on deposit with the depositary bank and/or custodian. As of the date of this prospectus, each ADS represents the ownership of one of our ordinary shares. An ADS also represents the right to receive, and to exercise the beneficial interests in, any other property received by the depositary bank or the custodian on behalf of the owner of the ADS but that has not been distributed to the owners of ADSs because of legal restrictions or practical considerations. We and the depositary bank may agree to change the ADS-to-Share ratio by amending the deposit agreement. This amendment may give rise to, or change, the depositary fees payable by ADS owners. The custodian, the depositary bank and their respective nominees will hold all deposited property for the benefit of the holders and beneficial owners of ADSs. The deposited property does not constitute the proprietary assets of the depositary bank, the custodian or their nominees. Beneficial ownership in the deposited property will under the terms of the deposit agreement be vested in the beneficial owners of the ADSs. The depositary bank, the custodian and their respective nominees will be the record holders of the deposited property represented by the ADSs for the benefit of the holders and beneficial owners of the corresponding ADSs. A beneficial owner of ADSs may or may not be the holder of ADSs. Beneficial owners of ADSs will be able to receive, and to exercise beneficial ownership interests in, the deposited property only through the registered holders of the ADSs, the registered holders of the ADSs (on behalf of the applicable ADS owners) only through the depositary bank, and the depositary bank (on behalf of the owners of the corresponding ADSs) directly, or indirectly, through the custodian or their respective nominees, in each case upon the terms of the deposit agreement.

If you become an owner of ADSs, you will become a party to the deposit agreement and therefore will be bound to its terms and to the terms of any ADS that represents your ADSs. The deposit agreement and the ADS specify our rights and obligations as well as your rights and obligations as owner of ADSs and those of the depositary bank. As an ADS holder you appoint the depositary bank to act on your behalf in certain circumstances. The deposit agreement and the ADSs are governed by New York law. However, our obligations to the holders of ordinary shares will continue to be governed by Swiss law which may be different from the laws of the U.S..

In addition, applicable laws and regulations may require you to satisfy reporting requirements and obtain regulatory approvals in certain circumstances. You are solely responsible for complying with such reporting requirements and obtaining such approvals. Neither the depositary bank, the custodian, us or any of their or our respective agents or affiliates shall be required to take any actions whatsoever on your behalf to satisfy such reporting requirements or obtain such regulatory approvals under applicable laws and regulations.

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As an owner of ADSs, we will not treat you as one of our shareholders and you will not have direct shareholder rights. The depositary bank will hold on your behalf the shareholder rights attached to the ordinary shares underlying your ADSs. As an owner of ADSs you will be able to exercise the shareholders rights for the ordinary shares represented by your ADSs through the depositary bank only to the extent contemplated in the deposit agreement. To exercise any shareholder rights not contemplated in the deposit agreement you will, as an ADS owner, need to arrange for the cancellation of your ADSs and become a direct shareholder.

The manner in which you own the ADSs (e.g., in a brokerage account vs. as registered holder, or as holder of certificated vs. uncertificated ADSs) may affect your rights and obligations, and the manner in which, and extent to which, the depositary bank’s services are made available to you. As an owner of ADSs, you may hold your ADSs either by means of an ADS registered in your name, through a brokerage or safekeeping account, or through an account established by the depositary bank in your name reflecting the registration of uncertificated ADSs directly on the books of the depositary bank (commonly referred to as the direct registration system or DRS). The direct registration system reflects the uncertificated (book-entry) registration of ownership of ADSs by the depositary bank. Under the direct registration system, ownership of ADSs is evidenced by periodic statements issued by the depositary bank to the holders of the ADSs. The direct registration system includes automated transfers between the depositary bank and The Depository Trust Company DTC, the central book-entry clearing and settlement system for equity securities in the U.S.. If you decide to hold your ADSs through your brokerage or safekeeping account, you must rely on the procedures of your broker or bank to assert your rights as ADS owner. Banks and brokers typically hold securities such as the ADSs through clearing and settlement systems such as DTC. The procedures of such clearing and settlement systems may limit your ability to exercise your rights as an owner of ADSs. Please consult with your broker or bank if you have any questions concerning these limitations and procedures. All ADSs held through DTC will be registered in the name of a nominee of DTC. This summary description assumes you have opted to own the ADSs directly by means of an ADS registered in your name and, as such, we will refer to you as the “holder.” When we refer to “you,” we assume the reader owns ADSs and will own ADSs at the relevant time.

The registration of the ordinary shares in the name of the depositary bank or the custodian shall, to the maximum extent permitted by applicable law, vest in the depositary bank or the custodian the record ownership in the applicable ordinary shares with the beneficial ownership rights and interests in such ordinary shares being at all times vested with the beneficial owners of the ADSs representing the ordinary shares. The depositary bank or the custodian shall at all times be entitled to exercise the beneficial ownership rights in all deposited property, in each case only on behalf of the holders and beneficial owners of the ADSs representing the deposited property.

Intended termination of our ADR program

Subject to the listing of our ordinary shares on the Nasdaq Stock Market or another regulated U.S. exchange, we intend to terminate the ADR program on or around the date of such listing.

Dividends and Distributions

As a holder of ADSs, you generally have the right to receive the distributions we make on the securities deposited with the custodian. Your receipt of these distributions may be limited, however, by practical considerations and legal limitations. Holders of ADSs will receive such distributions under the terms of the deposit agreement in proportion to the number of ADSs held as of the specified record date, after deduction of the applicable fees, taxes and expenses.

Distributions of Cash

Whenever we make a cash distribution for the securities on deposit with the custodian, we will deposit the funds with the custodian. Upon receipt of confirmation of the deposit of the requisite funds, the depositary bank will arrange for the funds received in a currency other than U.S. dollars to be converted into U.S. dollars and for the distribution of the U.S. dollars to the holders, subject to the laws and regulations of Switzerland.

The conversion into U.S. dollars will take place only if practicable and if the U.S. dollars are transferable to the U.S. The depositary bank will apply the same method for distributing the proceeds of the sale of any property (such as undistributed rights) held by the custodian in respect of securities on deposit.

The distribution of cash will be made net of the fees, expenses, taxes and governmental charges payable by holders under the terms of the deposit agreement. The depositary bank will hold any cash amounts it is unable to distribute in a non-interest-bearing account for the benefit of the applicable holders and beneficial owners of ADSs until the distribution can be affected or the funds that the depositary bank holds must be escheated as unclaimed property in accordance with the laws of the relevant states of the U.S.

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Distributions of Shares

Whenever we make a free distribution of ordinary shares for the securities on deposit with the custodian, we will deposit the applicable number of ordinary shares with the custodian. Upon receipt of confirmation of such deposit, the depositary bank will either distribute to holders new ADSs representing the ordinary shares deposited or modify the ADS-to-ordinary shares ratio, in which case each ADS you hold will represent rights and interests in the additional ordinary shares so deposited. Only whole new ADSs will be distributed. Fractional entitlements will be sold and the proceeds of such sale will be distributed as in the case of a cash distribution.

The distribution of new ADSs or the modification of the ADS-to-ordinary shares ratio upon a distribution of ordinary shares will be made net of the fees, expenses, taxes and governmental charges payable by holders under the terms of the deposit agreement. In order to pay such taxes or governmental charges, the depositary bank may sell all or a portion of the new ordinary shares so distributed.

No such distribution of new ADSs will be made if it would violate a law (e.g., the U.S. securities laws) or if it is not operationally practicable. If the depositary bank does not distribute new ADSs as described above, it may sell the ordinary shares received upon the terms described in the deposit agreement and will distribute the proceeds of the sale as in the case of a distribution of cash.

Distributions of Rights

Whenever we intend to distribute rights to subscribe for additional ordinary shares, we will give prior notice to the depositary bank and we will assist the depositary bank in determining whether it is lawful and reasonably practicable to distribute rights to subscribe for additional ADSs to holders.

The depositary bank will establish procedures to distribute rights to subscribe for additional ADSs to holders and to enable such holders to exercise such rights if it is lawful and reasonably practicable to make the rights available to holders of ADSs, and if we provide all of the documentation contemplated in the deposit agreement (such as opinions to address the lawfulness of the transaction). You may have to pay fees, expenses, taxes and other governmental charges to subscribe for the new ADSs upon the exercise of your rights. The depositary bank is not obligated to establish procedures to facilitate the distribution and exercise by holders of rights to subscribe for new ordinary shares other than in the form of ADSs.

The depositary bank will not distribute the rights to you if:

•	We do not timely request that the rights be distributed to you or we request that the rights not be distributed to you;
•	We fail to deliver satisfactory documents to the depositary bank; or
---	---
•	It is not reasonably practicable to distribute the rights.
---	---

The depositary bank will sell the rights that are not exercised or not distributed if such sale is lawful and reasonably practicable. The proceeds of such sale will be distributed to holders as in the case of a cash distribution. If the depositary bank is unable to sell the rights, it will allow the rights to lapse.

Elective Distributions

Whenever we intend to distribute a dividend payable at the election of shareholders either in cash or in additional shares, we will give prior notice thereof to the depositary bank and will indicate whether we wish the elective distribution to be made available to you. In such case, we will assist the depositary bank in determining whether such distribution is lawful and reasonably practicable.

The depositary bank will make the election available to you only if it is reasonably practicable and if we have provided all of the documentation contemplated in the deposit agreement. In such case, the depositary bank will establish procedures to enable you to elect to receive either cash or additional ADSs, in each case as described in the deposit agreement.

If the election is not made available to you, you will receive either cash or additional ADSs, depending on what a shareholder in Switzerland would receive upon failing to make an election, as more fully described in the deposit agreement.

Other Distributions

Whenever we intend to distribute property other than cash, ordinary shares or rights to subscribe for additional ordinary shares, we will notify the depositary bank in advance and will indicate whether we wish such distribution to be made to you. If so, we will assist the depositary bank in determining whether such distribution to holders is lawful and reasonably practicable.

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If it is reasonably practicable to distribute such property to you and if we provide to the depositary bank all of the documentation contemplated in the deposit agreement, the depositary bank will distribute the property to the holders in a manner it deems practicable.

The distribution will be made net of fees, expenses, taxes and governmental charges payable by holders under the terms of the deposit agreement. In order to pay such taxes and governmental charges, the depositary bank may sell all or a portion of the property received.

The depositary bank will not distribute the property to you and will sell the property if:

•	We do not request that the property be distributed to you or if we request that the property not be distributed to you;
•	We do not deliver satisfactory documents to the depositary bank; or
---	---
•	The depositary bank determines that all or a portion of the distribution to you is not reasonably practicable. The proceeds of such a sale will be distributed to holders as in the case of a cash distribution.
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Redemption

Whenever we decide to redeem any of the securities on deposit with the custodian, we will notify the depositary bank in advance. If it is practicable and if we provide all of the documentation contemplated in the deposit agreement, the depositary bank will provide notice of the redemption to the holders.

The custodian will be instructed to surrender the shares being redeemed against payment of the applicable redemption price. The depositary bank will convert into U.S. dollars, upon the terms of the deposit agreement, the redemption funds received in a currency other than U.S. dollars and will establish procedures to enable holders to receive the net proceeds from the redemption upon surrender of their ADSs to the depositary bank. You may have to pay fees, expenses, taxes and other governmental charges upon the redemption of your ADSs. If less than all ADSs are being redeemed, the ADSs to be retired will be selected by lot or on a pro rata basis, as the depositary bank may determine.

Changes Affecting Ordinary Shares

The ordinary shares held on deposit for your ADSs may change from time to time. For example, there may be a change in nominal or par value, split-up, cancellation, consolidation or any other reclassification of such ordinary shares or a recapitalization, reorganization, merger, consolidation or sale of assets of the company.

If any such change were to occur, your ADSs would, to the extent permitted by law and the deposit agreement, represent the right to receive the property received or exchanged in respect of the ordinary shares held on deposit.

The depositary bank may in such circumstances deliver new ADSs to you, amend the deposit agreement, the ADSs and the applicable Registration Statement(s) on Form F-6, call for the exchange of your existing ADSs for new ADSs and take any other actions that are appropriate to reflect as to the ADSs the change affecting the ordinary shares. If the depositary bank may not lawfully distribute such property to you, the depositary bank may sell such property and distribute the net proceeds to you as in the case of a cash distribution.

Issuance of ADSs upon Deposit of Ordinary Shares

The depositary bank may create ADSs on your behalf if you or your broker deposit ordinary shares with the custodian. The depositary bank will deliver these ADSs to the person you indicate only after you pay any applicable issuance fees and any charges and taxes payable for the transfer of the ordinary shares to the custodian. Your ability to deposit ordinary shares and receive ADSs may be limited by U.S. and English legal considerations applicable at the time of deposit.

The issuance of ADSs may be delayed until the depositary bank or the custodian receives confirmation that all required approvals have been given and that the ordinary shares have been duly transferred to the custodian. The depositary bank will only issue ADSs in whole numbers.

When you make a deposit of ordinary shares, you will be responsible for transferring good and valid title to the depositary bank. As such, you will be deemed to represent and warrant that:

•	The ordinary shares are duly authorized, validly issued, fully paid, non-assessable and legally obtained.
•	All preemptive (and similar) rights, if any, with respect to such ordinary shares have been validly waived or exercised.
---	---
•	You are duly authorized to deposit the ordinary shares.
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•	The ordinary shares presented for deposit are free and clear of any lien, encumbrance, security interest, charge, mortgage or adverse claim, and are not, and the ADSs issuable upon such deposit will not be, “restricted securities” (as defined in the deposit agreement).
•	The deposit of ordinary shares does not violate any provisions of our articles of association or any of the applicable laws and regulations of Switzerland.
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If any of the representations or warranties are incorrect in any way, we and the depositary bank may, at your cost and expense, take any and all actions necessary to correct the consequences of the misrepresentations.

Transfer, Combination and Split Up of ADSs

As an ADS holder, you will be entitled to transfer, combine or split up your ADSs and the ADSs evidenced thereby. For transfers of ADSs, you will have to surrender the ADSs to be transferred to the depositary bank and also must:

•	ensure that the surrendered ADS is properly endorsed or otherwise in proper form for transfer;
•	provide such proof of identity and genuineness of signatures as the depositary bank deems appropriate;
---	---
•	provide any transfer stamps required by state or federal law; or
---	---
•	pay all applicable fees, charges, expenses, taxes and other governmental charges payable by ADS holders pursuant to the terms of the deposit agreement, upon a combination or split up of ADSs.
---	---

To have your ADSs either combined or split up, you must surrender the ADSs in question to the depositary bank with your request to have them combined or split up, and you must pay all applicable fees, charges and expenses payable by ADS holders, pursuant to the terms of the deposit agreement, upon a combination or split up of ADSs.

Withdrawal of Ordinary Shares Upon Cancellation of ADSs

As a holder, you will be entitled to present your ADSs to the depositary bank for cancellation and then receive the corresponding number of underlying ordinary shares at the custodian’s offices. Your ability to withdraw the ordinary shares held in respect of the ADSs may be limited by U.S. and Swiss law considerations applicable at the time of withdrawal. In order to withdraw the ordinary shares represented by your ADSs, you will be required to pay to the depositary bank the fees for cancellation of ADSs and any charges and taxes payable upon the transfer of the ordinary shares. You assume the risk for delivery of all funds and securities upon withdrawal. Once canceled, the ADSs will not have any rights under the deposit agreement.

If you hold ADSs registered in your name, the depositary bank may ask you to provide proof of identity and genuineness of any signature and such other documents as the depositary bank may deem appropriate before it will cancel your ADSs. The withdrawal of the ordinary shares represented by your ADSs may be delayed until the depositary bank receives satisfactory evidence of compliance with all applicable laws and regulations. Please keep in mind that the depositary bank will only accept ADSs for cancellation that represent a whole number of securities on deposit.

You will have the right to withdraw the securities represented by your ADSs at any time except for:

•	Temporary delays that may arise because (i) the transfer books for the ordinary shares or ADSs are closed, or (ii) ordinary shares are immobilized on account of a shareholders’ meeting or a payment of dividends.
•	Obligations to pay fees, taxes and similar charges.
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•	Restrictions imposed because of laws or regulations applicable to ADSs or the withdrawal of securities on deposit.
---	---

The deposit agreement may not be modified to impair your right to withdraw the securities represented by your ADSs except to comply with mandatory provisions of law.

Each holder and beneficial owner of ADSs agrees to provide such information as the company may request in a disclosure notice given pursuant to the Swiss Code of Obligations (CO), or the Articles of Association. Each holder and beneficial owner of ADSs acknowledges that it understands that failure to comply with such request may result in the imposition of sanctions against the holder of the ordinary shares in respect of which the non-complying person is or was, or appears to be or has been, interested as provided in the CO and the Articles of Association which currently include, the withdrawal of the voting rights of such Shares and the imposition of restrictions on the rights to receive dividends on and to transfer such Shares.

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Voting Rights

As a holder, you generally have the right under the deposit agreement to instruct the depositary bank to exercise the voting rights for the ordinary shares represented by your ADSs. The voting rights of holders of ordinary shares are described in “Description of Share Capital and Articles of Association— Articles of Association.”

At our request, the depositary bank will distribute to you any notice of shareholders’ meeting received from us together with information explaining how to instruct the depositary bank to exercise the voting rights of the securities represented by ADSs. In lieu of distributing such materials, the depositary bank may distribute to holders of ADSs instructions on how to retrieve such materials upon request.

If the depositary bank timely receives voting instructions from a holder of ADSs, it will endeavor to vote the securities (in person or by proxy) represented by the holder’s ADSs as follows:

•	In the event of voting by show of hands, the depositary bank will vote (or cause the custodian to vote) all ordinary shares held on deposit at that time in accordance with the voting instructions received from a majority of holders of ADSs who provide timely voting instructions.
•	In the event of voting by poll, the depositary bank will vote (or cause the Custodian to vote) the ordinary shares held on deposit in accordance with the voting instructions received from the holders of ADSs.
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Securities for which no voting instructions have been received will not be voted (except as otherwise contemplated in the deposit agreement). Please note that the ability of the depositary bank to carry out voting instructions may be limited by practical and legal limitations and the terms of the securities on deposit. We cannot assure you that you will receive voting materials in time to enable you to return voting instructions to the depositary bank in a timely manner.

Fees and Charges

As an ADS holder, you will be required to pay the following fees under the terms of the deposit agreement:

Service	Fees
Cash distributions made, or elective cash/stock options offered, pursuant to the Deposit Agreement	Up to $0.05 per ADS issued.
Distribution or sale of securities under the Deposit Agreement	An amount equal to the fee for the execution and delivery of ADSs which would have been charged as a result of the deposit of such securities, but which securities or the net cash proceeds from the sale thereof are instead distributed by the depositary to the holders entitled thereto.
Services performed by the Depositary in administering the ADSs	Up to $0.05 per ADS per calendar year

As an ADS holder you may also be responsible to pay certain charges such as:

•	Reimbursement of fees, charges and expenses incurred by the Depositary and/or any of its agents in connection with the servicing of the shares or deposited securities, the delivery of deposited securities or otherwise in connection with the Depositary’s or the Custodian’s compliance with applicable law, rule or regulation;
•	Stock transfer or other taxes and other governmental charges;
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•	SWIFT, cable, telex and facsimile transmission and delivery charges incurred at the request of persons depositing, or holders delivering shares, ADSs or deposited securities; and
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•	Transfer or registration fees for the registration or transfer of deposited securities on any applicable register in connection with the deposit or withdrawal of deposited securities.

ADS fees and charges for (i) the issuance of ADSs, and (ii) the cancellation of ADSs are charged to the person for whom the ADSs are issued (in the case of ADS issuances) and to the person for whom ADSs are cancelled (in the case of ADS cancellations). In the case of ADSs issued by the depositary bank into DTC, the ADS issuance and cancellation fees and charges may be deducted from distributions made through DTC, and may be charged to the DTC participant(s) receiving the ADSs being issued or the DTC participant(s) holding the ADSs being cancelled, as the case may be, on behalf of the beneficial owner(s) and will be charged by the DTC participant(s) to the account of the applicable beneficial owner(s) in accordance with the procedures and practices of the DTC participants as in effect at the time. ADS fees and charges in respect of distributions and the ADS service fee are charged to the holders as of the applicable ADS record date. In the case of distributions of cash, the amount of the applicable ADS fees and charges is deducted from the funds being distributed. In the case of (i) distributions other than cash and (ii) the ADS service fee, holders as of the ADS record date will be invoiced for the amount of the ADS fees and charges and such ADS fees and charges may be deducted from distributions made to holders of ADSs. For ADSs held through DTC, the ADS fees and charges for distributions other than cash and the ADS service fee may be deducted from distributions made through DTC, and may be charged to the DTC participants in accordance with the procedures and practices prescribed by DTC and the DTC participants in turn charge the amount of such ADS fees and charges to the beneficial owners for whom they hold ADSs. In the case of (i) registration of ADS transfers, the ADS transfer fee will be payable by the ADS holder whose ADSs are being transferred or by the person to whom the ADSs are transferred, and (ii) conversion of ADSs of one series for ADSs of another series, the ADS conversion fee will be payable by the holder whose ADSs are converted or by the person to whom the converted ADSs are delivered.

In the event of refusal to pay the depositary bank fees, the depositary bank may, under the terms of the deposit agreement, refuse the requested service until payment is received or may set off the amount of the depositary bank fees from any distribution to be made to the ADS holder. Certain depositary fees and charges (such as the ADS services fee) may become payable shortly after the purchase of ADSs. Note that the fees and charges you may be required to pay may vary over time and may be changed by us and by the depositary bank. You will receive prior notice of such changes. The depositary bank may reimburse us for certain expenses incurred by us in respect of the ADS program, by making available a portion of the ADS fees charged in respect of the ADS program or otherwise, upon such terms and conditions as we and the depositary bank agree from time to time.

Amendments and Termination

We may agree with the depositary bank to modify the deposit agreement at any time without your consent. We undertake to give holders 30 days’ prior notice of any modifications that would materially prejudice any of their substantial rights under the deposit agreement. We will not consider to be materially prejudicial to your substantial rights any modifications or supplements that are reasonably necessary for the ADSs to be registered under the Securities Act or to be eligible for book-entry settlement, in each case without imposing or increasing the fees and charges you are required to pay. In addition, we may not be able to provide you with prior notice of any modifications or supplements that are required to accommodate compliance with applicable provisions of law.

You will be bound by the modifications to the deposit agreement if you continue to hold your ADSs after the modifications to the deposit agreement become effective. The deposit agreement cannot be amended to prevent you from withdrawing the ordinary shares represented by your ADSs (except as permitted by law).

We have the right to direct the depositary bank to terminate the deposit agreement. Similarly, the depositary bank may in certain circumstances on its own initiative terminate the deposit agreement. In either case, the depositary bank must give notice to the holders at least 30 days before termination. Until termination, your rights under the deposit agreement will be unaffected.

Termination

After termination, the depositary bank will continue to collect distributions received (but will not distribute any such property until you request the cancellation of your ADSs) and may sell the securities held on deposit. After the sale, the depositary bank will hold the proceeds from such sale and any other funds then held for the holders of ADSs in a non-interest bearing account. At that point, the depositary bank will have no further obligations to holders other than to account for the funds then held for the holders of ADSs still outstanding (after deduction of applicable fees, taxes and expenses).

In connection with any termination of the deposit agreement, the depositary bank may make available to owners of ADSs a means to withdraw the ordinary shares represented by ADSs and to direct the depositary of such ordinary shares into an unsponsored American depositary share program established by the depositary bank. The ability to receive unsponsored American depositary shares upon termination of the deposit agreement would be subject to satisfaction of certain U.S. regulatory requirements applicable to the creation of unsponsored American depositary shares and the payment of applicable depositary fees.

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Books of Depositary

The depositary bank will maintain ADS holder records at its depositary office. You may inspect such records at such office during regular business hours but solely for the purpose of communicating with other holders in the interest of business matters relating to the ADSs and the deposit agreement.

The depositary bank will maintain in New York facilities to record and process the issuance, cancellation, combination, split-up and transfer of ADSs. These facilities may be closed from time to time, to the extent not prohibited by law.

Limitations on Obligations and Liabilities

The deposit agreement limits our obligations and the depositary bank’s obligations to you. Please note the following:

•	We and the depositary bank are obligated only to take the actions specifically stated in the deposit agreement without negligence or bad faith.
•	The depositary bank disclaims any liability for any failure to carry out voting instructions, for any manner in which a vote is cast or for the effect of any vote, provided it acts in good faith and in accordance with the terms of the deposit agreement.
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•	The depositary bank disclaims any liability for any failure to determine the lawfulness or practicality of any action, for the content of any document forwarded to you on our behalf or for the accuracy of any translation of such a document, for the investment risks associated with investing in ordinary shares, for the validity or worth of the ordinary shares, for any tax consequences that result from the ownership of ADSs, for the credit-worthiness of any third party, for allowing any rights to lapse under the terms of the deposit agreement, for the timeliness of any of our notices or for our failure to give notice.
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•	We and the depositary bank will not be obligated to perform any act that is inconsistent with the terms of the deposit agreement.
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•	We and the depositary bank disclaim any liability if we or the depositary bank are prevented or forbidden from or subject to any civil or criminal penalty or restraint on account of, or delayed in, doing or performing any act or thing required by the terms of the deposit agreement, by reason of any provision, present or future of any law or regulation, or by reason of present or future provision of any provision of our Articles of Association, or any provision of or governing the securities on deposit, or by reason of any act of God or war or other circumstances beyond our control.
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•	We and the depositary bank disclaim any liability by reason of any exercise of, or failure to exercise, any discretion provided for in the deposit agreement or in our Articles of Association or in any provisions of or governing the securities on deposit.
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•	We and the depositary bank further disclaim any liability for any action or inaction in reliance on the advice or information received from legal counsel, accountants, any person presenting Shares for deposit, any holder of ADSs or authorized representatives thereof, or any other person believed by either of us in good faith to be competent to give such advice or information.
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•	We and the depositary bank may rely without any liability upon any written notice, request or other document believed to be genuine and to have been signed or presented by the proper parties.
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•	We and the depositary bank also disclaim liability for any consequential or punitive damages for any breach of the terms of the deposit agreement.
---	---
•	No disclaimer of any Securities Act liability is intended by any provision of the deposit agreement.
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•	Nothing in the deposit agreement gives rise to a partnership or joint venture, or establishes a fiduciary relationship, among us, the depositary bank and you as ADS holder.
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•	Nothing in the deposit agreement precludes the depositary bank (or its affiliates) from engaging in transactions in which parties adverse to us or the holders or beneficial owners of ADS have interests, and nothing in the deposit agreement obligates the depositary bank to disclose those transactions, or any information obtained in the course of those transactions, to us or to the holders or beneficial owners of ADS, or to account for any payment received as part of those transactions.
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Taxes

You will be responsible for the taxes and other governmental charges payable on the ADSs and the securities represented by the ADSs. We, the depositary bank and the custodian may deduct from any distribution the taxes and governmental charges payable by holders and may sell any and all property on deposit to pay the taxes and governmental charges payable by holders. You will be liable for any deficiency if the sale proceeds do not cover the taxes that are due.

The depositary bank may refuse to issue ADSs, to deliver, transfer, split and combine ADSs or to release securities on deposit until all taxes and charges are paid by the applicable holder. The depositary bank and the custodian may take reasonable administrative actions to obtain tax refunds and reduced tax withholding for any distributions on your behalf. However, you may be required to provide to the depositary bank and to the custodian proof of taxpayer status and residence and such other information as the depositary bank and the custodian may require to fulfill legal obligations. You are required to indemnify us, the depositary bank and the custodian for any claims with respect to taxes based on any tax benefit obtained for you.

Foreign Currency Conversion

The depositary bank will arrange for the conversion of all foreign currency received into U.S. dollars if such conversion is practical, and it will distribute the U.S. dollars in accordance with the terms of the deposit agreement. You may have to pay fees and expenses incurred in converting foreign currency, such as fees and expenses incurred in complying with currency exchange controls and other governmental requirements.

If the conversion of foreign currency is not practical or lawful, or if any required approvals are denied or not obtainable at a reasonable cost or within a reasonable period, the depositary bank may take the following actions in its discretion:

•	Convert the foreign currency to the extent practicable and lawful and distribute the U.S. dollars to the holders for whom the conversion and distribution is lawful and practicable.
•	Distribute the foreign currency to holders for whom the distribution is lawful and practical.
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•	Hold the foreign currency (without liability for interest) for the applicable holders.
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Governing Law / Waiver of Jury Trial

The deposit agreement, the ADSs, and the ADSs will be interpreted in accordance with the laws of the State of New York. The rights of holders of ordinary shares (including ordinary shares represented by ADSs) are governed by the laws of Switzerland.

AS A PARTY TO THE DEPOSIT AGREEMENT, YOU IRREVOCABLY WAIVE, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, YOUR RIGHT TO TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF, OR RELATING TO, THE DEPOSIT AGREEMENT OR THE ADSs, OR ANYTHING CONTAINED THEREIN AGAINST U.S. AND/OR THE DEPOSITARY.

The deposit agreement provides that, to the extent permitted by law, ADS holders waive the right to a jury trial of any claim they may have against us or the depositary arising out of or relating to our ordinary shares, the ADSs or the deposit agreement, including any claim under U.S. federal securities laws. If we or the depositary opposed a jury trial demand based on the waiver, the court would determine whether the waiver was enforceable in the facts and circumstances of that case in accordance with applicable case law. However, you will not be deemed, by agreeing to the terms of the deposit agreement, to have waived our or the depositary’s compliance with U.S. federal securities laws and the rules and regulations promulgated thereunder.

PART II

ITEM 13	DEFAULTS, DIVIDEND ARREARAGES AND DELINQUENCIES

Not applicable.

ITEM 14	MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS

Not applicable.

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ITEM 15	CONTROLS AND PROCEDURES

Not applicable.

ITEM 16	RESERVED
ITEM 16A.	AUDIT COMMITTEE FINANCIAL EXPERT
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The Board of Directors has determined that Michelle Lock qualifies as an Audit Committee Financial Expert as defined in Regulation S-K under the Exchange Act. The listing rules of the Nasdaq Stock Market, where the Company intends to list its ordinary shares, require the audit committee to be comprised only of independent directors. All of the members of the Audit and Finance Committee, including Ms. Lock, are independent directors.

ITEM 16B.	CODE OF ETHICS

We have adopted a Code of Business Conduct and Ethics, which covers a broad range of matters including the handling of conflicts of interest, compliance issues and other corporate policies such as insider trading and equal opportunity and non-discrimination standards. Our Code of Business Conduct & Ethics applies to all of our directors, executive officers and employees. We have published our Code of Business Conduct and Ethics on our website, https://relieftherapeutics.com/investor-relations. The information contained on our website is not a part of this Annual Report.

ITEM 16C.	PRINCIPAL ACCOUNTANT FEES AND SERVICES

Not applicable.

ITEM 16D.	EXEMPTIONS FROM THE LISTING STANDARDS FOR AUDIT COMMITTEES

Not applicable.

ITEM 16E.	PURCHASES OF EQUITY SECURITIES BY THE ISSUER AND AFFILIATED PURCHASERS

In 2022, no purchases of our equity securities were made by or on behalf of the Company or any affiliated purchaser.

ITEM 16F.	CHANGE IN REGISTRANT’S CERTIFYING ACCOUNTANT

None.

ITEM 16G.	CORPORATE GOVERNANCE

Summary of significant corporate governance differences from Nasdaq Listing Standards

Our corporate governance practices differ in certain respects from those that U.S. companies must adopt in order to maintain a Nasdaq listing. A brief, general summary of those differences is provided as follows.

Independent Directors

Swiss law does not require that a majority of our board of directors consist of independent directors. Our board of directors therefore may include fewer independent directors than would be required if we were subject to Nasdaq Listing Rule 5605(b)(1). In addition, we are not subject to Nasdaq Listing Rule 5605(b)(2), which requires that independent directors must regularly have scheduled meetings at which only independent directors are present.

Nomination and Compensation, Audit and Corporate Governance Committees

As Swiss law requires that we have a compensation committee (and we have in line with best practice installed a nomination and compensation committee as well as an audit committee and a corporate governance committee), we will follow home country requirements with respect to such committees. As a result, our practice will vary from the requirements of Nasdaq Listing Rule 5605(d), which sets forth certain requirements as to the responsibilities, composition and independence of the nomination and compensation, audit and corporate governance committees.

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Quorum Requirements

In accordance with Swiss law and generally accepted business practices, our articles of association do not provide quorum requirements generally applicable to general meetings of shareholders. Our practice thus varies from the requirement of Nasdaq Listing Rule 5620(c), which requires an issuer to provide in its bylaws for a generally applicable quorum, and that such quorum may not be less than one-third of the outstanding voting stock.

Solicitation of Proxies

Our articles of association provide for an independent proxy holder elected by our shareholders, who may represent our shareholders at a general meeting of shareholders, and we must provide shareholders with an agenda and other relevant documents for the general meeting of shareholders. However, Swiss law does not have a regulatory regime for the solicitation of proxies, and company solicitation of proxies is prohibited for public companies in Switzerland. Thus, our practice will vary from the requirement of Nasdaq Listing Rule 5620(b), which sets forth certain requirements regarding the solicitation of proxies.

ITEM 16H.	MINE SAFETY DISCLOSURE

Not applicable.

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PART III

ITEM 17	FINANCIAL STATEMENTS

We have elected to furnish financial statements and related information in Item 18.

ITEM 18	FINANCIAL STATEMENTS

See pages F-1 through F-41 of this Annual Report.

ITEM 19	EXHIBITS

The Exhibits listed in the Exhibit Index at the end of this Annual Report are filed as Exhibits hereto.

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EXHIBIT INDEX

Exhibit<br>Number	Description of Exhibit	Form	File Number	Date of Filing	Exhibit<br>Number	Filed<br>Herewith
3.1	Articles of Association dated April 28, 2023					X
4.1	Form of Deposit Agreement	F-6	333-260712	11/3/2021	99(a)
4.2	Amendment No. 1 to Deposit Agreement	F-6 POS	333-260712	8/1/2022	99(a)(2)
4.3	Amendment No. 2 to Deposit Agreement	F-6 POS	333-260712	10/21/2022	99(a)(3)
4.4	Amendment No. 3 to Deposit Agreement	F-6 POS	333-260712	4/24/2023	99(a)(4)
4.4	Form of American Depositary Receipt (included in Exhibit 4.4)	F-6 POS	333-260712	4/24/2023	99(a)(4)
4.5	Form of Nominee Agreement	F-6	333-260712	11/3/2021	99(b)
8.1	Subsidiaries of the Registrant					X
10.1	Share Purchase Agreement, dated June 28, 2021, between the Company and the shareholders of APR Applied Pharma Research SA	20-F	001-41174	7/11/2022	10.1
10.2(a)	Share Exchange Agreement, dated July 28, 2021, between the Company and the shareholders of AdVita Lifescience GmbH	20-F	001-41174	7/11/2022	10.2
10.2(b)*	Amendment to Share Exchange Agreement, dated December 19, 2022, between the Company and the shareholders of AdVita Lifescience GmbH.					X
10.3	Share Subscription Facility Agreement, dated as of January 20, 2021, by and among the Company, GEM Global Yield LLC SCS, and GEM Yield Bahamas Ltd.	20-F	001-41174	7/11/2022	10.3
10.4	Collaboration and License Agreement, dated March 19, 2021, between the Company and Acer Therapeutics, Inc.	20-F	001-41174	7/11/2022	10.5
10.5(a)	Collaboration Agreement, dated November 23, 2021 between the Company and InveniAI LLC	20-F	001-41174	7/11/2022	10.6(a)
10.5(b)	Amendment No. 1 to Collaboration Agreement, dated August 3, 2022, between the Company and InveniAI LLC	20-F	001-41174	7/11/2022	10.6(b)
10.6(a)	Master Service Agreement on Order to Cash Service, dated effective September 14, 2018, between APR and Arvato Services Italia S.R.L.	20-F	001-41174	7/11/2022	10.7.(a)
10.6(b)	Amendment No. 1 to the Master Service Agreement on Order to Cash Service, dated effective February 1, 2021, between APR and Arvato	20-F	001-41174	7/11/2022	10.7(b)
10.7(a)	Royalty Purchase Agreement, dated as of July 31, 2014, made between APR and SWK Funding LLC	20-F	001-41174	7/11/2022	10.8(a)
10.7(b)	Royalty Purchase Agreement, dated December 2, 2015, made by and between APR and SWK Funding LLC	20-F	001-41174	7/11/2022	10.8(b)
10.8(a)*	Settlement Agreement, made and entered into as of November 12, 2022, between the Company, Relief Therapeutics International SA, NeuroRx, Inc. and NRx, Inc.					X
10.8(b)*	Asset Purchase Agreement, made and entered into as of November 12, 2022, by and between the Company, Relief Therapeutics International SA, NeuroRx, Inc. and NRx, Inc.					X
10.9	Stock Option Plan 2021					X
12.1	Certification of Jack Weinstein, Chief Executive Officer of the Company, pursuant to Section 302 of the Sarbanes-Oxley Act of 2002					X

134

Exhibit<br>Number	Description of Exhibit	Filed<br>Herewith
12.2	Certification of Jeremy Meinen, Chief Financial Officer of the Company, pursuant to Section 302 of the Sarbanes-Oxley Act of 2002	X
13.1	Certification of Jack Weinstein, Chief Financial officer of the Company, pursuant to Section 906 of the Sarbanes-Oxley Act of 2002	X
13.2	Certification of Jeremy Meinen, Chief Financial Officer of the Company, pursuant to Section 906 of the Sarbanes-Oxley Act of 2002	X
101.INS	XBRL Instance Document	X
101.SCH	XBRL Taxonomy Extension Schema Document	X
101.CAL	XBRL Taxonomy Extension Calculation Linkbase Document	X
101.DEF	XBRL Taxonomy Extension Definition Linkbase Document	X
101.LAB	XBRL Taxonomy Extension Label Linkbase Document	X
101.PRE	XBRL Taxonomy Extension Presentation Linkbase Document	X
104	Cover Page Interactive Data File (embedded within the Inline XBRL document and included in Exhibit 101)	X
*	Contains information that has been excluded from this exhibit because it is both (i) not material and (ii) would be competitively harmful if publicly disclosed.
---	---

135

SIGNATURES

The registrant hereby certifies that it meets all of the requirements for filing on Form 20-F and that it has duly caused and authorized the undersigned to sign this annual report on its behalf.

Date: May 12, 2023

RELIEF THERAPEUTICS HOLDING SA
By:	/s/ Jack Weinstein
	Jack Weinstein
	Chief Executive Officer
By:	/s/ Jeremy Meinen
	Jeremy Meinen
	Chief Financial Officer

136

LOGO

RELIEF THERAPEUTICS Holding SA

Geneva

Independent Auditor’s Report

Consolidated Financial Statements

December 31, 2022

INDEX TO FINANCIAL STATEMENTS

Years ended December 31, 2022 and 2021

Report of Independent Registered Public Accounting Firm (PCAOB ID Number 6868)	F-2
Consolidated Balance Sheets	F-3
Consolidated Statements of Comprehensive Loss	F-4
Consolidated Cash Flow Statements	F-5
Consolidated Statements of Changes in Equity	F-6
Notes to the Consolidated Financial Statements	F-7

F-1

Table of Contents

Mazars SA<br><br>Chemin de Blandonnet 2<br><br>CH-1214 Vernier-Geneva<br><br><br><br>Tel: +41 22 708 10 80<br><br>www.mazars.ch

Report of independent registered public accounting firm to the Board of Directors and Stockholders of RELIEF THERAPEUTICS Holding SA

Opinion on the Financial Statements

We have audited the accompanying consolidated balance sheets of RELIEF THERAPEUTICS Holding SA (the Company) as of December 31, 2022 and 2021, and the related consolidated statements of comprehensive loss, the consolidated cash flow statements and the consolidated statements of changes in equity for each of the years in the two-year period ended December 31, 2022, and the related notes (collectively referred to as the consolidated financial statements).

In our opinion the consolidated financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 2022 and 2021, and the results of its operations and its cash flows for each of the years in the two-year period ended December 31, 2022, in conformity with International Financial Reporting Standards as issued by the International Accounting Standards Board.

Going concern uncertainty

The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 4.1 to the consolidated financial statements, the Company has suffered recurring losses from operations and is dependent upon external funding, including public or private financing, or license and collaboration agreements, that raise substantial doubt about its ability to continue as a going concern. Management’s plans in regard to these matters are also described in Note 4.1. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.

Basis for Opinion

These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

/s/ MAZARS SA - Signature

Franck Paucod<br><br>Licensed Audit Expert	Yoann Bois<br><br>Licensed Audit Expert
(Auditor in Charge)

We have served as the Company’s auditor since 2017.

Switzerland, Geneva

May 12, 2023

F-2

Table of Contents

Consolidated balance sheets

in CHF thousands	Notes
ASSETS
Intangible assets	8	162,915		192,299
Right-of-use<br> assets	9	2,642		2,498
Property and equipment		49		38
Other <br>non-current<br> assets		114		76
Deferred tax assets	29	495		1,737
Non-current<br> assets		166,215		196,648
Inventories	10	227		391
Trade receivables	11	1,321		1,302
Other current assets	12	1,798		8,516
Cash and cash equivalents	13	19,237		44,761
Current assets		22,583		54,970
Total assets		188,798		251,618
EQUITY AND LIABILITIES
Share capital	14	56,163		44,133
Reserves	15	220,961		210,147
Treasury shares		(12,108	)	(2,999	)
Accumulated losses		(119,599	)	(69,751	)
Equity		145,417		181,530
Non-current<br> lease liabilities	9	2,232		2,192
Non-current<br> borrowings	16	16		396
Defined benefit obligations	17	1,772		2,793
Provisions	18	7,909		19,470
Deferred tax liabilities	29	20,736		25,504
Non-current<br> liabilities		32,665		50,355
Current lease liabilities	9	444		331
Current borrowings	16	372		95
Trade payables		1,625		1,700
Financial liabilities due to related parties	19	1,280		1,250
Provisions	18	3,094		12,083
Other current payables and liabilities	20	3,901		4,274
Current liabilities		10,716		19,733
Total equity and liabilities		188,798		251,618

The accompanying notes form an integral part of these consolidated financial statements.

F-3

Table of Contents

Consolidated statements of comprehensive loss

in CHF thousands	Notes
Revenue	6	6,081		3,321
Other gains	21	9,921		1,171
Total income		16,002		4,492
Raw materials and consumables expenses	22	(1,250	)	(750	)
External selling and distribution expenses	22	(3,307	)	(365	)
External research and development expenses	23	(12,393	)	(19,024	)
Personnel expenses	24	(12,998	)	(9,121	)
Other administrative expenses	25	(7,747	)	(6,750	)
Other losses	26	(63	)	(752	)
EBITDA		(21,756	)	(32,270	)
Impairment losses on intangible assets	8	(26,424	)	—
Amortization and depreciation expense	27	(3,860	)	(2,036	)
Operating result		(52,040	)	(34,306	)
Financial income	28	18		97
Financial expenses	28	(2,294	)	(1,316	)
Net loss before taxes		(54,316	)	(35,525	)
Income taxes	29	3,526		820
Net loss for the period		(50,790	)	(34,705	)
OTHER COMPREHENSIVE INCOME
Remeasurement of defined benefit obligation	17	942		152
Items that will not be reclassified to profit or loss		942		152
Currency translation differences	15.3	461		255
Items that may be reclassified to profit or loss		461		255
Other comprehensive income for the period, net of tax		1,403		407
Total comprehensive result for the period		(49,387	)	(34,298	)
EARNINGS PER SHARE
Basic and diluted loss per share (in CHF)	31	(0.012	)	(0.010	)

The accompanying notes form an integral part of these consolidated financial statements.

F-4

Table of Contents

Consolidated cash flow statements

in CHF thousands	Notes
Net loss for the period
Adjustments for:		(50,790	)	(34,705	)
Income tax (income)/expense	29.1	(3,526	)	(820	)
Depreciation and amortization expense	27	3,860		2,036
Impairment of intangible assets	8	26,424		—
Impairment of receivables	11	24		470
Reversal of impairment loss on receivables	21	(453	)	—
Loss from disposal of other financial assets	14	—		54
Gain from loan forgiveness	21	—		(890	)
Gain from fair value adjustments to contingent payments	18	(8,892	)	—
Finance expenses	28	1,920		1,316
Finance income	28	(18	)	(97	)
Interest expenses paid on borrowings and lease liabilities		(374	)	(260	)
Loss on disposal of property and equipment		—		3
Change in defined benefit obligations	17	(79	)	1,266
Share-based payment expense	30	2,186		1,143
Changes in working capital:
Decrease/(Increase) in inventories		164		(111	)
Decrease/(Increase) in trade receivables		(19	)	(208	)
Decrease/(Increase) in other assets		6,481		(2,585	)
(Decrease)/increase in trade payables		(75	)	(823	)
(Decrease)/increase in provisions		(586	)	100
(Decrease)/increase in other payables and liabilities		(373	)	(1,607	)
Cash flow used in operating activities		(24,126	)	(35,718	)
Payments for property, plant and equipment		(33	)	—
Payments for intangible assets	8	(488	)	(13,708	)
Payments for other financial assets		(38	)	(23	)
Proceeds from sale of <br>right-of-use<br> assets		—		11
Net cash outflow on acquisition of subsidiaries	7	—		(16,681	)
Milestone payments related to acquisition of subsidiaries	18	(7,920	)	—
Proceeds from other financial assets		462		132
Interest received		18		7
Cash flow used in investing activities		(7,999	)	(30,262	)
Proceeds from capital increase	14	7,111		76,088
Equity transaction costs	15	(223	)	(2,848	)
Repayment of lease liabilities		(390	)	(185	)
Repayment of borrowings		(81	)	(5,366	)
Cash flow from financing activities		6,417		67,689
Net increase in cash and cash equivalents		(25,708	)	1,709
Cash and cash equivalents at beginning of period		44,761		43,154
Exchange difference on cash and cash equivalents		184		(102	)
Cash and cash equivalents at end of period		19,237		44,761

The accompanying notes form an integral part of these consolidated financial statements.

F-5

Table of Contents

Consolidated statements of changes in equity

in CHF thousands
Balance at January 1, 2021		32,467	—		69,774		(35,198	)	67,043
Result for the period		—	—		—		(34,705	)	(34,705	)
Other comprehensive income for the period		—	—		255		152		407
Total comprehensive result for the period		—	—		255		(34,553	)	(34,298	)
Issuance of treasury shares	14	11,535	(11,535	)	—		—		—
Direct Share Placement program	14	—	3,982		46,905		—		50,887
Private placements	14	—	1,129		23,871		—		25,000
Acquisition payments	7	—	3,425		70,977		—		74,402
Exercise of options	14	131	—		70		—		201
Share-based compensation cost	30	—	—		1,143		—		1,143
Transaction cost in relation to capital increases	15	—	—		(2,848	)	—		(2,848	)
Balance at December 31, 2021		44,133	(2,999	)	210,147		(69,751	)	181,530
Balance at January 1, 2022		44,133	(2,999	)	210,147		(69,751	)	181,530
Result for the period		—	—		—		(50,790	)	(50,790	)
Other comprehensive income for the period		—	—		461		942		1,403
Total comprehensive result for the period		—	—		461		(49,848	)	(49,387	)
Issuance of treasury shares	14	12,000	(12,000	)	—		—		—
Direct Share Placement program	14	—	1,389		5,662		—		7,051
Acquisition milestone share payments	18	—	1,502		2,698		—		4,200
Exercise of options	14	30	—		30		—		60
Share-based compensation cost	30	—	—		2,186		—		2,186
Transaction cost in relation to capital increases	15	—	—		(223	)	—		(223	)
Balance at December 31, 2022		56,163	(12,108	)	220,961		(119,599	)	145,417

The accompanying notes form an integral part of these consolidated financial statements.

F-6

Table of Contents

Notes to the consolidated financial statements

General information

RELIEF THERAPEUTICS Holding SA (“Relief”, the “Company” or the “Group”) is a Swiss stock corporation domiciled at 15 Avenue de Sécheron, 1202 Geneva, Switzerland. The Company’s shares are listed on the SIX Swiss Exchange (ticker: RLF) and quoted in the U.S. on OTCQB (tickers: RLFTF, RLFTY).

The Group focuses on identification, development and commercialization of novel, patent protected products intended for the treatment of metabolic, dermatological and pulmonary rare diseases with a portfolio of clinical and marketed products that serve unmet patient needs. On June 28, 2021, the Group acquired APR Applied Pharma Research SA (“APR”), a privately held Swiss pharmaceutical company specialized in formulating, developing, and commercializing known molecules designed with proprietary drug delivery systems for niche and specialty diseases. The acquisition transformed Relief into a fully integrated commercial-stage biopharmaceutical group. The acquisition further diversified Relief’s pipeline and portfolio with both commercial products and clinical-stage programs, provided a commercial infrastructure in Europe and strengthened internal research and development (“R&D”) capabilities. On July 27, 2021, the Group acquired AdVita Lifescience GmbH (“AdVita”). The acquisition strengthened the Group’s expertise and intellectual property rights around the inhaled formulation and delivery of aviptadil.

These consolidated financial statements were approved for publication by the Board of Directors on April 13, 2023.

Application of new and revised International Financial Reporting Standards (IFRS)

2.1 New and revised IFRS Standards and Interpretations

In the current year, the Group has applied the following new or amended Standards that became effective from January 1, 2022. The revised Standards did not have a material effect on these financial statements.

•	Narrow-scope amendments to IFRS 3, IAS 16, IAS 8, IAS 37 and IFRS 16; and
•	Annual improvements of IFRS 1, IFRS 9 and IAS 41.
---	---

2.2 IFRS Standards and Interpretations issued and not yet adopted

Certain new Standards and Interpretations have been issued that are not mandatory for the current reporting period and have not been early adopted by the Group. These standards are not expected to have a material impact on the Group’s overall results and financial position.

•	Amendments to IAS 1 ‘Presentation of financial statements’ on classification of liabilities; and
•	Narrow-scope amendments to IAS 8 and IAS 12.
---	---

Summary of significant accounting policies

3.1 Basis of preparation

The consolidated financial statements of the Group have been prepared in accordance with the International Financial Reporting Standards (IFRS) as issued by the International Accounting Standards Board (IASB) and comply with Swiss law. They have been prepared under the historical cost convention, as modified by the revaluation of financial instruments at fair value, and are presented in Swiss francs (CHF). All values are rounded to the nearest thousand (TCHF), except when otherwise indicated.

3.2 Basis of consolidation

The consolidated financial statements comprise the financial statements of the parent company RELIEF THERAPEUTICS Holding SA and its subsidiaries as of December 31, 2022 and 2021. Control is achieved when the Group is exposed, or has rights, to variable returns from its involvement with the investee and has the ability to affect those returns through its power over the investee.

F-7

Table of Contents

Specifically, the Group controls an investee if and only if the Group has:

•	power over the investee (i.e., existing rights that give it the current ability to direct the relevant activities of the investee);
•	exposure, or rights, to variable returns from its involvement with the investee; and
---	---
•	the ability to use its power over the investee to affect its returns.
---	---

When the Group has less than a majority of the voting or similar rights of an investee, the Group considers all relevant facts and circumstances in assessing whether it has power over an investee, including:

•	any contractual arrangement with the other vote holders of the investee;
•	rights arising from other contractual arrangements; and
---	---
•	the Group’s voting rights and potential voting rights.
---	---

The Group reassesses whether or not it controls an investee if facts and circumstances indicate that there are changes to one or more of the three elements of control. Consolidation of a subsidiary begins when the Group obtains control over the subsidiary and ceases when the Group loses control of the subsidiary. Assets, liabilities, income and expenses of a subsidiary acquired or disposed of during the year are included in the statement of comprehensive income from the date the Group gains control until the date the Group ceases to control the subsidiary.

Profit or loss and each component of other comprehensive income are attributed to the equity holders of the parent of the Group and to the non-controlling interests, even if this results in the non-controlling interests having a deficit balance. When necessary, adjustments are made to the financial statements of subsidiaries to bring their accounting policies into line with the Group’s accounting policies. Inter-company transactions, balances and unrealized gains/losses on transactions between Group companies are eliminated. The accounting policies of subsidiaries are consistent with the policies adopted by the Group.

3.3 Current versus non-current classification

The Group presents assets and liabilities in its statement of financial position based on current/non-current classification. An asset is classified as current when it is:

•	expected to be realized or intended to be sold or consumed in a normal operating cycle, which is twelve months;
•	held primarily for the purpose of trading;
---	---
•	expected to be realized within twelve months after the reporting period; or
---	---
•	cash or cash equivalents unless restricted from being exchanged or used to settle a liability for at least twelve months after the reporting period.
---	---

All other assets are classified as non-current.

A liability is current when:

•	it is expected to be settled in a normal operating cycle, which is twelve months;
•	it is held primarily for the purpose of trading;
---	---
•	it is due to be settled within twelve months after the reporting period; or
---	---
•	there is no unconditional right to defer the settlement of the liability within twelve months after the reporting period. The Group classifies all other liabilities as <br>non-current.
---	---

Deferred tax assets and liabilities are classified as non-current assets and liabilities.

3.4 Business combinations and goodwill

Business combinations are accounted for using the acquisition method. The cost of an acquisition is measured as the aggregate of the consideration transferred measured at acquisition date fair value and the amount of any non-controlling interests in the acquiree. For each business combination, the Group elects whether to measure the non-controlling interests in the acquiree at fair value or at the proportionate share of the acquiree’s identifiable net assets. Acquisition-related costs are expensed as incurred and included in ‘other administrative expenses’.

When the Group acquires a business, it assesses the financial assets and liabilities assumed for appropriate classification and designation in accordance with the contractual terms, economic circumstances and pertinent conditions as of the acquisition date. This includes the separation of embedded derivatives in host contracts by the acquiree.

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Table of Contents

If the business combination is achieved in stages, any previously held equity interest is re-measured at its acquisition date fair value and any resulting gain or loss is recognized in profit or loss. It is then considered in the determination of goodwill.

Any contingent consideration to be transferred by the acquirer will be recognized at fair value at the acquisition date. Contingent consideration classified as an asset or liability that is a financial instrument and within the scope of IFRS 9, is measured at fair value with changes in fair value recognized in profit or loss. If the contingent consideration is not within the scope of IFRS 9, it is measured in accordance with the applicable IFRS. Contingent consideration that is classified as equity, if any, is not re-measured and subsequent settlement is accounted for within equity.

Goodwill is initially measured at cost, being the excess of the aggregate of the consideration transferred and the amount recognized for non-controlling interests and any previous interest held, over the net identifiable assets acquired and liabilities assumed. If the fair value of the net assets acquired is in excess of the aggregate consideration transferred, the Group re-assesses whether it has correctly identified all of the assets acquired and all of the liabilities assumed and reviews the procedures used to measure the amounts to be recognized at the acquisition date. If the re-assessment still results in an excess of the fair value of net assets acquired over the aggregate consideration transferred, then the gain is recognized in profit or loss.

After initial recognition, goodwill is measured at cost less any accumulated impairment losses. For the purpose of impairment testing, goodwill acquired in a business combination is, from the acquisition date, allocated to the Group’s cash-generating units that are expected to benefit from the combination, irrespective of whether other assets or liabilities of the acquiree are assigned to those units.

Where goodwill has been allocated to a cash-generating unit and part of the operation within that unit is disposed of, the goodwill associated with the disposed operation is included in the carrying amount of the operation when determining the gain or loss on disposal. Goodwill disposed in these circumstances is measured based on the relative values of the disposed operation and the portion of the cash-generating unit retained.

3.5 Revenue recognition

Relief may generate revenues from collaboration and license agreements under which Relief grants licenses to use, research, develop, manufacture and commercialize product candidates and products. Relief determined that those collaboration and license agreements qualify as contracts with its customers. If the grant of a license is bundled together with the rendering of services, it is assessed whether these agreements are comprised of more than one performance obligation. A performance obligation is only accounted for as the grant of a license if the grant of a license is the sole or the predominant promise of the performance obligation.

If the consideration in an agreement includes a variable amount, Relief estimates the amount of consideration to which Relief will be entitled in exchange for transferring the goods to the customer. At contract inception, the variable consideration is estimated based on the most likely amount of consideration expected from the transaction and constrained until it is highly probable that a significant revenue reversal in the amount of cumulative revenue recognized will not occur when the associated uncertainty with respect to the variable consideration is subsequently resolved. The estimated revenue is updated at each reporting date to reflect the current facts and circumstances.

If a contract with a customer contains more than one performance obligation, the transaction price is allocated to each performance obligation based on relative stand-alone selling prices.

For each separate performance obligation, it is evaluated whether control is transferred either at a point in time or over time. For performance obligations that are satisfied over time, revenue is recognized based on a measure of progress, which depicts the performance in transferring control to the customer. If under the terms of its licensing arrangements Relief provides the licensee with a research and development license, which represents a right to access Relief’s intellectual property as it exists throughout the license period, the promise to grant a license is accounted for as a performance obligation satisfied over time, as the licensee simultaneously receives and consumes the benefits of Relief’s performance.

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Earnings based on the collaboration partners’ gross profit, which is shared under the respective collaboration agreements, are recognized when the underlying sales occur, which is when the performance obligation has been satisfied. Relief uses certain information from its collaboration partners, some of which is based on preliminary data shared between the partners and might vary once final data is available.

Revenue arrangements that involve two or more partners who contribute to the provision of a specific good or service to a customer are assessed in terms of principal-agent considerations in order to determine the appropriate treatment for the transactions between Relief, the partner(s), and third parties. The classification of transactions under such arrangements is determined based on the nature and contractual terms of the arrangement along with the nature of the operations of the participants. Any consideration related to activities in which Relief is considered the principal, which includes being in control of the good or service before such good or service is transferred to the customer, are accounted for as gross revenue. Any consideration related to activities in which Relief is considered the agent, are accounted for as net revenue.

Revenue from the sale of products is recognized when Relief transfers control of the product to the customer. Control of the product normally transfers when the customer gains physical possession and Relief has not retained any significant risks of ownership or future obligations with respect to the product. A receivable is recognized, as the consideration is unconditional and only the passage of time is required before payment is due. The transaction price is quoted in the relevant price lists in force at the date of customer placing the respective order for such products.

Revenue from research and development services provided by the Company is recorded as earned based on the performance requirements of the underlying contracts. Where agreements include milestones that are determined to be substantive and at risk at the inception of the agreement, revenue is recognized upon confirmation by the counterparty that the milestone has been achieved.

3.6 Foreign currency translation

Functional and presentation currency

Items included in the financial statements of each of the Group’s entities are measured using the currency of the primary economic environment in which the entity operates (i.e., the functional currency). The consolidated financial statements are presented in CHF, which is the presentation currency of the Group.

Transactions and balances

In preparing the financial statements of each individual group entity, transactions in currencies other than the entity’s functional currency are recognized at the rates of exchange prevailing at the dates of the transactions. At the end of each reporting period, monetary items denominated in foreign currencies are re-translated at the rates prevailing at that date. Non-monetary items that are measured at historical cost in a foreign currency are not re-translated. Exchange differences on monetary items are recognized in profit or loss in the period in which they arise.

Group companies

Assets and liabilities of Group entities using a functional currency different from the presentation currency are translated into the presentation currency using year-end rates of exchange. Income and expenses and cash flows are translated at average exchange rates. All resulting translation differences are recognized directly in other comprehensive income. On the divestment of a foreign entity, the identified cumulative currency translation difference relating to that foreign entity is recognized in profit or loss as part of the gain or loss on divestment.

3.7 Intangible assets

Intangible assets acquired separately are measured on initial recognition at cost. The cost of intangible assets acquired in a business combination is their fair value at the date of acquisition. Following initial recognition, intangible assets are carried at cost less any accumulated amortization and impairment losses.

Internally generated intangibles, excluding capitalized development costs, are not capitalized and the related expenditure is reflected in profit or loss in the period in which the expenditure is incurred.

The useful lives of intangible assets are assessed as either finite or indefinite. Intangible assets with finite lives are amortized over the useful economic life and assessed for impairment whenever there is an indication that the intangible asset may be impaired. The amortization period and the amortization method for an intangible asset with a finite useful life are reviewed at least at the end of each reporting period. Changes in the expected useful life or the expected pattern of consumption of future economic benefits embodied in the asset are considered to modify the amortization period or method, as appropriate, and are treated as changes in accounting estimates.

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Amortization of capitalized in process research & development (“IPR&D”) starts once the asset is available for use, which is usually the point in time at which marketing approval is granted by the relevant authority. Before that date, capitalized IPR&D that is not available for use is tested at least annually for impairment, irrespective of whether any indication of impairment exists.

Intangible assets with indefinite useful lives are not amortized, but are tested for impairment annually, either individually or at the cash-generating unit level. The assessment of indefinite life is reviewed annually to determine whether the indefinite life continues to be supportable. If not, the change in useful life from indefinite to finite is made on a prospective basis.

Gains or losses arising from de-recognition of an intangible asset are measured as the difference between the net disposal proceeds and the carrying amount of the asset and are recognized in the statement of profit or loss when the asset is derecognized.

3.8 Leases

The Group assesses whether a contract is or contains a lease at inception of the contract. The Group recognizes a right-of-use asset and a corresponding lease liability with respect to all lease arrangements in which it is the lessee, except for short-term leases (defined as leases with a lease term of twelve months or less) and leases of low value assets. For these leases, the Company recognizes the lease payments as an operating expense on a straight-line basis over the term of the lease unless another systematic basis is more representative of the time pattern in which economic benefits from the leased assets are consumed.

The lease liability is initially measured at the present value of the lease payments that are not paid at the commencement date, discounted by using the rate implicit in the lease. If this rate cannot be readily determined, the Group uses its incremental borrowing rate for such liabilities.

Lease payments included in the measurement of the lease liability comprise:

•	fixed lease payments (including <br>in-substance<br> fixed payments), less any lease incentives;
•	variable lease payments that depend on an index or rate, initially measured using the index or rate at the commencement date;
---	---
•	the amount expected to be payable by the lessee under residual value guarantees;
---	---
•	the exercise price of purchase options, if the lessee is reasonably certain to exercise the options; and
---	---
•	payments of penalties for terminating the lease if the lease term reflects the exercise of an option to terminate.
---	---

The lease liability is subsequently measured by increasing the carrying amount to reflect interest on the lease liability (using the effective interest method) and by reducing the carrying amount to reflect the lease payments made.

The right-of-use assets comprise the initial measurement of the corresponding lease liability, lease payments made at or before the commencement day and any initial direct costs. They are subsequently measured at cost less accumulated depreciation and impairment losses.

Right-of use assets are depreciated over the shorter period of lease term and useful life of the underlying asset. If a lease transfers ownership of the underlying asset or the cost of the right-of-use asset reflects that the Group expects to exercise a purchase option, the related right-of-use asset is depreciated over the useful life of the underlying asset. The depreciation starts at the commencement date of the lease.

The Group has elected not to recognize right-of-use assets and lease liabilities for short-term leases that have a lease term of 12 months or less, or leases of low-value assets. The Group recognizes the lease payments associated with these leases as an expense in the consolidated statements of operations on a straight-line basis over the lease term.

3.9 Financial assets

Classification

The Group has only financial assets classified within the categories, “financial assets at fair value through profit or loss (FVTPL)” and “financial assets at amortized cost.” The classification at initial recognition depends on the financial asset’s contractual cash flow characteristics and the Group’s business model for managing them. The Group’s financial assets at amortized cost include other current assets and other receivables that are non-derivative financial assets with fixed or determinable payments that are not quoted in an active market. The Group’s financial assets at fair value through profit or loss include publicly traded securities, if any.

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Recognition and measurement

Financial assets at amortized cost are measured initially at their fair value and are subsequently measured at amortized cost using the effective interest rate method and are subject to impairment.

A financial asset is derecognized when:

•

the contractual rights to the cash flows from the asset have expired; or

•

the Group has transferred its rights to receive cash flows from the asset or has assumed an obligation to pay the received cash flows in full without material delay to a third party under a pass-through arrangement; and either (a) the Group has transferred substantially all the risks and rewards of the asset, or (b) the Group has neither transferred nor retained substantially all the risks and rewards of the asset but has transferred control of the asset.

---

Financial assets at FVTPL are measured at fair value at the end of each reporting period, with any fair value gains or losses recognized in profit or loss. Fair value is determined in the manner described in note 32.3.

Impairment of financial assets

The Group recognizes an allowance for expected credit losses (“ECL”) for all debt instruments not held at fair value through profit or loss. ECL are based on the difference between the contractual cash flows due in accordance with the contract and all the cash flows that the Group expects to receive, discounted at an approximation of the original effective interest rate. The expected cash flows will include cash flows from the sale of collateral held or other credit enhancements that are integral to the contractual terms.

ECLs are recognized in two stages. For credit exposures for which there has not been a significant increase in credit risk since initial recognition, ECLs are provided for credit losses that result from default events that are possible within the next twelve months (a twelve-month ECL). For those credit exposures for which there has been a significant increase in credit risk since initial recognition, a loss allowance is required for credit losses expected over the remaining life of the exposure, irrespective of the timing of the default (a lifetime ECL).

The Group considers a financial asset in default when contractual payments are 90 days past due. However, in certain cases, the Group may also consider a financial asset to be in default when internal or external information indicates that the Group is unlikely to receive the outstanding contractual amounts in full before taking into account any credit enhancements held by the Group. A financial asset is written off when there is no reasonable expectation of recovering the contractual cash flows.

3.10 Inventories

Raw materials and merchandise purchased are recognized at cost; semi-finished and finished goods at their production cost. Discounts are recognized as a reduction in the purchase price. Manufacturing costs include the associated direct production costs and production overheads, where applicable. If the acquisition or manufacturing costs are higher than the net market value, an impairment loss is recorded on the income statement in the current period to write the inventories down to the net market value (lower of cost or market principle). Net market value is equivalent to the current market price less the usual sales deductions, marketing costs and administrative costs yet to be incurred. Inventories that cannot be sold are written off in full. The costs of inventories are determined by using the FIFO method.

Inventory related to drug products that have not yet obtained regulatory approval are immediately written down to zero. The write-down is charged to research and development expenses. If regulatory approval is subsequently obtained, the recorded expenses are not reversed.

3.11 Cash and cash equivalents

Cash and cash equivalents include cash in hand, deposits held at call with banks and other short-term highly liquid investments with original maturities of three months or less. Bank overdrafts are shown within financial debts in current liabilities on the balance sheet. This definition is also used for the purposes of the cash flow statement.

3.12 Financial liabilities

The Group’s financial liabilities include trade and other payables as well as borrowings.

Financial liabilities are recognized initially at fair value and are subsequently measured at amortized cost using the effective interest rate method, with interest expense recognized on an effective yield basis.

The Group derecognizes financial liabilities when, and only when, the Group’s obligations are discharged, cancelled or expired.

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3.13 Current and deferred income tax

The tax expense for the period comprises current and deferred tax. Tax is recognized in the income statement, except to the extent that it relates to items recognized in other comprehensive income or directly in equity. In this case, the tax is also recognized in other comprehensive income or directly in equity, respectively.

Deferred income tax is recognized, using the liability method, on temporary differences arising between the tax bases of assets and liabilities and their carrying amounts in the consolidated financial statements. However, the deferred income tax is not accounted for if it arises from initial recognition of an asset or liability in a transaction other than a business combination that, at the time of the transaction, affects neither accounting nor taxable profit or loss. Deferred income tax is determined using tax rates (and laws) that have been enacted or substantively enacted by the balance sheet date and are expected to apply when the related deferred income tax asset is realized or the deferred income tax liability is settled.

Deferred income tax assets are recognized to the extent that it is probable that future taxable profit will be available against which the temporary differences can be utilized.

Deferred income tax is provided on temporary differences arising on investments in subsidiaries and associates, except for deferred income tax liability where the timing of the reversal of the temporary difference is controlled by the Group and it is probable that the temporary difference will not reverse in the foreseeable future.

3.14 Fair values

Fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value measurement is based on the presumption that the transaction to sell the asset or transfer the liability takes place either:

•	in the principal market for the asset or liability, or
•	in the absence of a principal market, in the most advantageous market for the asset or liability.
---	---

The Group uses valuation techniques that are appropriate in the circumstances and for which sufficient data are available to measure fair value, maximizing the use of relevant observable inputs and minimizing the use of unobservable inputs.

The fair values of financial assets and liabilities at the balance sheet date are not materially different from their reported carrying values unless specifically mentioned in the notes to the consolidated financial statements.

3.15 Research and development costs

Research and development costs consist primarily of remuneration and other expenses related to research and development personnel, costs associated with preclinical testing and clinical trials of product candidates, expenses for research and development services under collaboration agreements and outsourced research and development expenses. Furthermore, the Group may acquire in-process research and development assets, either through business combinations or through purchases of specific assets. In-process research and development assets acquired either through business combinations or separate purchases are capitalized as intangible assets and reviewed for impairment annually. Once available for use, such intangible assets are amortized on a straight-line basis over the period of expected benefits.

Internal development costs are capitalized as intangible assets only when there is an identifiable asset that can be completed and that will generate probable future economic benefits and when the cost of such an asset can be measured reliably.

3.16 Employee benefits

General

Wages, salaries, social security contributions, paid annual leave and sick leave, bonuses, and non-monetary benefits are accrued in the year in which the associated services are rendered by employees of the Group.

Pension obligations

The cost of providing benefits under the defined benefit plan is determined using the projected unit credit method.

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Re-measurements, including actuarial gains and losses, the effect of the asset ceiling, and the return on plan assets (excluding net interest), are recognized immediately in the statement of financial position with a corresponding debit or credit to retained earnings through other comprehensive income (“OCI”) in the period in which they occur. Re-measurements are not reclassified to profit or loss in subsequent periods.

Past service costs are recognized in profit or loss on the earlier of:

•	the date of the plan amendment or curtailment, or
•	the date that the Group recognizes restructuring-related costs.
---	---

Net interest is calculated by applying the discount rate to the net defined benefit liability or asset. The Group recognizes the following changes in the net defined benefit obligation under ‘personnel expense’ in the statement of comprehensive income:

•	service costs comprising current service costs, past-service costs, gains and losses on curtailments and <br>non-routine<br> settlements; and
•	net interest expense or income.
---	---

3.17 Share-based payments

The cost of equity-settled transactions is determined by the fair value at the date when the grant is made using an appropriate valuation model.

That cost is recognized, together with a corresponding increase in other capital reserves in equity, over the period in which the performance and/or when service conditions are fulfilled as employee benefit expenses. The cumulative expense recognized for equity-settled transactions at each reporting date until the vesting date reflects the extent to which the vesting period has expired and the Group’s best estimate of the number of equity instruments that will ultimately vest. The statement of profit or loss expense or credit for a period represents the movement in cumulative expense recognized at the beginning and end of that period and is recognized in employee benefits expense.

No expense is recognized for awards that do not ultimately vest, except for equity-settled transactions for which vesting is conditional upon a market or non-vesting condition. These are treated as vested, irrespective of whether or not the market or non-vesting condition is satisfied, provided that all other performance and/or service conditions are satisfied.

When the terms of an equity-settled award are modified, the minimum expense recognized is the expense as if the terms had not been modified if the original terms of the award have been met. An additional expense is recognized for any modification that increases the total fair value of the share-based payment transaction or is otherwise beneficial to the employee as measured at the date of modification.

The dilutive effect of outstanding options is reflected as additional share dilution in the computation of diluted earnings per share.

Summary of critical accounting judgments and key sources of estimation uncertainty

The preparation of the consolidated financial statements in conformity with IFRS requires management to make estimates and assumptions that affect the application of policies and reported amounts of assets, liabilities, income, expenses and related disclosures. The estimates and underlying assumptions are based on historical experience and various other factors that are believed to be reasonable under the circumstances, the results of which form the basis for making the judgments about carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates. The estimates and assumptions that have a significant risk of causing a material adjustment to the carrying amounts of assets and liabilities within the next financial year are described below.

4.1 Critical judgments in applying accounting policies

Collaboration and license agreement with Acer

In March 2021, Relief and Acer Therapeutics Inc. (“Acer”) entered into a collaboration and license agreement for worldwide development and commercialization of ACER-001.

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The management assessed the payment of USD 15 million (CHF 13.7 million) made in 2021, comprised of USD 14 million as initial payment due upon signing of the agreement plus USD 1 million paid in exchange of an exclusivity period to negotiate the agreement, is in substance the acquisition cost of the development project. Hence, the license and the price paid for its acquisition met the requirements of an intangible asset and were capitalized as an intangible asset.

The USD 20 million upfront development payments paid by Relief to Acer in 2021 and 2022 for further development activities did not meet the capitalization criteria for intangible assets. Hence, they were recognized as a prepayment in the balance sheet upon payment and released to the income statement over the period of the development activity as incurred. Development expenses occurred under the collaboration agreement, which were incurred by Acer and subsequently reported to Relief, were recorded as external research and development expenses. As of December 31, 2022, the entirety of the upfront development payments has been consumed and expensed.

With regards to the possible future milestone payments, the Group, in accordance with industry practice, is following the cost accumulation approach. Hence, the milestone payments are not considered on initial recognition of the asset but will be added to the cost of the asset if and when incurred.

Revenue recognition

Revenue is primarily from fees related to license fees, royalties and product sales. Given the complexity of certain agreements, judgment is required to identify distinct performance obligations, allocate the transaction price to these performance obligations and determine when the performance obligations are met.

Going concern

These consolidated financial statements have been prepared assuming the Group will continue as a going concern which contemplates the continuity of operations, realization of assets and the satisfaction of liabilities in the ordinary course of business.

Since its inception, the Group has primarily relied on external financing to fund its cash needs and has experienced recurring losses since its inception. The Group expects to continue to generate operating losses for the foreseeable future. As of December 31, 2022, the Group had CHF 19.2 million cash on hand, which, based on liquidity forecasts and development plans, is expected to cover cash needs only until the third quarter of 2023. These factors indicate that there is a material uncertainty that raises substantial doubt about the Group’s ability to continue as a going concern for one year from the date of issuance of these consolidated financial statements.

The Group’s viability depends on its ability to raise additional capital until it generates positive cash flows to support its operations. The Group may never achieve sustainable profitability and is exposed to all the risks inherent in establishing a business. Management continues to explore options to obtain additional funding, including public or private financing, or license and collaboration agreements. However, there can be no assurance that capital will be available in sufficient amounts or on terms acceptable to the Group. If Relief is unable to obtain the required funding, it will be forced to delay, reduce or eliminate some or all of its research and development programs, product portfolio expansion or commercialization efforts, which could adversely affect its business prospects or result in the Group’s inability to continue operations.

4.2 Key sources of estimation uncertainty

2021 business combinations

The allocation of the purchase price for business acquisitions to the identifiable assets acquired and liabilities assumed based on their respective fair values requires the use of accounting estimates and judgment. Acquired intangible assets were valued using valuation models under which fair values were derived from future net cash flows, which were discounted to the acquisition date using an appropriate discount factor. Relief estimated fair values of assets acquired, liabilities assumed, and contingent considerations based on various assumptions all subject to significant judgment.

To determine the value in use, the estimated future cash flows are discounted on a pre-tax basis and require the use of various assumptions (such as growth rate, discount rate and budgeted margins) all subject to significant judgment. The weighted average cost of capital is used to determine the applicable pre-tax discount rate. Further details regarding the valuation methods used and the key assumptions and judgments made in relation to intangible assets and goodwill acquired in the business combinations are provided in note 8.

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Assessment of contingent liabilities

IFRS 3 requires the recognition of contingent considerations arising from business combinations at fair value at the acquisition date. The fair value of the contingent consideration is estimated based on management’s assessment of the likelihood of the contingency occurring and the amount of payment that would be required if the contingency were to occur.

Contingent considerations are subsequently remeasured to fair value at the end of each reporting period. The estimation of the fair value requires the use of estimates and assumptions that are subject to significant judgment, as further detailed in note 18.

Valuation and impairment of intangible assets

Determining whether intangible assets and goodwill are impaired requires management to estimate the recoverable value of the cash-generating unit to which the intangible assets are attributable. If the recoverable value of the cash-generating unit is lower than the carrying amount of the cash-generating unit to which the intangible assets have been allocated, an impairment allowance is recorded. Changes to the assumptions may result in additional impairment losses or impairment reversals in subsequent periods.

Share-based compensation

The fair values of the options at the grant date are assessed using the Black-Scholes valuation model and are spread over the applicable vesting period of each option. The amount recognized as an expense in the income statement represents the value of the services received during the reporting period in exchange for the options granted.

The fair value of the options granted is estimated at the grant date based on the Black-Scholes valuation model. The main inputs subject to estimation used in the model are the expected life of each option and the volatility of the underlying share.

Deferred income tax assets

The recoverability of deferred income tax assets is assessed based on management’s judgment, taking into consideration the Group’s forecasted future taxable profits that are subject to uncertainty. Deferred income tax assets are recognized only to the extent that it is probable that taxable profits will be available against which the deductible temporary differences and carried forward losses can be utilized.

The carrying amount of deferred tax assets is reviewed at each reporting date and reduced to the extent that it is no longer probable that sufficient taxable profits will be available to allow all or part of the asset to be recovered. The assessment of the recoverability of deferred tax assets requires significant judgment and involves the use of assumptions and estimates regarding future taxable profits. The Group considers all available positive and negative evidence when assessing the recoverability of deferred tax assets, including historical profitability, future plans, and reasonable and supportable forecasts of future taxable profits.

Defined benefit obligation

A retirement benefit obligation for personnel is recognized based on various financial and actuarial assumptions. The key assumptions used to assess these obligations are the discount rate, future salary increases, future pension increases, and the probability of the employee reaching retirement. An actuarial expert performed the calculations, and the principal assumptions used are summarized in note 17.

Group companies

The following table lists subsidiaries controlled by Relief at the end of the reporting period.

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Name	Country	Location
Relief Therapeutics International SA	Switzerland	Geneva	100	%	100	%
Relief Therapeutics US, Inc.	United States	Connecticut	100	%	100	%
Relief Therapeutics, Inc.	United States	Delaware	100	%	100	%
APR Applied Pharma Research SA	Switzerland	Balerna	100	%	100	%
APR Applied Pharma Research Holding SA	Switzerland	Balerna	100	%	100	%
APR Applied Pharma Research - Italy s.r.l.	Italy	Rome	100	%	100	%
APR Applied Pharma Research Deutschland GmbH	Germany	Offenbach am Main	100	%	100	%
AdVita Lifescience GmbH	Germany	Freiburg im Breisgau	100	%	100	%
AdVita Lifescience AG	Switzerland	Basel	100	%	100	%
AdVita Lifescience, Inc.	United States	New York	100	%	100	%

The equity interest percentage shown in the table also represents the share in voting rights in those entities as of December 31, 2022 and 2021.

Segment information

6.1 Description of segment

The Group operates in one segment, namely research, development and commercialization of biopharmaceutical products. The Board of Directors and the Executive Committee, being together the chief operating dec isio n maker, allocate resources and assess the performance of the Group at a consolidated level. The accounting policies used for segment reporting are the same as those used for the preparation of these financial statements.

6.2 Information on revenue

The Group generates revenue primarily from out-licensing transactions and sales of products. Revenue is mainly derived from the portfolio of marketed products acquired in the business combination with APR at the end of June 2021.

In 2022, the three largest customers of the Group represented 21.5%, 16.2% and 10.3%, respectively, of the total net sales (2021:19.1%, 13.6% and 13.3%).

Revenue is reported by geographical location based on the location of the customer or licensee and, for R&D services, based on the location where the services were performed. The disaggregation of the Group’s revenue is presented in the following table:

TCHF	2022
Revenue streams
Royalties		2,482	1,268
Product sales		2,525	1,305
License fees		380	289
Revenue from research & development services		694	459
Total revenue		6,081	3,321
Geographical area
Switzerland		800	527
Europe (excluding Switzerland)		2,412	1,115
North America		1,699	835
Rest of the world		1,170	844
Total revenue		6,081	3,321
Timing of revenue recognition
Point in time		6,081	3,321
Over time		—	—
Total revenue		6,081	3,321
*	Revenue recognized since the acquisition of APR, i.e., from July 1, 2021, to December 31, 2021. The Group did not recognize any revenue from January 1 to June 30, 2021.
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6.3 Geographical location of non-current assets

TCHF	December 31, 2022
Switzerland		165,711	194,935
Rest of the world		122	183
Total <br>non-current<br> assets *		165,833	195,118
*	Without financial assets and deferred tax assets.
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Business combinations in 2021

7.1 Acquisition of APR

On June 28, 2021, the Group acquired all outstanding shares and voting rights of APR Applied Pharma Research SA (Ticino, Switzerland). The APR subgroup was constituted by its parent company APR Applied Pharma Research SA and three fully owned subsidiaries: APR Applied Pharma Research Holding SA (Ticino, Switzerland), APR Applied Pharma Research Deutschland GmbH (Offenbach am Main, Germany), and APR Applied Pharma Research - Italy S.r.l. (Rome, Italy).

The main corporate purpose of APR was the research and development of new technologies and methods in the chemical, pharmaceutical and food sectors, the registration of patents, as well as the registration of dietetic products, cosmetics and medical-surgical aids; it also manufactured and traded medical products on an international scale and acquired, held, used or sold licenses, patents and trademarks.

The acquisition of APR provided Relief with a platform for future growth, including established commercial infrastructure that would facilitate future therapeutic product launches in key European markets and in the U.S., as well as commercial revenues and qualified human resources. Under the terms of the agreement, APR’s former shareholders received from Relief a cash payment of CHF 21.5 million and CHF 42.9 million in Relief ordinary shares.

Consideration transferred
	TCHF
Cash		21,500
Non-cash<br> (Relief shares)		42,912
Contingent consideration		20,157
Total consideration transferred		84,569

Under IFRS 3, the cost of the acquisition was based on the market value of Relief’s listed shares at the acquisition date. Therefore, the fair value of the consideration transferred was calculated as follows: 206,786,784 shares at a fair value of CHF 0.20752 per share resulting to TCHF 42,912. The fair value of the shares based on the share price at the date of the transaction differed from the contractual value of CHF 45 million.

The acquisition agreement included contingent considerations to the previous owners in the aggregate maximum amount of up to CHF 35 million, at the time of the acquisition, upon achievement of pre-agreed milestones. The fair value of the contingent consideration, based on the estimated probability of occurrence and the time factor, is provisioned and adjusted at the end of each reporting period (note 18).

Acquisition-related costs of TCHF 775 were excluded from the consideration transferred and recognized in ‘other administrative expense’ in the 2021 statement of comprehensive loss and were included in cash flows used in operating activities in the 2021 consolidated statement of cash flows.

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Assets acquired and liabilities recognized at the date of acquisition

The fair values of the assets and liabilities of APR as of the date of acquisition were as follows:


Non-current<br> assets
Right-of-use<br> assets	2,599
Property and equipment	34
Intangible assets	90,236
Deferred tax assets	1,239
Other <br>non-current<br> assets	55
Current assets
Inventories	192
Trade receivables	1,107
Other current assets and other receivables	851
Cash and cash equivalents	5,710
Non-current<br> liabilities
Non-current<br> lease liabilities	(2,248	)
Defined benefit obligation	(1,707	)
Deferred tax liabilities	(14,402	)
Current liabilities
Current lease liabilities	(371	)
Current borrowings	(5,170	)
Trade payables	(952	)
Other current liabilities	(1,262	)
Net assets acquired	75,911

Goodwill arising from the acquisition


Consideration transferred	84,569
Fair value of identifiable net assets	(75,911	)
Goodwill	8,658

The purchase price allocation included the recognition of intangible assets of TCHF 90,236 and a related deferred tax liability of TCHF 14,402. As no other individual identifiable assets meeting the recognition criteria were identified, the residual amount paid of TCHF 8,658 was allocated to goodwill. This goodwill is not expected to be deductible for income tax purposes.

Net cash outflow from the acquisition


Cash and cash equivalent balance acquired	5,710
Consideration paid in cash and cash equivalents	(21,500	)
Net cash outflow	(15,790	)

7.2 Acquisition of AdVita

On July 27, 2021, the Company closed the definitive agreement to acquire all outstanding shares of AdVita Lifescience GmbH (“AdVita”). Under the terms of the agreement, AdVita’s former shareholders received from Relief 135,741,063 Relief common listed shares.

Consideration transferred

	TCHF
Cash		—
Non-cash<br> (Relief shares)		31,490
Contingent consideration		10,465
Total consideration transferred		41,955

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Under IFRS 3, the cost of the acquisition was based on the market value of Relief’s listed shares at the acquisition date. Therefore, the fair value of the consideration transferred was calculated as follows: 135,741,063 shares at a fair value of CHF 0.232 (share price on transaction date) resulting to TCHF 31,490.

The acquisition agreement with AdVita included additional contingent considerations to the previous owners in the aggregate maximum amount of up to EUR 20 million (CHF 20.7 million), at the time of the acquisition, in cash upon achievement of pre-agreed milestones. The fair value of the contingent consideration, based on the estimated probability of occurrence and the time factor is provisioned and adjusted at the end of each reporting period (note 18).

Acquisition-related costs amounting to TCHF 325 were excluded from the consideration transferred and recognized in ‘other administrative expense’ in the 2021 statement of comprehensive loss and were included in cash flows used in operating activities in the 2021 consolidated statement of cash flows.

Assets acquired and liabilities recognized at the date of acquisition

The fair values of the assets and liabilities of AdVita as at the date of acquisition were as follows:


Non-current<br> assets
Tangible assets	14
Right-of-use<br> assets	98
Intangible assets	50,716
Current assets
Trade receivables	64
Inventory	88
Other current assets	717
Cash and cash equivalents	1,302
Non-current<br> liabilities
Non-current<br> lease liabilities	(76	)
Other <br>non-current<br> borrowings	(2,900	)
Deferred tax liabilities	(7,086	)
Current liabilities
Current lease liabilities	(22	)
Other current borrowings	—
Trade payables	(63	)
Provisions	(649	)
Other current liabilities	(248	)
Net assets acquired	41,955

The purchase price allocation included the recognition of intangible assets of TCHF 50,716 and a related deferred tax liability of TCHF 7,086. The activity, expertise and then-pending intellectual property rights of AdVita were centered exclusively on the medical compound aviptadil. The Group has identified one intangible asset constituted by an in-process research and development program, which was recorded with the existing aviptadil asset of Relief (note 8). The acquisition did not result in the recognition of goodwill.

Net cash outflow from the acquisition


Cash and cash equivalent balance acquired	1,302
./. Loan due to Relief by the acquired subsidiary	(2,193	)
./. Consideration paid in cash and cash equivalents	—
Net cash outflow	(891	)

7.3 Impact of the acquisitions on the 2021 results of the Group

From the dates of acquisition through December 31, 2021, APR and AdVita contributed, respectively, TCHF 3,207 and TCHF 113 revenue, and TCHF 2,169 and TCHF 1,200 operating loss, to the respective results of the Group, excluding amortization of intangible assets and related income tax effect.

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If APR and AdVita were consolidated since January 1, 2021, the consolidated loss and the consolidated revenue of the Group for the full year 2021 would have been TCHF 37,117 and TCHF 7,007, respectively.

Intangible assets

TCHF
Historical cost
January 1, 2021	—		—	30,800		—		30,800
Addition	—		13,729	—		—		13,729
Business combination	39,357		—	101,595		8,658		149,610
December 31, 2021	39,357		13,729	132,395		8,658		194,139
Addition	174		—	314		—		488
December 31, 2022	39,531		13,729	132,709		8,658		194,627
Accumulated amortization and impairment
January 1, 2021	—		—	—		—		—
Amortization	(1,840	)	—	—		—		(1,840	)
December 31, 2021	(1,840	)	—	—		—		(1,840	)
Amortization	(3,448	)	—	—		—		(3,448	)
Impairment	(24,255	)	—	(529	)	(1,640	)	(26,424	)
December 31, 2022	(29,543	)	—	(529	)	(1,640	)	(31,712	)
Carrying amount per class
December 31, 2021	37,517		13,729	132,395		8,658		192,299
December 31, 2022	9,988		13,729	132,180		7,018		162,915
Carrying amount per asset
PKU Golike	4,678		—	—		—		4,678
Diclofenac	5,310		—	—		360		5,670
ACER-001	—		13,729	—		641		14,370
RLF-100	—		—	81,516		3,805		85,321
RLF-TD011	—		—	47,392		2,212		49,604
Sentinox	—		—	2,958		—		2,958
RLF-OD32	—		—	314		—		314
Other	—		—	—		—		—
December 31, 2022	9,988		13,729	132,180		7,018		162,915
PKU Golike	30,236		—	—		1,458		31,694
Diclofenac	6,907		—	—		360		7,267
ACER-001	—		13,729	—		641		14,370
RLF-100	—		—	81,516		3,805		85,321
RLF-TD011	—		—	47,392		2,212		49,604
Sentinox	—		—	3,487		163		3,650
Other	374		—	—		19		393
December 31, 2021	37,517		13,729	132,395		8,658		192,299

Intangible assets include acquired patents, trademarks, licenses, technologies and other assets without physical substance. These items are measured at cost less accumulated amortization and impairment. The cost of an intangible asset acquired in a business combination corresponds to its estimated fair value at the date of the acquisition.

8.1 Technologies, patents and trademarks

These intangible assets mainly relate to the following on-market products acquired through the business combination with APR in 2021:

•	PKU Golike<br>®<br>, an amino acid mix product commercialized by Relief for the dietary management of phenylketonuria.

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•

Diclofenac, a product line indicated for the treatment of inflammatory conditions and pain management. The active ingredient diclofenac is combined with Relief’s proprietary technologies in products with immediate release formulation, or in the form of a topical patch. These products are commercialized by third parties under different brand names, including Cambia ® , Voltfast ® and Voltadol ® .

The acquisition costs are amortized over the estimated remaining useful lives of the assets, which range from approximately 2 to

14 years with a weighted average of

8.7 years as of December 31, 2022. Amortization is charged on a straight-line basis over the estimated economic or legal useful life, whichever is shorter.

In the current period, TCHF 174 directly attributable expenses for product development in relation with PKU Golike were capitalized as internally generated asset.

8.2 Licenses

The intangible asset is the acquisition cost of licensing and royalty rights under the collaboration and license agreement with Acer Therapeutics, Inc. (“Acer”). The agreement provides for the development, regulatory approval and worldwide commercialization of ACER-001 by Relief and Acer. Acer retains development and commercialization rights in the U.S., Canada, Brazil, Turkey, and Japan. The companies will split net profits from Acer’s territories 60%:40% in favor of Relief. In addition, Relief has licensed the rights for the rest of the world, where Acer will receive from Relief a 15% royalty on net revenues from ACER-001 in Relief’s territories.

ACER-001 is a proprietary taste masked formulation of sodium phenylbutyrate for application in the treatment of Urea Cycle Disorders and, potentially, Maple Syrup Urine Disease, both genetic metabolic diseases. In December 2022, ACER-001 was approved in the U.S. by the Food and Drug Administration (FDA) under the trademark OLPRUVA ™ for the treatment of Urea Cycle Disorders. Amortization of the asset will begin on January 1, 2023.

8.3 In-process research and development (“IPR&D”) IPR&D assets mainly relate to the following programs:

•	RLF-100<br><br>®<br>, a medicinal product candidate under development in inhaled and intravenous formulations to prevent and resolve respiratory failure and its complications. It was initially acquired in 2016 in the business combination between Relief Therapeutics SA and THERAMetrics Holding AG. The Group gained additional expertise and intellectual property rights around the inhaled formulation of aviptadil with the acquisition of AdVita in 2021. Relief is developing <br>RLF-100<br> for the treatment of acute respiratory distress syndrome (“ARDS”) associated with <br>COVID-19,<br> <br>non-COVID-19-related<br> ARDS, pulmonary sarcoidosis, checkpoint inhibitor-induced pneumonitis, and chronic berylliosis.
•	RLF-TD011,<br> a phase 2 clinical-stage drug candidate for the management of wounds in patients with epidermolysis bullosa. Manufactured using the Group’s proprietary TEHCLO Nanotechnology<br>™<br>, <br>RLF-TD011<br> is a differentiated acid oxidizing solution of hypochlorous acid with an anti-microbial and anti-inflammatory activity with the potential to treat wound colonization, reduce local inflammation, alleviate symptoms and hasten wound healing in epidermolysis bullosa.
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•	Sentinox<br>™<br>, a <br>near-to-market<br> product for the reduction of upper respiratory infections caused by both bacteria and viruses. It was certified as a class III medical device in Europe in 2021 and is undergoing late-stage clinical studies prior to market launch.
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•	RLF-OD32,<br> a novel dosage form of a prescription drug already approved by the U.S. Food and Drug Administration and intended for the treatment of patients with phenylketonuria. In July 2022, the Group executed a definitive agreement with Meta Healthcare Ltd., acquiring the worldwide rights, except for the United Kingdom, for the in-development product. The acquisition cost of TCHF 314 was capitalized as intangible asset at December 31, 2022. Future contingent payments that may become due to Meta Healthcare Ltd. will be capitalized as part of the cost of the asset when paid (note 36.3).
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IPR&D assets are indefinite-life intangible assets until completion or abandonment of the associated research and development programs. Amortization will commence when the assets become available for use, generally once regulatory and marketing approvals are obtained.

8.4 Goodwill

A goodwill of TCHF 8,658 was recognized through the acquisition of APR in 2021. The goodwill was recognized at cost on the acquisition date for the difference between the consideration transferred and the net fair value of assets, liabilities and contingent liabilities identified in the purchase price allocation.

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Goodwill was attributable to APR’s established organization, history of successful partnerships and developments, and expected synergies with the Group’s development and intended commercialization of aviptadil and ACER-001. The combination of Relief and APR resulted in an integrated commercial-stage biopharmaceutical group with improved internal capabilities to lead the clinical and regulatory development and commercialization of the Group’s existing and future products. Synergies were expected through several of Relief’s and APR’s pre-existing activities. The Group had identified that the group of cash-generating units (“CGUs”) constituting the sole operating segment (note 6.1) was expected to benefit from the combination. Accordingly, goodwill is allocated to this group of CGUs. Goodwill is monitored by management at the level of the operating segment.

8.5 Impairment test

The Group generally tests its intangible assets for impairment at the end of the year, taking into account various factors including the relationship between its market capitalization and its equity book value when reviewing for indication of impairment. As of June 30 and December 31, 2022, Relief’s market capitalization was below its equity book value, indicating a potential impairment of Relief’s assets. Additionally, the Group identified unfavorable events and changes in circumstances during the preceding 2022 year-to-date periods that could negatively affect the recoverable value of certain of its assets. Consequently, the Group carried out impairment tests of its intangible assets and goodwill as of June 30 and December 31, 2022, and reviewed assumptions underlying estimated future cash flows.

For the purpose of impairment testing, goodwill was allocated to each CGU constituting the sole operating segment of the Group (note 6.1). The recoverable amount of the group of CGUs is based on the cumulated value in use estimated for each CGU or group of CGUs. The Group’s material CGUs relate to on-market drugs and drug candidates referred to above. The impairment test was performed by determining the recoverable amount of each CGU as the risk-adjusted net present value of future cashflows.

Key assumptions used in value in use calculations

The estimation of recoverable amounts involves significant management judgment. The values assigned to each assumption on an asset basis are based on historical data from external and internal sources and on management’s estimates. The key assumptions used in the valuation models were determined as follows:

•	Cash flow projections were based on a financial forecast developed by management, which includes projections for net sales, cost of sales, and development costs. These projections are periodically reviewed and updated by management.
•	Revenue projections were based on a product-specific analysis that considered relevant market sizes, disease prevalence, incidence rates, expected market share, expected patent life, and the expected year of regulatory approval for unapproved product candidates based on the current stage of development and expected development plan.
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•	Forecast periods were defined on a product basis and based on product life cycles. For <br>on-market<br> products, cash flows were projected for each CGU over a period of five years and cash flows beyond the forecast period were extrapolated using an attrition rate of 5% until the expected end of the exclusivity period of each product. For in-process projects, cash flows were projected over a period of up to 19 years, reflecting the length of the development and subsequent commercialization period. Relief’s approach to compiling development and commercial forecasts is based on a combination of external sources and internal estimates, which includes the use of patient-based models. This methodology is commonly employed in the pharmaceutical industry and has demonstrated satisfactory results over time. No terminal value was considered.
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•	Probabilities of success for <br>in-process<br> projects to reach final development and commercialization ranged from 15% to 80%. These probabilities were based on empirical success rate analysis of multi-stage studies for comparable indications, or if this approach could not be applied, management exercised its judgment.
---	---
•	Pre-tax<br> discount rate was 16.54% based on the assumed cost of capital for the Group (December 31, 2021: 17%).
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Impairment test conclusion

For the year ended December 31, 2022, the Group recognized a total of TCHF 26,424 of impairment charge to partially write down the carrying value of intangible assets associated with PKU Golike, Sentinox and certain other products. The impairment charge was recorded in the comprehensive statement of loss under the heading ‘impairment expense’.

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As Relief launched the direct commercialization of PKU Golike in the U.S. and expanded its sales operations in Europe and in the rest of the world, assumptions underlying expected future cash flows were revised. Changes in pricing scenarios, costs of launch in new addressable markets, and general and administrative costs allocated to PKU Golike, resulted in a reduction of estimated future net cash flows from the asset. Based on the analysis, an annual impairment charge of TCHF 23,913 was recognized against the intangible asset associated with PKU Golike with a carrying amount of TCHF 4,678 as of December 31, 2022. In addition, goodwill allocated to PKU Golike was entirely impaired.

The Group also revised its development plan for Sentinox program resulting in a one-year delay in the estimated launch date. This resulted in an impairment charge of TCHF 529 in the current period against the IPR&D asset associated with Sentinox with a carrying amount of TCHF 2,958 as of December 31, 2022. In addition, goodwill allocated to Sentinox was entirely impaired.

For other intangible assets and remaining goodwill, the Group determined based on the results of the impairment test that their estimated value in use exceeded their respective carrying amounts as of the measurement date. Therefore, the Company did not record an impairment charge on these other assets for the year ended December 31, 2022.

In relation to the IPR&D assets associated with RLF-100, the Group noted that its collaboration partner in the U.S., NeuroRx, was denied an Emergency Use Authorization application by the U.S. Food and Drug Administration for aviptadil in patients with critical COVID-19. Further, two clinical studies with aviptadil were discontinued for non-efficacy in the treatment of critical COVID-19. Nevertheless, management believes RLF-100 remains a promising drug candidate to prevent and resolve respiratory complications provided that the active drug is correctly delivered to the target tissues at an adequate dose. Regulatory approval in COVID-19-induced ARDS has not been granted in the U.S. but an unrelated pharmaceutical company received approval for this indication in India in early 2022 for their formulation of aviptadil, thereby substantiating Relief’s hypothesis that RLF-100 remains a viable treatment for COVID-19 related ARDS. The Group reassessed its development plan for RLF-100 and remains committed to developing it for the treatment of pulmonary sarcoidosis, non-COVID-19-related ARDS, checkpoint inhibitor-induced pneumonitis, chronic berylliosis, as well as mild and severe COVID-19. However, due to uncertainties surrounding the evolution of the COVID-19 pandemic, the Group excluded potential revenue from this indication in its impairment test model. After performing the impairment test, the Group concluded that the asset was not impaired.

Sensitivity to changes in assumptions

The Group performed a sensitivity analysis taking into account reasonably possible changes in the assumptions the value in use is most sensitive to, as listed in the key assumptions section above, including higher discount rate, lower projected income, increased development budget, and postponed market launch. The results of the sensitivity analysis as of December 31, 2022, are presented hereafter.

•	The intangible assets associated with <br>RLF-TD11<br> had an estimated recoverable amount that approximated the carrying amount of TCHF 49,604. Any negative change in assumptions would result in an impairment, with the anticipated time to market and market penetration rate having the most significant impact on the value in use calculation. A <br>one-year<br> delay in regulatory approval, or a reduction of 20% in market penetration rate throughout the commercialization period, would cause an impairment of TCHF 5,816 or TCHF 12,245, respectively, assuming other assumptions remain constant.
•	The intangible assets associated with <br>RLF-100<br> had an estimated recoverable amount that exceeded by TCHF 19,639 the carrying amount of TCHF 85,321. However, a change in assumptions such as an increase in the <br>pre-tax<br> discount rate by 200 basis points, a 15% reduction in expected gross margin during commercialization, a 235 basis point reduction in the probability of success, a 75% increase in development costs, or a <br>two-year<br> market launch delay would result in an impairment.
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•	The intangible assets associated with Diclofenac had an estimated recoverable amount that approximated the carrying amount of TCHF 5,670. They are inherently sensitive to any changes in assumptions which would result in future impairments.
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•	The intangible assets associated with PKU Golike and Sentinox had estimated recoverable amounts that exactly matched their carrying amounts due to impairment at the end of the current reporting period. They are inherently sensitive to any changes in assumptions which would result in future impairments.
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For other intangible assets, including those associated with the ACER-001 license, the Group concluded that no reasonable possible change of key assumptions would cause the carrying amount to exceed the recoverable amount.

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While management believes the assumptions used are reasonable, changes in these assumptions, including changes to or abandonment of development programs, could result in a future material impairment. The completion of the development of IPR&D assets and the ongoing commercialization of on-market products are subject to the availability of capital, which is uncertain as discussed in note 4.1 of these consolidated financial statements. If the Group is unable to secure sufficient capital, it will be forced to delay or abandon certain development and commercialization activities, which could lead to a material impairment of the affected assets.

Leases

9.1 Right-of-use assets

TCHF
Historical cost
January 1, 2021	—		—		—
Business combination	2,548		151		2,699
Disposal	—		(11	)	(11	)
Foreign exchange difference	(10	)	(1	)	(11	)
December 31, 2021	2,538		139		2,677
Addition	—		549		549
Foreign exchange difference	(9	)	(2	)	(11	)
December 31, 2022	2,529		686		3,215
Accumulated depreciation
January 1, 2021	—		—		—
Depreciation	(147	)	(33	)	(180	)
Foreign exchange difference	—		1		1
December 31, 2021	(147	)	(32	)	(179	)
Depreciation	(292	)	(105	)	(397	)
Foreign exchange difference	3		—		3
December 31, 2022	(436	)	(137	)	(573	)
Carrying amount
at December 31, 2021	2,391		107		2,498
at December 31, 2022	2,093		549		2,642

The Group leases various assets, including office equipment, laboratory equipment, cars, and office buildings in Switzerland, the U.S., Italy, and Germany. The remaining expected lease terms for these assets range between 2 years and 10 years. Except for office and laboratory equipment, the Group does not have an option to purchase the assets at the end of the lease term.

9.2 Maturity of lease liabilities

TCHF
< 1 year	444	331
1-5<br> years	1,455	1,161
> 5 years	777	1,031
Total	2,676	2,523

9.3 Amounts recognized in profit or loss

TCHF	December 31, 2022
Lease expense for short-term and low value leases	182	27
Depreciation expense on <br>right-of-use<br> assets (note 27)	392	180
Interest expense on lease liabilities (note 28)	33	17

9.4 Further information on leases

The Group has no material, non-cancellable commitment for short-term lease. In 2022, the cash outflow for leases amounted to TCHF 390 (2021: TCHF 185).

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Inventories

TCHF
Raw material	2,758		2,742
Finished goods	139		366
Gross inventories	2,897		3,108
Valuation allowance	(2,670	)	(2,717	)
Total	227		391

As of the reporting date, the Company’s inventory is mainly constituted by aviptadil active ingredient valued at acquisition cost of TCHF 2,670. As the aviptadil was manufactured prior to obtaining regulatory approval, the inventory is fully impaired. The remaining inventory consists mainly of active pharmaceutical ingredients and finished products for market supply.

Trade receivables

TCHF
Current receivables	1,548		1,506
Expected credit loss allowance	(227	)	(204	)
Total	1,321		1,302

Trade receivables do not bear interest and generally have maturities ranging from 30 and 90 days.

Expected credit loss allowance

The Group uses a provision matrix to estimate the expected credit losses from trade receivables outstanding at the end of the reporting period. The provision rates are based on days past due of customer invoices. The provision is initially based on the Group’s historical observed default rates. The Group calibrates the matrix to adjust the historical credit losses with forecasts on economic conditions or similar forecast data for the various geographical areas at each reporting date.

TCHF
Balance at beginning of year	(204	)	—
Acquired through business combination	—		(126	)
Impairment losses recognized	(23	)	(78	)
Balance at end of year	(227	)	(204	)

Other current assets

TCHF
Prepaid expenses	836	6,422
Accrued revenue	723	313
VAT receivable	147	115
Deposits	28	28
Indemnification asset (note 18)	—	622
Other current receivables	64	1,016
Total	1,798	8,516

As of December 31, 2021, prepaid expenses consisted primarily of CHF 5.3 million for the portion of upfront development payments made to Acer that remained unconsumed under the collaboration and license agreement. These prepayments were fully expensed in 2022.

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Other current receivables as of December 31, 2021, amounted to TCHF 1,016 and consisted of advance payments made by the Group that were reimbursed by vendors during 2022.

Cash and cash equivalents

As of December 31, 2022 and 2021, cash and cash equivalents consisted of cash in bank and on hand.

Share capital

	Number of shares
	Common shares		Treasury shares			Total
Balance at January 1, 2021		3,246,727,248		—			3,246,727,248
Issuance of treasury shares		1,153,502,908		(1,153,502,908	)		—
Direct Share Placement program		—		398,219,762			398,219,762
Private placements		—		112,887,942			112,887,942
Acquisition payments		—		342,527,847			342,527,847
Exercises of options		13,104,461		—			13,104,461
Balance at December 31, 2021		4,413,334,617		(299,867,357	)		4,113,467,260
Balance at January 1, 2022		4,413,334,617		(299,867,357	)		4,113,467,260
Issuance of treasury shares		1,200,000,000		(1,200,000,000	)		—
Direct Share Placement program		—		138,857,806			138,857,806
Milestone payments		—		150,200,120			150,200,120
Exercises of options		3,000,000		—			3,000,000
Balance at December 31, 2022		5,616,334,617		(1,210,809,431	)		4,405,525,186

14.1 Issued share capital

As of December 31, 2022, the share capital consisted of 5,616,334,617 issued shares with a par value of CHF 0.01

each. The Company issued a total of 1,203,000,000 shares in 2022 and held 1,210,809,431 shares in treasury on December 31, 2022.

Equity transactions in 2022

In 2022, the following capital increase transactions resulted in cash gross proceeds of TCHF 7,111 before deducting transaction costs of TCHF 223.

•

DSP program: sale of 138,857,806 shares at an average price per share of CHF 0.0508 for total gross proceeds of TCHF 7,051. Under its Direct Share Placement program, the Company issues shares out of its authorized capital to constitute and monetize its treasury shares reserve in order to diversify its funding sources and raise capital in a cost-efficient and flexible manner. The Company’s shares are periodically offered into the trading market at prevailing bid prices.

•

Exercises of options: issuance upon exercise of 3,000,000 shares at CHF 0.02 per share for gross proceeds of TCHF 60.

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In addition, the Company made a payment in shares of TCHF 4,200, corresponding to 150,200,120 shares at CHF 0.028 per share, as settlement of a milestone obligation under the APR acquisition agreement (note 18).

The Company issued a total of 1,200,000,000 treasury shares from its authorized capital during the year. The shares were entirely subscribed at par value by a wholly owned subsidiary for subsequent placements.

Equity transactions in 2021

In 2021, the following capital increase transactions provided the Group with cash gross proceeds of TCHF 76,088, before deducting transaction costs of TCHF 2,848. Transactions costs were primarily constituted by issuance stamp taxes and placement agent fees.

•	Private placement in March 2021: sale of 41,459,370 shares at CHF 0.2412 per share to an institutional investor for total gross proceeds of TCHF 10,000.

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•	Private placement in July 2021: sale of 71,428,572 shares at CHF 0.2100 per share to two institutional investors for total gross proceeds of TCHF 15,000.
•	DSP program: sale of 398,219,762 shares at an average price of CHF 0.1278 for total gross proceeds of TCHF 50,887.
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•	Exercises of options: issuance upon exercise of 13,104,461 shares at prices between CHF 0.01 and 0.02 per share, resulting in gross proceeds of TCHF 201.
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Relief also transferred 342,527,847 shares to APR’s and AdVita’s sellers as equity payments for the acquisition of APR and AdVita (note 7). The two non-cash transactions resulted in an increase in equity of TCHF 74,402.

The Company issued a total of 1,153,502,908 treasury shares from its authorized capital during the year. The shares were entirely subscribed at par value by a wholly owned subsidiary for subsequent placements.

14.2 Authorized share capital

As of December 31, 2022, the Company had an authorized nominal share capital of TCHF 1,000, consisting of 1,000,000,000 shares with a par value of CHF 0.01 each, which the Board of Directors was authorized to issue at any time until May 30, 2024.

14.3 Conditional share capital

The conditional share capital of the Company as of December 31, 2022, was TCHF 16,688, consisting of 1,668,769,814 shares with a par value of CHF 0.01 each, of which 105,769,814 shares to be used for stock options and 1,563,000,000 shares for grant of option rights in connection with bonds, notes or similar financial instruments issued by the Company.

As of December 31, 2022, there were 74,363,197 outstanding stock options allowing their holders to acquire the same number of shares, subject to certain vesting conditions (note 30).

Reserves

TCHF
Share premium (note 15.1)	215,688	207,521
Share-based payment reserve (note 15.2)	4,557	2,371
Foreign currency translation reserve (note 15.3)	716	255
Total	220,961	210,147

15.1 Share premium

TCHF
Balance at beginning of year	207,521		68,546
Additional <br>paid-in<br> capital from capital increases	8,390		141,823
Transaction cost in relation to capital increases	(223	)	(2,848	)
Balance at end of year	215,688		207,521

15.2 Share-based payment reserve

TCHF
Balance at beginning of year	2,371	1,228
Share-based payments (note 30)	2,186	1,143
Balance at end of year	4,557	2,371

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15.3 Foreign currency translation reserve

TCHF
Balance at beginning of year	255	—
Exchange differences arising on translating foreign operations	461	255
Balance at end of year	716	255

Borrowings

TCHF	December 31, 2022				December 31, 2021
	Non-current		Current		Non-current		Current
Bank loans		16		372		396		28
Other financial liability		—		—		—		67
Total		16		372		396		95

As of December 31, 2022, the company had two outstanding bank loans: a TCHF 366 loan from a German bank carrying interest at 2.7% per year until December 30, 2023 (with an extension option), and a TCHF 22 loan tha t is inte rest-free and repayable in monthly installments until 2026.

Defined benefit obligations

The following table provides information on the amounts recognized in the balance sheet:

TCHF
Present value of pension benefit obligation	4,044		4,496
Fair value of pension plan assets	(3,494	)	(2,946	)
Net pension defined benefit obligation	550		1,550
Present value of other benefit obligations	1,222		1,243
Total defined benefit obligations	1,772		2,793

17.1 Defined benefit plan

Swiss pension plans need to be administered by a separate pension fund that is legally separated from the entity. The law prescribes certain minimum benefits. The pension plans of the employees of the parent entity and its Swiss subsidiaries are carried out by collective funds with Swiss Life Collective Foundation and Caisse Inter-Entreprises de Prévoyance Professionnelle. Under the pension plans, the employees are entitled to retirement benefits and risk insurance for death and disability.

In accordance with IAS 19, the above-mentioned pension plans are classified as defined benefit plans. The pension plans are described in detail in the corresponding statutes and regulations. The contributions of employers and employees, in general, are defined in percentages of the insured salary. The retirement pension is calculated based on the old-age credit balance on retirement multiplied by the fixed conversion rate. The employee has the option to withdraw the capital at once. The death and disability pensions are defined as percentage of the insured salary. The assets are invested directly with the corresponding pension funds.

The pension funds can change their financing system (contributions and future payments) at any time. Also, when there is a deficit which cannot be eliminated through other measures, the pension funds can oblige the entity to pay a restructuring contribution. For the pension funds of the Group such a deficit currently cannot occur as the plans are fully reinsured. However, the pension funds could cancel the contracts and the entities of the Group would have to join another pension fund.

In the current and comparative periods no plan amendments, curtailments or settlements occurred.

The fully reinsured pension funds have concluded insurance contracts to cover the biometric and investment risk. The board of each pension fund is responsible for the investment of assets and the investment strategies are defined in a way that the benefits can be paid out on due date.

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The actuarial valuations of plan assets and the present value of the defined benefit obligation were carried out on December 31, 2022. The present value of the defined benefit obligation, and the related current service cost and past service cost, were measured using the projected unit credit method.

Amounts recognized in profit or loss in respect of these defined benefit plans were as follows:

TCHF
Current service cost	207	132
Net interest expense	4	2
Administration cost excl. cost for managing plan assets	23	11
Expense recognized in profit or loss	234	145

Amounts recognized in other comprehensive income in respect of these defined benefit plans were as follows:

TCHF
Remeasurement (gain)/loss on defined benefit obligation due to changes in financial assumptions	(1,150	)	(39	)
due to changes in experience adjustments	156		(166	)
Return on plan assets excl. interest income	52		24
(Income) recognized in other comprehensive income	(942	)	(181	)

Movements in the present value of the defined benefit obligation were as follows:

TCHF
Opening defined benefit obligation	4,496		-
Current service cost	240		132
Past service cost	(33	)	—
Interest expense on defined benefit obligation	13		6
Contributions from plan participants	129		54
Benefits (paid)/deposited	193		(640	)
Remeasurement (gain)/loss due to changes in financial assumptions	(1,150	)	(39	)
Remeasurement (gain)/loss due to changes in experience adjustments	156		(166	)
Acquired through business combinations	—		5,149
Closing defined benefit obligation	4,044		4,496

Movements in the present value of the plan assets in the current period were as follows:

TCHF
Opening fair value of plan assets	2,946		—
Interest income on plan assets	9		4
Return on plan assets excluding interest income	(52	)	(24	)
Contributions from the employer	292		121
Contributions from plan participants	129		54
Benefits (paid)/deposited	193		(640	)
Administration cost	(23	)	(11	)
Acquisition through business combination	—		3,442
Closing fair value of plan assets	3,494		2,946

The respective insurance companies provide reinsurance of these assets and bear all market risk on these assets.

The actual return on plan assets was TCHF (43) (2021: TCHF (20)) .

Principal assumptions used for the purposes of the actuarial valuations were as follows:

TCHF	2022			2021
Discount rates		2.15	%		0.30	%
Expected rates of salary increase		1.50	%		1.50	%

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The following sensitivity analyses based on the principal assumptions have been undertaken based on reasonably possible changes to the assumptions occurring at the end of the reporting period:

•	A 25 basis points increase (decrease) in the discount rate, holding all other assumptions constant, would result in a 3.5% decrease (3.7% increase) in the defined benefit obligation.
•	If the expected salary growth were to increase (decrease) by 0.25%, and all other assumptions remained constant, the defined benefit obligation would increase by 1.1% (decrease by 1.1%).
---	---

The average duration of the defined benefit obligation at the end of the reporting period was 14.4 years (2021: 17.5 years).

The Group expects to make contributions of TCHF 299 to the defined benefit plans during the next financial year.

17.2 Other employee benefits

The obligations for other employee benefits mainly consist of end of service indemnities, which do not have the character of pensions, and are classified as a defined benefit plan in accordance with IAS 19.

Provisions

TCHF
Balance at January 1, 2022	30,831		722		31,553
Reversal of provision	—		(622	)	(622	)
Payment upon reaching milestones	(12,120	)	—		(12,120	)
Unwinding of discount on provisions	1,308		—		1,308
Variation due to assumption adjustment	(8,892	)	36		(8,856	)
Foreign exchange difference	(260	)	—		(260	)
Balance at December 31, 2022	10,867		136		11,003
thereof current	2,958		136		3,094
thereof <br>non-current	7,909		—		7,909

(i) Contingent liabilities

The Group recognized provisions of TCHF 10,867 for contingent payments that may become due to the former shareholders of APR and AdVita upon completion of pre-agreed milestones. As a result of unfavorable changes in the estimated market potential and development programs for certain assets, the Group reevaluated its assessment for contingent payments related to those assets. Further information on these changes is disclosed in note 8.5. This led to a decrease in the estimated likelihood and payable amount for milestone achievements, resulting in a TCHF 8,892 reduction of the provision. The adjustment is recorded in ‘other gain’ in the 2022 income statement (note 21).

Contingent consideration for the acquisition of APR

As of December 31, 2022, remaining milestone payments under the acquisition agreement were (i) the execution of a definitive agreement for the commercialization of Sentinox ™ , (ii) the launch of Sentinox in the first of France, Germany, Spain, Italy, and the United Kingdom, and (iii) the launch of RLF-TD011 in the first of France, Germany, Spain, Italy and the United Kingdom. Contingent payments aggregate to a maximum amount of CHF 28 million, in a combination of cash and Relief shares.

In October 2022, the commercial launch of PKU GOLIKE ® in the U.S. marked the completion of a contractual milestone for which Relief issued a cash payment of CHF 2.8 million and CHF 4.2 million in Relief shares to the former shareholders of APR.

Contingent consideration for the acquisition of AdVita

As of December 31, 2022, remaining milestone payments under the acquisition agreement were (i) the approval in the U.S. or Europe of the inhaled form of aviptadil for the treatment of sarcoidosis or berylliosis, and (ii) the conduct of a phase II clinical study for the inhaled form of aviptadil in the treatment of checkpoint inhibitor-induced pneumonitis. Contingent payments aggregate to a maximum amount of EUR 10 million (CHF 9.9 million), in cash.

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In April 2022, AdVita was issued a patent entitled, “Vasoactive Intestinal Peptide for the use in the treatment of drug-induced pneumonitis,” which triggered a milestone payment of EUR 5 million (TCHF 5,120) in cash from Relief to the former shareholders of AdVita.

Provisioned amounts are calculated at the end of each reporting period by determining the probability-weighted present value of potential payments. As of December 31, 2022, probabilities ranged from 15% to 90% based on the estimated likelihood of completion for each underlying milestone. These probabilities are consistent with those estimated for the impairment test conducted for intangible assets and goodwill (note 8.5). Time to completion of each milestone ranged from approximately one year to six years. A discount rate of 5% was determined based on the estimated time value of comparable liabilities, excluding risks factored into the probabilities of success.

(ii) Legal and regulatory proceedings

In June 2021, SIX Exchange Regulation AG initiated an investigation against the Company due to a potential violation of the rules on ad-hoc publicity. As part of the investigation, SIX Exchange Regulation AG is examining whether there has been an actual violation of the regulations. The provision of TCHF 136 reflects management’s best estimate of the most likely outcome and is subject to uncertainty. It is expected to be paid within the next 12 months.

As of December 31, 2021, a subsidiary of the Group was party to a legal proceeding for the payment to a third party of TCHF 622. The claim was acquired in a business combination in 2021 and was entirely provisioned as of December 31, 2021. An indemnification asset of the same amount was recorded on the balance sheet as of December 31, 2021. In 2022, the claim was settled between the parties at no cost for the Group and the legal procedure was closed. The provision and the indemnification asset were derecognized from the balance sheet.

Financial liabilities due to related parties

In January 2021, the Company signed a financing agreement with its largest shareholder, GEM Global Yield LLC (“GEM”), for the implementation of a Share Subscription Facility (“SSF”) in the amount of up to CHF 50 million until January 20, 2024. As of December 31, 2022, the Company had not drawn on the SSF.

The Company agreed to pay GEM a commitment fee (the “Fee”) of TCHF 1,250 plus accrued interest. As of December 31, 2022, the Fee was payable on demand and bore interest at 1% above the base rate of Barclays Bank plc. As the obligation to pay the Fee arose with the execution of the agreement, the Company recorded it in full as a liability on the signature date. The corresponding expense is recognized as financial expense (note 28) over the SSF commitment period of three years ending January 20, 2024.

Other current payables and liabilities

TCHF
Accrued expenses	2,138	2,143
Payroll tax and social security liabilities	497	1,573
Stamp duty and capital tax liabilities	347	486
Deferred revenue	776	—
Other current liabilities	143	72
Total	3,901	4,274

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Other gains

TCHF	2022
Gain from adjustment in fair value of contingent liabilities (note 18)		8,892	—
Gain from reversal of impairment on financial assets (i)		453	—
Reversal of impairment losses on receivables		235	—
Income from sublease agreements		94	87
Write-off<br> of liabilities due to a former subsidiary		—	891
Write-off<br> of old liabilities		—	168
Various other		247	25
Total other gains		9,921	1,171
(i)	In 2020, the Group had provided a loan of TUSD 500 (TCHF 488) to NeuroRx, Inc. for the development of <br>RLF-100<br> as part of a collaboration agreement. The loan was repaid in April 2022 pursuant to its terms. The impairment allowance, which was recognized in prior periods, was reversed in 2022 resulting in a gain of TCHF 488. This gain was recognized in ‘other gains’ for TCHF 453 and within ‘financial income’ for TCHF 35 in the statement of comprehensive loss.
---	---

Cost of sales

Expenses incurred with third parties in relation with the purchase and manufacturing of drug products for sale, as well as laboratory supplies in connection with research and development services provided to customers, are classified in ‘raw materials and consumables expenses’. Expenses incurred with third parties in relation to advertising, marketing, sales promotion, shipping, distribution and commission on sales, are classified as ‘external selling and distribution expenses’.

The consolidated statement of comprehensive loss aggregates transactions according to their nature. The overall cost of sales, which includes expenses of different natures, is therefore not presented in a distinct line.

External research and development expenses

In 2022, external research and development expenses mainly comprised the development costs incurred by Acer under the license and collaboration agreement, as well as the clinical and drug product development costs associated with aviptadil and, to a lesser extent, other drug candidates. In the current period the Group capitalized TCHF 174 in directly attributable expenses for product development (note 8).

Personnel expenses

TCHF
Salaries and social security	10,513		4,515
Independent contractors fees	320		2,220
Share-based payment expense (note 30)	2,186		1,143
Service cost for other benefit obligations (note 17)	(21	)	1,243
Total personnel expenses	12,998		9,121

Personnel expenses increased mainly as a result of the addition of APR’s and AdVita’s personnel to the Group’s workforce from July 2021 and of the gradual deployment of a U.S. sales force in 2022. Correspondingly, Relief’s reliance on independent contractors significantly decreased.

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Other administrative expenses

TCHF
Professional services	6,053	6,022
Other administrative expenses	1,694	728
Total other administrative expenses	7,747	6,750

Professional services primarily include expenses incurred in relation to legal, communication, listing, accounting and audit services, as well as other consulting activities not related to research and development. Other administrative expenses comprise IT, travels, insurances, IP maintenance and prosecution, and various other expenses. The increase in 2022 was mostly attributable to the expanded activities of the Group with the addition of APR and AdVita, as well as to legal and consulting service needs to support the operations and development plans of the Group.

Other losses

TCHF
Losses on financial assets at fair value through profit or loss	—	54
Impairment losses on loans to third parties	—	692
Various other	63	6
Total other losses	63	752

Amortization and depreciation expense

TCHF
Amortization of intangible assets (note 8)	3,448	1,840
Depreciation of <br>rights-of-use<br> assets (note 9)	392	180
Depreciation of property and equipment	20	16
Total amortization and depreciation expense	3,860	2,036

Financial income and expenses

TCHF
Interest income	18		40
Foreign exchange gain, net	—		57
Total financial income	18		97
Unwinding of discount on provisions (note 18)	(1,308	)	(653	)
SSF commitment fee (note 19)	(416	)	(395	)
Negative interest on cash deposits	(93	)	(127	)
Interest expense related to leases	(33	)	(17	)
Other interest expenses	(30	)	(50	)
Bank charges	(40	)	(74	)
Foreign exchange loss, net	(374	)	—
Total financial expenses	(2,294	)	(1,316	)

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Income taxes

29.1 Income tax recognized in profit or loss

TCHF
Current tax
Current tax expense for the year	—		—
Adjustments in current tax of prior years	—		—
	—		—
Deferred tax
Deferred tax (income)/expense recognized in the year	(4,977	)	(820	)
Write-down of deferred tax assets	1,451		—
	(3,526	)	(820	)
Net income tax gain	(3,526	)	(820	)

The following table provides a reconciliation between the income tax income recognized for the year and the tax calculated by applying the applicable tax rates on the net result before income taxes.

TCHF
Loss before tax	(54,316	)	(35,525	)
Income tax expense calculated at 13.99% (2021: 13.99%)	(7,599	)	(4,970	)
Unrecognized deferred tax assets during the year	4,235		4,392
Write-down of deferred tax assets	1,451		—
Effect of deferred tax balances due to difference in applicable tax rates	(802	)	(178	)
Effect of net (income)/expense that is not added/(deductible)	(811	)	(64	)
Income tax recognized in the current year	(3,526	)	(820	)

As of December 31, 2022, the applicable tax rate of the Group was 13.99% (2021: 13.99%), which was equal to the statutory tax rate of the holding company.

29.2 Income tax recognized in other comprehensive income

In 2022, no income tax was recognized in the statement of other comprehensive income. In 2021, the remeasurement of the defined benefit obligation by TCHF 181 led to a credit in the corresponding tax asset of TCHF 29 recognized in the statement of other comprehensive income.

29.3 Deferred tax balance

The following table sets out the changes in deferred tax assets and liabilities:

2022<br><br>TCHF
Tax losses	1,206	—	(711	)	495
Defined benefit obligation	247	—	(247	)	—
Intangible assets	280	—	(280	)	—
Leases	4	—	(4	)	—
Total deferred tax assets	1,737	—	(1,242	)	495
Intangible assets	25,504	—	(4,768	)	20,736
Total deferred tax liabilities	25,504	—	(4,768	)	20,736

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2021<br><br>TCHF
Tax losses	—	615	—		591		1,206
Defined benefit obligation	—	272	(29	)	4		247
Intangible assets	—	309	—		(29	)	280
Financial instruments	—	40	—		(40	)	—
Leases	—	3	—		1		4
Total deferred tax assets	—	1,239	(29	)	527		1,737
Intangible assets	4,309	21,488	—		(293	)	25,504
Total deferred tax liabilities	4,309	21,488	—		(293	)	25,504

29.4 Unrecognized deferred tax assets

The Group did not capitalize deferred tax assets from carryforward tax losses located in companies of the Group for which the availability of future taxable profits is uncertain. The cumulated tax losses on which no deferred tax assets have been capitalized will expire as follows:

TCHF
Within one year	7,833	33,389
Later than one year and not later than five years	70,009	53,506
More than five years	67,016	49,466
Total tax losses carry forward	144,858	136,361

The deferred tax assets not recognized as of December 31, 2022, amounted to CHF 22 million (2021: CHF 19 million).

Share-based payments

The Company maintains a stock option plan established in 2021 (the “Stock Option Plan 2021”), as well as a legacy stock option plan (the “Equity Awards Program 2015”) for which options remain outstanding. Stock option plans were established for the Company’s employees, directors, and consultants whereby each option gives its holder the right to purchase one share of the Company at a pre-determined price. As of December 31, 2022, 105,769,814 shares were available for issuance of shares from the Company’s conditional capital under the stock option plans. Stock options granted are subject to certain vesting conditions based on a service period defined on an individual basis at grant date.

As of December 31, 2022, the Company had 74,363,197 options outstanding. The following table reconciles the stock options outstanding at the beginning and end of the year:

	2022
At beginning of the year		68,650,697		24,367,658
Granted		12,100,000		62,200,000
Exercised<br>1		(3,000,000	)	(13,104,461	)
Forfeited		(3,387,500	)	(4,812,500	)
At end of the year		74,363,197		68,650,697
1	In 2022, the weighted average exercise price was CHF 0.02 (2021: CHF 0.015).
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Share options outstanding at the end of the reporting period had the following expiry dates:

Expiration year
2022	—	3,187,500
2023	100,000	100,000
2024	100,000	100,000
2025	100,000	100,000
2026	7,396,530	7,063,197
2027	21,566,667	22,300,000
2028	22,266,667	19,300,000
2029	19,133,333	16,500,000
2030	3,700,000	—
	74,363,197	68,650,697
Weighted average remaining contractual life in months	69	76

As of December 31, 2022, 27,816,530 out of the 74,363,197 outstanding options were exercisable, with exercise prices ranging from CHF 0.01 to CHF 0.49.

The fair values of the options were assessed using the Black-Scholes valuation model at the grant date and recognized over their vesting period.

In 2022, the weighted average fair value of options granted was CHF 0.02. The significant inputs considered for the options granted in 2022 were the share price at the grant date (ranging from CHF 0.027 to CHF 0.06), the exercise price (ranging from CHF 0.027 to CHF 0.06), the volatility of returns (ranging from 71% to 80%), and the risk-free interest rate (ranging from 0% to 1%). The expected volatility assumes that historical volatility over a period similar to the life of the options is indicative of future trends, which may not necessarily be the actual outcome. The expected life of the options was estimated based on historical data by the Group, or when insufficient data was available, based on management’s estimates.

In 2021, the weighted average fair value of options granted was CHF 0.09 in 2022. The significant inputs considered for the options granted in 2021 were the share price at the grant date (ranging from CHF 0.061 to CHF 0.269), the exercise price (ranging from CHF 0.01 to CHF 0.269), the volatility of returns (ranging from 83% to 122%), and a risk-free interest rate of 0%.

In 2022, TCHF 2,186 (2021: TCHF 1,143) was recorded in personnel expense with a corresponding credit to the share-based payment reserve (note 15).

Earnings per share


Loss attributable to shareholders (in TCHF)	(50,790	)	(34,705	)
Weighted average number of shares	4,228,112,520		3,593,069,451
Basic and diluted loss per share (in CHF)	(0.012	)	(0.010	)

Basic and diluted result per share is calculated by dividing the net result attributable to the shareholders of the parent company by the weighted average of shares outstanding during the period. In 2022 and 2021, the number of shares outstanding varied as a result of different transactions on the share capital structure of the Company (note 14).

Neither outstanding options nor effects from the contingent liabilities payable in shares have been considered in the diluted loss calculation as their effect is anti-dilutive.

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Financial instruments

32.1. Categories of financial instruments

December 31, 2022<br><br>TCHF	Financial assets<br>at amortised cost		Financial liabilities<br>at amortised cost		Financial liabilities<br>at FVTPL		Total
Other non-current assets		114		—		—		114
Trade receivables		1,321		—		—		1,321
Other current assets and receivables		956		—		—		956
Cash and cash equivalents		19,237		—		—		19,237
Total financial assets		21,628		—		—		21,628
Non-current lease liabilities		—		2,232		—		2,232
Non-current borrowings		—		16		—		16
Current lease liabilities		—		444		—		444
Current borrowings		—		372		—		372
Provisions for milestone payments		—		—		10,867		10,867
Trade payables		—		1,625		—		1,625
Financial liabilities due to related parties		—		1,280		—		1,280
Other current payables and liabilities		—		2,214		—		2,214
Total financial liabilities		—		8,183		10,867		19,050
December 31, 2021<br><br>TCHF	Financial assets<br>at amortized cost		Financial liabilities<br>at amortized cost		Financial liabilities<br>at FVTPL		Total
---	---	---	---	---	---	---	---	---
Other non-current assets		76		—		—		76
Trade receivables		1,302		—		—		1,302
Other current assets and receivables		2,094		—		—		2,094
Cash and cash equivalents		44,761		—		—		44,761
Total financial assets		48,233		—		—		48,233
Non-current lease liabilities		—		2,192		—		2,192
Non-current borrowings		—		396		—		396
Current lease liabilities		—		331		—		331
Current borrowings		—		95		—		95
Provisions for milestone payments		—		—		30,831		30,831
Trade payables		—		1,700		—		1,700
Financial liabilities due to related parties		—		1,250		—		1,250
Other current payables and liabilities		—		2,024		—		2,024
Total financial liabilities		—		7,988		30,831		38,819

32.2 Reconciliation of liabilities arising from financing activities

						Non cash-changes
2022<br><br>TCHF	Opening<br>balance		Financing<br>cash flows			New leases		Accrued<br>interest		Foreign<br>exchange			Closing<br>balance
Lease liabilities (note 9.2)		2,523		(390	)		551		—		(8	)		2,676
Borrowings (note 16)		491		(81	)		—		1		(23	)		388
Due to related parties (note 19)		1,250		—			—		30		—			1,280
Total		4,264		(471	)		551		31		(31	)		4,344

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						Non-cash changes
2021<br><br>TCHF	Opening<br>balance		Financing<br>cash flows			Gain on<br>settlement			Business<br>Combinat.		Accrued<br>interest		Foreign<br>exchange			Closing<br>balance
Lease liabilities		—		(185	)		—			2,719		—		(11	)		2,523
Borrowings (note 16)		—		(5,366	)		—			5,886		3		(32	)		491
Due to third parties		891		—			(891	)		—		—		—			—
Due to related parties (note 19)		—		—			—			—		1,250		—			1,250
Total		891		(5,551	)		(891	)		8,605		1,253		(43	)		4,264

32.3 Fair value measurement

Financial liabilities at fair value through profit and loss (“FVTPL”) consist of contingent considerations resulting from business combinations. Further details on the fair value measurement of these liabilities are provided in note 18.

32.4 Amortized cost measurement

For all other financial assets and liabilities, their carrying amount at amortized cost approximates their fair value.

Financial risk management

The Group is exposed to various financial risks, including credit risk, capital and liquidity risk, interest rate risk and currency risk. The following sections provide an overview of each of these risks, as well as the objectives, principles, and processes that the Group employs to mitigate them.

Credit risk

Credit risk refers to the risk that a counterparty will default on its contractual obligations towards the Group, resulting in financial loss to the Group. For product sales and trade account receivables, Relief may conduct selective analysis of the creditworthiness of distributors and other customers. Other financial assets mainly consist of cash for which the counterparty risk is minimized by deposits at well-known banks in Switzerland with an A rating as per Standard & Poor’s so that any expected credit loss is considered immaterial. In addition, the Group diversifies its exposure to banking risk by maintaining banking relationships with several institutions.

The carrying amounts of financial assets recorded in the financial statements represent the Group’s maximum exposure to credit risk without taking into account the value of any collateral obtained.

Capital and liquidity risk

The Group’s objectives when managing capital are to safeguard its ability to fund development and marketing activities in order to provide returns for shareholders and benefits for other stakeholders. The funds raised in various private financing rounds and other share placements executed since the listing of the Company have been the principal source of liquidity, to date. Equity financing through placement of shares remains the expected main source of liquidity in the near term.

Liquidity risk management implies maintaining sufficient cash and cash equivalents to meet the financial obligations of the Group. Management monitors the Group’s net liquidity position through rolling forecasts of projected cash flows. Maintaining adequate cash reserves is dependent on the Group’s ability to raise funds or generate profits; therefore, the liquidity risk is significant (see note 4.1 ‘going concern’).

Interest rate risk

The Group is exposed to interest risk in respect of its cash deposits, bank loans and other interest-bearing liabilities. The Group deems the interest rate risk as low on its performance and its equity.

Currency risk

The Group operates internationally and is exposed to currency risk arising from various exposures, primarily with respect to the Swiss francs, Euros and US dollars. Currency risk arises from future transactions, recognized assets and liabilities and net investments in foreign operations. To manage such risk, the Group monitors its exposure by periodically assessing future spending needs in foreign currencies and maintains foreign currency cash balances to cover anticipated future requirements. The Group does not enter into any forward currency transactions and did not hold any derivative currency contracts at the end of the reporting period.

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While the Group considers its current exposure to foreign currency risk to be low, adverse changes in the value of the Swiss franc could still have a significant negative impact on the Group’s financial condition, results of operations, and future prospects.

Based on the Group’s balance sheet position denominated in foreign currencies on December 31, 2022, and with all other variables held constant, a 5% variation in USD and EUR exchange rates against Swiss franc would result in a TCHF 251 impact on the Group’s 2022 result (2021: TCHF 1,000).

Related party transactions

Balances and transactions between the Group and its subsidiaries have been eliminated on consolidation and are not disclosed in this note. Transactions between the Group and related parties are disclosed below.

34.1 Related party transactions

With members of the Board of Directors and of the Executive Committee

TCHF
Short-term employee benefits	2,873	2,759
Post-employment benefits	89	30
Share-based compensation	—	814
Compensation to key management	2,962	3,603

Further details on management’s compensation are provided in the compensation report.

With other related parties

In 2022, there were no other related party transactions. In 2021, the Group entered into a financing agreement with GEM as described in note 19.

34.2 Related party balances

As of December 31, 2022, the liability of TCHF 1,280 due to GEM (December 31, 2021: TCHF 1,250) was the only material related party balance.

35. Non-cash transactions

In 2022, the Group engaged in non-cash investing or financing activities that are not reflected in the consolidated statement of cash flow. These activities included the execution of new leasing contracts for equipment (note 9), as well as the issuance of a TCHF 4,200 share payment in October 2022 following the completion of a milestone related to the APR acquisition (note 18).

In 2021, the Group’s significant non-cash investing or financing activities included the recording of the SSF commitment fee as a financial liability (note 19), the payment of USD 14 million for the ACER-001 license in March 2021 which was partly settled by offsetting a loan of USD 4 million previously granted to Acer in January 2021 (note 4.1), and the partial financing of the APR acquisition through a payment in shares in June 2021, as well as the complete financing of the AdVita acquisition through a payment in shares in July 2021 (note 7).

Contingent liabilities

36.1 License and collaboration agreement with Acer (note 8.2)

Under the license and collaboration agreement with Acer, the Group has committed to make remaining milestone payments of up to USD 6 million (CHF 5.6 million) in cash upon obtention of European marketing approvals of ACER-001 for Urea Cycle Disorders and Maple Syrup Urine Disease. Further, Relief has agreed to pay royalties of 15% on future net revenue from ACER-001 in Relief’s territories.

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36.2 Business combinations with APR and AdVita (notes 7.1 and 7.2)

The acquisition agreements for APR and AdVita contain remaining contingent milestone payments in the aggregate maximum amounts of CHF 28 million and EUR 10 million (CHF 9.9 million), respectively, payable upon achievement of pre-agreed objectives. As of December 31, 2022, a provision totaling CHF 10.9 million (2021: CHF 30.8 million) was recognized to account for the probability-weighted present value at balance sheet date of these possible future payments. Refer to note 18 for further details.

36.3 Acquisition of RLF-OD32 (note 8.3)

Under the agreement concluded with Meta Healthcare Ltd. for the acquisition of RLF-OD32 in July 2022, Relief may issue additional payments of approximately TCHF 400 contingent to pre-specified development milestones. Relief committed to pay Meta Healthcare Ltd. royalties on net commercialization profit of a low double-digit percentage.

36.4 Settlement agreement with NeuroRx

In November 2022, Relief agreed to a settlement with NRx Pharmaceuticals, Inc. (“NRx”), the parent company of NeuroRx, to terminate their collaboration in the development of aviptadil and resolve their legal dispute. As part of the agreement, Relief committed to paying NRx up to USD 13 million (CHF 12.4 million) in aggregate as milestone payments upon marketing approval of an aviptadil product. Relief also agreed to pay single-digit percentage royalties on possible future sales of an aviptadil product, up to a maximum of USD 30 million (CHF 28.6 million) in aggregate. Finally, Relief agreed to use commercially reasonable efforts to maintain a Right to Try Program in the U.S. until December 2024.

Events after the reporting period

There were no material events after the balance sheet date that would require adjustment to these consolidated financial statements or disclosure under this heading.

F-41

EX-3.1

Exhibit 3.1

Statuts de RELIEF THERAPEUTICSHolding SA (Ltd./AG)	Articles of Association of RELIEFTHERAPEUTICS Holding SA (Ltd./AG)
I. Raison sociale, siège, durée et but	I. Company, Location, Duration, Purpose
Article 1<br> <br>Raison sociale,siège et durée	Article 1<br> <br>Company Name, RegisteredSeat and Duration
1 Sous la raison sociale<br> <br><br><br><br>RELIEF THERAPEUTICS Holding SA<br> <br><br><br><br>(RELIEF THERAPEUTICS Holding Ltd.)<br> <br><br><br><br>(RELIEF THERAPEUTICS Holding AG)<br> <br><br><br><br>il existe une société anonyme qui est régie par le titre 26 du Code Suisse des Obligations (CO) et par les présents Statuts, avec<br>siège à Genève, Canton de Genève (la “Société”).	1 Under the name<br> <br><br><br><br>RELIEF THERAPEUTICS Holding SA<br> <br><br><br><br>(RELIEF THERAPEUTICS Holding Ltd.)<br> <br><br><br><br>(RELIEF THERAPEUTICS Holding AG)<br> <br><br><br><br>there exists a share corporation as defined in title 26 of the Swiss Code of Obligations (CO) and in these Articles of Association with its registered office<br>in Geneva, canton of Geneva (the “Company”).
2 La durée de la Société est indéterminée.	2 The duration of the Company is unlimited.
Article 2<br> <br>But	Article 2<br> <br>Purpose
1 La Société a pour but la recherche, le développement, la production et la vente de produits dans les domaines de la biotechnologie, de la pharmacie, du diagnostic, de la thérapie ainsi que l’achat,<br>la vente et l’exploitation de brevets et de licences dans ce domaine. La Société peut s’engager dans tous types de transactions qui semblent appropriées pour promouvoir le but de la Société ou qui y sont<br>liées, y compris l’acquisition, la détention, la gestion, l’aliénation et le financement de	1 The purpose of the Company is to research, develop, produce and sell products in the fields of biotechnology, pharmaceutical, diagnosis, therapy as well as to purchase, sell and use patents and licenses in this field. The Company<br>may engage in all types of transactions that appear appropriate to promote the purpose of the Company or that are related thereto, including the acquisition, the holding, the management, the sale and the financing of direct and indirect<br>participations in enterprises of

Article 3a<br> <br>Capital-actionsautorisé	Article 3a<br> <br>Authorized sharecapital
[Supprimé]	[Deleted]
Article 3a^bis^<br><br><br>Capital-actions autorisé	Article 3a^bis^<br><br><br>Authorized share capital
[Supprimé]	[Deleted]
Article 3a^ter^<br><br><br>Marge de fluctuation de capital	Article 3a^ter^<br><br><br>Capital band
1 Le conseil d’administration est autorisé, en tout temps jusqu’au 30 mai 2024, à augmenter le capital-actions aussi souvent qu’il le souhaite dans les limites inférieures de<br>CHF 56’163’348.00 et supérieures de CHF 66’163’348.00 par l’émission de 2’500’000 actions nominatives au maximum, à libérer entièrement, d’une valeur nominale de<br>CHF 4.00 chacune (marge de fluctuation de capital). Une réduction de capital est exclue. Une augmentation par paiements partiels est autorisée. De plus, dans les limites des art. 659 ss du Code des obligations suisse, une<br>augmentation par nouvelle souscription d’actions par la Société pour offre subséquente à des actionnaires ou à des tiers, ou pour placement auprès de ceux-ci, est<br>autorisée. Le conseil d’administration fixe le montant de l’émission, la date du droit au dividende et le type d’apport. Le conseil d’administration peut émettre de nouvelles actions par le biais d’une<br>prise ferme ou tout autre moyen par une ou plusieurs banques suivie par une offre aux actionnaires ou à des tiers. Le Conseil d’administration est autorisé à autoriser, à restreindre ou à refuser<br>l’échange de droits de souscription. Le conseil d’administration peut	1 The Board of Directors shall be authorized, at any time until 30 May 2024, to increase the share capital at any time and as often as desired within the lower limit of CHF 56’163’348.00 and the upper limit of<br>CHF 66’163’348.00 by issuance of up to 2’500’000 fully paid in registered shares with a nominal value of CHF 4.00 each (capital band). A capital reduction shall be excluded. An increase in partial amounts is permitted.<br>Furthermore, within the limits of Article 659 and ss. of the Swiss Code of Obligations, an increase by original subscription of shares by the Company for the purpose of subsequent offers to shareholders or third parties or distribution among them is<br>permitted. The Board of Directors will determine the appropriate issue price, the date of dividend entitlement and the way of contribution. The Board of Directors may issue new shares by means of underwriting or in any other manner by one or more<br>banks and subsequent offer to shareholders or third parties. The Board of Directors is authorized to permit, to restrict or to deny the trade of subscription rights. The Board of Directors may forfeit unexercised subscription rights, or it can<br>distribute these or the shares for which subscription rights have been granted but not exercised at market conditions or otherwise use them in the interest of the Company.

laisser les droits de souscription non exercés s’éteindre ou peut placer ceux-ci ou les actions nominatives, auxquelles des droits de souscription sont conférés, mais non exercés, sur le marché aux conditions du marché ou les utiliser autrement dans l’intérêt de la Société.

2 Le conseil d’administration est habilité à restreindre ou à exclure les droits de souscription des actionnaires et à l’attribuer à des tiers, ou à la Société, en cas d’utilisation des actions : (1) pour l’acquisition d’entreprises, de parties d’entreprises ou de participations, pour l’acquisition de produits, de propriété intellectuelle ou de licences, ou pour des projets d’investissement ou pour le financement ou le refinancement de telles transactions par le biais d’un placement d’actions; ou (2) dans le but d’élargir le cercle des actionnaires ou dans le cadre d’une cotation d’actions sur des bourses nationales ou étrangères; ou (3) pour la participation de collaborateurs, de membres du Conseil d’administration et de consultants de la Société ou de ses filiales conformément à un ou plusieurs règlements adoptés par le conseil d’administration; ou (4) dans le cadre d’une offre de titres destinée à couvrir l’option “green shoe” (option de répartition des excédents) accordée à une ou plusieurs banques ; ou (5) pour des projets d’investissement et/ou des instruments financiers utilisés sur les marchés des capitaux nationaux ou internationaux; ou (6) pour lever des capitaux de manière rapide et flexible, ce qui serait difficilement réalisable sans l’exclusion des droits de souscription statutaires des actionnaires existants.

2 The Board of Directors is entitled to restrict or exclude the subscription rights of shareholders and to allocate them to third parties, or to the Company, in the event of the use of shares: (1) for the acquisition of companies, parts of companies or participations, for the acquisition of products, intellectual property or licenses, or for investment projects or for the financing or refinancing of such transactions through a placement of shares; or (2) for the purpose of broadening the shareholder constituency or in connection with a listing of shares on domestic or foreign stock exchanges; or (3) for the participation of employees, members of the Board of Directors and consultants of the Company or its subsidiaries in accordance with one or more regulations adopted by the Board of Directors; or (4) in connection with an offering of securities in order to cover the green shoe option (surplus allocation option) granted to one or more banks; or (5) for investment projects and/or financial instruments which are used in national or international capital markets, or (6) for raising capital in a fast and flexible manner, which would hardly be achievable without the exclusion of the statutory subscription rights of the existing shareholders.

3 Si dans le cadre de rachats d’entreprises, de parts d’entreprises ou de participations, ou de nouveaux projets d’investissement, des engagements sont contractés en vue de servir

3 If the Company assumes commitments to serve convertible bonds, loans or similar financial instruments in the context of acquisitions of businesses, business divisions or

les intérêts d’emprunts convertibles, de prêts ou d’autres instruments financiers similaires, le conseil d’administration peut émettre de nouvelles actions afin de remplir les engagements de<br>livraison correspondants, les droits de souscription des actionnaires étant dans ce cas exclu.	participations, or of investment projects, the Board of Directors is entitled to issue new shares under exclusion of the subscription rights of shareholders in order to fulfil the corresponding delivery obligations.
Article 3b^bis^<br><br><br>Capital-actions conditionnel	Article 3b^bis^<br><br><br>Conditional share capital
1 Le capital-actions de la Société est augmenté par l’émission d’un maximum de 264’424 actions nominatives d’une valeur nominale de CHF 4.00 chacune et devant être<br>entièrement libérées, pour un montant nominal de CHF 1’057’696.00, en cas d’exercice de droits d’option octroyés à des employés, des membres du conseil d’administration et des<br>conseillers de la Société ou de ses filiales. En cas d’émission d’actions, d’options ou de droits de souscription connexes, le droit de souscription ainsi que le droit de souscription préférentiel<br>des actionnaires de la Société sont exclus. Les droits d’option pour des employés, des membres du conseil d’administration et des conseillers sont octroyés par la Société. Le conseil<br>d’administration fixe les conditions d’option, telles que le montant d’émission, la date du droit au dividende et le type d’apport dans le cadre de règlements. L’exercice des droits d’option et la<br>renonciation à ce droit sont effectués par écrit sur papier ou sous forme électronique.	1 The share capital of the Company may be increased by the issuance of up to 264’424 registered shares to be fully paid up, each with a par value of CHF 4.00 to the nominal value of CHF 1’057’696.00 through<br>the exercise of options granted to employees, members of the Board of Directors and consultants of the Company or its subsidiaries. The subscription rights and preemptive rights of the shareholders of the Company are excluded in connection with the<br>issuance of any shares, options or subscription rights thereof. The option rights for employees, members of the Board of Directors and consultants are issued by the Company. The terms of the options, such as the issue price of the shares, date of<br>dividend entitlement and way of contribution are determined by the Board of Directors in the context of regulations. The exercise of the option rights and the waiver of such right shall be made in writing on paper or in electronic form.
2 Le capital-actions de la Société est augmenté par l’émission d’un maximum de 3’907’500 d’actions nominatives d’une valeur nominale de CHF 4.00 chacune et devant<br>être entièrement libérées, pour un montant nominal maximum de CHF 15’630’000.00, en cas d’exercice de droits de conversion ou d’option, qui ont été octroyés	2 The Company’s share capital may be increased by the issuance of up to 3’907’500 registered shares to be fully paid up, each with a par value of CHF 4.00 to a nominal value of CHF 15,630,000.00 by the<br>exercising of conversion or option rights granted to entitled parties in connection with bonds and similar

aux personnes légitimées en rapport avec l’émission d’emprunts ou d’instruments financiers semblables, ou de prêts par la Société ou de ses filiales et qui donne le droit à une conversion en actions, ou de droits d’option qui ont été octroyés aux actionnaires existants et/ou de nouveaux actionnaires dans le cadre d’augmentations de capital. Les droits de souscription des actionnaires sont exclus. Les conditions d’exercice des droits de conversion et/ou d’option, le montant d’émission et la date du droit au dividende seront déterminés par le conseil d’administration. Le conseil d’administration peut limiter ou exclure les droits de souscription préférentiels des actionnaires: (1) pour le financement ou le refinancement de l’acquisition d’entreprises, de parties d’entreprises, de participations ou d’investissements; (2) pour le financement ou le refinancement de la Société ou de ses filiales; (3) pour l’émission d’emprunts convertibles ou à option dans le but de placements sur les marchés des capitaux nationaux ou internationaux pour l’élargissement stratégique du cercle d’investisseurs, y compris le placement auprès d’un ou de plusieurs partenaires stratégiques (placement privé inclus); (4) dans le but d’une prise ferme de telles obligations et d’autres instruments financiers par une ou plusieurs banques suivie d’une offre publique; ou si l’émission a lieu sur des marchés de capitaux nationaux ou internationaux; ou (5) par le biais d’un placement privé. Si les droits de souscription préférentiels sont exclus ou ne sont pas accordés indirectement: (i) les emprunts convertibles ou à option doivent être placés aux conditions du marché et (ii) la période d’exercice des droits de conversion et d’option doit être fixée à 10 ans au maximum à compter du moment de l’émission correspondante. Les droits d’options qui ont été

financial instruments or loans of the Company or its subsidiaries that allow for conversion into shares of the Company, or option rights granted to existing and/or new shareholders in connection with capital increases. Subscription rights of shareholders are excluded. The Board of Directors shall determine the conversion and option terms, the issue price and the date of dividend entitlement. The Board of Directors is authorized to limit or exclude the preemptive rights of existing shareholders in the event: (1) of the financing or refinancing of the acquisition of enterprises, parts of enterprises, participations or investments, (2) of the financing or refinancing of the Company or its subsidiaries, (3) of the issuance of convertibles and/or option bonds for the purpose of placement on national or international capital markets (including private placements), (4) for purposes of the underwriting of such bonds and other financial instruments by one or more banks with subsequent public offer; or if the issuance occurs in national or international capital markets, or (5) through a private placement. If the preemptive rights of existing shareholders are excluded and not even granted indirectly, (i) convertibles or option bonds are to be issued on market terms and (ii) the time limit for the exercising of conversion and/or option rights must be set at a maximum of 10 years from the date of the relevant issue. Option rights granted to existing and/or new shareholders in connection with capital increases shall have a time limit for exercising of up to 5 years. The exercise of the option rights and the waiver of such right shall be made in writing on paper or in electronic form.

octroyés aux actionnaires existants et aux nouveaux actionnaires dans le cadre d’augmentations du capital ont une période d’exercice d’au maximum 5 ans. L’exercice des droits d’option et la<br>renonciation à ce droit sont effectués par écrit sur papier ou sous forme électronique.
Article 3c	Article 3c
[Supprimé]	[Deleted]
Article 3d<br> <br>Capital-actionsconditionnel II	Article 3d<br> <br>Conditional share capitalII
[Supprimé]	[Deleted]
Article 3e	Article 3e
[Supprimé]	[Deleted]
Article 4<br> <br>Forme desactions	Article 4<br> <br>Form ofShares
1 Sous réserve des alinéas 4 et 6, les actions nominatives de la Société sont émises sous forme de droits-valeurs et sont gérées sous la forme de titres<br>intermédiés.	1 The Company’s registered shares are issued and managed subject to paragraphs 4 and 6 as book-entry securities.
2 Les actes de dispositions sur les titres intermédiés, y compris la constitution de sûretés, sont soumis à la Loi fédérale sur les titres intermédiés.	2 Regulations on book-entry securities, including the provision of collateral, are subject to the law on book-entry securities
3 Les titre intermédiés basés sur des actions nominatives de la Société ne peuvent pas être transférés par voie de cession. En outre, une sûreté sur de tels titres<br>intermédiés ne peut pas être accordée par voie de cession.	3 Book-entry securities based on registered shares of the Company cannot be transferred by way of assignment. Further, a security interest in any such book-entry securities cannot be granted by way of assignment.

4 La Société peut retirer du système de détention les actions émises sous la forme de titres intermédiés.	4 The Company may withdraw shares managed as book-entry securities from the custody system.
5 L’actionnaire peut, pour autant qu’il soit inscrit au registre des actions, demander en tout temps à la Société de lui établir une attestation relative à ses actions nominatives.	5 The shareholder may, if he is registered in the stock book, at any time request the Company to issue a certificate of his registered shares.
6 L’actionnaire n’a pas de droit à l’impression et à la livraison de titres ou à la conversion en une autre forme des actions nominatives émises sous une certaine forme. Par contre, la<br>Société peut à tout moment imprimer et livrer des titres (titres individuels, certificats ou certificats globaux) ou remplacer des droits-valeurs ou des titres par une autre forme, et annuler des titres émis qui lui sont<br>restitués.	6 The shareholder has no right to print and deliver certificates or conversions of registered shares issued in a specific form in another form. The Company may however at any time issue certificates (individual documents and<br>certificates or global certificates) or convert book-entry securities or certificates into a different form and cancel issued certificates delivered to it.
Article 5<br> <br>Registre des actions,restrictions d’inscription, Nominees	Article 5<br> <br>Share register,Registration Restrictions, Nominees
1 Il est tenu un registre des actions nominatives qui mentionne le nom et le prénom (pour les personnes morales, la raison sociale), l’adresse et la nationalité (pour les personnes morales, le siège) des<br>propriétaires et des usufruitiers. Si une personne inscrite au registre des actions change son adresse, elle est tenue d’en informer la Société. Tant que cette annonce n’est pas intervenue, toutes les communications<br>par courrier sont valablement faites à l’adresse inscrite en dernier dans le registre des actions. A l’égard de la Société, seules les personnes inscrites au registre des actions sont considérées<br>comme actionnaires ou usufruitiers.	1 For the registered shares a share register is kept, in which the surname and the first name of holders and usufructuaries are entered (for legal entities, the Company name), together with address and nationality (for legal<br>entities, the registered office). Should a person entered in the share register change their address, they must inform the Company. Where this has not been done, all written communications are valid if made to the address entered in the share<br>register. In relation to the Company, only the person or entity entered in the share register is recognized as a shareholder or usufructuary.

2 Les acquéreurs d’actions nominatives sont inscrits sur demande au registre des actions en tant qu’actionnaires avec droit de vote s’ils déclarent expressément avoir acquis ces actions nominatives en leur propre nom et pour leur propre compte.

2 Purchasers of registered shares will be entered upon request in the share register as shareholders with voting rights if they explicitly declare that they have acquired these registered shares in their own name and for their own account.

3 Nonobstant ce qui précède, le conseil d’administration peut inscrire des personnes qui ne déclarent pas avoir acquis leurs actions nominatives en leur propre nom et pour leur propre compte (chacune de ces personnes étant un “Nominee”) en tant qu’actionnaires avec droit de vote dans le registre des actions de la Société pour un nombre d’actions nominatives de la Société qui représente jusqu’à 2% du capital-actions de la Société inscrit au registre du commerce. Le conseil d’administration peut également inscrire un Nominee en tant qu’actionnaire avec droit de vote au-delà de la limite de 2% susmentionnée si le Nominee concerné s’engage à communiquer à la Société, sur demande, le nom et le prénom (pour les personnes morales, la raison sociale), ainsi que l’adresse (pour les personnes morales, le siège social) des personnes pour le compte desquelles le Nominee concerné détient 2% ou plus du capital-actions de la Société inscrit au registre du commerce, ainsi que le nombre d’actions nominatives de la Société détenues par le Nominee concerné pour le compte de ces personnes.

3 Notwithstanding the foregoing, the Board of Directors may register persons who do not declare that they have acquired their registered shares in their own name and for their own account (each such person a “Nominee”) as shareholders with voting rights in the share register of the Company with respect to a number of registered shares of the Company that represents up to 2% of the share capital of the Company registered in the commercial register. The Board of Directors may further register a Nominee as a shareholder with voting rights beyond the 2% limit referred to above if the relevant Nominee undertakes to communicate to the Company, upon request, the surname and first name (for legal entities, the company name), together with the address (for legal entities, the registered office) of the persons for whose account the relevant Nominee holds 2% or more of the share capital of the Company registered in the commercial register, and the number of registered shares of the Company held by the relevant Nominee for the account of such persons.

4 Après avoir entendu l’actionnaire inscrit concerné, le conseil d’administration peut le cas échéant radier l’inscription de cet actionnaire en tant qu’actionnaire avec droit de vote au registre des actions avec effet rétroactif à la date d’inscription si l’inscription a été faite sur la base d’informations fausses ou trompeuses ou en cas

4 The Board of Directors may, after hearing the registered shareholder concerned, where appropriate, remove the registration of such shareholder as a shareholder with voting rights in the share register with retroactive effect to the date of registration if the registration was made on the basis of false or misleading information or

de violation du contrat entre la Société et l’actionnaire concerné. L’intéressé doit être informé de la radiation.	in the event of a breach of the agreement between the Company and the shareholder concerned. The party concerned must be informed of the cancellation.
5 Le conseil d’administration établit les détails et émet les instructions nécessaires au respect des dispositions précédentes. Dans des cas particuliers, il peut accorder des<br>dérogations à la règle concernant les Nominees. Le conseil d’administration peut déléguer ses tâches.	5 The Board of Directors establishes the details and issues the instructions necessary for compliance with the preceding provisions. In special cases, it may grant exemptions from the rule concerning Nominees. The board of directors<br>may delegate its duties.
6 Le conseil d’administration indique dans la convocation à l’assemblée générale le jour de référence de l’inscription dans le registre des actions pour la participation et<br>les droits de vote à l’assemblée générale.	6 The Board of Directors announces in the invitation to the General Meeting the closing date for entry in the share register for participation and voting rights.
Article 6<br> <br>Offre publiqued’acquisition	Article 6<br> <br>Public takeoverbid
L’acquéreur d’actions de la Société n’est pas tenu de présenter une offre publique d’acquisition conformément aux dispositions de l’art. 135 de la Loi sur<br>l’infrastructure des marchés financiers (LIMF).	A purchaser of shares in the Company is not obliged to make a public purchase offer in accordance with the provisions of Article 135 of the Financial Market Infrastructure Act (FMIA).
III. Organes de la Société	III. Company organization
Article 7<br> <br>Organes	Article 7<br> <br>Organs
Les organes de la Société sont:	The organs of the Company are as follows:
A. l’assemblée générale	A. General Meeting
B. le conseil d’administration	B. Board of Directors
C. l’organe de révision	C. Auditors

A. Assemblée générale	A. General Meeting
Article 8<br> <br>Pouvoirs	Article 8<br> <br>Powers
L’assemblée générale est le pouvoir suprême de la société. Elle a les droits intransmissibles prévus par la loi.	The supreme organ of the Company is the General Meeting. It shall have the inalienable powers decreed by law.
Article 9<br> <br>Assembléesgénérales ordinaires et extraordinaires	Article 9<br> <br>Ordinary and ExtraordinaryGeneral Meetings
1 L’assemblée générale ordinaire a lieu chaque année dans les six mois qui suivent la clôture de l’exercice.	1 The Annual General Meeting takes place within six months after the close of the financial year.
2 Les assemblées générales extraordinaires ont lieu lorsque le conseil d’administration ou l’organe de révision estime que cela est nécessaire ou par décision d’une<br>assemblée générale. Au surplus, les actionnaires représentant ensemble 10 pour cent au moins du capital-actions peuvent requérir par écrit la convocation d’une assemblée générale<br>extraordinaire, en indiquant l’objet à porter à l’ordre du jour et les propositions, ou, dans la mesure où il s’agit d’élections, en indiquant les noms des candidats proposés.	2 Extraordinary General Meetings take place when the Board of Directors or the Auditors deem this to be appropriate, or as decided by a General Meeting. In addition, shareholders representing at least 10 percent of the share<br>capital, may jointly request the calling of an extraordinary General Meeting, in writing specifying the items to be discussed, and the proposal, and in the case of elections, the name of the proposed candidate.
Article 10 Convocation	Article 10 Convocation
1 L’assemblée générale est convoquée par le conseil d’administration ou par les organes et les personnes indiquées par la loi.	1 The General Meeting is convened by the Board of Directors or by the organs and people designated by law.
2 L’assemblée générale est convoquée par une seule annonce dans la feuille officielle suisse du	2 The meeting is called by a single announcement in the Swiss Commercial

commerce. Les actionnaires nominatifs peuvent au surplus être informés par courrier simple à l’adresse inscrite en dernier dans le registre des actions. Sont mentionnés dans la convocation de<br>l’assemblée générale les objets portés à l’ordre du jour, ainsi que les propositions du conseil d’administration et des actionnaires qui ont demandé la convocation de l’assemblée<br>ou l’inscription d’un objet à l’ordre du jour.	Gazette. Registered shareholders may in addition be informed in writing. In the convocation, the agenda as well as the proposals of the Board of Directors and the shareholders who requested a General Meeting or the listing of an<br>item on the agenda are to be announced.
3 Le rapport de gestion et le rapport de révision doivent être mis à la disposition des actionnaires au siège de la Société, au moins 20 jours avant l’assemblée<br>générale ordinaire. Cela doit être mentionné dans la convocation.	3 At least twenty days before the Annual General Meeting, the Annual Report and the Audit Report are to be presented at the Company’s head office for inspection by the shareholders. This must be mentioned in the<br>convocation.
4 Les propriétaires ou les représentants de la totalité des actions peuvent, s’il n’y a pas d’opposition, tenir une assemblée générale sans observer les formes prévues<br>pour sa convocation (assemblée universelle). Aussi longtemps que les propriétaires ou les représentants de la totalité des actions sont présents, cette assemblée a le droit de délibérer et de<br>statuer valablement sur tous les objets qui sont du ressort de l’assemblée générale.	4 The owners or representatives of all shares may, if no objection is raised, hold a General Meeting without compliance with the prescribed formalities for convening (General Meeting). This meeting can validly discuss and decide<br>upon any matters within the remit of the General Meeting provided that the holders or representatives of all the shares are present.
Article 11 Ordre du jour	Article 11 Agenda
1 Un ou plusieurs actionnaires qui représentent ensemble des actions totalisant une valeur nominale d’au moins CHF 1’000’000 ou au moins 10 pour cent du capital-actions peuvent requérir<br>l’inscription d’un objet à l’ordre du jour. La réquisition de l’inscription d’un objet à l’ordre du jour doit être faite au conseil d’administration par écrit au moins 45 jours<br>avant l’assemblée, avec indication de l’objet à inscrire à l’ordre du jour et les propositions des actionnaires.	1 Shareholders representing either alone or together shares with a nominal value of at least CHF 1,000,000 or at least 10 percent of the share capital may request the inclusion of an agenda item. The inclusion of the agenda<br>item must be applied for in writing to the Board of Directors at least 45 days before the meeting and shall specify the agenda item and the shareholders’ proposals.

2 Aucune décision ne peut être prise sur des objets qui n’ont pas été dûment portés à l’ordre du jour, à l’exception des propositions de convoquer une<br>assemblée générale extraordinaire ou d’instituer un contrôle spécial.	2 The General Meeting cannot take any decisions regarding applications for items not duly announced; exceptions to this are applications for the convening of an extraordinary General Meeting or the conducting of a special<br>audit.
3 Il n’est pas nécessaire d’annoncer à l’avance les propositions entrant dans le cadre des objets portés à l’ordre du jour ni les délibérations qui ne doivent pas<br>être suivies d’un vote.	3 Requests for items to be included on the agenda and for discussion without the taking of a decision do not require prior notice.
Article 12 Présidence de l’assemblée générale, représentation, scrutateurs, procès-verbal	Article 12 Chair of the General Meeting, Representatives, Vote Counters, Minutes
1 L’assemblée générale est présidée par le président du conseil d’administration ou, à défaut de celui-ci, par un membre du<br>conseil d’administration. Lorsque ces derniers sont également absents, un président du jour sera désigné par l’assemblée générale.	1 The Chairman of the Board of Directors shall preside at the General Meeting, and in his absence any member of the Board of Directors. If they are absent too, the chairman is elected by the General Meeting.
2 Le président dispose de toutes les compétences nécessaires pour assurer un déroulement ordonné et régulier de l’assemblée générale.	2 The chairman has all the powers and authority necessary for the proper conducting of the General Meeting.
3 Le président de l’assemblée désigne un secrétaire et les scrutateurs, qui ne doivent pas nécessairement être actionnaires.	3 The chairman appoints a recording secretary and scrutinizer, who do not need to be shareholders.
4 Le conseil d’administration veille à la rédaction du procès-verbal, lequel doit être signé par le président et le secrétaire de<br>l’assemblée. Le procès-verbal mentionnera les décisions et le résultat des élections, de même que les déclarations dont les actionnaires demandent<br>l’inscription.	4 The Board of Directors is responsible for writing the minutes, which are to be signed by the chairman and the secretary. The minutes shall give information about decisions and elections and to declarations made on record by the<br>shareholders.

Article 13 Droit de vote, représentation	Article 13 Voting rights, Representation
1 Chaque action qui est inscrite au registre des actions en tant qu’action assortie d’un droit de vote donne droit à une voix. Les droits de vote et les droits annexes qui y sont associés ne peuvent<br>être exercés à l’égard de la société par un actionnaire, un usufruitier d’actions ou une personne désignée que dans la mesure où cette personne est inscrite au registre des<br>actions en tant qu’actionnaire ayant les droit de vote.	1 Each share registered as a share with voting rights in the share register gives entitlement to one vote. Voting rights and appurtenant rights associated therewith may be exercised in relation to the Company by a shareholder,<br>usufructuary of shares or nominee only to the extent that such person is recorded in the share register as a shareholder with voting rights.
2 Un actionnaire ne peut être représenté à l’assemblée générale que par son représentant légal, qui ne doit pas nécessairement être actionnaire, ou par<br>le biais d’une procuration écrite ou électronique, ou par un autre actionnaire ayant les droits de vote, ou par le représentant indépendant des droits de vote (par biais d’une procuration écrite ou<br>électronique). Toutes les actions détenues par un actionnaire ne peuvent être représentées que par un seul représentant. La Société n’accepte qu’un seul représentant par<br>action.	2 A shareholder may only be represented at the General Meeting of shareholders by his legal representative, who does not have to be a shareholder, or by means of a written or electronic proxy, or another shareholder with voting<br>rights, or the independent proxy (by way of a written or electronic proxy). All shares held by one shareholder must be represented by only one representative. The Company shall only accept one representative per share.
3 Le conseil d’administration peut prendre les dispositions relatives à la participation à l’assemblée générale, à la représentation et la reconnaissance de procuration,<br>ainsi que celles relatives à l’utilisation de procurations et instructions par voie électronique.	3 The Board of Directors may issue the procedural rules regarding admission to the General Meeting, representation and the recognition of proxies as well as the grant of proxies and instructions by electronic means.
4 L’assemblée générale élit chaque année le représentant indépendant pour un mandat qui s’achève à la fin de l’assemblée générale<br>ordinaire suivante. Le représentant indépendant est rééligible.	4 The General Meeting elects the independent proxy annually. The term of office ends with the conclusion of the next ordinary General Meeting. Re-election is possible.

5 Lorsque la Société n’a pas de représentant indépendant pour quelque raison que ce soit, le conseil d’administration désigne le représentant indépendant pour la prochaine<br>assemblée générale des actionnaires.	5 If the Company does not have an independent proxy for whatever reason, the Board of Directors shall appoint the independent proxy for the next General Meeting.
Article 14 Décisions, élections	Article 14 Decisions, Elections
1 L’assemblée générale est habilitée à prendre ses décisions quel que soit le nombre des actionnaires présents ou des actions représentées.	1 The General Meeting forms a quorum regardless of the number of shareholders present or the shares represented.
2 Si la loi ou les statuts n’en disposent pas autrement, l’assemblée générale prend ses décisions et procède aux élections à la majorité absolue des voix<br>attribuées aux actions représentées, abstraction faite des abstentions et des bulletins blancs ou nuls. Si une élection n’aboutit pas au premier tour et s’il y a plusieurs candidats en lice, la majorité<br>relative suffit au second tour.	2 The General Meeting shall pass its resolutions and carry out its elections with an absolute majority of the votes cast, excluding abstentions, blank and invalid votes, provided that the law or the articles of association contain<br>no provisions to the contrary. In case of elections, if an election is not made in the first-round of voting and if more than one candidate is available, a relative majority is sufficient in the second round.
3 En cas d’égalité des voix, le président de l’assemblée n’a pas voix prépondérante.	3 In case of equal votes, the chairman has no casting vote.
4 Les décisions et les élections interviennent à main levée, à moins que l’assemblée générale ne décide de prendre les décisions ou de procéder aux<br>élections par bulletin secret ou que le président de l’assemblée ne l’ordonne. Le président de l’assemblée peut ordonner qu’il soit procédé aux décisions ou élections<br>par voie électronique. Le président de l’assemblée peut toujours remplacer une décision ou une élection à main levée par une délibération à bulletin secret, s’il estime<br>qu’il y a un doute quant au résultat du vote. Si tel est le cas, la délibération antérieure à main levée est réputée n’avoir pas eu lieu.	4 Decisions are taken by open vote in the General Meeting, unless the General Meeting approves a written vote or the chairman orders such. Voting can also be carried out electronically on the orders of the chairman. The chairman may<br>have an open vote repeated at any time by a written or electronic ballot, where, in his opinion, there are doubts about the vote. In this case, the previous vote is considered not to have occurred.

Article 15 Décisions importantes	Article 15 Important decisions
1 Une décision de l’assemblée générale recueillant au moins les deux tiers des voix<br>représentées et la majorité absolue des valeurs nominales représentées est nécessaire pour :<br> <br><br><br><br>1. La modification du but social;<br><br><br><br> <br>2. La création et la<br>suppression des actions à droit de vote privilégié;<br> <br><br><br><br>3. La restriction de la transmissibilité des actions nominatives;<br><br><br><br> <br>4. L’augmentation<br>autorisée ou conditionnelle du capital-actions;<br> <br><br><br><br>5. L’augmentation du capital par conversion d’un excédent de capital, par apport en<br>nature ou en vue de l’acquisition d’actifs, ou par l’octroi de privilèges spéciaux;<br> <br><br><br><br>6. La limitation ou la suppression du droit de souscription préférentiel;<br><br><br><br> <br>7. Le transfert du siège de<br>la Société;<br> <br><br> <br>8. La<br>dissolution de la Société.	1 A decision by the General Meeting consolidating at least two thirds of the votes represented and an absolute majority of the share par<br>values represented is required for:<br> <br><br><br><br>1. A change in the corporate purpose;<br><br><br><br> <br>2. The creation and abolition of<br>shares with privileged voting rights;<br> <br><br><br><br>3. Restriction on the transferability of registered shares;<br><br><br><br> <br>4. Authorized or conditional capital<br>increase;<br> <br><br> <br>5. Capital increase<br>through the conversion of capital surplus, through contribution in kind or for the purpose of acquisition of assets, or the granting of special privileges;<br> <br><br><br><br>6. The restriction or abolition of subscription rights;<br><br><br><br> <br>7. The relocation of the registered<br>office of the Company;<br> <br><br> <br>8. The<br>dissolution of the Company.
2 Les décisions concernant la fusion, la scission et la transformation sont régies par les dispositions de la Loi Suisse sur la fusion.	2 Decisions on mergers, divisions and transformations shall be governed by the provisions of the Swiss merger law.
3 Les dispositions statutaires qui prévoient pour la prise de certaines décisions une plus forte majorité que celle prévue par la loi ne peuvent être adoptées ou modifiées<br>qu’à la majorité prévue.	3 Provisions of the articles of association that specify a majority greater than that decreed by law for the taking of certain decisions shall only be introduced or modified with the specified majority.

B. Conseil d’administration	B. Board of Directors
Article 16 Election, durée des fonctions, constitution	Article 16 Election, Term of Office, Constitution
1 La Société est gérée par un conseil d’administration composé d’1 (un) ou plusieurs membres, élus individuellement par l’assemblée générale chaque<br>année pour un mandat qui s’achève à la fin de l’assemblée générale ordinaire suivante. Une réélection est possible.	1 The Company is managed by a Board of Directors composed of 1 (one) to more members, elected annually and individually by the General Meeting for a term of office extending until completion of the next ordinary General Meeting. Re-election is possible.
2 Lorsque la fonction de président du conseil d’administration est vacante, le conseil d’administration désigne le vice-président ou éventuellement un<br>autre membre comme nouveau président pour la période allant jusqu’à la fin de l’assemblée générale ordinaire suivante.	2 If the office of the chairman is vacant, the Board of Directors shall appoint a new chairman from among its members for the remaining term of office.
3 Sous réserve de l’élection du président du conseil d’administration et des membres du comité de nomination et de rémunération, le conseil d’administration se constitue lui-même. Si le conseil d’administration est composé de plus d’1 (un) membre, il élit un président et, éventuellement, un<br>vice-président et/ou un secrétaire, qui n’a pas besoin d’être un membre.	3 Except for the election of the chairman and the members of the nomination and compensation committee by the General Meeting, the Board of Directors shall constitute itself. If the Board of Directors is composed of more than 1<br>(one) member, it shall elect a chairman, possibly a vice-chairman and/or a secretary. The latter need not be a member of the Board of Directors.
4 Le conseil d’administration définit par ailleurs, dans les limites de la loi et des statuts, son organisation et les modalités de prise de ses décisions dans un règlement d’organisation.	4 The Board of Directors arranges moreover, subject to law and the articles of association, its own organization and decision-making by means of regulations.

Article 17 Pouvoirs et compétences	Article 17 Functions and powers
1 Le conseil d’administration exerce la haute direction de la Société et la surveillance sur les personnes chargées de la gestion.	1 The Board is responsible for the leadership of the Company and the monitoring of its management.
2 Le conseil d’administration peut prendre des décisions sur toutes les affaires qui ne sont pas attribuées par la loi ou les statuts à l’assemblée générale. Il gère les<br>affaires de la Société, dans la mesure où il n’en a pas délégué la gestion. Il représente la Société<br>vis-à-vis des tiers et s’occupe de toutes les affaires dont la responsabilité n’est pas, en vertu de la loi, des statuts ou du règlement,<br>du ressort d’un autre organe de la Société.	2 The Board of Directors may take decisions on all matters that are not delegated by law or the articles of association to the General Meeting. It shall lead all operations of the Company, where it has not delegated its management.<br>It represents the Company externally and attends to all matters that are not under the law, articles of association or regulations of the Company delegated to another body.
3 Le conseil d’administration peut, sur la base d’un règlement d’organisation, déléguer tout ou partie de la gestion de la Société à une ou plusieurs personnes, membres du<br>conseil d’administration ou des tiers qui ne doivent pas nécessairement être actionnaires. Le règlement d’organisation fixe les modalités de la gestion, détermine les postes nécessaires à cet<br>égard, en définit les attributions et règle en particulier l’obligation de rendre compte.	3 The Board of Directors may, in accordance with organizational rules, assign the Company management or individual parts thereof to one or more persons, members of the Board of Directors or third parties, who do not need to be<br>shareholders. The organizational rules regulate the management, the positions required for it, define their tasks and in particular regulate reporting.
Article 18 Décisions, procès-verbal	Article 18 Decisions, Minutes
Le président ou, en cas d’empêchement, le vice-président ou tout autre membre du conseil d’administration convoque les réunions du conseil<br>d’administration si et quand le besoin s’en fait sentir ou lorsqu’un membre en indiquant les raisons en fait la demande par écrit. Les réunions peuvent également se tenir par téléphone ou par<br>vidéoconférence.	1 The chairman or, should he be unable to do so, the vice-chairman or any other member of the Board of Directors shall convene meetings of the Board of Directors if and when the need arises or whenever a member indicating the<br>reasons so requests in writing. Meetings may also be held by telephone or video conference.

2 Le conseil d’administration atteint le quorum si la majorité de ses membres sont présents. Pour les résolutions prises par acte authentique notamment celles relatives aux augmentations de capital, aux<br>fusions, aux scissions ou aux paiements ultérieurs du capital, la présence d’un membre du conseil d’administration est suffisante.	2 The Board of Directors forms a quorum if a majority of its members are present. For resolutions taken by Public deed, in particular related to capital increases, mergers, demergers or subsequent payments of capital, the presence<br>of one member of the Board of Directors is sufficient.
3 Sous réserve des dispositions du règlement d’organisation, le conseil d’administration se réunit aussi souvent que les affaires l’exigent et aussi souvent que l’un de ses membres en fait la<br>demande. Sous réserve des dispositions du règlement d’organisation, le conseil d’administration prend ses décisions à la majorité des voix des membres présents. En cas d’égalité<br>des voix, le président a voix prépondérante.	3 Subject to the provisions of the organizational rules, the Board of Directors meets as often as business requires and as often as is requested by a member. Subject to the provisions of the organizational rules, decisions are made<br>by majority vote of members present. In the event of a tie, the chairman has the casting vote.
4 Les résolutions du conseil peuvent, dans la mesure où la loi n’en dispose pas autrement, être adoptées par circulaire en utilisant le fax, le courrier conventionnel, le courrier électronique<br>ou d’autres moyens de transmission qui permettent une vérification de la résolution par le texte, à moins qu’un membre ne demande une consultation verbale.	4 Resolutions of the Board of Directors can, as far as not stated otherwise by law, be adopted by circular using fax, conventional mail, e-mail or other means of transmission which allow for a<br>verification of the resolution through text, unless a member demands verbal consultation.
5 Les résolutions sont confirmées dans le procès-verbal, qui doit être signé par le président en exercice et le secrétaire.	5 The resolutions shall be confirmed in the minutes, which are to be signed by the acting chairman and the secretary.

C. Comité de nomination et de rémunération du conseild’administration	C. Nomination and Compensation Committee of the Board of Directors
Article 19 Membres, durée des fonctions, constitution	Article 19 Election, Term of Office, Constitution
1 Le comité de nomination et de rémunération est composé d’au moins 1 (un) membre du conseil d’administration.	1 The Nomination and Compensation Committee shall be composed of a minimum of 1 (one) member of the Board of Directors.
2 L’assemblée générale élit les membres du comité de nomination et de rémunération chaque année et individuellement pour la durée d‘un mandat<br>jusqu’à la prochaine assemblée générale ordinaire. La réélection est possible.	2 The members of the Nomination and Compensation Committee are elected annually and individually by the General Meeting for a term of office extending until completion of the next ordinary General Meeting. Re-election is possible.
3 Lors de vacances dans le comité de nomination et de rémunération, le conseil d’administration désigne parmi ses membres les membres manquants jusqu’à la prochaine assemblée<br>générale ordinaire.	3 If the Nomination and Compensation Committee is not complete, the Board of Directors shall fill the open positions for the remaining term of office.
4 Le comité de nomination et de rémunération se constitue lui-même. Il désigne parmi ses membres un président. Le conseil d’administration peut<br>adopter un règlement sur l‘organisation, les devoirs et la prise de décisions du comité de nomination et de rémunération.	4 The Nomination and Compensation Committee is self-constituting. It determines its chairman. The Board of Directors may determine the duties and organization in a separate Charter for the Nomination and Compensation<br>Committee.
Article 20 Pouvoirs et compétences	Article 20 Functions and powers
1 Le comité de nomination et de rémunération soutient le conseil d’administration lors de la planification de la succession des membres du conseil d’administration et de la direction.	1 The Nomination and Compensation Committee shall support the Board of Directors in the successors planning of the members of the Board of Directors and of the Executive Committee.

2 Le comité de nomination et de rémunération soutient le conseil d’administration lors de la détermination et du contrôle de la politique et des directives de rémunération ainsi<br>que des objectifs de performance. De plus, il soutient aussi le conseil d’administration lors de la préparation des propositions destinées à l’assemblée générale concernant la<br>rémunération du conseil d’administration et de la direction. Le comité de nomination et de rémunération peut soumettre des propositions au conseil d’administration sur d’autres questions relatives<br>aux rémunérations.	2 The Nomination and Compensation Committee shall support the Board of Directors in establishing and reviewing the compensation strategy and guidelines and the performance objectives as well as in preparing the proposals to the<br>General Meeting regarding the compensation of the Board of Directors and of the Executive Committee, and may submit proposals to the Board of Directors in other compensation-related issues.
3 Le conseil d’administration peut attribuer au comité de nomination et de rémunération d’autres obligations relatives aux rémunérations, au personnel et aux domaines connexes.	3 The Board of Directors may delegate further tasks to the Nomination and Compensation Committee regarding compensation, personnel, and any other related fields.
D. Organe de révision	D. External Auditor
Article 21	Article 21
1 L’assemblée générale élit, pour une durée d’un an jusqu’à la fin de la prochaine assemblée générale ordinaire une entreprise de révision soumise<br>à la surveillance de l’Etat au sens de la Loi sur la surveillance de la révision (LSR) en tant qu’organe de révision. L’organe de révision assume les pouvoirs et obligations qui lui sont attribués<br>par la loi.	1 The General Meeting shall elect an external auditor under state supervision in accordance with the Federal Law on the Accreditation and Supervision of Auditors (RAG) for a term in office, which shall expire upon conclusion of the<br>next ordinary General Meeting. The external auditor shall comply with auditing and reporting duties in accordance with the relevant statutory provisions.

IV. Rémunération des membres du conseil d’administration et de ladirection	IV. Remuneration of the members of the Board of Directors and the ExecutiveCommittee
Article 22<br> <br>Approbation desrémunérations	Article 22<br> <br>Approval ofRemuneration
1 L’assemblée générale approuve chaque année, de façon spécifique et contraignante les<br>propositions du conseil d’administration concernant les montants globaux:<br> <br><br> <br>-<br>pour la rémunération maximale du conseil d’administration pour la durée jusqu’à la prochaine assemblée générale ordinaire; et<br><br><br><br> <br>- pour la rémunération maximale de la direction pour le prochain exercice<br>social.	1 The General Meeting shall annually, separately and bindingly approve the proposals of the Board of Directors concerning the maximum overall<br>amounts:<br> <br><br> <br>- of the maximum remuneration of the Board of Directors for the<br>time-period until the next ordinary General Meeting; and<br> <br><br> <br>- of the maximum<br>remuneration of the Executive Committee for the following financial year.
2 Le conseil d’administration peut faire des propositions s’écartant de ou supplémentaires à l’alinéa 1, ou diviser les divers éléments de rémunération et/ou les<br>soumettre pour approbation à l’assemblée générale par rapport aux autres périodes de temps.	2 The Board of Directors may present deviating or additional proposals for approval by the General Meeting than determined in para 1 above, or may divide its respective proposals into other compensation elements and/or submit them<br>for approval by the General Meeting with respect to different periods.
3 Si l’assemblée générale refuse l’approbation à un montant global ou plusieurs parties de montant, le conseil d’administration peut alors faire une nouvelle proposition lors de la<br>même assemblée générale. S’il ne fait pas de proposition ou si celle-là est aussi refusée, le conseil d’administration peut alors convoquer une nouvelle<br>assemblée générale et lui soumettre de nouvelles propositions à approuver quant aux montants globaux ou aux montants partiels.	3 If the General Meeting withholds its approval, the Board of Directors may submit new proposals for approval to the same General Meeting. If the Board of Directors makes no new proposals or if the General Meeting likewise declines<br>the new proposals, the Board of Directors may convene a new General Meeting and submit new proposals.

4 La Société ou les sociétés qu’elle contrôle peuvent, sous réserve de l’approbation par l’assemblée générale ainsi que des dispositions pertinentes sur le<br>remboursement, verser des indemnités avant l’approbation par l’assemblée générale.	4 The Company or companies controlled by it may pay or grant compensation prior to approval by the General Meeting, subject to subsequent approval and respective claw-back provisions.
5 Le conseil d’administration soumet le rapport annuel de rémunération à l’assemblée générale pour une votation consultative.	5 The Board of Directors shall submit the annual compensation report to an advisory vote of the General Meeting.
Article 23<br> <br>Montantsupplémentaire pour les rémunérations lors de changements au sein de la direction	Article 23<br> <br>AdditionalAmount
1 Si l’indemnité approuvée n’est pas suffisante, la Société ou les sociétés qu’elle contrôle sont autorisées à verser une indemnité<br>supplémentaire pour la durée des périodes de rémunération déjà approuvées à chaque personne qui entre à la direction après l’approbation de la<br>rémunération par l’assemblée générale ou qui est promue au sein de la direction. Le montant supplémentaire ne peut dépasser, pour chaque période de rémunération, un total de<br>40% du dernier montant global approuvé. Le montant supplémentaire peut aussi être utilisé pour le paiement de compensation d’inconvénients subis par le nouveau membre de la direction comme conséquence de<br>son changement de poste (indemnité d’entrée).	1 In case of insufficient compensation, the Company or the companies controlled by it shall be empowered to pay an additional amount for the duration of the remuneration periods already approved to any member who joins the Executive<br>Committee or is promoted within the Executive Committee after remuneration has been approved by the general meeting. Such additional amount shall not exceed, per each compensation period, in the aggregate 40% of the last approved overall amount of<br>compensation for the Executive Committee. Such additional amount may also be used to compensate disadvantages and/or replace forfeited awards of a new member of the Executive Committee due to the change of employment (replacement awards).

Article 24<br> <br>Principes derémunération des membres du conseil d’administration et de la direction	Article 24<br> <br>Principles of Remunerationto the members of the Board of Directors and the Executive Committee
1 La rémunération peut être faite sous forme d’argent, d’actions, d’autres titres de participations, d’options, d’instruments ou d’unités comparables. Par ailleurs, des<br>prestations en nature ou des services peuvent être fournis.	1 Compensation may be paid or granted in the form of cash, shares, other securities, options, comparable instruments or units, as well as contribution in kind, or in the form of other types of benefits.
2 En plus d’une rémunération fixe, les membres du conseil d’administration et de la direction peuvent recevoir une indemnité variable, qui est fixée en fonction du chiffre d’affaires de la<br>Société et de l’atteinte des objectifs de performance. Les objectifs de performance peuvent être des objectifs personnels, des objectifs de l’entreprise ou de certains secteurs ainsi que des objectifs calculés<br>par rapport au marché, à d’autres entreprises de dimension similaire, en tenant compte de la fonction et du niveau de responsabilité du bénéficiaire de l’indemnité variable. Le conseil<br>d’administration ou, après délégation, le comité de rémunération, détermine l‘importance des objectifs et leurs valeurs respectives et évalue la réalisation des objectifs au<br>terme de l’exercice social.	2 In addition to a fixed compensation, members of the Board of Directors and of the Executive Committee may be paid a variable compensation, depending on the achievement of certain performance criteria. The performance criteria may<br>include individual targets, targets of the Company or parts thereof and targets in relation to the market, indexes, other companies or comparable benchmarks, taking into account position and level of responsibility of the recipient of the variable<br>compensation. The Board of Directors, or where delegated to it, the nomination and compensation committee, shall determine the relative weight of the performance criteria and the respective target values and shall assess the goals at the end of a<br>financial year.
3 En cas d‘attribution de participations ainsi que de droits de conversion et d’option, ou d’autres droits se rapportant à des titres de participations, le montant de la rémunération correspond<br>à la valeur des titres ou des droits attribués au moment de l’attribution selon les méthodes de calcul notoirement reconnues. Le conseil d’administration détermine les conditions d’attribution, les<br>conditions d’acquisition, les conditions et les délais	3 In case of granting of awards, conversion or option rights or comparable instruments or units, compensation shall be valued in accordance with generally recognized valuation methods as per the grant date of the respective<br>compensation element. The Board of Directors, shall determine grant, vesting, blocking, exercise or forfeiture conditions. In the event of pre-determined events such as a change-of-control or termination of an employment or

d’exercice ainsi que tout délai de blocage ou de déchéance. Celles-ci peuvent prévoir qu’à cause de la réalisation<br>d’évènements déterminés à l’avance, comme un changement de contrôle ou la fin de rapports de travail ou de mandat, des conditions d’acquisition, des conditions et délais d’exercice<br>ainsi que des délais de blocage sont encore valables, réduits ou abrogés, que des indemnités seront versées si les valeurs des objectifs sont atteintes, ou que les indemnités tombent en tout ou en partie en<br>déchéance. Le conseil d’administration règle les détails dans un ou des règlements. La Société peut acquérir les actions nécessaires ou d’autres titres de participations sur le<br>marché ou les rendre disponibles en utilisant son capital conditionnel ou capital autorisé.	mandate agreement, the Board of Directors may provide, among other things, for continuation, acceleration or removal of vesting, blocking or exercise conditions, for payment or grant of compensation based upon assumed target<br>achievement, or for part or full forfeiture. The details shall be determined in one or more separate plan rules. The Company may procure the required shares through purchases in the market or by using conditional share capital or authorized share<br>capital.
4 Les membres du conseil d’administration peuvent être indemnisés en liquide pour leur activité fournie à la Société, ou à des sociétés directement ou indirectement<br>contrôlées par la Société, qui n‘est pas faite dans le cadre de leur mandat comme membre du conseil d’administration, selon les principes habituels du marché. Ces indemnités font partie de la<br>rémunération globale selon l’article 22.	4 The members of the Board of Directors providing services to the Company or other group companies in a function other than as members of the Board of Directors may receive a cash compensation according to standard market rates.<br>Such compensation is part of the total compensation according to Article 22.
5 La rémunération peut être versée par la Société ou par les sociétés qu’elle contrôle.	5 Compensation may be paid or granted by the Company or companies controlled by it.
6 L‘attribution de participations ainsi que de droits de conversion et d’option, ou d’autres droits sur des titres de participation, que les membres du conseil d’administration et de la direction ont reçu<br>en leur qualité d’actionnaire de la Société (par exemple des droits de souscription dans le cadre d’une augmentation du capital ou des options dans le cadre d’une réduction de capital), n’est pas<br>considérée comme une rémunération et n‘est pas concernée par cette disposition.	6 The allocation of equity securities, conversion rights, option rights or other rights with equity securities as underlying that members of the Board of Directors and members of the Executive Committee receive in their function as<br>shareholders of the Company (e.g. subscription right within a capital increase or option rights within a capital reduction) shall not be considered as compensation and are not subject to this provision.

V. Contrats avec les membres du Conseil d’administration et de la Direction	V. Contracts with members of the Board of Directors and of the Executive Committee
Article 25 Contrats	Article 25 Contracts
1 La Société ou les sociétés qu’elle contrôle peuvent conclure avec les membres du conseil d’administration des contrats sur la rémunération. La durée et la fin sont<br>fixées en fonction de la durée du mandat et de la loi.	1 The Company or companies controlled by it may enter into agreements with members of the Board of Directors relating to their compensation. Duration and termination shall comply with the term of office and the law.
2 La Société ou les sociétés qu’elle contrôle peuvent conclure avec les membres de la Direction des contrats de travail de durée déterminée ou indéterminée.<br>Les contrats de durée déterminée sont conclus pour une durée maximale d’une année; un renouvellement est possible. Les contrats de durée indéterminée contiennent un délai de<br>congé de douze mois au maximum.	2 The Company or companies controlled by it may enter into definite or indefinite employment contracts with members of the Executive Committee. The duration of definite employment contracts shall not exceed one year; renewal is<br>possible. The termination notice period of indefinite employment contracts may not exceed 12 months.
3 La Société ou les entreprises qu’elle contrôle peuvent convenir avec les membres de la direction d’une prohibition de faire concurrence d’une durée maximale d’une année<br>après la fin des rapports de travail. L’indemnité correspondante ne doit pas dépasser le montant global de rémunération qui a été versée aux membres de la direction concernés lors<br>de l’exercice social précédent la fin des rapports de travail.	3 The Company or companies controlled by it may enter into non-compete agreements with each member of the Executive Committee for the time after termination of the employment agreement for a<br>duration of up to one year. The compensation for such agreements shall not exceed the total annual compensation of such member of the Executive Committee during his last year of employment.

VI. Mandats externes au groupe, prêts et crédits	VI. External Mandates, Loans and Credits
Article 26<br> <br>Mandats	Article 26<br> <br>ExternalMandates
1 Aucun membre du conseil d’administration ne peut détenir plus de dix mandats supplémentaires, parmi lesquels pas plus de quatre ne peuvent être détenus pour des sociétés cotées<br>en bourse.	1 No member of the Board of Directors may hold more than ten (10) additional mandates of which no more than four (4) mandates in listed companies.
2 Aucun membre de la direction ne peut détenir plus de dix mandats supplémentaires, parmi lesquels pas plus de deux ne peuvent être détenus pour des sociétés cotées en bourse.	2 No member of the Executive Committee may hold more than ten (10) additional mandates of which no more than two (2) mandates in listed companies.
3 Ne sont pas soumis à ces limitations les mandats (a) dans des sociétés contrôlées par la Société ou qui contrôlent la Société, (b) détenus par un<br>membre du conseil d’administration ou de la direction à la demande de la Société ou de sociétés contrôlées par elle, ainsi que (c) dans des associations et des fédérations, des<br>organisations caritatives, des fondations, des trusts et des fondations de prévoyance pour les employés. Aucun membre du conseil d’administration ou de la direction ne peut détenir plus de 40 mandats tels que ceux<br>mentionnés sous (a), respectivement plus de 15 mandats tels que ceux mentionnés sous (b) et (c).	3 The following mandates are not subject to these limitations: (a) mandates in companies which are controlled by the Company or which control the Company; (b) mandates held at the request of the Company or companies<br>controlled by it; as well as (c) mandates in associations, charitable organizations, foundations, trusts, employee pension foundations. No member of the Board of Directors or of the Executive Committee shall hold more than forty (40) of<br>such mandates as mentioned under (a) above, respectively fifteen (15) of such mandates as mentioned under (b) and (c) above.
4 Sont considérés comme mandats, les mandats dans l’organe suprême de direction d’une entité juridique tenue d’être inscrite au registre du commerce ou dans un registre<br>équivalent à l’étranger. Les mandats dans des entités juridiques différentes, mais sous contrôle uniforme ou d’un même ayant droit économique, sont considérés comme un<br>seul mandat.	4 Mandates shall mean mandates in the supreme governing body of a legal entity, which is required to be registered in the commercial register or a comparable foreign register. Mandates in different legal entities that are under<br>joint control are deemed one mandate.

Article 27<br> <br>Prêts etcrédits	Article 27<br> <br>Loans andCredits
1 Avec l’approbation du conseil d’administration, la Société peut, sous réserve de dispositions légales applicables, accorder des prêts ou des crédits à des membres du<br>conseil d’administration ou de la direction aux conditions usuelles du marché, et à condition que leur montant n’excède pas 100% de la dernière rémunération annuelle du membre concerné.	1 Upon approval by the Board of Directors and subject to applicable laws, the Company may grant credits and loans to members of the Board of Directors or Executive Committee at market conditions. The total amount of such credits and<br>loans shall not exceed 100% of the last annual remuneration of the member concerned.
VII. Exercice social, finances	VII. Financial year, financial issues
Article 28<br> <br>Exercicesocial	Article 28<br> <br>Financialyear
L’exercice social est fixé par le conseil d’administration.	The financial year is determined by the Board of Directors.
Article 29<br> <br>Affectation dubénéfice résultant du bilan, réserves, dividendes	Article 29<br> <br>Use of retained earnings,reserves, dividends
1 L’assemblée générale décide de l’affectation du bénéfice résultant du bilan conformément aux dispositions légales.	1 The General Meeting shall decide upon the use of the balance sheet profit, taking into account the provisions of the law.
2 L’assemblée générale peut décider de la constitution de réserves supplémentaires, en sus des réserves prévues par la loi.	2 In addition to the statutory reserves, the General Meeting may establish additional reserves.
3 Tous les dividendes qui n’ont pas été réclamés dans les 5 ans à compter de leur exigibilité échoient à la société et sont attribués à la<br>réserve générale.	3 Dividends that have not been drawn for 5 years from their due date shall pass to the Company and will be allocated to the general reserve.

VIII. Dissolution et liquidation	VIII. Dissolution and liquidation
Article 30	Article 30
1 L’assemblée générale peut en tout temps décider la dissolution et la liquidation de la Société conformément aux dispositions légales et statutaires.	1 The General Meeting may at any time decide the dissolution and liquidation of the Company in accordance with the legal and statutory provisions.
2 La liquidation a lieu par les soins du conseil d’administration, à moins que l’assemblée générale ne désigne d’autres liquidateurs. La liquidation de la Société<br>s’effectue conformément à la loi. Les liquidateurs sont autorisés à vendre les actifs (y compris les immeubles) de gré à gré.	2 Liquidation is carried out by the Board of Directors, unless the general meeting appoints other liquidators. The liquidation of the Company shall be in accordance with the law. The liquidators may sell assets (including immovable<br>property) at its discretion.
3 L’actif disponible, après paiement des dettes, est réparti entre les actionnaires conformément à leurs participations respectives, déterminées en fonction de la valeur nominale.	3 After the clearance of debts, the assets will be distributed among the shareholders in proportion to their respective shares, determined according to par value.
IX. Publications, communications et convocations	IX. Notices, announcements and convening of meetings
Article 31	Article 31
1 La feuille officielle suisse du commerce est l’organe de publication de la Société. Le conseil d’administration peut désigner des organes de publication supplémentaires.	1 The Company’s organ of publication is the Swiss Commercial Gazette. The Board is authorized to designate additional publication organs.
2 Les communications de la Société aux actionnaires se font par publication dans la feuille officielle suisse du commerce ou, pour les actionnaires nominatifs, par courrier simple à l’adresse de<br>l’actionnaire inscrite en dernier dans le registre des actions.	2 Communications of the Company to shareholders shall be by publication in the Swiss Commercial Gazette or, for registered shareholders, by ordinary mail to the last address entered in the shareholder register.

Article 32	Article 32
1 Dans le cadre de l’augmentation ordinaire du capital du 13 septembre 2013, la Société reprend de Pierrel S.p.A, avec siège à Milan, Italie - selon le contrat d’apport en nature du 13 septembre<br>2013 - 742’574 actions nominatives d’une valeur nominale de CHF 1 chacune de Pierrel Research International AG, avec siège à Thalwil, pour un prix et une valeur de EUR 26.68 (arrondi) chacune, au total EUR<br>19’808’805.11 (arrondi), mais au moins équivalant à CHF 0.01 par action, pour lesquelles 232’045’803 actions nominatives entièrement libérées d’une valeur nominale de CHF 0.01 chacune<br>reviennent à l’apporteuse.	1 According to the ordinary share capital increase of 13 September 2013 and the contribution in kind agreement of 13 September 2013 the Company takes over from Pierrel S.p.A., having its registered office in Milan, Italy,<br>742’574 registered shares with a nominal value of CHF 1 each in PRINT at a price and value of each EUR 26.68 (rounded), in total EURO 19’808’805.11, at least however, when converted, CHF 0.01 for each share, for which Pierrel S.p.A.,<br>as consideration, receives 232’045’803 fully paid-in registered shares of the Company, with nominal value of CHF 0.01.
2 Dans le cadre de l’augmentation ordinaire du capital du 13 septembre 2013, la Société reprend de Fin Posillipo S.p.A, avec siège à Milan, Italie - selon le contrat d’apport en nature du 13<br>septembre 2013 - 231’549 actions nominatives d’une valeur nominale de CHF 1 chacune de Pierrel Research International AG, avec siège à Thalwil, pour un prix et une valeur de EUR 26.68 (arrondi) chacune, au total EUR<br>6’176’770.28 (arrondi), mais au moins équivalant à CHF 0.01 par action, pour lesquelles 72’356’405 actions nominatives entièrement libérées d’une valeur nominale de CHF 0.01 chacune<br>reviennent à l’apporteuse.	2 According to the ordinary share capital increase of 13 September 2013 and the contribution in kind agreement of 13 September 2013 the Company takes over from Fin Posillipo S.p.A., having its registered office in Milan,<br>Italy, 231’549 registered shares with a nominal value of CHF 1 each in PRINT at a price and value of each EUR 26.68 (rounded), in total EUR 6’176’770.28, at least however, when converted, CHF 0.01 for each share, for which Fin<br>Posillipo S.p.A., as consideration, receives 72’356’405 fully paid-in registered shares of the Company, with nominal value of CHF 0.01.
Article 33	Article 33
Dans le cadre de l’augmentation ordinaire du capital du 14 juillet 2016, la Société reprend des apporteurs suivants - selon les contrats d’apport en nature du 24 juin 2014 - 208’163 actions nominatives<br>d’une valeur nominale de CHF 1 chacune de Relief Therapeutics SA, avec siège	According to the ordinary share capital increase of 14 July 2016 and the contribution in kind agreements of 24 June 2016, the Company takes over from the following investors 208‘163 registered shares with a nominal<br>value of CHF 1 each in Relief Therapeutics SA in Geneva, at a

à Genève, pour une valeur totale de CHF 11’969’372.50, pour lesquelles 1’196’937’250 actions nominatives de la Société entièrement libérées d’une valeur<br>nominale de CHF 0.01 chacune sont émises à une valeur de CHF 0.04 chacune en faveur des apporteurs.	total value CHF 11’969’372.50, for which 1’196’937’250 fully paid-in registered shares in the Company with a par value of CHF 0.01 each will be issued at a value of<br>CHF 0.04 each.
Apporteur /<br><br><br>Investor ****		Apport en<br>nature /<br>Investment		Actions /<br>Shares		Valeur / Value
---	---	---	---	---	---	---	---
GEM Global Yield Fund LLC S.C.S.	Luxemburg - Luxemburg		106’163		610‘437‘250		6‘104‘372.50
Michel Dreano	F-74106 Collonges sous Salève		34‘000		195‘500‘000		1‘955‘000
Django Trading Sàrl	CH-1400 Yverdon-Les-Bains		34‘000		195‘500‘000		1‘955‘000
Yves Sagot	F-74160 Beaumont		34’000		195‘500‘000		1‘955‘000
Total			208‘163		1’196’937’250		11’969’372.50
Article 34	Article 34
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En cas de divergences entre la version française et la traduction anglaise des présents statuts, la version française fait foi.	In case of any discrepancies between the French version of these articles of association and the English translation, the French version shall prevail.

STATUTS ACTUELLEMENT EN VIGUEUR CERTIFIES CONFORMES, dûment mis à jour suite aux décisions du Conseil d’administration et de l’assemblée générale extraordinaire des actionnaires prises le 28 avril 2023

Genève, le 28 avril 2023

EX-8.1

Exhibit 8.1

RELIEF THERAPEUTICS Holding SA

LIST OF SUBSIDIARIES

Subsidiary	Jurisdiction
Relief Therapeutics International SA	Switzerland
Relief Therapeutics US, Inc.	Connecticut (U.S.)
Relief Therapeutics, Inc.	Delaware (U.S.)
APR Applied Pharma Research S.A.	Switzerland
APR Applied Pharma Research Holding SA	Switzerland
APR Applied Pharma Research – Italy s.r.l.	Italy
APR Applied Pharma Research Deutschland GmbH	Germany
AdVita Lifescience GmbH	Germany
AdVita Lifescience AG	Switzerland
AdVita Lifescience, Inc.	New York (U.S.)

EX-10.2(B)

Exhibit 10.2(b)

Execution Copy

Certainidentified information has been excluded from this exhibit because it is both (i) not material, and (ii) would likely cause competitive harm to the registrant if publicly disclosed. [***] indicates that information has been redacted.

AMENDMENT No. 2

dated as of 19 December 2022

(the “Amendment No. 2 Effective Date”)

to the

SHARE EXCHANGEAGREEMENT

dated as of 28 May 2021

between

Wolfgang Peter Hoppe

(the “Seller 1”)

HenrikBulskov

(the “Seller 2”)

Prof. Dr. Joachim Müller-Quernheim

(the “Seller 3”)

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	2

Dr. Björn Christian Frye

(the “Seller 4”)

MarcAlexander Kessemeier

(the “Seller 5”)

BG Consulter GmbH

(the “Seller6”)

APARA-Bioscience GmbH

(the “Seller 7”)

UlrichBirsner

(the “Seller 8”)

Annette Marlene Schätzle

(the “Seller 9”)

(Seller 1 through Seller 9 together the “Sellers”

and each individually a “Seller”)

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	3

and

RELIEF THERAPEUTICS Holding SA

avenue de Sécheron 15

CH-1202 Geneva Switzerland

(the “Buyer”)

regarding the sale and purchase of all shares in

AdVita Lifescience GmbH

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	4

TABLE OF CONTENT

PREAMBLE		5
1.	DEFINITIONS, INTERPRETATION AND NEW DEFINITIONS	6
1.1	DEFINITIONS AND INTERPRETATION	6
1.2	NEW DEFINITIONS	6
2.	NEW SECTION 3.1 AND RESTRUCTURING OF ORIGINAL MILESTONES PAYMENTS	6
2.1	NEW SECTION 3.1	6
2.2	SELLERS’ ACKNOWLEDGMENT ON THE RECEIPT OF THE PAYMENT SHARES AND<br>THE MILESTONE OF SECTION 3.1B) I)	7
2.3	SELLERS’ WAIVER AND RELEASE OF CLAIMS IN RELATION TO FORMER<br>SECTION 3.1 OF THE AGREEMENT	7
3.	MILESTONE ACCELERATION TOOL	7
4.	PROGRESS REPORTS ON MILESTONE PRODUCTS	8
5.	APPOINTMENT OF A JOINT STEERING COMMITTEE	8
5.1	JSC INCORPORATION	8
5.2	LIMITATION OF JSC POWERS	9
5.3	JSC MEMBERSHIP AND MEETINGS	9
6.	MISCELLANEOUS	10
6.1	NOTICES	10
6.2	WAIVER	10
6.3	ENTIRE AGREEMENT	10
6.4	SEVERABILITY	10
6.5	AMENDMENT	10
6.6	GOVERNING LAW AND JURISDICTION	10
6.7	COUNTERPARTS	11
Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	5
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Preamble

A.	The Parties entered into a Share Exchange Agreement dated as of 28 May 2021 regarding the acquisition by<br>the Buyer from the Sellers of all Shares in AdVita Lifescience GmbH (the “Company”), which was supplemented on 24 June 2021, closed on 27 July 2021 and amended by an Amendment No. 1 dated as of 6 November 2021 (hereinafter<br>individually and collectively referred to as the “Agreement”).
B.	In the Agreement the Parties agreed that the Purchase Price for all the Shares consisted in the Payment Shares<br>and possible future contingent milestone payments in the aggregate maximum amount of up to EUR 20,000,000, each payable upon achievement of specific objectives (each an “Original Milestone” and together the “OriginalMilestones”), including the Original Milestone of Section 3.1.b) iv) of the Agreement of EUR 5,000,000 (the “CIP Original Milestone”) for the identification of a partner for<br>co-development or start of a clinical trial phase II in checkpoint inhibitor induced pneumonitis (hereinafter the “CIP”).
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C.	[***]
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D.	[***]
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E.	[***]
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F.	[***]
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G.	[***]
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H.	[***]
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I.	In addition, the Parties intend to agree on a mechanism allowing the Sellers to receive some advance payments<br>on the future contingent Milestones (as defined herein) payable according to the Agreement, corresponding to a certain percentage of proceeds received by the Buyer from third parties pursuant to certain agreements related to the subject matter of<br>those Milestones.
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J.	Finally, the Parties intend to agree on (i) certain Buyer’s reporting obligations lasting until<br>achievement of the last to achieve Milestone, and (ii) the incorporation of a joint steering committee having solely advisory and consulting purposes in relation to projects related to the future contingent Milestones.
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Therefore, the Sellers and the Buyer (each a “Party” and together the “Parties”) have come to the following agreement:

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	6
1.	Definitions, Interpretation and New Definitions
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1.1	Definitions and Interpretation.
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a)	Capitalized terms, not specifically defined herein, shall have the meaning assigned to them in the Agreement.<br>
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b)	To the extent not expressly amended by this Amendment No. 2, the Agreement shall remain unchanged and<br>shall continue to apply.
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c)	Section 1.2 of the Agreement shall entirely apply to this Amendment No. 2.
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d)	This Amendment No. 2 and the related discussions between the Parties hereto shall not be interpreted as<br>changing the meaning of any provision of the Agreement that is not amended by this Amendment No. 2.
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1.2	New Definitions.
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The Parties agree that, as of the Amendment No. 2 Effective Date, the following definitions are included to the Annex 1 of the Agreement:

Aviptadil	shall mean the synthetic form of human Vasoactive Intestinal Peptide (VIP).
Phase II Clinical Study	shall mean a research study of Aviptadil with human
	subjects inter alia aimed at determining the safe and effective dose range in the proposed indication and prospectively designed to generate sufficient data to enter and commence Phase III clinical trials.
Regulatory Approval	shall mean with respect to a country or jurisdiction, any and all approvals, licenses, registrations, or authorizations of any regulatory or other governmental authority necessary to market and sell a product in such country or<br>jurisdiction.
2.	New Section 3.1 and Restructuring of Original Milestones Payments
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2.1	New Section 3.1
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The Parties agree that, as of the Amendment No. 2 Effective Date, Section 3.1 of the Agreement is deleted and replaced in its entirety with the following new Section 3.1:

3.1 Payment Shares and Milestones

The purchase price for all the Shares shall consist of:

a)	a fixed price of EUR 25,000,000 solely payable in Buyer Shares (the “PaymentShares”), being computed as the product of the lower of:
i)	the closing price of Buyer Shares as of the Trading Day immediately preceding the Closing Date in EUR,applying the CHF-EUR Exchange Rate of the Trading Day immediately preceding the Closing Date, and
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ii)	the 60 Day VWAP preceding the Closing Date,
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multiplied by the number of Buyer Shares to equal EUR 25,000,000 (less any Leakage other than Permitted Leakage) (with any fractions ofBuyer Shares to be rounded up).

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	7
b)	possible future contingent milestone payments in the aggregate maximum amount of up to EUR 15,000,000, eachpayable upon achievement by the Buyer or one of its Affiliates of specific objectives as follows (each a “Milestone” and together the “Milestones”):
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i)	EUR 5,000,000 upon the issuance of one of the Patents;
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ii)	EUR 5,000,000 upon the first Regulatory Approval in the US or Europe for the inhaled form of Aviptadil forthe treatment of sarcoidosis or berylliosis;
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iii)	EUR 3,000,000 upon the start of a Phase II Clinical Study for the inhaled form of Aviptadil in the treatmentof checkpoint inhibitor induced pneumonitis (“CIP”); and
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iv)	EUR 2,000,000 upon completion of a Phase II Clinical Study for the inhaled form of Aviptadil in thetreatment of CIP.
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Each Milestone shall be payable only once.

((a) and b) together referred to as the “Purchase Price”).

For the sake of clarity: a) the start of a Phase II Clinical Study corresponds to the date of dosing of the first patient and b) thecompletion of a Phase II Clinical Study corresponds to the date of signing of the final clinical study report indicating whether the primary endpoints were achieved.

2.2	[***]
2.3	Sellers’ waiver and release of<br>claims in relation to former Section 3.1 of the Agreement
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a)	Except for the Milestone under Section 3.1b) i) of the Agreement already duly paid by the Buyer, and<br>subject to Article 2.3b) hereafter, the Sellers waive any and all rights, claims or requests against the Buyer and release the Buyer from any obligations in relation to the Original Milestones, including any claims for the CIP Original Milestone.<br>
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b)	As of the Amendment No. 2 Effective Date, the rights and obligations of the Parties in relation to the<br>Milestones shall be determined in accordance with the terms of the new Section 3.1 of the Agreement as amended by this Amendment No. 2 exclusively.
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3.	Milestone Acceleration Tool
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The Parties agree about the Sellers’ right to receive, in relation to the Milestones not yet completed under the Agreement (as amended), some advance payments pursuant to the following terms and conditions of this Article 3 of this Amendment No. 2.

a)	The Buyer shall pay to the Sellers the 20% (twenty percent) of all the Proceeds (as defined herein) received by<br>the Buyer in connection with any agreement entered into between the Buyer and/or any of its Affiliates on the one hand and any third party on the other hand governing a collaboration for development and/or commercialization of a product containing<br>Aviptadil intended for the treatment of sarcoidosis and/or berylliosis and/or CIP (such agreement, a “Commercial Agreement”).
Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	8
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b)	The advance payments received by the Sellers as per the foregoing Article 3a) shall be entirely considered as<br>portion of and deducted from any payments falling due upon achievement of any of the Milestones described in Section 3.1b) ii), iii) or iv) of the Agreement (as amended), and shall be due by the Buyer in one or more occasions until fulfillment<br>of the overall amount related to those Milestones described in Section 3.1b) ii), iii) or iv) of the Agreement (as amended). For the sake of clarity, (i) in case no Milestone becomes due and payable, the Sellers shall be entitled to retain<br>any payment received from the Buyer through the Commercial Agreements pursuant to this Article 3; (ii) in case the advance payments made by the Buyer to the Sellers through the Commercial Agreements pursuant to this Article 3 exceed the amount of<br>the first subsequent Milestone payment, that subsequent Milestone shall be considered as fully paid up and any remaining amount shall be deducted from any other subsequent Milestone payment (if any).
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c)	The Buyer shall execute the advance payments in favor of the Sellers within 10 (ten) Business Days from the<br>Buyer’s receipt of the Proceeds.
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d)	For the purposes of the Agreement and this Amendment No. 2, “Proceeds” shall mean any non-contingent, non-recoverable and non-refundable proceeds (in cash or in kind) effectively received by the Buyer pursuant to any<br>Commercial Agreement, net of any taxes that may be levied by the payer or due by the Buyer on such Proceeds.
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4.	Progress Reports on Milestone Products
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The Parties agree that, starting from the Amendment No. 2 Effective Date and until the date of achievement and full payment of the last Milestone, the Buyer shall deliver to the Sellers’ Representative, within the term of 30 (thirty) calendar days after the end of each half calendar year (i.e., end of January and end of July, respectively) a written report (each, a “Progress Report”) summarizing, to the extent permitted by applicable Laws and stock exchange rules and regulations, in reasonable detail and on a reasonably current basis, all material developments relating to the development of, regulatory approval for, manufacture and launch of all the products being subject of a Milestone that have occurred in the period between the end of the one covered by the latest report and the date of the Progress Report.

5.	Appointment of a Joint Steering Committee
5.1	JSC Incorporation
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As of the Amendment No. 2 Effective Date, the Parties agree to establish a joint steering committee (the “JSC”) to allow the Buyer to consult with the Sellers’ representative appointed pursuant to this Article 5 in relation to the development, regulatory and commercial aspects of the products being subject of the Milestones contemplated under the Agreement. The JSC is created for consulting purposes only, in order to allow the Sellers (through the Sellers’ representative) to provide opinions and recommendations to be submitted to the senior management of the Buyer. The JSC shall not have any decision power in relation to the matters of discussion and the Buyer shall be free to make its own decisions about such matters at its own reasonable discretion, including when such decisions are contrary to the recommendations received from the Sellers through this JSC.

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	9
5.2	Limitation of JSC Powers
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The JSC will only have the powers expressly assigned to it in this Article 5 and will not have the authority to: (a) modify or amend the terms and conditions of the Agreement; or (b) decide any issue in a manner that would conflict with the express terms and conditions of the Agreement, or (c) modify, influence or change the development or commercialization strategy decided by the Buyer.

5.3	JSC Membership and Meetings
a)	JSC Members. The JSC will consist of two (2) members, one (1) appointed by the Sellers and one<br>(1) appointed by the Buyer. Initial members for the JSC will be Paolo Galfetti, COO of Relief Therapeutics Holding SA and Marc Alexander Kessemeier as Sellers’ representative. The JSC members shall each be appointed for an initial period<br>of three (3) years, following which they may be reappointed for consecutive three (3) years periods, if needed. Each Party may replace its representative on the JSC by written notice to the other Party at any time; in case of replacement<br>the new representative shall be in charge until the end of the applicable three (3) years period. The Parties will alternate, on a meeting-by-meeting basis, in having their representatives on the JSC to<br>act as the chairperson of the JSC for the meeting. The chairperson will prepare and circulate agendas prior to each JSC meeting and subsequently promptly provide to the Parties reasonably detailed drafts of the minutes of each such meeting. The<br>Parties will promptly discuss any comments on such minutes and finalize the minutes no later than the earlier of seven (7) days prior to the date of the next JSC meeting and seven (7) days prior to the date of the next meeting of the board<br>of directors of the Buyer at which a topic covered by the minutes will be discussed. The minutes of the JSC meetings shall serve the Buyer as basis and recommendation for any decision the board of directors of the Buyer may take on the topics<br>covered by the minutes.
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b)	Meetings. The JSC will hold meetings at such times as it elects to do so or following the request of one<br>of the JSC members, but such meetings will be held in any event at least twice every calendar year, unless the JSC decides on a different frequency. Meetings of the JSC may be held in person, or by audio or video teleconference, at the JSC’s<br>discretion, with in-person JSC meetings being held at locations selected on an alternating basis by the Parties. Each Party will be responsible for all of its own expenses in connection with participating in<br>the JSC meetings.
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c)	Non-Member Attendance. Each Party may from time to time invite a<br>reasonable number of its representatives, who are not members of the JSC, to attend a JSC meeting; provided, that such participants are bound by confidentiality and non-use obligations consistent with the<br>terms of this Agreement; and provided, further, that each Party will provide reasonable prior written notice to the other Party if it has invited any third party (including any consultant) to attend such a meeting and the attendance of such third<br>party will be subject to the consent of the other Party.
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Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	10
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d)	The Buyer and the Sellers hereby agree that, as of the Amendment No. 2 Effective Date, the Sellers’<br>representative indicated in Article 5.3a) hereinabove or any other Sellers’ representative as may be appointed over time according to the terms of this Amendment No. 2 shall also act as the Sellers’ Representative as set forth in<br>Section 13.2 of the Agreement and shall operate according to the terms as set forth therein.
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6.	Miscellaneous
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6.1	Notices
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All notices and other communications to be given by any Party under this Amendment No. 2 shall be made in writing and shall be delivered according to the terms of Section 13.3 of the Agreement.

6.2	Waiver

The failure of any of the Parties to enforce any of the provisions of this Amendment No. 2 or any rights with respect thereto shall (i) in no way be considered as a waiver of such provisions or rights and (ii) not in any way affect the validity of this Amenment No. 2. The waiver of any breach of agreement by any Party shall not operate to be construed as a waiver of any other prior or subsequent breach.

6.3	Entire Agreement

Upon execution by the Parties, this Amendment No. 2 including its Preamble shall become an integral part of the Agreement as amended over time. Save the changes introduced by the present Amendment No. 2, all the provisions of the Agreement, which shall, for the avoidance of doubt, include Amendment No. 1, shall keep their full effectiveness.

6.4	Severability

If any provision of this Amendment No. 2 is held to be invalid or unenforceable for any reason it shall be revised rather than rendered void, if possible, in order to achieve the intent of the Parties to this Amendment No. 2 to the fullest extent possible. In any event, all other provisions of this Amendment No. 2 shall be deemed valid and enforceable to the fullest extent possible. The same shall apply in case of a gap.

6.5	Amendment

This Amendment No. 2 may be amended only in writing through a document duly signed by each Party.

6.6	Governing Law and Jurisdiction

This Amendment No. 2 shall be subject, with reference to the choice of governing law and the place of jurisdiction to the terms of Sections 13.9 and 13.10 of the Agreement respectively.

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	11
6.7	Counterparts
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This Amendment No. 2 may be executed in two (2) or more counterparts, each of which will be deemed an original, but all of which together will constitute one and the same instrument. The Parties agree that execution of this Amendment No. 2 by exchanging executed signatures by email, portable document format (.pdf) or by any other electronic means intended to preserve the original graphic and pictorial appearance of this Amendment No. 2 shall have the same legal force and effect as the physical delivery of the paper document bearing original signature.

[Remainder of the page left intentionally blank. Signature pages follow.]

Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	12
The Seller 1: Wolfgang Peter Hoppe
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/s/ Wolfgang Peter Hoppe<br><br><br>Wolfgang Peter Hoppe
The Seller 2: Henrik Bulskov
/s/ Henrik Bulskov<br><br><br>Henrik Bulskov
The Seller 3: Prof. Dr. Joachim Müller-Quernheim
/s/ Joachim Müller-Quernheim<br><br><br>Prof. Dr. Joachim Müller-Quernheim
The Seller 4: Dr. Björn Christian Frye
/s/ Björn Christian Frye<br><br><br>Dr. Björn Christian Frye
The Seller 5: Marc A. Kessemeier
/s/ Marc A. Kessemeier<br><br><br>Marc A. Kessemeier
The Seller 6: BG Consulter GmbH
/s/ Patrick Galli<br><br><br>Name: Patrick Galli
Function: CEO
Amendment No. 2 to the Share Exchange Agreement regarding AdVita Lifescience GmbH	13
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The Seller 7: APARA-Bioscience GmbH
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/s/ Ulrich Birsner
Name:	Ulrich Birsner
Function:	Director
The Seller 8: Ulrich Birsner
/s/ Ulrich Birsner<br><br><br>Ulrich Birsner
The Seller 9: Annette Marlene Schätzle
/s/ Annette Marlene Schätzle<br><br><br>Annette Marlene Schätzle
The Buyer: RELIEF THERAPEUTICS Holding SA
/s/ Ram Selvaraju
Name:	Ram Selvaraju
Function:	Chairman of the Board of Directors
/s/ Jeremy Meinen
Name:	Jeremy Meinen
Function:	Chief Financial Officer

EX-10.8(A)

Exhibit 10.8(a)

Execution Version

Certain identified information has been excluded from this exhibit because it is both (i)

not material, and (ii) would likely cause competitive harm to the registrant if publicly

disclosed. [***] indicates that information has been redacted.

ASSET PURCHASE AGREEMENT

THIS ASSET PURCHASE AGREEMENT (this “Agreement”) is made and entered into as of November 12, **** 2022 (the “Execution Date”), by and between NRX PHARMACEUTICALS, INC., a Delaware corporation (“NRxPharma”), and its wholly-owned subsidiary, NeuroRx, Inc., a Delaware corporation (“NeuroRx”, and collectively with NRx Pharma, “NRx”), on the one hand, and RELIEF THERAPEUTICSHOLDING SA, a corporation organized under the laws of Switzerland (“Holding”), and its wholly-owned subsidiary, Relief Therapeutics International SA, f/k/a Therametrics Discovery AG (“International”, and collectively with Holding, “Relief”), on the other hand. NRx and Relief are sometimes referred to herein individually as a “Party” and collectively as the “Parties.”

RECITALS

A. Holding, International, and NeuroRx are parties to that certain Binding Collaboration Agreement, dated as of September 18, 2020 (the “Collaboration Agreement”), which established the terms under which the Parties would collaborate and assist each other with the development and future sale of aviptadil, including but not limited to intravenous and inhalation use primarily as a treatment for COVID-19.

B. The Parties have each filed suit in the Supreme Court of the State of New York for the county of New York, captioned (i)Relief Therapeutics Holding AG and Relief Therapeutics International SA (f/k/a Therametrics Discovery AG) v. Jonathan Cogswell Javitt (“Javitt”) and NeuroRx, Inc.(Index No. 655857/2021), and (ii)NeuroRx, Inc. v. Relief Therapeutics Holding AG and Relief Therapeutics International SA (f/k/a Therametrics Discovery AG) (Index No. 650162/2022) (collectively, the “Litigations”).

C. In order to settle these disputes, simultaneously with the execution of this Agreement, the Parties (and the other parties to the Litigations other than Javitt) are executing a Settlement Agreement in the form attached hereto as Exhibit D (“Settlement Agreement”), which will, as of the Closing Date (as hereinafter defined), settle the Litigations between the Parties, and the Parties are entering into this Agreement pursuant to which NRx will sell to Relief, and Relief will purchase from NRx, the Transferred Assets (as defined below), all upon the terms and subject to the conditions set forth herein and in the Ancillary Agreements (the “Transactions”).

D. Under the Settlement Agreement, at the Closing Date the Collaboration Agreement shall be cancelled and shall be of no further force or effect.

In consideration of the mutual benefits to be derived from this Agreement and of the representations, warranties, conditions, agreements and promises contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, hereby agree as follows:

AGREEMENT

SECTION 1. DEFINITIONS

1.1“Affiliate” means, with respect to any specified Person, any other Person that, directly or indirectly, through one or more intermediaries, controls, is controlled by or is under common control with such specified Person. The term “control” (including, with correlative meaning, the terms “controlled by” and “under common control with”), as used with respect to any Person, means the possession, directly or indirectly, of the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of equity, voting securities, beneficial interest, by contract or otherwise.

1.2 “Ancillary Agreements” means, collectively, the Patent Assignment Agreement in the form attached hereto as Exhibit A, the **** Assignment and Assumption Agreement in the form attached hereto as Exhibit B and the Bill of Sale in the form attached hereto as Exhibit C.

1.3 “Assumed Liabilities” has the meaning set forth in Section 2.3.

1.4 “Bankruptcy, Equity and Indemnity Exception” has the meaning set forth in Section 3.5.

1.5 “Business Day” means any day that is not a Saturday, a Sunday or other day on which banks are required or authorized by Law to be closed in the State of New York or the Canton of Geneva, City of Geneva, Switzerland.

1.6 “Calendar Half Year” means each successive period of six (6) calendar months commencing on January 1, and July 1, except that the first Calendar Half Year shall commence on the Closing Date and end on the day immediately prior to the first to occur of January 1 or July 1 after the Closing Date.

1.7 “Calendar Year” means each successive period of twelve (12) calendar months commencing on January 1 and ending on December 31, except that the first Calendar Year shall commence on the Closing Date and end on December 31, 2022.

1.8 “Claim Notice” has the **** meaning set forth in Section 7.3(b).

1.9 “Closing” **** has the **** meaning set forth in Section 2.5.

1.10 “Closing Date” has the **** meaning set forth in Section 2.5.

1.11 “ Commercially Reasonable Efforts” means with respect to the efforts to be expended by a Party, with respect to any objective under this Agreement, reasonable, diligent, and good faith efforts to accomplish such objective as a reasonable party with the expertise that the relevant Party would normally use to accomplish a similar objective under similar circumstances, taking into account all reasonable factors and exercising reasonable business or legal judgment, as appropriate.

1.12 “Competing Product” means any product containing the Compound as an active ingredient, including the Product.

1.13 “Compound” means aviptadil, as further described on Schedule 1.13.

1.14 “Confidential Information” means all non-public information of a confidential or proprietary nature disclosed under this Agreement by or on behalf of a Party to the other Party (whether or not specifically labeled or identified as “confidential”), in any form or medium, including any such information that relates to the Transferred Assets, the Compound and the Product, and any rights or obligations under this Agreement. Confidential Information includes the following: (i) internal business information (including information relating to plans for studies, trials and formulations, strategic and staffing plans and practices, business, training, marketing, promotional and sales plans and practices, cost, rate and pricing structures, accounting and business methods and potential acquisition candidates); (ii) information that identifies individual requirements of, and specific contractual arrangements with, suppliers, distributors, customers, independent contractors or other business relations and their confidential information; (iii) Trade Secrets and other Know-How; and (iv) compilations of data and analyses, techniques, systems, formulae, research, records, reports, manuals, documentation, models, data and databases relating thereto; and inventions, innovations, improvements, developments, methods, designs, analyses, drawings, and reports. On and after the Closing Date, subject to Section 8.2, all Confidential Information relating solely to the Transferred Assets and the Product shall be deemed to be the Confidential Information of Relief, and NRx shall be deemed the receiving Party and Relief shall be deemed the disclosing Party with respect thereto.

1.15 “Controlling Party” has the meaning set forth in Section 7.3(c).

1.16“COVID-19” means any disease, condition or ailment caused by, or associated with, or reasonably related to, the novel 2019 coronavirus, SARS-COV-2.

1.17 “Damages” means actual losses, costs, damages and expenses, including reasonable out-of-pocket attorneys’ fees and expenses, and reasonable fees and expenses of other professionals and experts (including any such reasonable costs, expenses and attorneys’ fees incurred in enforcing an Indemnified Party’s right to indemnification against any indemnifying Party, provided, however, that “Damages” shall not include punitive, incidental, consequential, special or indirect damages (including loss of revenue, diminution in value and any damages based on any type of multiple).

1.18 “Disclosure Schedule” means the disclosure schedule that has been prepared by NRx and delivered to Relief on the Execution Date.

1.19 “Dollars” or “$” means the legal tender of the United States.

1.20 “Execution Date” has the **** meaning set forth in the Preamble of this Agreement.

1.21 “Excluded Assets” has the meaning set forth in Section 2.2.

1.22 “Excluded Liabilities” has the meaning set forth in Section 2.4.

1.23 “FDA” means the United States Food and Drug Administration, or any successor agency thereto.

1.24 “FDCA” means the Federal Food, Drug and Cosmetic Act, as amended, and all related rules, regulations and guidelines.

1.25 “Field” means the treatment, prevention, detection, diagnosis, prognosis, palliation, monitoring or predisposition testing of any indication, disease or condition in humans.

1.26 “Governmental Authority” means any national, federal, regional, state, provincial, local or other governmental authority or instrumentality, legislative body, court, registrar (such as the United States Patent and Trademark Office), administrative agency, regulatory body or commission, including any multinational authority having governmental powers.

1.27 “IFRS” means International Financial Reporting Standards as issued by the International Accounting Standards Board, consistently applied.

1.28 “IND” means an application filed with a Regulatory Authority for authorization to commence clinical studies of a Product, including (i) an Investigational New Drug Application as defined in the FDCA, (ii) any equivalent of a United States IND in other countries or regulatory jurisdictions, and (iii) all supplements, amendments, variations, extensions, and renewals thereof.

1.29 “IndemnifiedParty” means the Person entitled to indemnification under Section 7 of this Agreement.

1.30“Indemnifying Party” means the Party obligated to indemnify the Indemnified Party under Section 7.

1.31 “Intentionally Left Blank

1.32 “Knowledge” means, with respect to a particular fact or matter and a Party, the actual knowledge of any Knowledge Party of such Party, in each case following reasonable inquiry with respect to such fact or matter; provided, however, that such reasonable inquiry shall not require the Party to obtain a “freedom to operate” opinion or similar opinion of counsel or any Patent, trademark, or other intellectual property clearance search or review.

1.33“Knowledge Party” means with respect to any Party, such Party’s (i) Chief Executive Officer, (ii) Chief Scientific or Medical Officer, and (iii) Chief Legal Officer, or any individual employed by the Party who performs such tasks. For clarity, the NRx’s Knowledge Parties include the individuals listed on Schedule 1.33.

1.34 “Know-How” means non-public proprietary knowledge, scientific information, formulae, processes, plans, technical information, new product information, test procedures, experience, data, technology, design information, Trade Secrets, and other information and knowledge, regardless of whether patentable or patented or not. The fact that a part of a compilation of data is in the public domain shall not prevent the compilation of data as such, or any one or more of the other elements of the compilation, from being Know-How.

1.35 “Know-How ConfidentialInformation” has the meaning set forth in Section 3.6(h).

1.36 “Law” means any federal, state, local, municipal, foreign or other law, statute, constitution, common law, rule, regulation, executive order, injunction, judgment, order, award, decree, ruling or requirement issued, enacted, adopted, promulgated, implemented or otherwise put into effect by or under the authority of any Governmental Authority.

1.37 “Legal Proceeding” means any action, suit, charge, complaint, litigation, arbitration, proceeding (including any civil, criminal, administrative, investigative or appellate proceeding), hearing, inquiry, audit, examination or investigation commenced, brought, conducted or heard by or before, or otherwise involving, any court or other Governmental Authority or any arbitrator or arbitration panel. Legal Proceeding excludes office actions occurring in the course of prosecution of a trademark or a Patent.

1.38 “Liability” **** or **** “Liabilities” means any and all debts, liabilities, costs, assessments, expenses, claims, losses, and Damages.

1.39 “Lien” **** or “Liens” means any security interest, pledge, license, encumbrance, hypothecation, mortgage, deed of trust, conditional sales charge or other similar arrangement, or interest in real or personal property or other property, including intellectual property.

1.40 “Marketing Approval” means, with respect to a country or jurisdiction, any and all approvals (including approvals of NDAs), licenses, registrations, or authorizations of any Regulatory Authority or other Governmental Authority necessary for the commercial marketing and sale of the Product in such country or other jurisdiction.

1.41 “Material Adverse Effect” means an event, development, change, effect or circumstance that has had or could reasonably be expected to have a material and adverse effect on the Transferred Assets or the Assumed Liabilities taken as a whole; provided that the following shall not be deemed to constitute, and shall not be taken into account in determining whether there has been, a Material Adverse Effect: any adverse effect resulting from (a) general business or economic conditions affecting all industries (unless such conditions affect the Transferred Assets or Assumed Liabilities to a greater degree than other similar businesses), (b) conditions generally affecting the healthcare or pharmaceutical industry (unless such conditions affect the Transferred Assets or Assumed Liabilities to a greater degree than other similar businesses), (c) the announcement, execution or delivery of this Agreement or the pendency of the Transactions, or the taking of any action required by and in accordance with this Agreement, including the impact of any of the foregoing on the relationships, contractual or otherwise with any customers, suppliers, distributors, partners, employees or contractors or other business relations, (d) any change in IFRS or any change in applicable Laws or the interpretation thereof, (e) any change in geopolitical conditions, the outbreak or escalation of hostilities, any acts of war, sabotage, cyberattack or terrorism, or any escalation or worsening of any such acts of war, sabotage, cyberattack or terrorism threatened or underway as of the Execution Date of this Agreement, (f) the taking of any action by NRx at the request or with the consent of Relief, or (g) any epidemic, plague, pandemic or other outbreak of illness or public health event, hurricane, earthquake, flood or other natural disasters, acts of God or change resulting from weather conditions.

1.42 “NDA” means a New Drug Application, as defined in the FDCA.

1.43 “Net Sales” means [***]

1.44 “Non-Competition Term” has the meaning set forth in Section 5.6.

1.45 “Non-Controlling Party” has the **** meaning set forth in Section 7.3(c).

1.46 “NRx Representative”****has the **** meaning set forth in Section 3.6(f).

1.47 “NRX’s Right to TryProgram” means the program started by NRx relating to the use of the Product according to S.204, the “Trickett Wendler, Frank Mongiello, Jordan McLinn and Matthew Bellina Right to Try Act,” and any national applications in force in the U.S. to the Execution Date.

1.48 “Patents” means all rights in United States and foreign patents and patent applications (including provisional applications) published or unpublished, filed or not yet filed and patent disclosures, and including, without limitation, all divisionals, utility patents, continuations, substitutions, continuations-in-part, re-examinations, re-issues, additions, renewals, extensions, confirmations, registrations, any confirmation patent or registration patent or patent of addition based on any such patent, patent term extensions, and supplemental protection certificates, and foreign counterparts of any of the foregoing.

1.49 “Permitted Liens” means any Lien: (i) caused by applicable Law that does not or would not be reasonably expected to detract from the current value of, or interfere with, the current use and enjoyment of any Transferred Asset subject thereto or affected thereby in the ordinary course of business of the development, manufacture or commercialization of the Product; (ii) arising under original purchase price conditional sales contracts and equipment leases with third parties entered into in the ordinary course of business that are transferred to Relief as part of the Transactions; and (iii) and other imperfections of title or Liens, if any, that have not had, and would not have, a Material Adverse Effect.

1.50 “Person” means any individual, Governmental Authority, corporation (including any nonprofit corporation), general partnership, limited partnership, limited liability partnership, joint venture, estate, trust, company (including any limited liability company or joint stock company), firm or other enterprise, association, organization, or entity.

1.51 “Pre-Closing Period” has the meaning set forth in Section 5.1.

1.52 “ Product ” means any product containing the Compound as an active ingredient for all routes of administration. Relief has historically called the Product RLF-100^®^ (and it is referred to as such in the Collaboration Agreement) and NRx has historically called the Product Zyesami^®^.

1.53 “Regulatory Authority” means, in a particular country or regulatory jurisdiction, any applicable supranational, national, regional, state, or local regulatory agency, department, bureau, commission, council, or other Governmental Authority involved in regulating pharmaceutical products in such country or regulatory jurisdiction, including the FDA.

1.54 “Regulatory Filings” means all applications, registrations, licenses, permits, authorizations and approvals, including all non-clinical and clinical study authorization applications or notifications (including all INDs), and amendments and supplements to any of the foregoing, in each case related to the Product.

1.55 “Relief Indemnified Party” has the****meaning set forth in Section 7.1.

1.56 “Royalty Payment” or “Royalty Payments” **** has the meaning set forth in Section 2.6(a).

1.57“Royalty Term” has the meaning set forth in Section 2.6(c).

1.58“SEC” has the meaning set forth in Section 8.3(b).

1.59 “SellingParty” has the meaning set forth in Section 1.43.

1.60 “Tax” or “Taxes” means any tax (including any income tax, franchise tax, capital gains tax, estimated tax, gross receipts tax, surtax, excise tax, transfer tax, sales tax, use tax, property tax, business tax, occupation tax, inventory tax, occupancy tax, withholding tax or payroll tax), documentary charges, recording fees, levy, assessment, tariff, impost, imposition, toll, duty (including any customs duty), deficiency or fee, and any related charge or amount (including any fine, penalty or interest), that is, has been or may in the future be (a) imposed, assessed or collected by or under the authority of any Governmental Authority, or (b) payable pursuant to any tax-sharing agreement or similar contract.

1.61 “Third Party” means, with respect to either Party, any Person other than such Party or an Affiliate of such Party.

1.62 “Third-Party Claim” has the meaning set in Section 7.3(a).

1.63 “Trade Secrets” means all rights in United States and foreign trade secrets and other confidential information that derives independent economic value, actual or potential, from not being generally known to, and not readily ascertainable without improper means by, other parties, in any format, whether tangible or intangible, which in each case is the subject of reasonable efforts to maintain its confidentiality. Trade Secrets include all rights in such confidential information that is contained in non-public unpublished applications for Patents.

1.64“Transactions” has the **** meaning set forth in the Recitals of this Agreement.

1.65“Transferred Assets” has the **** meaning set forth in Section 2.1.

1.66“Transferred Claims” has the meaning set forth in Section 2.1(e).

1.67 “Transferred Contracts” means the contracts between NRx or any of its Affiliates and Third Parties that are exclusively related to the Product and are either assignable without the consent of the counterparty or where consent to assignment to Relief has been obtained from the counterparty, in each case as listed on Schedule 1.67.

1.68 “Transferred IP” means: (i) the United States patent application(s) relating exclusively to the Product set forth on Schedule 1.68 attached hereto, (ii) any other intellectual property (including, but not limited to, trademarks and licenses) related exclusively to the Product and set forth on Schedule 1.68; and (iii) NRx’s license agreement with Stony Brook.

1.69 “Transferred Materials” means: (i) all inventory of Product, together with all inventory of the Compound and raw materials (such as API), work-in-progress, components, supplies, finished goods and other inventories used in the manufacture of the Product for development or use, or commercialization that is in the possession or control of NRx or its Affiliates as of the Execution Date (including any inventory or such other materials held by any licensees, contractors, or subcontractors of NRx or its Affiliates as of the Execution Date but only to the extent that NRx or one of its Affiliates has legal title to and the right to transfer such inventory or other materials as of the Execution Date), wherever held, (ii) reference standards of the Compound, and (iii) retention and stability samples. Schedule 1.69 attached hereto contains a correct and complete list of all inventory of Product and all inventory of Compound (including, in each case (a) held by NRx and its Affiliates, contractors and subcontractors as of the Execution Date, including the quantities and location where such inventory is held and whether NRx or its Affiliate, contractor or subcontractor has legal title to such inventory, and (b) shipped by NRx or its Affiliate, contractor or subcontractor prior to the Execution Date to physicians or investigators, and reasonably expected by NRx to be held by such physicians or investigators as of the Execution Date, including the quantities and location to which such inventory was shipped. For avoidance of doubt, inventory shipped to physicians or investigators under NRx’s Right to Try Program shall be included on such schedule.

1.70 “Transferred Records” means the documents (or copies of such documents) that in each case are exclusively related to development, formulation, use, manufacture, or commercialization of the Product and are in the possession or control of NRx or its Affiliates as of the Execution Date (including any such documents in the possession of any licensees, contractors or subcontractors, including service providers (including data, records and information management companies, CMOs, CROs and CDMO’s of NRx or its Affiliates). For avoidance of doubt, this includes (i) NRx’s IND for the Product, (ii) NRx’s Regulatory Filings with the FDA or any other Regulatory Authority relating exclusively to the Product, including any IND or NDA filed for the Product, and any applications for Breakthrough-Therapy Designation or Emergency Use Authorization, (iii) NRx’s written correspondence with the FDA or any other Regulatory Authority exclusively relating to the Product, (iv) all data from all clinical and pre-clinical trials and studies undertaken by NRx relating to the Product (including data from the TESCO/Active 3b trial previously run by the National Institutes of Health), (v) all CMC data and all stability data exclusively relating to the Product, and (vi) any written FTO analysis and prior art analysis performed exclusively relating to the Product. Copies of all Transferred Records have, or as of the Closing Date, shall have been placed in the data room.

1.71 “United States” means the United States of America and its territories and possessions (including the District of Columbia and Puerto Rico).

1.72 “Updated DisclosureSchedule ” has the meaning set forth in Section 5.13.

1.73 “ Valid Claim” means a claim of any Patent that covers the research, development, making, using, or selling of a Product, whose validity, enforceability, or patentability has not been affected by any of the following: (i) irretrievable lapse, abandonment, revocation, dedication to the public, or disclaimer; or (ii) a holding, finding, or decision of invalidity, unenforceability, or non-patentability by a court, governmental agency, national or regional patent office, or other appropriate body that has competent jurisdiction, such holding, finding, or decision being final and unappealable or un-appealed within the time allowed for appeal.

SECTION 2. PURCHASE AND SALE OF ASSETS

2.1 Purchase and Sale of Assets. Subject to the terms and conditions of this Agreement, effective at the Closing, NRx on behalf of itself, NeuroRx, and its Affiliates hereby sells, conveys, assigns and transfers to Relief and Relief hereby purchases, acquires and accepts from NRx, free and clear of all Liens (other than Permitted Liens, if any), all of NRx’s and its Affiliates’ right, title, and interest in, to and under the Transferred Assets, which assets include all of the assets currently held by NRx which were used by NRx in connection with its efforts to develop the Product.

As used herein, “Transferred Assets” mean the following assets ((a) through (e)) existing as of the Closing:

(a) the Transferred Records, provided, however, that NRx may retain copies of all Transferred Records after the Closing for record-keeping purposes and to ensure compliance with applicable Law;

(b) the Transferred Materials, provided, however, that Relief shall be solely responsible for all costs and expenses associated with transporting the Transferred Materials from the location where such Transferred Materials are located as of the Execution Date to the contract manufacturer that will hold the Transferred Materials on behalf of Relief following the Closing Date;

(c) the Transferred Contracts, excluding, in each case, any and all rights, defenses, claims or causes of action (including warranty claims) of NRx or any of its Affiliates thereunder related to Excluded Assets or Excluded Liabilities;

(d) the Transferred IP; and

(e) all claims, counterclaims, defenses, causes of action, rights under express or implied warranties, rights of recovery, rights of set-off, rights of subrogation and all other rights of any kind against any Third Party, to the extent relating to any of the foregoing Transferred Assets, including all rights to sue and recover and retain damages, costs and attorneys’ fees for past, present and future infringement of any Transferred IP (collectively, “Transferred Claims”); provided, however, that, for the avoidance of doubt, the Transferred Claims shall in no event include any claims, counterclaims, defenses, causes of action, rights under express or implied warranties, rights of recovery, rights of set-off, rights of subrogation and all other rights that NRx or its Affiliates may have arising under the Settlement Agreement or this Agreement, any Ancillary Agreement or as a result of the consummation of the Transactions contemplated hereby.

2.2 Excluded Assets. Relief is not acquiring pursuant to this Agreement or any Ancillary Agreement, and NRx and its Affiliates shall retain, any and all right, title or interest in: (i) any assets, properties or rights of NRx or any of its Affiliates of any kind or nature other than the Transferred Assets or (ii) any rights, claims, counterclaims, defenses, causes of action, rights under express or implied warranties, rights of recovery, rights of set-off, rights of subrogation and all other rights of any kind or nature that NRx or its Affiliates may have that are not exclusively related to the Transferred Assets, this Agreement, any Ancillary Agreement, or the Settlement Agreement (collectively, the “Excluded Assets”).

2.3 Assumed Liabilities. Effective at the Closing, Relief hereby assumes and agrees to bear, pay, perform, satisfy and discharge when due (all of the following being collectively referred to herein as the “Assumed Liabilities”):

(a) all Liabilities arising on or after the Closing Date under the Regulatory Filings transferred and assigned to Relief hereunder;

(b) all Liabilities arising on or after the Closing Date under the Transferred Contracts but only to the extent such Liabilities (i) do not arise from any breach, default, violation or failure to perform by NRx or any of its Affiliates of any provision under any Transferred Contract before the Closing Date, (ii) do not arise by reason of events or circumstances occurring prior to the Closing Date which with notice or lapse of time, would constitute or result in a breach of any Transferred Contract, (iii) if arising or relating to a circumstance in existence prior to the Closing Date, arise in accordance with the express terms of such Transferred Contracts, excluding any such Liabilities that relate to or arise from any failure to perform, improper performance, warranty or other breach, default or violation by NRx under any Transferred Contract before the Closing Date, (iv) are not Excluded Liabilities, and (v) represent solely the performance of post-Closing obligations that were not required to be performed under the Transferred Contracts prior to the Closing Date; and

(c) all other Liabilities arising out of, relating to, or associated directly or indirectly with, Relief’s or its Affiliates’ or any of their licensees’, sublicensees’ or distributors’ ownership or use of the Compound, the Product or the Transferred Assets after the Closing Date.

2.4 Excluded Liabilities. Relief expressly does not assume and shall not be liable to bear, pay, perform, satisfy or discharge any Liability whatsoever of NRx or its Affiliates, other than the Assumed Liabilities (the “Excluded Liabilities”), and NRx shall retain and shall bear, pay, perform, satisfy and discharge all Excluded Liabilities.

2.5 C losing.

(a) The consummation of the purchase and sale of the Transferred Assets and the assumption of the Assumed Liabilities in accordance with this Agreement (the “Closing”) shall take place on such date as NRx and Relief agree upon in writing (“Closing Date”); provided that, subject to Section 6, the Closing shall occur no later than thirty (30) days after the Execution Date, unless otherwise agreed to in writing by the Parties. Unless otherwise agreed in writing by the Parties, the Closing shall be deemed to have occurred at 12:00 a.m., Eastern time, on the Closing Date, such that Relief shall be deemed the owner of the Transferred Assets on and after the Closing Date. All events which shall occur at the Closing shall be deemed to occur simultaneously. Further, NRx agrees from time to time, and without further consideration, to use Commercially Reasonable Efforts to execute all specific assignments, oaths, declarations, deeds or other instruments that are reasonably requested by Relief to transfer to Relief and vest in Relief the legal title to the Transferred Assets.

(b) On the Closing Date, NRx shall transfer to Relief the tangible embodiments of the Transferred Assets (including (i) the Transferred IP, (ii) the Transferred Records, (iii) the Transferred Materials, provided that Relief shall be responsible for and shall pay and arrange for the transfer of all Transferred Materials from its present location to the contract manufacturer that will hold the Transferred Materials on behalf of Relief following the Closing, (iv) the Transferred Contracts, and (v) the Regulatory Filings. Further, on the Closing Date, NRx shall use Commercially Reasonable Efforts to notify any party that was materially and substantively involved with or worked with NRx in the development of the Product, was a counterparty with respect to the Transferred Contacts, or was a material advisor to NRx with respect to the Transferred IP, the Regulatory Filings or the Transferred Materials that such party is free to discuss their work with NRx as if Relief were NRx for this purpose, as such party sees fit in their sole discretion. A detailed list of all tangible embodiments of the Transferred Assets, the Transferred Contracts and the Regulatory Filings shall be contained in Schedule 2.5(b), which shall include a schedule as to the timing of each such delivery (other than as to the Transferred Materials for which Relief shall be responsible for transferring and delivery), and the third parties as to whom NRx has given permission to discuss their work with Relief.

(c) Upon confirmation by the Parties that the Transferred Assets have been transferred to Relief as required by Schedule 2.5(b), the Parties shall close the Transactions and deliver the following documents (each of which shall have been executed and placed in escrow as of the Execution Date), at which time the Closing shall be completed:

(i) NRx and Relief shall each deliver an executed counterpart Intellectual Property Assignment Agreement in the form attached hereto as Exhibit A;

(ii) NRx and Relief shall each deliver an executed counterpart Assignment and Assumption Agreement in the form attached hereto as Exhibit B;

(iii) NRx and Relief shall each deliver an executed counterpart Bill of Sale in the form attached hereto as Exhibit C;

(iv) Each Party shall deliver a certificate executed by an authorized officer of the delivering Party, in his or her capacity as such, confirming the satisfaction of the conditions to Closing applicable to such Party as set forth in Section 6; and

(v) Each Party shall deliver a certificate executed by an authorized officer of the delivering Party, in his or her capacity as such, confirming the accuracy of such Party’s representation and warranty regarding power and authority (Section 3.4, with respect to NRx, and Section 4.3, with respect to Relief), together with copies of such Party’s Articles of Incorporation, Bylaws and Board and shareholder (if required) resolutions evidencing such power and authority.

2.6 Royalty and Milestone Payments.

(a) Relief shall pay royalties on aggregate Net Sales of all Products during the Royalty Term at the following rates (each, a “Royalty Payment*,*” and, collectively, the “Royalty Payments”):

(i) for sales of the Product in the United States for the treatment of COVID-19, [***] of Net Sales;

(ii) for sales of the Product in the United States for an indication other than COVID-19, [***] of Net Sales; and

(iii) for sales of any product containing the Compound (including the Product) for any indication, on a country-by-country basis in any country outside the United States, [***] of Net Sales.

provided, however, that all Royalty Payments payable hereunder shall not exceed $30 million in the aggregate.

(b) Relief shall pay milestone payments to NRx upon the occurrence of any of the following (each, a “Milestone Payment” and collectively, the “Milestone Payments ”):

(i) If the Product is commercially launched by Relief or any of its Affiliates or its or their respective licensees and sublicensees thereof for the treatment of COVID-19 in the United States, upon the first commercial sale, a one-time milestone payment of [***];

(ii) if the Product is commercially launched by Relief or any of its Affiliates or its or their respective licensees and sublicensees thereof for the treatment of COVID-19 in any country in Europe, upon the first commercial sale, a one-time milestone payment of [***]; and

(iii) if any product containing the Compound (including the Product) is approved or otherwise authorized for use for any indication other than COVID-19 in either the United States or in any country in Europe, a one-time milestone payment of [***].

(c) Royalty Payments will be payable with respect to all Products sold until the expiration of the last Valid Claim for the Product, including for this purpose Valid Claims for other products containing the Compound (“Royalty Term”). Relief shall use Commercially Reasonable Efforts to develop, market, and commercialize the Product; provided, however, that Relief shall have the sole and absolute discretion to select the indications for which it will seek to develop, market and commercialize the Product and shall not be obligated to develop, market, or commercialize the Product for any particular indication (including COVID-19).

(d) All Royalty Payments shall be made in Dollars. All Royalty Payments for an accounting period computed in other currencies shall be converted into Dollars at the buying rate for bank transfers from such currency to Dollars as quoted by the head office of Citibank N.A., New York, at the close of banking on the last day of such accounting period (or the Business Day thereafter if such last day shall be a Sunday or other non-business day). Within forty-five (45) days after the last day of each Calendar Half Year, Relief shall provide to NRx a report setting out: (i) aggregate gross sales of Product in the relevant Half Year, listed by Product and showing the quantities, selling price and country of sale; (ii) aggregate Net Sales of Products in the relevant Half Year, listed by Product and country of sale, showing the quantities and selling price and all deductions; (iii) Calendar Year-to-date aggregate Net Sales of Products; (iv) the amount of the Royalty Payment due for the relevant Half Year, and (v) identification by type, number, quantity, and description of each Product used, leased, sold or otherwise transferred, by or for Relief or any Affiliate during the Half Year and which is exempt from royalty and the reason such exemption applies. In the event no Royalty Payments are due, Relief’s report shall so state. Relief’s Half Year reports shall be certified by the Chief Financial Officer of Relief or his or her designee. Simultaneously with the delivery of each such report, Relief shall pay to NRx the total Royalty Payments due under Section 2.6(a) for the Half Year covered by such report. All Royalty Payments under this Agreement will be irrevocable, non-refundable, non-recoupable, and non-creditable. All Royalty Payments and Milestone Payments shall be treated as amounts paid by Relief in consideration for the sale and transfer of the Transferred Assets.

2.7 Withholding. Relief shall be entitled to deduct and withhold all Taxes that Relief is required by applicable Law to deduct and withhold. To the extent that such amounts are withheld and timely paid to the appropriate Governmental Authority and Relief provides NRx with a timely report of such withholding, all such withheld amounts shall be treated as delivered to NRx hereunder. Relief will promptly pay such withholding to the proper Governmental Authority and will furnish NRx with copies of any tax certificates or other documentation evidencing such withholding after remittance. The Parties agree to cooperate with one another and use reasonable efforts to avoid or reduce tax withholding or similar obligations in respect of any payment made by Relief to NRx hereunder. Notwithstanding the foregoing, if NRx is entitled under any applicable Law to a reduction of rate of, or elimination of, applicable withholding amounts, it may deliver to Relief or the appropriate Governmental Authority (with the assistance of Relief) the prescribed forms necessary to reduce the applicable rate of withholding or to relieve Relief of its obligation to withhold such amount and Relief shall apply the reduced rate of withholding or dispense with withholding, as the case may be.

2.8 Late Payments. Relief shall pay interest on any overdue payments from the due date until the date of payment at an annual rate of one and one-half percent (1.5%) per month or the maximum rate allowed by applicable Law, whichever is less.

SECTION 3. REPRESENTATIONS AND WARRANTIES OF NRX

NRx hereby represents and warrants to Relief as of (i) the Execution Date, subject to any exceptions listed on the Disclosure Schedule specifically identifying the relevant subparagraph hereof, and (ii) the Closing Date, subject to any exceptions listed on the Updated Disclosure Schedule specifically identifying the relevant subparagraph hereof, and acknowledges that Relief is entering into this Agreement in reliance thereon, as follows:

3.1 Full Disclosure. No representation or warranty by NRx in this Agreement and no statement contained in the Disclosure Schedule or any certificate or other document furnished or to be furnished by NRx to Relief pursuant to this Agreement contains any untrue statement of a material fact or omits to state a material fact necessary to make the statements contained therein, in light of the circumstances in which they are made, not misleading.

3.2 Organization and Standing. NRx Pharma and NeuroRx are corporations duly organized, validly existing and in good standing under the laws of the State of Delaware.

3.3 Ownership; Liens; Sufficiency of Assets. NRx has good and marketable title or otherwise has transferrable rights, licenses or interests to the Transferred Assets (subject to Permitted Liens). No Affiliate of NRx (including for this purpose any current or former officer or director of NRx Pharma or NeuroRx) has any right, title or interest in or to any Transferred Asset. The Transferred Assets are not subject to any Liens (other than Permitted Liens) and, subject to Relief’s and its Affiliates’ compliance with applicable Laws (including Laws concerning intellectual property rights and export control) and except as set forth in and subject to Relief’s and its Affiliates’ compliance with the Transferred Contracts and any consents required thereunder, there are no restrictions or limitations on the assignments, transfer, or sale of the Transferred Assets to Relief. The Transferred Assets constitute all of the material tangible and intangible assets owned or licensed by NRx and its Affiliates that are exclusively related to the Product. None of the assets that would be Transferred Assets if they were held by NRx on the Execution Date have previously been transferred to any Affiliate of NRx (including for this purpose any current or former officer or director of NRx Pharma or NeuroRx), and no assets that would be Transferred Assets will be transferred to any Affiliate of NRx (including for this purpose any current or former officer or director of NRx Pharma or NeuroRx) between the Execution Date and the Closing Date.

3.4 P ower and Authority. (a) NRx has all requisite corporate power and authority to execute, deliver and perform this Agreement and to consummate the Transactions, (b) the execution, delivery and performance of this Agreement by NRx does not, and the consummation of the Transactions will not, violate any provisions of NRx’s or its Affiliates’ organizational documents or bylaws, or, violate any provisions of any Law applicable to NRx or its Affiliates, or any agreement (assuming all required consents to assignment are obtained by Relief), instrument, order, judgment or decree to which NRx or any of its Affiliates is a party or by which NRx or any of its Affiliates is bound, and (c) there are no claims by creditors of NRx or any of its Affiliates affecting the Transferred Assets or the Product or the ability of NRx to consummate the Transactions, except in each case as would not reasonably be expected to have a Material Adverse Effect on NRx or materially and adversely affect NRx’s ability to consummate the Transactions.

3.5 Corporate Action; Binding Effect. (a) NRx has duly and properly taken the actions required by Law, its organizational documents or otherwise, to authorize the execution, delivery and performance of this Agreement and the consummation of the Transactions, and (b) when duly executed and delivered by NRx, this Agreement will constitute, legal, valid and binding obligations of NRx enforceable against it in accordance with its terms, subject to bankruptcy, insolvency, fraudulent transfer, reorganization, moratorium or similar Laws of general application affecting or relating to the enforcement of creditors’ rights generally, and subject to equitable principles of general applicability, whether considered in a proceeding at Law or in equity (the “Bankruptcy, Equity and IndemnityException”).

3.6 Intellectual Property.

(a) NRx has no Knowledge of any Patent rights of any of its Affiliates or any Third Parties that would be infringed by the commercial development, sale, or distribution of the Product.

(b) Schedule 1.68 contains a correct, current, and complete list of all patent applications included in the Transferred IP, specifying as to each such patent: (i) the title, (ii) the patent application serial number, and (iii) the filing date. The Patents included in the Transferred IP listed on Schedule1.68 are the only patent applications made by NRx and its Affiliates anywhere in the world solely with respect to the Product owned or controlled by NRx and its Affiliates as of the Execution Date that would be infringed by the development, use, manufacture, or sale of the Product as it exists on the Execution Date.

(c) Except as was disputed in the Litigations, NRx is the sole and exclusive owner of the Transferred IP and has the right to assign the Transferred IP to Relief free and clear of all Liens (other than Permitted Liens). Other than the Transferred IP listed on Schedule 1.68, there are no Patents owned or controlled by NRx or its Affiliates, and neither NRx nor any of its Affiliates has filed any Patents on or prior to the Execution Date, that (i) contain any claims directed to inventions within any Competing Product or that otherwise claim, disclose or describe any Competing Product Know-How, or (ii) would be infringed by the use of the Product by Relief.

(d) The execution, delivery, or performance of this Agreement, and the consummation of the Transactions, will not result in the material loss or impairment of or payment of any additional amounts (other than amounts payable as part of the Assumed Liabilities) with respect to Relief’s right to own or use the Transferred IP (assuming consent to assignment is obtained from the contract counterparties where applicable). This representation does not apply to the payment of recordation fees to the USPTO and the intellectual property rights offices of other Governmental Authorities with respect to the Transferred IP.

(e) NRx has no Knowledge of any information, facts or circumstances that would reasonably be expected to be a valid basis for a challenge to, or that otherwise would reasonably be expected to have a Material Adverse Effect on, the ownership, use, patentability, enforceability or validity of the Transferred IP, other than office actions in the course of prosecution of the Transferred IP. Except as disclosed by the patent applications included in the Transferred IP and for office actions in the course of prosecution of the Transferred IP, none of the Transferred IP is subject to any action or order of any Governmental Authorities restricting the conduct of NRx to accommodate or avoid intellectual property rights of a Third Party.

(f) Except as set forth in Section 3.6(f) of the Disclosure Schedule or alleged in the Litigations:

(i) there has not been, and currently there is no, pending or, to NRx’s Knowledge, threatened written action, proceeding, or other written claim contesting the ownership, use, patentability, enforceability, validity, or right of NRx to exercise any of the Transferred IP other than office actions in the course of prosecution of the Transferred IP;

(ii) there has not been, and currently there is no pending or, to NRx’s Knowledge, threatened written action or proceeding, or other written claim against NRx alleging actual or potential infringement, misappropriation or other violation (directly or indirectly, via contribution or inducement) of a Third Party’s patents, trademarks, service marks, trade names, copyrights, Trade Secrets or other proprietary rights, due to the use or development, of the Transferred IP or the Product;

(iii) to the Knowledge of NRx, there is no legitimate basis for any such claims in (i) and (ii);

(iv) to the Knowledge of NRx: (i) NRx and its Affiliates have not in the past three (3) years infringed (directly, contributorily, by inducement, or otherwise), misappropriated, or otherwise violated any Patents, Know-How, or other intellectual property rights of any Third Party or engaged in unfair competition; in each case solely in connection with the creation, discovery, acquisition, development, manufacture, or use of the Product, or any Transferred IP in a manner that has or would reasonably be expected to result in a material liability to NRx and its Affiliates, taken as a whole; and (ii) no Transferred IP or method or process of manufacturing or use of the Product by NRx or its Affiliates prior to the Execution Date infringes, violates, or makes unlawful use of any Patents or other intellectual property rights misappropriated from, any Third Party in a manner that has or would reasonably be expected to result in a material liability to NRx and its Affiliates, taken as a whole.

(v) there has not been, and currently there is no pending, or to NRx’s Knowledge threatened, written action, proceeding, or other written claim that any NRx representative (including its current and former officers, directors and employees) or consultant or contractor of NRx or its Affiliates (“NRx Representative”) has or claims any ownership interest in any of the Transferred IP, and to the Knowledge of NRx, there is no legitimate basis for any such assertions or claims;

(vi) NRx and its Affiliates have not received any written notice or written offer from any Third Party offering a license under any Third-Party patents for the purpose of avoiding a claim that such patents would be infringed by the use, manufacture, sale, offering for sale, or importation of the Product or any Transferred IP.

(g) To NRx’s Knowledge, and except as alleged in the Litigations, no Person has infringed or misappropriated in the past or is currently infringing or misappropriating any Transferred IP.

(h) NRx and its Affiliates have taken security measures reasonable under the circumstances to protect the secrecy and confidentiality of all Know-How that NRx or any of its Affiliates maintains as Trade Secrets or otherwise treats as confidential or proprietary (“Know-How Confidential Information”), as determined by NRx and its Affiliates in its and their reasonable business judgment and except where the failure would not reasonably be expected to have a Material Adverse Effect. No NRx Representative or consultant or contractor of NRx or its Affiliates with access to any Know-How Confidential Information has any right, license, claim or interest whatsoever in or with respect to any Transferred IP.

(i) NRx has a policy that requires employees, officers, consultants, contractors and other Persons who developed for or on behalf of NRx or any of its Affiliates any part of any Transferred IP to enter into a written agreement that assigns to NRx or any of its Affiliates ownership of all intellectual property developed by such person in the scope of such person’s employment with or engagement by NRx or any of its Affiliates (other than intellectual property excluded by operation of California Labor Code section 2870 or any similar law and non-assignable moral rights). NRx has entered into such agreements with all such persons according to this policy.

(j) No current or former NRx employee, officer, director, or Affiliate owns any inventions relating to the development of the Product made prior to or outside the scope of their relationship with NRx which has not been or will not be assigned to NRx or any of its Affiliates with respect to the Transferred IP.

(k) Except as alleged in the Litigations, NRx has not received any written notice that any employee of NRx (i) has been or is in material violation of any term or covenant of any employment contract, patent disclosure agreement, invention assignment agreement, nondisclosure agreement, noncompetition agreement or any other similar contract with any Third Party by virtue of such employee being employed by, or performing services for NRx or using trade secrets or proprietary information of any Third Party without permission; or (ii) has developed any technology underlying the Transferred IP that is subject to any contract under which such employee has assigned or otherwise granted to any Third Party any rights (including intellectual property rights) in or to such technology.

3.7 Regulatory Matters.

(a) NRx and its Affiliates have complied, and are now complying, in all material respects with all applicable Laws applicable to NRx’s or its Affiliates’ (as applicable) ownership or use and of the Transferred Assets and Product. NRx has delivered or will deliver on or prior to the Closing Date to Relief, solely with respect to the Product, copies of any written material reports in NRx’s and its Affiliates’ possession and control as of or before the Closing Date of inspectional observations, establishment inspection reports, untitled letters, warning letters and any other material documents received by NRx or any of its Affiliates from a Governmental Authority relating exclusively to the Product, in each case that arise from a lack of compliance, in any material respect, with any applicable Laws. All CMC data, stability reports, manufacturing batch records and CMC related regulatory filings have, or as of the Closing Date, shall have been placed in the data room.

(b) NRx and its Affiliates have not, and, to NRx’s Knowledge, NRx’s current and former employees, officers, directors, or Affiliates have not made, in each case solely with respect to the Product, any statement or failed to make any statement, that (in any such case) establishes a reasonable basis for the FDA to invoke its Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Gratuities Policy. In relation to the Product, NRx and its Affiliates are not the subject of any pending or, to NRx’s Knowledge, threatened investigation by the FDA pursuant to its Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Gratuities Policy. To NRx’s Knowledge, there are no FDA commitments with respect to the Product and the Transferred Assets.

(c) NRx and its Affiliates are not subject to any pending or, to NRx’s Knowledge, threatened enforcement, regulatory or administrative proceedings against NRx or any of its Affiliates with respect to any alleged or actual violation by NRx or its Affiliates of any applicable Law or other requirement of any Governmental Authority relating to the Product, including under the FDCA. NRx has no Knowledge of any existing facts in any jurisdiction that would lead to any future enforcement, regulatory, or administrative actions that would have a Material Adverse Effect on the Product, the Transferred Assets, or the Transactions.

(d) NRx and its Affiliates have not been debarred or suspended under 21 U.S.C. §335(a) or (b), are not the subject of a conviction described in Section 306 of the FDCA, have not been excluded from a federal health care program, debarred from federal contracting, convicted of or pled nolo contendere to any felony, or to any federal or state legal violation (including misdemeanors) relating to prescription drug products or fraud, and are not subject to any similar sanction of other Regulatory Authorities outside of the United States (“Debarred/Excluded”) and, to NRx’s Knowledge, none of the NRx Representatives (while employed by NRx) involved in the use of the Product has been Debarred/Excluded.

(e) NRx has made available to Relief copies of all material information and data in NRx’s and its Affiliates’ possession or control as of the Execution Date, or the Closing Date, as applicable, specifically and exclusively relating to the safety of the Product, including written summaries in NRx’s and its Affiliates’ possession or control of complaints and notices of alleged Product defects or adverse reactions resulting from administration of the Product.

3.8 Legal Proceedings . Except for the Litigations, there is no pending Legal Proceeding against NRx or its Affiliates, and, to NRx’s Knowledge, except as alleged in the Litigations, no Person has threatened to commence any Legal Proceeding against NRx or its Affiliates: (a) that involves the Transferred Assets or the Product and would reasonably be expected to have a Material Adverse Effect on the Transferred Assets; or (b) that challenges, or that may have the effect of preventing, delaying, making illegal or otherwise materially interfering with, the Transactions. To NRx’s Knowledge, no event has occurred that would give rise to any such Legal Proceeding. NRx has made available or will make available to Relief copies of all filed complaints and claims related to the Product by NRx and its Affiliates or the ownership or use of the Transferred Assets by NRx and its Affiliates that are in the possession of NRx or its Affiliates.

3.9 Transferred Contracts.

(a) Schedule 1.67 sets forth a correct, current, and complete list of all material contracts between NRx or its Affiliates and Third Parties that are exclusively related to the Product. NRx has made available to Relief unredacted copies of all such contracts where doing so would not be in violation of such contract or other obligation owed to the Third Party. Schedule 1.67 lists which contracts are Transferred Contracts. All material contracts exclusively related to the Product that are not designated as Transferred Contracts on Schedule 1.67 shall be cancelled by NRx. Copies of all material contracts related to the Product (whether or not a Transferred Contract) have, or as of the Closing Date, shall been made available in the data room.

(b) (i) Each Transferred Contract is valid and binding on NRx and, to NRx’s Knowledge, the counterparty thereto, subject to the Bankruptcy, Equity and Indemnity Exception, (ii) except as would not reasonably be expected to have any Material Adverse Effect, NRx is not, and to NRx’s Knowledge no counterparty to any Transferred Contract is, in material breach in the performance, observance or fulfillment of any material obligation or covenant contained in any Transferred Contract and, to NRx’s Knowledge, no event has occurred, that with the giving of notice or lapse of time or both, would constitute a material breach thereunder, and (iii) NRx has not received: (A) any written notice from any counterparty to any Transferred Contract at any time during the past twelve (12) months regarding NRx’s material violation of, material default under, or such counterparty’s intention to cancel or make any material change to any Transferred Contract, (B) any communication from any counterparty to any Transferred Contract that (1) it has materially changed, modified, amended or reduced, or is reasonably likely to materially change, modify, amend or reduce, its business relationship with NRx in a manner that is, or would be, materially adverse to NRx or (2) it will fail to perform, or is reasonably likely to fail to perform, its obligations under any Transferred Contract with NRx in any manner that is, or is reasonably likely to be, materially adverse in any material respect to NRx.

(c) To NRx’s Knowledge, there exists no legitimate basis with respect to NRx or with respect to any counterparty to a Transferred Contract, which, with the giving of notice or the lapse of time would reasonably be expected to give such counterparty the right to accelerate the maturity or performance of any obligation of NRx under any Transferred Contract, or the right to cancel, terminate or modify any Transferred Contract. NRx has not received any written, or to NRx’s Knowledge, any oral request for indemnification pursuant to any Transferred Contract to which NRx is party.

3.10 Solvency. No Governmental Authority order has been made or petition presented, or resolution passed for the winding-up or liquidation of NRx Pharma or NeuroRx and there is not outstanding: (a) any petition or Governmental Authority order for the winding-up of NRx Pharma or NeuroRx; (b) any appointment of a receiver over the whole or part of the undertaking or assets of NRx Pharma or NeuroRx; (c) any petition or Governmental Authority order for administration of NRx Pharma or NeuroRx; (d) any voluntary arrangement between NRx Pharma or NeuroRx and their creditors; (e) any distress or execution or other process levied in respect of NRx Pharma or NeuroRx which remains undischarged; or (f) any unfulfilled or unsatisfied Governmental Authority order against NRx Pharma or NeuroRx

3.11 Brokers and Finders. No broker, finder or investment banker is entitled to any brokerage or finder’s fee in connection with the Transactions based upon arrangements made by or on behalf of NRx.

SECTION 4. REPRESENTATIONS ANDWARRANTIES OF RELIEF

Relief hereby represents and warrants to NRx as of the Closing Date as follows:

4.1 Full Disclosure. **** No representation or warranty by Relief in this Agreement or any certificate or other document furnished or to be furnished by Relief to NRx pursuant to this Agreement contains any untrue statement of a material fact or omits to state a material fact necessary to make the statements contained therein, in light of the circumstances in which they are made, not misleading.

4.2 Organization and Standing. Holding and International are corporations duly organized, validly existing and in good standing under the laws of the Country of Switzerland, Canton of Geneva.

4.3 Power and Authority. (a) Relief has all requisite corporate power and authority to execute, deliver and perform this Agreement and to consummate the Transactions, and (b) the execution, delivery and performance of this Agreement by Relief does not, and the consummation of the Transactions will not, violate any provisions of Relief’s organizational documents or bylaws, or, to Relief’s Knowledge, violate any provisions of any Law applicable to Relief, or any agreement, instrument, order, judgment or decree to which Relief is a party or by which Relief is bound, except in each case as would not reasonably be expected to have a Material Adverse Effect on Relief or materially and adversely affect Relief’s ability to consummate the Transactions.

4.4 Corporate Action; Binding Effect. (a) Relief has duly and properly taken all action required by Law, its organizational documents or otherwise, to authorize the execution, delivery and performance of this Agreement and the consummation of the Transactions, and (b) when duly executed and delivered by Relief, this Agreement will constitute, legal, valid and binding obligations of Relief enforceable against it in accordance with its terms, subject to the Bankruptcy, Equity and Indemnity Exception.

4.5 Legal Proceedings. Except for the Litigations and except as set forth in Schedule 4.5, there is no pending Legal Proceeding against Relief, and, to Relief’s Knowledge, no Person has threatened to commence any Legal Proceeding against Relief: (a) that would reasonably be expected to have a Material Adverse Effect on the Product or otherwise on Relief’s ability to perform its obligations under this Agreement; or (b) that challenges, or that may have the effect of preventing, delaying, making illegal or otherwise interfering with, the Transactions.

4.6 Not Debarred. Relief has not been debarred or suspended under 21 U.S.C. §335(a) or (b), is not the subject of a conviction described in Section 306 of the FDCA, has not been excluded from a federal health care program, debarred from federal contracting, convicted of or pled nolo contendere to any felony, or to any federal or state legal violation (including misdemeanors) relating to prescription drug products or fraud, and is not subject to any similar sanction of other Regulatory Authorities outside of the United States.

4.7 Solvency. No Governmental Authority order has been made or petition presented, or resolution passed for the winding-up or liquidation of Relief and there is not outstanding: (a) any petition or Governmental Authority order for the winding-up of Relief; (b) any appointment of a receiver over the whole or part of the undertaking or assets of Relief; (c) any petition or Governmental Authority order for administration of Relief; (d) any voluntary arrangement between Relief and its creditors; (e) any distress or execution or other process levied in respect of Relief which remains undischarged; or (f) any unfulfilled or unsatisfied Governmental Authority order against Relief.

4.8 Independent Investigation. Relief, in making the decision to acquire the Transferred Assets, has relied upon an independent investigation of the Transferred Assets and has not relied upon any information or representations made by any third parties or upon any oral or written representations or assurances from NRx, it Affiliates, officers, directors or employees or any other representatives or agents of NRx, other than as set forth in this Agreement. Relief has had an opportunity to ask questions of, and receive answers from the NRx’s officers and directors concerning NRx, the Product, and the Transferred Assets. Relief confirms that all documents that it has requested have been made available and that it has been supplied with all of the additional information concerning this purchase of the Transferred Assets which it has requested.

4.9 Brokers and Finders. No broker, finder or investment banker is entitled to any brokerage or finder’s fee in connection with the Transactions based upon arrangements made by or on behalf of Relief.

SECTION 5. COVENANTS OF THE PARTIES

5.1 Pre-Closing Period. During the period from the Execution Date through the Closing Date (the “Pre-Closing Period”), NRx will, after receiving reasonable advance written notice from Relief, give Relief reasonable access (during normal business hours) to NRx’s books and records relating solely and exclusively to the Transferred Assets, and will provide Relief with such information in the possession or control of NRx and its Affiliates solely and exclusively regarding the Transferred Assets as Relief may reasonably request, for the purposes of enabling Relief: (a) to further investigate, at Relief’s sole expense, the Transferred Assets; and (b) to verify the accuracy of the representations and warranties set forth in Section 3; provided that such access shall not interfere with NRx’s normal business and operations. All of the books, records and other information to which Relief is provided access pursuant to this Section 5.1 shall be treated as “Confidential Information” of NRx until the Closing. Notwithstanding anything to the contrary in this Agreement, NRx shall not be required to provide access to or disclose to Relief any of the foregoing information during the Pre-Closing Period if: (i) upon the advice of counsel, such access or disclosure would jeopardize attorney-client, work product or similar privilege of NRx or contravene any (A) applicable Laws, (B) order of a Governmental Authority of competent jurisdiction or (C) obligations of confidentiality to Third Parties (whether contractual or otherwise) (provided that, in the case of the foregoing clause (i), NRx will use Commercially Reasonable Efforts to find a suitable alternative to disclose information in such a way that such disclosure does not violate any such applicable Law, order or confidentiality obligations or jeopardize privilege); or (ii) such access or disclosure would disclose a Trade Secret.

5.2 Ordinary Course. Except as explicitly permitted by this Agreement or as otherwise approved by Relief in writing in advance, during the Pre-Closing Period:

(a) NRx will: (i) operate its business with respect to the Product in the ordinary course and consistent with past practices; (ii) comply with all applicable Laws applicable to its business; and (iii) use Commercially Reasonable Efforts to maintain good relations with the counterparties to the Transferred Contracts;

(b) NRx will not (i) sell, license, transfer, assign, license, discard, destroy, dispose of or create any Liens (other than Permitted Liens) in the Transferred Assets, or enter into any material agreement or undertake any new obligation with any Person with respect to the Transferred Assets; or (i) terminate or amend any of the Transferred Contracts other than as required by the terms of any such Transferred Contracts;

(c) NRx will use Commercially Reasonable Efforts to defend any challenge or opposition relating to the Transferred Patents, which challenge, or opposition shall have, or shall be reasonably likely to have, a Material Adverse Effect;

(d) promptly after obtaining knowledge thereof, NRx shall notify Relief of (i) the occurrence or non-occurrence of any fact or event which causes or would be reasonably likely to cause (A) any representation or warranty of NRx contained in this Agreement to be untrue or inaccurate in any material respect or (B) any covenant, condition or agreement of NRx in this Agreement not to be complied with or satisfied in any material respect, and (ii) any failure of NRx to comply with or satisfy any covenant, condition or agreement to be complied with or satisfied by it hereunder; provided that no such notification shall affect the representations or warranties of NRx or Relief or Relief’s right to rely thereon, or the conditions to the obligations of Relief hereunder. NRx shall give prompt notice in writing to Relief of any written notice or other communication from any Person alleging that the Consent of such Person is or may be required to be obtained by NRx in connection with the Transactions; and

(e) NRx and its Affiliates will continue to enforce all agreements protecting Know How and Confidential Information consistent with past practices to the extent such agreements are not otherwise transferred to Relief pursuant to this Agreement.

5.3 Cooperation;Transfer. After the Closing Date, NRx and Relief shall each cooperate with the other Party and its employees, legal counsel, accountants and other representatives and advisers in connection with the steps reasonably required to be taken as part of their respective obligations under this Agreement; and each of them shall, from time to time after the Closing Date, upon the reasonable written request of the other, execute, acknowledge and deliver, or use Commercially Reasonable Efforts to cause to be executed, acknowledged and delivered, all such further acts, deeds, assignments, transfers, conveyances, receipts, acknowledgments, acceptances and assurances as may be reasonably required (without incurring unreimbursed expense) in order to complete the Transactions on the terms and subject to the conditions set forth herein. Further, NRx agrees to continue to make available to Relief for 60 days following the Closing Date the data room and to allow Relief during such 60 day period to download full copies of everything contained in the data room.

5.4 Governmental Filings. After the Execution Date, NRx and Relief each agree to prepare and file whatever filings, requests or applications that are required to be filed with any Governmental Authority in order to consummate the Transactions and to cooperate with one another as reasonably necessary to accomplish the foregoing. Subject to Section 5.13, each Party shall bear its own costs of such filings, requests, or applications.

5.5 Regulatory Filings. Relief acknowledges and agrees that after transfer to Relief of all Regulatory Filings included in the Transferred Assets, it will have sole responsibility for all regulatory reporting and Regulatory Filing maintenance obligations, including, for the Product and the Transferred Assets, adverse event reporting. Until the transfer of such Regulatory Filings from NRx to Relief is completed, Relief and NRx shall give prompt written notice to the other Party upon becoming aware of any action by, or notification which it receives (directly or indirectly) from, any Governmental Authority (together with copies of correspondence related thereto), which raises any material concerns regarding the safety or efficacy of the Product, or indicates or suggests a potential material liability for either Party to Third Parties arising in connection with the Product.

5.6 Non-Competition. From the Closing Date until the later of (a) expiration of the Royalty Term, or (b) December 31, 2035 (the “Non-Competition Term”), NRx and its Affiliates shall not, directly or indirectly, either on its or their own or with or through any other Person, research, develop, manufacture, commercialize, distribute, use or otherwise exploit any Competing Product in the Field anywhere in the world without the prior written consent of Relief, which consent may be granted or withheld in Relief’s sole discretion. Further, if Javitt, directly or indirectly, attempts to develop the Compound (including the Product) in violation of this Section 5.6, NRx covenants that it will not assist Javitt in any way, whether directly or indirectly in his activities which are in violation of this Section 5.6.

5.7 Patents. After the Closing Date, NRx shall not, itself or through an Affiliate or Third Party, file any Patent that claims or covers, the development, use, manufacture, or commercialization of the Product without first discussing such proposed Patent with Relief and obtaining Relief’s prior written consent to file such Patent.

5.8 Insurance.^1^

5.9 Reasonableness of Covenants. **** NRx acknowledges that Relief will invest substantial time and money to acquire and exploit the Transferred Assets, and the covenants set forth in Sections 5.6, 5.7 and 8.4 are a material part of the agreement between the Parties, are an integral part of the obligations of NRx hereunder, are supported by good and adequate consideration, and are reasonable and necessary to protect the legitimate business interests of Relief, and Relief would not consummate the Transactions unless the covenants set forth in such Sections were in full force and effect and constituted a binding and enforceable contract of NRx. NRx further acknowledges that the duration and geographic territory contained in Section 5.6 are reasonable in all respects and necessary to protect the value of the Transferred Assets and that, without such protection, Relief’s or any of its Affiliates’ competitive advantage would be adversely affected. Notwithstanding any other provision of this Agreement, the Parties agree that: (a) the covenants in Sections 5.6, 5.7 and 8.4 are severable and separate, and the unenforceability of any specific covenant will not affect the continuing validity and enforceability of any other covenant; and (b) if any court of competent jurisdiction determines that any of the scope, time or territorial restrictions set forth in Sections 5.6, 5.7 or 8.4 are unreasonable and therefore unenforceable, then the Parties agree that such provision will be enforced to the fullest extent that the court deems reasonable and this Agreement will thereby be reformed.

^1^

Relief **** requests **** that **** NRx **** continue **** to **** carry **** productsliability **** insurance **** coverage **** for **** patients **** dosed **** with **** the **** Product **** in **** connection **** with **** NRx’s **** clinical **** trials **** of **** theProduct **** or **** in **** connection **** with **** NRx’s **** Right **** to **** Try **** program **** for **** a **** year **** following **** the **** Closing **** Date.

5.10 Audit . After the Closing, Relief shall keep, and shall require its Affiliates to keep, complete and correct books and records of Net Sales of Products in a manner compliant with IFRS and in sufficient detail to calculate Net Sales and all Royalty Payments payable hereunder. Relief shall maintain, and shall require its Affiliates to maintain, all such records for at least three (3) years after the Royalty Term. NRx may, once every Calendar Year and within 24 months after the end of the Royalty Term, upon reasonable (at least thirty (30) days’) prior written notice to Relief, conduct an audit of such books and records through an independent public accounting firm selected by NRx and reasonably acceptable to Relief. Such accountant shall have access, during regular business hours, to examine and inspect such books and records for the sole purpose of inspecting and confirming Net Sales and the Royalty Payments payable by Relief hereunder and that Net Sales was determined and calculated in accordance with IFRS. The accounting firm shall report to the Parties whether the Net Sales determination and calculation and Royalty Payments are correct and whether Net Sales was determined and calculated in accordance with IFRS and the details concerning any discrepancies. Any underpayments shall be paid by Relief within thirty (30) days of notification of the results of such audit. Any overpayments shall be credited against amounts payable by Relief in subsequent payment periods. If any such audit discloses an inaccuracy reflecting an under-reporting or underpayment of greater than three percent (3%) for the period of the audit report, then Relief also shall reimburse to NRx all costs and expenses incurred for such audit, within thirty (30) days of such audit; otherwise, the costs and expenses of such audit shall be paid by NRx. Any information received by NRx or its accounting firm under this Section 5.10 shall be subject to the confidentiality provisions of this Agreement.

5.11 Right to Try Program. Upon the Closing, NRx shall cease, and shall cause its Affiliates and their respective licensees, sublicensees and distributors to cease, all sales and distribution of the Product for compassionate use in the United States, including distribution of the Product under NRx’s Right to Try Program. Subject to applicable regulatory requirements, Relief shall use its Commercially Reasonable Efforts to continue NRx’s existing Right to Try Program for at least two (2) years after the Closing Date.

5.12 Updated Disclosure Schedule. At least three (3) Business Days prior to the Closing Date, NRx shall deliver to Relief an updated schedule setting forth any matter arising or occurring after the Execution Date that NRx determines (a) would have been required to be set forth or described in the Disclosure Schedule if such matter existed or occurred at or prior to the Execution Date, or (b) is necessary to correct any information in the Disclosure Schedule (the “Updated Disclosure Schedule”). The Updated Disclosure Schedule shall include all disclosure necessary to make the representations and warranties of NRx set forth in this Agreement true and correct in all material respects as though made as of the date of the Updated Disclosure Schedule (except that the accuracy of representations and warranties that by their terms speak as of a specified date will be determined as of such specified date); provided, that such disclosure shall consist solely of information regarding circumstances, facts, events or conditions that have arisen, occurred or come into existence after the Execution Date. Notwithstanding anything to the contrary herein, the Updated Disclosure Schedule (i) may only reflect changes necessary to disclose events or occurrences that occur after the Execution Date and (ii) shall not change the nature or scope of the applicable representations and warranties by effectively amending or modifying the language contained in such representations and warranties as opposed to merely listing exceptions thereto. The Updated Disclosure Schedule shall be in substantially the form of the Disclosure Schedule. Any amendment or supplement included in the Updated Disclosure Schedule shall not cure any breach or inaccuracy of any representation or warranty made as of the Execution Date; rather, such disclosures shall solely be deemed to modify and qualify any applicable representations and warranties as of the date of the Updated Disclosure Schedule; provided that, with respect to any information disclosed in the Updated Disclosure Schedule, if Relief shall consummate the Transactions at the Closing in accordance with this Agreement, Relief shall have irrevocably waived any right to assert after Closing that the failure of NRx to disclose any such information disclosed in the Updated Disclosure Schedule in the Disclosure Schedule constituted a breach by NRx of any representation or warranty and to make any indemnification claim pursuant to this Agreement in respect of such breach.

5.13 Transfer Taxes. All sales, use, transfer, stamp, registration, documentary, conveyance, recording, or other taxes required to consummate the Transactions (other than value added, franchise, or income taxes, or any taxes imposed by any Governmental Authority other than the United States) (“Transfer Taxes”) shall be paid equally by NRx and Relief, and NRx and Relief will be responsible for bearing and paying fifty percent (50%) of any and all Transfer Taxes that may become payable in connection with the sale and purchase of, payment for, delivery of, or transfer of title to the Transferred Assets to Relief pursuant to this Agreement. Each Party shall file all necessary tax returns and other documentation required to be filed by it under applicable Law with respect to all Transfer Taxes, and, if required by applicable Law, Relief and NRx, if applicable, will join in the execution of any such tax returns and other documentation. Relief and NRx shall cooperate in providing each other with any appropriate resale exemption certifications and other similar documentation required to obtain any exemption from (or reduction in) Transfer Taxes and shall cooperate in taking any Commercially Reasonable Efforts to minimize liability for Transfer Taxes.

SECTION 6. CONDITIONS TO CLOSING; TERMINATION

6.1 Conditions to Relief ’ s Performance. The obligation of Relief to complete the Closing of the Transactions is subject to the satisfaction (or written waiver by Relief), on or prior to the Closing Date, of each of the following conditions:

(a) NRx shall have performed in all material respects all covenants and obligations required by this Agreement to be performed by NRx on or prior to the Closing Date;

(b) NRx’s representations and warranties set forth in Section 3 shall be true and correct in all material respects (except for such representations and warranties that are qualified by their terms by a reference to “Material Adverse Effect,” which representations and warranties as so qualified shall be true and correct in all respects) as of the Closing Date;

(c) All filings with and consents of any Governmental Authority, if any, required to be made or obtained prior to the Closing by NRx in connection with NRx’s consummation of the Transactions by NRx shall have been made or obtained prior to the Closing Date and shall be in full force and effect; and

(d) No Law, temporary restraining order, preliminary or permanent injunction or other order enacted, entered, promulgated, enforced, or issued by any Governmental Authority or other legal restraint or prohibition by a Governmental Authority shall be pending or in effect seeking to prevent or actually preventing the consummation of the Transactions.

6.2 Conditions to NRx’s Performance. The obligation of NRx to complete the Closing of the Transactions is subject to the satisfaction (or written waiver by NRx), on or prior to the Closing Date, of each of the following conditions:

(a) Relief shall have performed in all material respects all covenants and obligations required by this Agreement to be performed by Relief on or prior to the Closing Date;

(b) Relief’s representations and warranties set forth in Section 4 shall be true and correct in all material respects (except for such representations and warranties that are qualified by their terms by a reference to “Material Adverse Effect,” which representations and warranties as so qualified shall be true and correct in all respects) as of the Closing Date;

(c) All filings with and consents of any Governmental Authority, if any, required to be made or obtained by Relief prior to the Closing in connection with Relief’s execution and delivery of this Agreement or consummation of the Transactions by Relief shall have been made or obtained prior to the Closing Date and shall be in full force and effect; and

(d) No Law, temporary restraining order, preliminary or permanent injunction or other order enacted, entered, promulgated, enforced or issued by any Governmental Authority or other legal restraint or prohibition by a Governmental Authority shall be pending or in effect seeking to prevent or actually preventing the consummation of the Transactions.

SECTION 7. INDEMNIFICATION

7.1 Indemnification by NRx. Subject to the other provisions of this Section 7, following the Closing, NRx shall indemnify, defend (as provided in Section 7.3), and hold harmless Relief, its Affiliates, and each of their respective officers, directors, employees, agents, successors and permitted assigns (each a “Relief Indemnified Party”) from and against and in respect of any and all Damages to the extent caused by, related to, or arising, directly or indirectly, from or in connection with any of the following:

(a) any Excluded Liabilities or Excluded Assets;

(b) any inaccuracy in or breach of any representation or warranty made by NRx in this Agreement; or

7.2 Indemnification by Relief. Subject to the other provisions of this Section 7, following the Closing, Relief shall indemnify, defend (as provided in Section 7.3), and hold harmless NRx, its Affiliates, and each of their respective officers, directors, employees, agents, successors and permitted assigns (each a “NRx IndemnifiedParty”) from and against and in respect of any and all Damages to the extent caused by, related to, or arising, directly or indirectly, from or in connection with any of the following:

(a) any Assumed Liabilities;

(b) any inaccuracy in or breach of any representation or warranty made by Relief in this Agreement; or

(c) any breach or nonfulfillment by Relief of any of its covenants, obligations or agreements contained in this Agreement;

7.3 Limitations. The Party making a claim under this Section is referred to as the “Indemnified Party”, and the party against whom such claims are asserted under this Section is referred to as the “Indemnifying Party”. The indemnification provided for in Section 7.1 and Section 7.2 shall be subject to the following limitations: (a) the Indemnifying Party shall not be liable to the Indemnified Party for indemnification under Section 7.1(b) or Section 7.2(b), as the case may be, until the aggregate amount of all Damages in respect of indemnification exceeds Five Hundred Thousand Dollars ($500,000) (the “Deductible”), in which event the Indemnifying Party shall only be required to pay or be liable for Damages in excess of the Deductible, and (b) the aggregate amount of all Damages for which an Indemnifying Party shall be liable or required to pay pursuant to Section 7.1(b) or Section 7.2(b), as the case may be, shall not exceed Two Million Dollars ($2,000,000) and the aggregate amount of all Damages for which NRx shall be liable or required to pay pursuant to Section 7.1(c) shall not exceed Three Million Dollars ($3,000,000). Notwithstanding the foregoing, if Relief fails to use Commercially Reasonable Efforts to develop, commercialize and market the Product or no Royalty Payments or Milestone Payments are actually paid, NRx shall have no obligation for indemnification hereunder other than under Section 7.1(a). Except for indemnification under Section 7.1(a), which shall not be covered by the limitation in this sentence, NRx’s total indemnity obligation to Relief under this Agreement shall not exceed the total amount of Royalty Payments and Milestone Payments actually paid to NRx hereunder. Relief acknowledges and agrees that it has had an opportunity to conduct a thorough investigation and due diligence inquiry on NRx and its Affiliates, and in no event shall NRx or any of its Affiliates have any liability to Relief or any of its Affiliates with respect to the breach of any representation or warranty in this Agreement to the extent Relief or any of its Affiliates knew of such breach as of the Closing Date. Each Indemnified Party shall take, and cause its Affiliates to take, all reasonable steps to mitigate any Damages upon becoming aware of any event or circumstance that would be reasonably expected to, or does, give rise thereto, including incurring costs only to the minimum extent necessary to remedy the breach that gives rise to such Damages.

7.4 Third-Party Claims.

(a) If any Indemnified Party becomes aware of a Third Party claim (including any action or proceeding commenced or threatened to be commenced by any Third Party) that the Indemnified Party reasonably believes may give rise to the Indemnifying Party’s obligation to indemnify pursuant to this Section 7 (any such claim, a “Third-Party Claim”), the Indemnified Party shall promptly notify the Indemnifying Party in writing of such Third-Party Claim (such notice, the “Claim Notice”). The Claim Notice shall be accompanied by copies of any relevant and material documentation submitted by the Third Party making such Third-Party Claim and shall describe in reasonable detail (to the extent known by the Indemnified Party) the facts constituting the basis for such Third-Party Claim and the amount of the claimed Damages; provided that no delay or failure on the part of the Indemnified Party in delivering a Claim Notice shall relieve the Indemnifying Party from any liability hereunder except and only to the extent the Indemnifying Party shall have been actually and materially prejudiced as a result of such delay or failure.

(b) Within twenty (20) Business Days after receipt of any Claim Notice, the Indemnifying Party may, upon written notice thereof to the Indemnified Party, assume control of the defense of the Third-Party Claim referred to therein at the Indemnifying Party’s sole cost and expense with counsel reasonably satisfactory to the Indemnified Party. Notwithstanding anything to the contrary contained herein, the Indemnifying Party shall not be entitled to assume or control the investigation, defense or prosecution of such Third-Party Claim if (i) a material portion of the Damages associated with such Third-Party Claim are not reasonably expected to be indemnifiable hereunder, (ii) at the time of assumption or thereafter, the Indemnifying Party fails to conduct the investigation, defense or prosecution actively and diligently, or (iii) such Third-Party Claim seeks non-monetary, equitable or injunctive relief against the Indemnified Party or alleges any violation of Law by the Indemnified Party; and in each such case ((i), (ii) or (iii)), the Indemnified Party may assume control of its defense.

(c) The Party not controlling the defense of such Third-Party Claim (the “Non-Controlling Party”) may participate therein at its own expense; provided, however, that if the Indemnifying Party assumes control of the defense of such Third-Party Claim and the Indemnifying Party and the Indemnified Party have materially conflicting interests or different defenses available with respect to such Third-Party Claim which cause the Indemnified Party to hire its own separate counsel with respect to such proceeding, the reasonable fees and expenses of counsel to the Indemnified Party shall be considered “Damages” for purposes of this Agreement. The Party controlling the defense of such Third-Party Claim (the “Controlling Party”) shall keep the Non-Controlling Party advised, in writing, of the status of such Third-Party Claim and the defense thereof and shall consider in good faith recommendations made by the Non-Controlling Party with respect thereto. The Non-Controlling Party shall furnish the Controlling Party with such information as it may have with respect to such Third-Party Claim (including copies of any summons, complaint or other pleading which may have been served on such Party and any written claim, demand, invoice, billing or other document evidencing or asserting the same) and shall otherwise cooperate with and assist the Controlling Party, as reasonably requested by the Controlling Party, in the defense of such Third-Party Claim.

(d) The Indemnifying Party shall not agree to any settlement of, or the entry of any judgment arising from, any Third-Party Claim without the prior written consent of the Indemnified Party, which shall not be unreasonably withheld or delayed; provided, however, that the consent of the Indemnified Party shall not be required with respect to any such settlement or judgment if (i) such settlement or judgment (A) involves no admission of wrongdoing by the Indemnified Party, and (B) the sole relief provided is monetary Damages, and (ii) the Indemnifying Party agrees in writing to pay or cause to be paid any amounts payable pursuant to such settlement or judgment and such settlement or judgment includes a complete release of the Indemnified Party and its Affiliates, directors, officers, employees and representatives from further liability. Whether or not the Indemnifying Party shall have assumed the defense of a Third-Party Claim, the Indemnified Party shall not admit liability with respect to, or agree to any settlement of or the entry of any judgment arising from, any such Third-Party Claim without the prior written consent of the Indemnifying Party, which shall not be unreasonably withheld or delayed; provided that the consent of the Indemnifying Party shall not be required with respect to any such settlement or judgment if the Indemnified Party agrees in writing to pay or cause to be paid any amounts payable pursuant to such settlement or judgment and that no Indemnified Party is entitled to indemnification under this Agreement in respect of such settlement or judgment. Furthermore, a Party’s consent to any settlement of a Third-Party Claim shall not be used as evidence of the truth of the allegations in any Third-Party Claim or the merits of such Third-Party Claim and the existence of any Third-Party Claim shall not create a presumption of any breach by a Party to this Agreement of any of its representations, warranties or covenants set forth in this Agreement.

7.5 LIMITS ON INDEMNIFICATION. NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR ANY INCIDENTAL, SPECIAL, EXEMPLARY, PUNITIVE OR CONSEQUENTIAL LOSSES, LOSSES BASED UPON LOST REVENUES OR PROFITS, DIMINUTION OF VALUE, MULTIPLE OF EARNINGS, PROFITS OR CASH FLOW OR SIMILAR MEASURES, HOWEVER CAUSED OR ON ANY THEORY OF LIABILITY, THAT ARISE OUT OF OR RELATE TO THIS AGREEMENT OR THE PERFORMANCE OR BREACH HEREOF OR THEREOF OR ANY OTHER TRANSACTION CONTEMPLATED HEREBY, ALL OF WHICH ARE HEREBY EXCLUDED BY AGREEMENT OF THE PARTIES REGARDLESS OF WHETHER OR NOT ANY PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH LOSSES; PROVIDED THAT NOTHING IN THIS SECTION 7.5 SHALL LIMIT OR RESTRICT (A) THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY UNDER THIS SECTION 7 WITH RESPECT TO THIRD-PARTY CLAIMS, (B) EITHER PARTY’S LIABILITY FOR BREACHES OF THE CONFIDENTIALITY OBLIGATIONS IN SECTION 8, or (C) NRX’S LIABILITY FOR BREACH OF SECTION 5.6.

7.6 Reserved.

7.7 Survival and Expiration of Representations, Warranties and Covenants.

(a) The representations and warranties made by each of NRx and Relief in Section 3 and Section 4, respectively, shall survive the Closing and remain in full force and effect until the date that is eighteen (18) months after the Closing Date (the “Expiration Date”). None of the covenants or other agreements contained in this Agreement shall survive the Closing Date other than those which by their terms contemplate performance after the Closing Date, and each such surviving covenant and agreement shall survive the Closing for the period contemplated by its terms. If Relief or NRx delivers to the other Party, before the Expiration Date, either a Claim Notice or based upon a breach of a representation or warranty in Section 3 or Section 4, then such claim and associated representation and warranty and right to indemnification (including any right to pursue such indemnification hereunder) will not terminate, and shall survive until (but only for purposes of) the resolution and final determination of such claim covered by such Claim Notice.

(b) Each covenant and agreement in this Agreement, and all associated rights to indemnification (including any right to pursue such indemnification hereunder), will survive the Closing and will continue in full force thereafter, without limitation as to time, until fully performed in accordance with its terms or until the date that is ninety (90) days past the expiration of the applicable statute of limitations period relating to such covenant or agreement. Any claims based on fraud will survive the Closing indefinitely.

7.8 Right of Set off. If a Third Party makes a Third-Party Claim against any Relief Indemnified Party, then, at any time that Relief incurs or otherwise suffers Damages (including reasonable fees and expenses of counsel and other professionals and experts if NRx (as the Indemnifying Party) fails to assume control of the defense of such Third-Party Claim for any reason or if Relief (as the Indemnified Party) assumes control of the defense of such Third-Party Claim pursuant to Section 7.4(b)), Relief may set off the amount of the Damages incurred or otherwise suffered by Relief in connection with such Third-Party Claim against milestone payments or Royalty Payments which has not been paid to NRx in accordance with this Agreement. Neither the exercise of, nor the failure to exercise, such right of set off shall constitute an election of remedies or limit Relief in any manner in the enforcement of any other remedies that may be available to Relief.

7.9 Construction. For purposes of determining whether a breach has occurred in connection with a claim for indemnification under this Section 7, each of the representations and warranties that contains any qualifications as to “materiality” shall be deemed to have been given as though there were no such qualifications.

SECTION 8. CONFIDENTIALITY

8.1 Confidential Information . Except as expressly provided herein, the Parties agree that the receiving Party of Confidential Information shall not, directly or indirectly, publish or otherwise disclose to any Third Party and shall not use for any purpose at any time any Confidential Information (whether or not such information is or was developed by any of them), except to the extent permitted under this Section 8. The receiving Party shall: (i) use the disclosing Party’s Confidential Information solely for the purpose for which it was provided, and (ii) maintain the Confidential Information as confidential and safeguard such Confidential Information and to protect it against disclosure, misuse, loss and theft. The Parties agree that Confidential Information is not deemed to be in the public domain merely because any part of the information is embodied in general disclosures or because individual features, components or combinations are now, or become, known to the public. Notwithstanding the foregoing, Confidential Information shall not include information that, in each case as demonstrated by written documentation:

(a) was already known to the receiving Party at the time of disclosure, other than under an obligation of confidentiality;

(b) was available to the public or otherwise part of the public domain at the time of its disclosure to the receiving Party;

(c) became available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving Party in breach of this Agreement;

(d) was independently developed by the receiving party after the Closing Date; or

(e) was disclosed to the receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation of confidentiality to the disclosing Party or any other Third Party.

8.2 Permitted Disclosures. Notwithstanding Section 8.1, each receiving Party may disclose Confidential Information of the disclosing Party to the extent that such disclosure is:

(a) made on or behalf of Relief to any Governmental Authority or any Regulatory Authority as required in connection with the filing, application or request for Marketing Approval of the Product; provided, however, that reasonable measures shall be taken to assure confidential treatment of such information to the extent practicable and consistent with applicable Law;

(b) made in response to a valid order of competent jurisdiction or other supra-national, federal, national, regional, state, provincial and local governmental or regulatory body of competent jurisdiction or, if in the reasonable opinion of the receiving Party’s legal counsel, such disclosure is required by applicable Law, including, without limitation, disclosure requirements with the SIX Swiss Exchange (the “SIX”) and the United States Securities and Exchange Commission (“SEC”), provided , however, that to the extent practicable and not otherwise prohibited by applicable Law, the receiving Party shall first have given notice to the disclosing Party and given the disclosing Party (i) a reasonable opportunity to quash such order or to obtain a protective order or confidential treatment requiring that the Confidential Information and documents that are subject of such order be held in confidence by such court or agency or, if disclosed, be used only for the purposes for which the order was issued, and (ii) a right to review and comment upon such disclosure, which comments shall be considered in good faith by the receiving Party, and provided further that the Confidential Information disclosed in response to such court or governmental order shall be limited to the information which is legally required to be disclosed in response to such court or governmental order;

(c) made by or on behalf of Relief as may reasonably be necessary for the purposes of the registration and pursuit of the Transferred IP, provided , however, that reasonable measures shall be taken to assure the confidential treatment of such information, to the extent such protection is available; or

(d) made in confidence by the receiving party to its or its Affiliates’ attorneys, auditors, advisers, consultants, or contractors who have a reasonable need to know.

8.3 Public Announcements. Notwithstanding anything to the contrary herein, except as may be required to comply with the requirements of any applicable Law, including the rules and regulations of the SIX or the SEC or other stock exchange upon which the securities of a Party is listed, from and after the Execution Date, no press release or similar public announcement or communication shall be made or caused to be made by either Party or any of its Affiliates relating to this Agreement or the Transactions without the prior written consent of the other Party (such consent not to be unreasonably withheld, conditioned or delayed); provided that the Parties will issue press releases, in each case that are approved by mutual agreement of the Parties, announcing (a) the execution of this Agreement and (b) the Closing of the Transactions. For clarity, Relief and NRx may issue such press releases, public announcements or communications or make such SEC filings as it determines are reasonably necessary to comply with disclosure requirements of the SIX and the SEC.

8.4 Survival. The receiving Party’s obligations of confidentiality and non-use with respect to any Confidential Information set forth in this Section 8 shall survive termination of this Agreement for a period of seven (7) years thereafter; provided that such obligations with respect to any Confidential Information comprising a Trade Secret of the disclosing Party shall survive and continue for as long as such Confidential Information qualifies as a Trade Secret of the disclosing Party under applicable Law. ****

SECTION 9. MISCELLANEOUS PROVISIONS

9.1 Force Majeure . Neither Party shall be liable for any nonperformance or delay in performance of its obligations under this Agreement to the extent such failure is attributable to acts or events (including acts of God, war, terrorist activities, conditions or events of nature, industry wide supply shortages, civil disturbances, embargo, work stoppage, power failures, fire, flood, earthquake, epidemic, pandemic (other than COVID-19), unavailability of supplies, materials or transportation, or any applicable Law or decision, order or judgment of any Governmental Authority), and in general any other cause or condition beyond its reasonable control which impair or prevent in whole or in part performance by such Party hereunder; provided that the payment of amounts due and owing hereunder shall not be excused or delayed as a result of any force majeure act or event. If a Party is unable to perform its duties and obligations hereunder as a result of an event of force majeure, as described in the first sentence of this Section 9.1, the affected Party shall, as promptly as reasonably practicable, give notice of the occurrence of such event to the other Party and shall use its Commercially Reasonable Efforts to resume the performance at the earliest reasonably practicable date.

9.2 Amendment. This Agreement may not be modified, amended, altered, or supplemented except upon the execution and delivery of a written agreement executed by an authorized representative of each Party.

9.3Expenses. Except as set forth in this Agreement, all fees and expenses incurred in connection with this Agreement and the Transactions shall be paid by the Party incurring such expenses.

9.4 Waiver.

(a) No failure on the part of a Party to exercise any power, right, privilege or remedy under this Agreement, and no delay on the part of a Party in exercising any power, right, privilege or remedy under this Agreement, shall operate as a waiver of such power, right, privilege or remedy; and no single or partial exercise of any such power, right, privilege or remedy shall preclude any other or further exercise thereof or of any other power, right, privilege or remedy.

(b) No Party shall be deemed to have waived any claim arising out of this Agreement, or any power, right, privilege or remedy under this Agreement, unless the waiver of such claim, power, right, privilege or remedy is expressly set forth in a written instrument duly executed and delivered on behalf of such Party; and any such waiver shall not be applicable or have any effect except in the specific instance in which it is given.

9.5 Entire Agreement. This Agreement, together with the Exhibits and Schedules hereto, the Disclosure Schedule, Updated Disclosure Schedule, Ancillary Agreements and the Settlement Agreement, constitutes the entire agreement between the Parties with respect to the subject matter hereof and supersedes all prior agreements and understandings, both written and oral, between the Parties with respect to such subject matter, including any confidentiality agreement previously in place between the parties which is superseded hereby.

9.6 Applicable Law; Jurisdiction; Waiver of Jury Trial. This Agreement shall be governed by, and construed in accordance with, the laws of the State of New York, regardless of the laws that might otherwise govern under applicable principles of conflicts of laws thereof. In the event of any dispute or controversy arising under or related to this Agreement that is not resolved amicably through good faith discussion, each of the Parties irrevocably and unconditionally consents and submits to the exclusive jurisdiction and venue of the federal or state courts in Manhattan, New York. Each of the Parties waives any defense of inconvenient forum to the maintenance of any action so brought and waives any bond, surety or other security that might be required of any other Party with respect thereto. Each Party hereby waives, to the fullest extent permitted by Law, any right to trial by jury of any claim, demand, action, or cause of action (a) arising under this Agreement or (b) in any way connected with or related or incidental to the dealings of the Parties in respect of this Agreement or the Transactions, in each case, whether now existing or hereafter arising, and whether in contract, tort, equity, or otherwise. Each Party hereby further agrees and consents that any such claim, demand, action, or cause of action shall be decided by court trial without a jury and that the Parties may file a copy of this Agreement with any court as written evidence of the consent of the Parties to the waiver of their right to trial by jury.

9.7 Assign ment. Neither this Agreement nor any of the rights or obligations hereunder may be assigned by NRx or Relief without the prior written consent of the Other Party, and any attempted assignment of this Agreement or any such rights or obligations without such consent shall be void and of no effect; provided that (a) either Party may assign this Agreement or any such rights or obligations to an Affiliate without the prior written consent of the other Party, and (b) either Party may assign this Agreement as a whole without the consent of the other Party, to a successor in connection with the acquisition (whether by merger, consolidation, sale or otherwise) of such Party or of that part of such Party’s business to which this Agreement relates. Subject to the foregoing, this Agreement shall be binding upon, and shall be enforceable by and inure solely to the benefit of, the Parties hereto and their respective successors and assigns.

9.8 Third Party Beneficiaries. Except for the rights to indemnification provided for in Section 7, nothing in this Agreement, express or implied, is intended to or shall confer upon any Person (other than the Parties) any right, benefit or remedy of any nature whatsoever under or by reason of this Agreement.

9.9 Notices. Any notice or other communication required or permitted to be delivered to either Party under this Agreement shall be in writing and shall be deemed properly delivered, given and received (a) upon receipt when delivered by hand, or (b) one Business Day after being sent by courier or express next-day delivery service, provided that in each case the notice or other communication is sent to the address set forth beneath the name of such Party below (or to such other address as such Party shall have specified in a written notice given to the other Party):

If to Relief:

RELIEF THERAPEUTICS Holding SA

Avenue de Sécheron 15

1202 Genève

Switzerland

Attention: Jack Weinstein, Chief Financial Officer

jack.weinstein@relieftherapeutics.com

with a copy to (which shall not constitute notice):

Philip B. Schwartz, Esq.

Akerman LLP

201 East Las Olas Boulevard

Suite 1800

Fort Lauderdale, FL 33301

954-468-2455

philip.schwartz@akerman.com

if to NRx Pharma and NeuroRx:

NRx Pharmaceuticals, Inc.

1201 North Market Street

Suite 111

Wilmington, DE 19801

Attention: Stephen H. Willard, Chief Executive Officer

willard@nrxpharma.com

with copies (which will not constitute notice hereunder) to:

Douglas Boggs, Esq.

DLA Piper (US) LLP

500 8th Street, NW

Washington, DC 20004

202-799-4070

douglas.boggs@us.dlapiper.com

9.10 Severability. If any term or other provision of this Agreement, or any portion thereof, is invalid, illegal or incapable of being enforced by any rule of Law or public policy, all other terms and provisions of this Agreement, or remaining portion thereof, shall nevertheless remain in full force and effect so long as the economic or legal substance of the Transactions is not affected in any manner materially adverse to any Party hereto. Upon such determination that any such term or other provision, or any portion thereof, is invalid, illegal or incapable of being enforced, the Parties shall negotiate in good faith to modify this Agreement so as to affect the original intent of the Parties as closely as possible in an acceptable manner to the end that the Transactions are consummated to the fullest extent possible.

9.11 Specific Performance ; Non-Exclusive Remedies. Each Party agrees that this Agreement is intended to be legally binding and specifically enforceable pursuant to its terms and that Relief and NRx would be irreparably harmed if any of the provisions of this Agreement were not performed in accordance with their specific terms and that monetary damages would not provide adequate remedy in such event. Accordingly, in addition to any other remedy to which a non-breaching Party may be entitled at Law, a non-breaching Party shall be entitled to seek injunctive relief to prevent breaches of this Agreement and to specifically enforce the terms and provisions hereof, in each case without posting a bond or undertaking, this being in addition to any other remedy to which they are entitled at law or in equity. Each of the Parties agrees that it will not oppose the granting of an injunction, specific performance, and other equitable relief when expressly available pursuant to the terms of this Agreement on the basis that the other Party has an adequate remedy at law or that an award of specific performance is not an appropriate remedy for any reason at law or equity. The rights and remedies provided in this Agreement are cumulative and do not exclude any other right or remedy provided by applicable Law or otherwise available.

9.12 Standstill Agreement. Unless approved in advance in writing by the board of directors of the other Party, for the five years following the Closing Date, neither NRx nor Relief, nor any of their respective officers, directors or Affiliates, will (a) acquire collectively an interest in the other Party exceeding 5% of the other Party’s outstanding common stock (in the case of NRx) or ordinary shares (in the case of Relief), on a fully diluted basis, (b) take any action that would reasonably be expected to effect such a transaction in the future, or (c) encourage, instigate or assist any third party to take an action to acquire such interest.

9.13 Construction.

(a) For purposes of this Agreement, whenever the context requires: the singular number shall include the plural, and vice versa; the masculine gender shall include the feminine and neuter genders; the feminine gender shall include the masculine and neuter genders; and the neuter gender shall include masculine and feminine genders.

(b) The Parties agree that any rule of construction to the effect that ambiguities are to be resolved against the drafting Party shall not be applied in the construction or interpretation of this Agreement.

(c) As used in this Agreement, the words “include” and “including,” and variations thereof, shall not be deemed to be terms of limitation, but rather shall be deemed to be followed by the words “without limitation.”

(d) the term “or” will be interpreted in the inclusive sense commonly associated with the term “and/or.”

(e) Except as otherwise indicated, all references in this Agreement to “Sections,” “Exhibits” and “Schedules” are intended to refer to Sections of this Agreement and Exhibits and Schedules to this Agreement.

(f) The bold-faced headings contained in this Agreement are for convenience of reference only, shall not be deemed to be a part of this Agreement and shall not be referred to in connection with the construction or interpretation of this Agreement.

(g) As used in this Agreement, the word “day” will mean calendar day unless Business Day is specified.

9.14 Counterparts. This Agreement may be executed in counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Each of the signatories to this Agreement may execute this Agreement in Adobe^™^ Portable Document Format (PDF) sent by electronic mail or by other electronic means. PDF or other electronic signatures of authorized signatories of the Parties will be deemed to be original signatures, will be valid and binding upon the Parties, and, upon delivery, will constitute due execution of this Agreement.

[Signature Page Follows]

IN WITNESS WHEREOF, the Parties have caused this Asset Purchase Agreement to be executed as of the Execution Date.

NRX PHARMACEUTICALS, INC.
By:
Name:
Title:
NORX, INC.
By:
Name:
Title:
RELIEF THERAPEUTICS HOLDING SA
By:
Name:
Title:
By:
Name:
Title:
RELIEF THERAPEUTICS INTERNATIONAL SA
By:
Name:
Title:

All values are in Euros.

Exhibit A

Form of Intellectual Property Assignment Agreement

[***]

Exhibit B

Form of Assignment and Assumption Agreement

[***]

Exhibit C

Form of Bill of Sale

[***]

Exhibit D

Settlement Agreement

[***]

Schedule 1.13

Compound

[***]

Schedule 1.67

Transferred Contracts

[***]

Schedule 1.68

Transferred IP

[***]

Schedule 1.69

Inventory of Product and Compound

[***]

Schedule 2.5(b)

Closing Deliveries

[***]

Schedule 4.5

Relief Litigation Regarding the Product

[***]

EX-10.8(B)

Exhibit 10.8(b)

Execution Version

Certain identified information has been excluded from this exhibit because it is both (i) not material, and (ii) would likelycause competitive harm to the registrant if publicly disclosed. [***] indicates that information has been redacted.

SETTLEMENTAGREEMENT

This Settlement Agreement (including Exhibit A) (this “Settlement Agreement”) is made and entered into as of this 12^th^ day of November, 2022 (the “Execution Date”), by and between RELIEF THERAPEUTICS HOLDING AG and RELIEF THERAPEUTICS INTERNATIONAL SA (together, “Relief”), on the one hand, and NEURORX, INC. (“NeuroRx”) and NRX PHARMACEUTICALS, INC. (“NRx,” and together with NeuroRx, the “NeuroRx Parties”), on the other hand. For all purposes, Relief and the NeuroRx Parties are each individually a “Party” and all are collectively the “Parties”).

RECITALS

A. WHEREAS, Relief and NeuroRx entered into a Binding Collaboration Agreement, dated as September 18, 2020 (the “Collaboration Agreement”), which established the terms under which the Parties would collaborate and assist each other with the development and future sale of aviptadil, including but not limited to intravenous and inhalation use primarily as a treatment for COVID-19;

B. WHEREAS, on October 6, 2021, Relief filed a complaint against NeuroRx and Jonathan Javitt (“Javitt”), NeuroRx’s former Chief Executive Officer, in the Supreme Court of the State of New York, County of New York (the “Court”), captioned Relief Therapeutics Holding AG and Relief Therapeutics International SA (f/k/a Therametrics Discovery AG) v. Jonathan Cogswell Javitt and NeuroRx , Inc. **** (Index No. 655857/2021), alleging claims for (1) breach of the Collaboration Agreement, (2) breach of covenant of good faith and fair dealing, (3) declaratory judgment, (4) an accounting, and (5) tortious interference with prospective economic advantage (the “Relief Action”);

C. WHEREAS, on January 10, 2022, NeuroRx filed a complaint in the Supreme Court of the State of New York, County of New York, captioned, NeuroRx, Inc. v. Relief Therapeutics Holding AG and Relief Therapeutics International SA (f/k/a Therametrics Discovery AG) (Index No. 650162/2022), alleging claims for (1) breach of the Collaboration Agreement, (2) declaratory judgment, and (3) defamation (the “NeuroRx Action” and together with the Relief Action, the “Litigations”);

D. WHEREAS, on July 6, 2022, Judge Jennifer Schecter of the New York Supreme Court entered an order consolidating the Relief Action and the NeuroRx Action under Index No. 655857/2021;

E. WHEREAS, without conceding the merit or lack of merit of any claim or defense or the existence of any liability whatsoever, the Parties now wish to fully and finally settle and resolve all disputes and differences that exist or heretofore have ever existed between them, respectively, including the claims asserted in the Relief Action, the NeuroRx Action, and all related claims, demands, rights of action, and causes of action, whether known or unknown;

F. WHEREAS, on the Execution Date, [***].

G. WHEREAS, contemporaneously with the execution of this Settlement Agreement, the NeuroRx Parties and Relief are executing an Asset Purchase Agreement (the “Asset Purchase Agreement”), to which this Settlement Agreement is an exhibit, pursuant to which the NeuroRx Parties will sell to Relief, and Relief will purchase from the NeuroRx Parties, certain assets, as more particularly set forth in the Asset Purchase Agreement;

H. WHEREAS, the settlement terms set forth in this Settlement Agreement shall become effective upon the Closing; and

I. WHEREAS, subject to the Closing, the Parties desire to settle the Litigations on the terms set forth in this Settlement Agreement.

NOW THEREFORE, in consideration of the foregoing Recitals, and the mutual promises, covenants, and undertakings contained herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:

1. Definitions

1.1	“Affiliate” means, with respect to any specified Person, any other Person that, directly or<br>indirectly, through one or more intermediaries, controls, is controlled by or is under common control with such specified Person. The term “control” (including, with correlative meaning, the terms “controlled by” and “under<br>common control with”), as used with respect to any Person, means the possession, directly or indirectly, of the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of equity,<br>voting securities, beneficial interest, by contract or otherwise.
1.2	“Business Day” means any day that is not a Saturday, a Sunday or other day on which banks are<br>required or authorized by law to be closed in the State of New York.
---	---
1.3	“Closing” means the closing under the Asset Purchase Agreement pursuant to which the NeuroRx<br>Parties and Relief will consummate the purchase and sale of the Transferred Assets (as defined in the Asset Purchase Agreement) and the other transactions contemplated by the Asset Purchase Agreement.
---	---
1.4	“Closing Date” means the date of the closing date under the Asset Purchase Agreement.<br>
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1.5	“Compound” means avipdadil.
---	---
1.6	“FDA” means the U.S. Food and Drug Administration (and any successor organization or agency<br>thereto).
---	---
1.7	“Litigations” means the Relief Action and the NeuroRx Action.
---	---
1.8	“Product” means any product containing the Compound as an active ingredient for all routes of<br>administration. Relief has historically called the Product RLF-100^®^ (and it is referred to as such in the Collaboration Agreement) and NRx has<br>historically called the Product Zyesami^®^.
---	---

1.9	“Transferred Assets” means the assets being transferred by the NeuroRx Parties to Relief under<br>the Asset Purchase Agreement, as more particularly set forth in the Asset Purchase Agreement.
1.10	“SEC” means the United States Securities and Exchange Commission.
---	---
1.11	“Settlement Documents” means this Settlement Agreement, including the Stipulation of Dismissal<br>(Exhibit A). [***].
---	---
1.12	“Third Party” means any person or entity other than a Party or its Affiliates.<br>
---	---
2.	Stipulations.
---	---
2.1	On the Closing Date, as provided in the Asset Purchase Agreement, the NeuroRx Parties will transfer, deliver<br>and convey the Transferred Assets to Relief.
---	---
2.2	On the Closing Date, in consideration of the mutual benefits of entering into this Settlement Agreement and the<br>Asset Purchase Agreement:
---	---
(a)	the Parties shall enter into and cause to be filed with the Court in the Litigations, within three<br>(3) Business Days after the Closing Date, the Stipulation of Dismissal in the form annexed hereto as Exhibit A dismissing the Litigations with prejudice, with each Party bearing its own costs and expenses and attorney’s fees. If the<br>Court does not dismiss the Litigations with prejudice substantially in the form annexed hereto as Exhibit A, the Parties agree to confer in good faith as to an alternative resolution; and
---	---
(b)	The Collaboration Agreement shall be terminated and shall be of no further force or effect.<br>
---	---
3.	Mutual General Releases. Effective on the Closing Date, except as set forth below, the Parties hereby<br>mutually release, acquit, satisfy and forever discharge each and every other Party and all of their respective Affiliates, successors, assigns, employees, directors, officers, agents, attorneys, and other representatives of and from any and all<br>charges, claims, counterclaims, actions, rights, demands, debts, liens, obligations, causes of action, liability, losses, damages, costs, expenses or accountings of any nature whatsoever, whether in law or in equity, whether known or unknown,<br>suspected or unsuspected, from the beginning of time up to the date of the Settlement Agreement, arising under any circumstances whatsoever, including without limitation claims in any way related to: (i) the claims and counterclaims asserted<br>in, and the conduct of, the Litigations; (ii) any counterclaims required to have been brought in the Litigations, and (iii) the conduct of the settlement negotiations; provided, however, that for the avoidance of doubt, excluding<br>any claims arising from or under this Settlement Agreement or the Asset Purchase Agreement.
---	---

[***].

The Parties have each made an investigation of the facts pertaining to this Settlement Agreement and to the released claims as each Party deems necessary. Each Party is aware that it may hereafter discover facts in addition to, contrary to, or different from those it now knows or believes to be true with respect to the matters set forth herein. Nevertheless, it is the intention of each Party to fully, finally, and forever settle and release all claims of any kind or nature whatsoever that were in existence as of the date of this Settlement Agreement. In furtherance of the Parties’ intent, the release in this Agreement shall remain in full and complete effect notwithstanding the discovery or existence of any additional, contrary, or different facts.

Furthermore, each Party certifies that it has read the provisions of California Civil Code Section 1542 and has consulted its own counsel regarding that section. Each Party waives any and all rights under California Civil Code Section 1542 (or any other similar law in any jurisdiction), which states:

A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS THAT THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR SUSPECT TO EXIST IN HIS OR HER FAVOR ATTHE TIME OF EXECUTING THE RELEASE AND THAT, IF KNOWN BY HIM OR HER, WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.

Each Party agrees and acknowledges that the released claims extend to and include unknown and unsuspected claims.

4.	Legal Fees. Each Party will pay its own costs and expenses, including attorney fees, incurred in<br>connection with the Litigations and in connection with the preparation, negotiation, and execution of this Settlement Agreement and its Exhibit.
5.	Legal Compliance.
---	---
5.1	This Agreement, other than this Section 5 and Sections 8 through 21, shall not become effective until the<br>Closing Date. Following the signing of this Agreement and the Asset Purchase Agreement, the Parties shall jointly ask the Court to stay the matter for a period of no more than an additional [thirty (30)] days to allow for the Closing of the<br>transactions contemplated by the Asset Purchase Agreement. The Parties also agree to submit to the court appropriate stipulations and proposed orders for extensions of time for all due dates in the Litigations so that neither Party is required to<br>incur unnecessary expenses in the Litigations between the Effective Date and the Closing Date.
---	---
5.2	In the event that the Closing under the Asset Purchase Agreement does not occur (as applicable) by the Closing<br>Date (or such date as the Parties agree to in writing) and either Party, at its option pursuant to the Asset Purchase Agreement, elects to terminate the Asset Purchase Agreement, then (i) this Agreement (other than this Section 5 and<br>Section 8) will automatically terminate, and (ii) the Parties will notify the Court that a settlement was not achieved and that the litigation schedule should resume on a schedule to be proposed by each Party and entered by the Court.<br>
---	---

6.	Final Agreement. This Settlement Agreement and its Exhibit, if not terminated pursuant to<br>Section 5.2, constitutes a final settlement between the Parties and, following the Closing Date but without limiting Relief’s obligations and the NeuroRx Parties’ rights under the Asset Purchase Agreement, the NeuroRx Parties shall<br>not contest, challenge, dispute or deny in any way Relief’s unilateral right to control the development of any aviptadil product (including the Product) containing the Compound anywhere in the world.
7.	Publicity. After the Closing Date, (i) the Parties shall issue a joint press release announcing<br>that the settlement of the Litigations has closed (the “Settlement”), and (ii) each of the Parties shall file the necessary disclosure with the SEC with respect to the Settlement, subject to Section 8 below and the Asset<br>Purchase Agreement. The Parties shall jointly agree upon the contents, and timing for the issuance, of the joint press release. The obligations of Relief and NeuroRx to share information about their disclosure of the Settlement is more particularly<br>set forth in the Asset Purchase Agreement.
---	---
8.	Confidentiality. From and after the Execution Date and except as expressly provided in Section 7<br>(Publicity), the terms of this Settlement Agreement and its Exhibits will be maintained in strict confidence by the Parties except that any Party may disclose this Settlement Agreement (i) with the prior written consent of the other Party;<br>(ii) to any governmental body having jurisdiction and specifically requiring such disclosure; (iii) in response to a valid subpoena or as otherwise may be required by law, legal process or order of a court; (iv) for the purposes of<br>disclosure in connection with any reports filed with the SEC, including, without limitation, SEC reporting requirements, or by the rules or regulations of any stock exchange that the Parties are subject to; (v) as required during the course of<br>litigation and subject to protective order; (vi) with obligations of confidentiality at least as stringent as those contained herein, to a counterparty in connection with a proposed merger, acquisition, asset sale, spin-out, debt or equity financing, or other corporate or business combination transaction; (vii) in connection with tax audits or to fulfill its corporate financial reporting obligations under GAAP or IFRS, as<br>the case may be; (viii) with obligations of confidentiality at least as stringent as those contained herein, by any Party and its Affiliates as required to enforce this Agreement or establish rights or defenses hereunder; (ix) to officers,<br>key shareholders, directors and/or employees with a need to know, who are under obligations of confidentiality at least as stringent as those contained herein; and (x) to its Affiliates, who are similarly bound by this Agreement or under<br>obligations of confidentiality at least as stringent as those contained herein. The Parties may also disclose this Settlement Agreement and its Exhibit(s) to their respective attorneys, accountants, auditors, or similar individuals providing<br>professional services to such Party in their capacity of advising the party in such matters, subject to obligations of confidentiality and/or privilege at least as stringent as those contained herein. The Parties acknowledge and agree that, upon the<br>filing of the Stipulation of Dismissal with the Court, the fact that the Parties have settled the Litigations will be a matter of public record and will not be subject to any confidentiality restrictions, but the terms of such settlement will be<br>maintained in confidence to the extent provided by this Section 8 and the confidentially provisions contained in the Asset Purchase Agreement. Prior to making any such disclosure pursuant to subparts 8(ii), (iii) or (v) above, the Party<br>seeking disclosure shall promptly notify the other Party in sufficient time (if reasonably feasible) to permit the other Party the opportunity to object (or, if the timing of the litigation makes advance notice impracticable, the notice is provided<br>within 10 days after the disclosure), to seek a court-entered protective order or comparable court-ordered restriction, and shall reasonably cooperate with the other Party in its efforts to obtain that protective order and take all other reasonable<br>actions in an effort to minimize the nature and extent of such disclosure and obtain confidential treatment to the extent available. Notwithstanding anything else in this Agreement to the contrary, a Party may also disclose to anyone information<br>that is publicly available.
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9.	Non-Disparagement. From the Execution Date of this Settlement<br>Agreement, neither Relief and its Affiliates (including their officers and directors), nor the NeuroRx Parties and their Affiliates (including their officers and directors) shall in any way libel, defame or otherwise disparage any other Party, or<br>its products or services, or that other Party’s officers and directors. For purposes of this section, “disparage” shall mean the making or publication of any materially negative statement, whether written or oral, that has as its<br>purpose or effect to lower someone’s opinion of, or confidence in, the person concerning whom the false statement is made or of that person’s knowledge, experience, reliability or competence. Notwithstanding the foregoing, testimony<br>provided by any person subject to this Section 9 in response to a valid subpoena, or as otherwise required by law, legal process or order of a court, shall not violate this Section 9 so long as the information provided is truthful.<br>
10.	No Assignment. This Settlement Agreement may not be assigned or transferred to a Third Party without the<br>express prior written consent of the other Party hereto, except as set forth in the Asset Purchase Agreement. Any attempted assignment in violation of this Section 10 shall be void. Subject to the foregoing, this Agreement shall be binding<br>upon, and shall be enforceable by and inure solely to the benefit of, the Parties and their respective permitted successors and assigns.
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11.	Entire Agreement. This Settlement Agreement and its Exhibit(s), together with the Asset Purchase<br>Agreement, constitute the entire agreement between the Parties with respect to the subject matter hereof and supersede and terminate any prior or contemporaneous agreements and/or understandings between the Parties, whether oral or in writing,<br>relating to such subject matter. There are no covenants, promises, agreements, warranties, representations, conditions or understandings, either oral or written, between the Parties other than as are set forth in this Settlement Agreement and in the<br>Asset Purchase Agreement. No subsequent alteration, amendment, change, waiver, or addition to this Settlement Agreement will be binding upon the Parties unless reduced to a writing that both identifies itself as an amendment to this Settlement<br>Agreement and is signed by an authorized officer of each Party. Each Party in deciding to execute this Settlement Agreement has been advised by counsel and has not relied on any understanding, agreement, representation or promise by the other Party<br>that is not explicitly set forth herein or in the Asset Purchase Agreement.
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12.	Governing Law. This Settlement Agreement shall be governed by and construed in accordance with the laws<br>of the State of New York, without regard to conflict or choice of law principles. If any civil action is filed to enforce or interpret any of the terms or provisions of this Settlement Agreement, or otherwise, the Parties agree that the appropriate<br>venue shall in the courts of New York, located in the County of New York, Borough of Manhattan. Each party hereby irrevocably submits to the exclusive jurisdiction of the courts of New York.
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13.	Severability. If any provision of this Settlement Agreement is declared illegal, invalid or<br>unenforceable by a court having competent jurisdiction, it is mutually agreed that this Settlement Agreement will endure except for the part declared invalid or unenforceable by order of such court; provided, however, that in the event that the<br>terms and conditions of this Settlement Agreement are materially altered, the Parties will, in good faith, renegotiate the terms and conditions of this Settlement Agreement to reasonably replace such invalid or unenforceable provisions in light of<br>the intent of this Settlement Agreement.
14.	Waiver. Any delay or failure in enforcing a Party’s rights under this Settlement Agreement, or any<br>acquiescence as to a particular default or other matter, will not constitute a waiver of such Party’s rights to the enforcement of such rights, nor operate to bar the exercise or enforcement thereof at any time or times thereafter, except as to<br>an express written and signed waiver as to a particular matter for a particular period of time.
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15.	Counterparts. This Settlement Agreement may be executed simultaneously in several counterparts<br>(including e-mail counterparts), each of which will be deemed an original as against a Party whose signature appears thereon, but all of which together will constitute one and the same instrument.<br>
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16.	Representations and Warranties. The Parties hereby represent and warrant that: (i) they have<br>approved the execution of this Settlement Agreement by all necessary corporate action and have authorized and directed the signatory officers below to execute and deliver this Agreement; (ii) they each have the full corporate right and power to<br>enter into this Settlement Agreement, and there are no other persons or entities whose consent or joinder in this Settlement Agreement is necessary to make fully effective those provisions of this Agreement that obligate, burden or bind them;<br>(iii) when so executed by each Party, this Settlement Agreement will constitute a valid and binding obligation of such Party, enforceable in accordance with its terms, except as may be limited by bankruptcy and insolvency laws and subject to<br>principles of equity; and (iv) they have not transferred or assigned or pledged to any Third Party or Affiliate the right to bring, pursue, or settle any of claims made in the Litigations.
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17.	Execution Knowing and Voluntary. Each Party acknowledges and represents that it: (i) has fully and<br>carefully read and considered this Settlement Agreement prior to its execution; (ii) has been or has had the opportunity to be fully apprised by an attorney of the legal effect and meaning of this document and all terms and conditions hereof;<br>(iii) has had the opportunity to make whatever investigation or inquiry deemed necessary or appropriate in connection with the subject matter of this Settlement Agreement; (d) has been afforded the opportunity to negotiate as to any and<br>all terms hereof; (v) is executing this Settlement Agreement voluntarily, free from any undue influence, coercion, duress, or fraud; (vi) no other Person or Party, nor any agent or attorney of a Party, made any promise, representation or<br>warranty whatsoever, express or implied, not contained in this Agreement concerning the subject matter of this Settlement Agreement to induce it to execute this Settlement Agreement; (vii) it has not executed this Settlement Agreement in<br>reliance on any promise, representation or warranty whatsoever, express or implied, not contained in this Agreement concerning the subject matter of this Settlement Agreement; and (viii) it has not executed this Settlement Agreement in reliance<br>on any promise, representation or warranty not contained herein. The Parties included this paragraph to preclude any claim that any Party was fraudulently induced to execute this Settlement Agreement.
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18.	Construction. This Settlement Agreement has been jointly negotiated and drafted by the Parties through<br>their respective counsel and no provision will be construed or interpreted for or against any of the Parties on the basis that such provision, or any other provision, or the Agreement as a whole, was purportedly drafted by the particular Party. All<br>references to periods of days for taking certain actions in this Settlement Agreement will be construed to refer to calendar days unless Business Days is specified. Capitalized terms used but not defined in this Settlement Agreement will have the<br>meanings ascribed to them in the Asset Purchase Agreement.
19.	Captions. The captions of this Settlement Agreement are solely for convenience of reference and will not<br>affect its interpretation.
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20.	Negation of Agency. Nothing contained herein will be deemed to create any relationship, whether in the<br>nature of agency, joint venture, partnership or otherwise, between Relief, on the one hand, and the NeuroRx Parties, on the other hand. No Party will be authorized to bind or obligate another Party in any manner.
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21.	Covenant Not to Sue. Except as otherwise provided in this Settlement Agreement, in no circumstances<br>shall Relief or any successor or assign of Relief seek any money or any other remedy of any kind from the NeuroRx Parties arising from a claim or counterclaim asserted in the Litigations, either as an alleged alter ego of Javitt or otherwise, and<br>whether by way of judgment enforcement or otherwise and Relief covenants and agrees, except as otherwise provided in this Settlement Agreement, never to make any claim or allegation against the NeuroRx Parties arising out of any alleged alter ego<br>status vis-à-vis Javitt as it relates to a claim or counterclaim asserted in the Litigations.
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22.	Notice. Any notice required or permitted to be given or sent under this Settlement Agreement will be<br>hand delivered or sent by express delivery service or certified or registered mail, postage prepaid, to the Parties at the addresses indicated below.
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If to Relief:

RELIEF THERAPEUTICS Holding SA

Avenue de Sécheron 15

1202 Genève

Switzerland

Attention: Jack Weinstein, Chief Financial Officer

jack.weinstein@relieftherapeutics.com

with copies (which will not constitute notice hereunder) to:

Craig Weiner, Esq.

Akerman LLP

1251 Avenue of the Americas

New York, NY 10020

cweiner@akerman.com

and

Philip B. Schwartz, Esq.

Akerman LLP

201 East Las Olas Boulevard

Suite 1800

Fort Lauderdale, FL 33301

954-468-2455

pschwartz@akerman.com

If to the NeuroRx Parties:

NRx Pharmaceuticals, Inc.

1201 North Market Street

Suite 111

Wilmington, DE 19801

Attention: Stephen H. Willard, Chief Executive Officer

willard@nrxpharma.com

with copies (which will not constitute notice hereunder) to:

Douglas Boggs, Esq.

DLA Piper (US) LLP

500 8th Street, NW

Washington, DC 20004

202-799-4070

douglas.boggs@us.dlapiper.com

Any such notice will be deemed to have been received on the date actually received. Either Party may change its address by giving the other Party written notice, delivered in accordance with this Section 22.

[Signatures on Next Page]

IN WITNESS WHEREOF, this Settlement Agreement has been executed by the undersigned authorized representatives of the Parties as of the date and year first above written.

RELIEF THERAPEUTICS HOLDING AG		NORX, INC.
By:	/s/ Paolo Galfetti	By:
Name:	Paolo Galfetti	Name:
Title:	Director	Title:
By:	/s/ Jeremy Meinen
Name:	Jeremy Meinen
Title:	VP Finance, CAO
RELIEF THERAPEUTICS INTERNATIONAL SA		NRX PHARMACEUTICALS, INC.
By:	/s/ Jeremy Meinen	By:
Name:	Jeremy Meinen	Name:
Title:	VP Finance, CAO	Title:

All values are in Euros.

EXHIBIT A

SUPREME COURT OF THE STATE OF NEW YORK

COUNTY OF NEW YORK

Relief Therapeutics Holding AG, and Relief<br>Therapeutics International SA (f/k/a Therametrics Discovery AG),<br> <br><br><br><br>Plaintiffs,<br><br><br><br> <br>-against-<br><br><br><br> <br>Jonathan C. Javitt and NeuroRx, Inc.<br><br><br><br><br><br>Defendants.	Index No. 655857/2021<br> <br><br><br><br>Hon. Jennifer G. Schecter
NeuroRx, Inc.,<br><br><br><br><br><br>Plaintiff,<br><br><br><br> <br>-against-<br><br><br><br> <br>Relief Therapeutics Holding AG, and Relief Therapeutics International SA<br>(f/k/a Therametrics Discovery AG),<br> <br><br><br><br>Defendants.	Index No. 650162/2022<br> <br><br><br><br>Hon. Jennifer G. Schecter

STIPULATION OF DISMISSAL

IT IS HEREBY STIPULATED AND AGREED, by and between Relief Therapeutics Holding AG, and Relief Therapeutics International SA (f/k/a Therametrics Discovery AG) on the one hand, and NeuroRx, Inc. on the other hand, through their undersigned counsel of record, that these matters in the above actions are hereby dismissed, WITH PREJUDICE.

Notwithstanding the foregoing, this Stipulation of Dismissal shall not release Jonathan Javitt from any claims brought by Relief Therapeutics Holding AG or Relief Therapeutics International SA (f/k/a Therametrics Discovery AG), and the above Actions shall continue as to Javitt.

Each party will bear its own attorneys’ fees and costs.

[SIGNATURE BLOCKS]

SO ORDERED:

This ________ day of ______________, 2022

JENNIFER G. SCHECTER, J.S.C.

Exhibit B

[***]

EX-10.9

Exhibit 10.9

I have read, understood and do accept the Stock Option Plan 2021.

I accept that any options granted qualify as a voluntary benefit for me (Gratifikation/gratification) and shall under no circumstances be regarded as salary (Lohn/salaire):

[name]	[company]
[date]	[signature]
[Signature]	[Place/Date]

STOCK OPTION PLAN 2021

(“SOP 2021”)

OF RELIEF THERAPEUTICS Holding Ltd.

TABLE OF CONTENTS

I. PRINCIPLES OF THE EQUITY AWARDS PROGRAM	3
A. GENERAL INFORMATION AND PURPOSE	3
B. ADMINISTRATION / DELEGATION / PARTICIPANTS	3
II. DETAILS OF STOCK OPTIONS	4
A. GRANTING OF OPTIONS	4
B. PRICE OF OPTIONS	4
C. TYPE OF OPTIONS / EXERCISE RATIO	5
D. OPTION TERM	5
E. VESTING PERIOD	5
F. EXERCISE PERIOD	5
G. METHOD OF EXERCISE	6
H. EXCHANGE OF OPTIONS FOR SHARES AGAINST PAYMENT OF EXERCISE PRICE IN CASH	6
I. DATE OF EXECUTION / REGISTRATION IN THE SHARE REGISTER	6
J. DIVIDEND PAYMENTS, VOTING, PARTICIPATION AND PROPERTY RIGHTS	7
K. INSIDER RULES / RULES ON MANAGEMENT TRANSACTIONS	7
III. TAXES AND SOCIAL SECURITY PAYMENTS	7
IV. SPECIAL PROVISIONS	8
A. TERMINATION OF EMPLOYMENT	8
1. RETIREMENT	8
2. WRITTEN MUTUAL TERMINATION AGREEMENT	8
3. DISABILITY / DEATH	8
4. TERMINATION / RESIGNATION	9
5. CAUSE	9
B. TRANSFER / LEAVE OF ABSENCE	10
C. NON-TRANSFERABILITY / NO HEDGING / CONFIDENTIALITY /<br>DATA PROTECTION	10
1. TRANSFER RESTRICTION ON OPTIONS	10
Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	2
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2. NO HEDGING	10
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3. CONFIDENTIALITY	10
4. DATA PROTECTION	11
D. FORFEITURE PROVISIONS	11
E. NO RIGHT OF CONTINUED EMPLOYMENT	11
F. NO RIGHT OF CONTINUED OPTION GRANT	11
G. INVESTMENT OPPORTUNITY	11
H. RECAPITALIZATION OF RELIEF OR EXTRAORDINARY DIVIDENDS	12
I. CHANGE IN CONTROL / LIQUIDATION / TRANSFER EVENT / RESTRUCTURING	12
J. U.S. SELLING RESTRICTIONS	13
V. CONSENT TO TERMS AND CONDITIONS OF THE PLAN	14
VI. AMENDMENT / APPLICABLE LAW AND JURISDICTION	14
A. AMENDMENTS TO OR CANCELLATION OF THE EQUITY AWARDS PROGRAM /<br>SUB-PLANS	14
B. COMPLIANCE WITH ARTICLES OF ASSOCIATION / SEVERABILITY	15
C. APPLICABLE LAW	15
D. JURISDICTION	15
VII. EFFECTIVE DATE	15
Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	3
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I. PRINCIPLES OF THE EQUITY AWARDS PROGRAM

A. General Information and Purpose

Under the corporate name of RELIEF THERAPEUTICS Holding Ltd., there exists a share corporation pursuant to art. 620 et seq. of the Swiss Code of Obligations (“CO”) with unlimited duration and current domicile in Geneva, Switzerland (“RELIEF”). The share capital of RELIEF consists of fully paid-in registered shares with a par value of CHF 0.01 each (the “Shares”), which are listed on the SIX Swiss Exchange.

This Stock Option Plan (the “Plan”) lays out the details for options granted in order to promote the interests of RELIEF and its Affiliates by providing selected key employees (full and part time employees), members of the board of directors of RELIEF (the “Board”), officers and / or advisors of RELIEF and its Affiliates (the “Employees”) with an opportunity to obtain stock options (the “Options”) on Shares and to acquire a proprietary interest in RELIEF and companies in which RELIEF holds directly or indirectly a controlling or non-controlling interest (the “Affiliates”) as an incentive for them to remain in the service of RELIEF and to contribute to the future success and prosperity of RELIEF. Any participation by any person is strictly voluntary and any grant made under this Plan shall be a voluntary benefit for the participant (as defined below) (Gratifikation/gratification; art. 322d CO) and shall under no circumstances be regarded as salary (Lohn/salaire).

The Plan shall (i) create a long-term bond between Employees and RELIEF, (ii) align the interests of Employees and shareholders of RELIEF, (iii) enable RELIEF to attract talented professionals, and / or (iv) provide an increased incentive for Employees to make significant and extraordinary contributions to the long-term performance and growth of RELIEF.

The maximum number of Shares of RELIEF for which Options may be granted to members of the Board and Employees respectively, under the Plan shall be such number as the Board shall determine from time to time.

This Plan follows the principles as determined in the articles of association of RELIEF.

B. Administration / Delegation / Participants

The Board shall have full power and authority (subject to the provisions of the Plan) to establish such rules and regulations as it may deem appropriate for proper administration of the Plan. Decisions of the Board shall be final and binding on all parties who have an interest in the Plan or any Option or Shares issued hereunder.

The Board may delegate all or part of its tasks to a committee consisting of members of the Board and/or the management or such other person(s) as the Board deems appropriate (the “Committee”).

The Board shall appoint the person or department who is responsible for receiving and executing option grant agreements (as defined below) and option exercise notices (as defined below) (the “Administrator”), and perform all other acts relating to the day-to-day administration of this Plan.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	4

The Administrator may appoint one or several custodian banks who, acting in the name and on behalf and for the account of RELIEF, shall, among other things, be responsible for (a) holding Options in custody and ensure blocking until lapse of the vesting period (as defined below), (b) establishing custody accounts for the participants, (c) establishing procedures which enable the participants to exercise Options, and (d) such other tasks as defined by the Administrator (the “Custodian”).

Upon nomination by executives and senior management, the executive committee of RELIEF (the “Executive Committee”) shall approve and designate from time to time in its sole discretion those nominated Employees to whom Options are to be granted and who thereby become participants under this Plan (the “Participants”). Any such approval and designation with respect to members of the Executive Committee shall be made by the Board.

RELIEF shall fulfil the reporting and other obligations set forth by the applicable federal, cantonal and communal tax and social security rules and regulations.

II. DETAILS OF STOCK OPTIONS

A. Granting of Options

Options granted under this Plan enable the Participant to acquire the numbers of stocks listed in the option grant agreement (the “Option Grant Agreement”) signed by RELIEF and the Participant in such form and with such terms and conditions as the Board shall determine in its sole discretion. The Option Grant Agreement shall include by reference the terms of the Plan as a condition under which the Options are issued and received and specify the number of Options granted, the date of grant of the Options (the “Grant Date”), the exercise price as well as the vesting and exercise periods. The maximum number of stocks, which may be issued, shall be determined by the Board. To the extent that RELIEF does not have sufficient conditional capital or treasury shares to honor its obligations at the time of exercise of any Options for stock, such Options shall automatically be requalified as an option for a corresponding number of Option rights.

The Option Grant Agreement (and / or equivalent or similar electronic forms and procedures) requires a Participant to accept grants and the terms and conditions of this Plan until a certain date. In the event that a Participant fails to meet any such deadline, RELIEF may assume that a Participant does not accept the granting of Options under the Plan. As a result, the relevant granting of Options shall be deemed forfeited and RELIEF will have no further obligations under the Plan and the relevant Option Grant Agreement towards the respective Participant.

The granting of Options will be subject to obtaining any approval or consent required under the provisions of an applicable stock exchange or of any applicable laws.

The Options are personal to the Participant to whom they are granted, i.e. may not be transferred in any way.

B. Price of Options

The Options shall be granted to Participants free of charge unless the Option Grant Agreement specifies otherwise.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	5

If the Option is not given free of charge, the exercise price shall be fixed by the Administrator within the guidelines set and approved by the Board or a Committee thereof. For Options, the exercise price becomes immediately due upon exercise of the Option, and shall be payable to RELIEF. An Option can be exercised only once RELIEF has received the payment. The Administrator may provide for alternative payment arrangements.

C. Type of Options / Exercise Ratio

The Options granted under the Plan are American style options meaning that the Options can be exercised, unless otherwise determined herein, at any time within the Exercise Period (as defined below).

One (1) Option entitles the Participant to purchase one (1) Share.

D. Option Term

Each Option shall be evidenced by one or more documents in the form proposed by the Board. Each document evidencing an Option shall, in addition, be subject to the provisions of this Plan.

Subject to the provisions of the Plan with respect to death, retirement, disability and termination of or resignation from employment, the option term commencing from the date that the Option is granted to the end of the exercise period (as defined below) (the “Option Term”) shall be specified in the Option Grant Agreement.

Exercisable Options can be exercised during the exercise period (as defined below) by providing the Administrator with a written notice and wiring the Exercise Price to RELIEF.

E. Vesting Period

Options granted under the Plan will restrict the Participant’s rights of ownership of the Options for a limited and specified period (the “Vesting Period”).

Subject to the conditions set forth in this Plan and the vesting schedule in the Option Grant Agreement, a Participant may only exercise an Option to the extent that the Option has become vested and has not lapsed under this Plan.

Unless otherwise determined in the Option Grant Agreement, Options will vest, according to a three (3) year vesting schedule, in three (3) equal installments, the first of which will fully vest after one (1) year after the Grant Date and each of the following ones one (1) year after the previous one respectively, as specified in the Option Grant Agreement.

F. Exercise Period

Unless otherwise determined in the Option Grant Agreement and subject to other provisions contained herein, the vested Options may be exercised in whole or in part for a period of five (5) years starting after lapse of the Vesting Period, as specified in the Option Grant Agreement (the “Exercise Period”).

Subject to other provisions contained herein, Options may not be exercised prior to the lapse of the Vesting Period.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	6

Options, which are not exercised during the Exercise Period, will expire without any compensation becoming due and payable. RELIEF has no obligation to notify Participants in the situation where Options are close to expire. The exercise of Options is in the sole responsibility of the Participants and RELIEF does not assume any liability if Options expire without being exercised.

G. Method of Exercise

During the Exercise Period, Options may, subject to any relevant provisions in the Plan, be exercised in accordance with the following method of exercise: Exchange of Options for Shares against payment of the exercise price in cash.

The Board may, in its sole discretion, provide for additional methods of exercise as outlined above at any time. RELIEF will inform the Participants on the detailed procedures regarding additional methods of exercise prior to the lapse of the Vesting Period.

When Options are exercised, Options shall be exercised by the delivery of a written and signed option exercise notice (the “Option ExerciseNotice”) by the Participant (see Appendix 2), setting forth the number of Options exercised.

H. Exchange of Options for Shares againstPayment of Exercise Price in Cash

The Participant is entitled, subject to the provisions of the Plan, to receive from RELIEF the number of Shares for which Options are exercised by payment of the exercise price of the related Options (payment of exercise price in cash via wire transfer to RELIEF). The entire exercise price plus any stamp tax or other taxes, duties and commissions, if any, shall be paid at the time the Options are exercised. No Shares shall be delivered pursuant to any exercise of Options until payment in full of the exercise price thereof plus any stamp tax or other taxes, duties and commissions have been received by RELIEF.

I. Date of Execution / Registration in the Share Register

The exercise date will be the latest of the date of receipt of the Option Exercise Notice by RELIEF and the date of receipt of the Exercise Price (the “Exercise Date”). The order to exercise Options shall be executed by RELIEF as soon as practicable.

RELIEF may hold the issuance of the shares until it has obtained from the Participant all requested information that may be necessary to assess the tax treatment of the exercise. The Participant shall provide its full cooperation before and after the Exercise Date for Relief to determine such tax treatment under Swiss and / or foreign regulations.

The Shares acquired upon the exercise of any Options shall be delivered to the Participant’s account within such period as it is compatible with applicable rules and / or procedures of the SIX Swiss Exchange.

By submitting the Option Exercise Notice the Participant declares to acquire the relevant Shares in his or her own name and on his or her own account.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	7

J. Dividend Payments, Voting, Participation and Property Rights

On Options no dividends are paid and there is no entitlement to participate in the general assembly of RELIEF. As soon as the Options are exercised and Shares have been received, and if the Participant has registered in the share register of RELIEF, all shareholders’ rights may be executed by the Participant.

K. Insider Rules / Rules on Management Transactions

The Participant acknowledges that due to his or her position confidential and privileged information may be conferred upon and/or become otherwise known to him or her from time to time, which, if disclosed to interested persons or known to the public, might have an impact on RELIEF’s share price (the “Insider Knowledge”). The Participant understands and acknowledges that he or she may not exploit and/or disclose Insider Knowledge.

Therefore, the Participant shall, also in connection with the exercise of any Option and / or the sale of any Share acquired upon the exercise of any Option and / or otherwise, at all times comply with the pertinent insider laws and regulations as well with any internal rules applicable to him or her. Accordingly, and notwithstanding anything contained in this Plan and in the documents related thereto, the Participant’s right to exercise any Option and / or to sell any Share acquired upon the exercise of any Option shall be limited accordingly. In case of doubt, the Participant shall seek advice from RELIEF’s finance department in Switzerland.

The Board may, furthermore, in its sole discretion determine or provide for time periods during which Participants are not allowed to exercise any Option.

The Participant is aware that the granting and / or exercising of Options may trigger notification and/or disclosure obligations with respect to him or her under applicable stock exchange rules and regulations. The Participant agrees to comply with any such rules and regulations.

III. TAXES AND SOCIAL SECURITY PAYMENTS

Any taxes or social security charges imposed on the Participant in connection with the grant, vesting, buy-out, acceleration or exercise of Options or the acquisition or ownership of Shares, shall be paid by the Participant. The Participant is personally responsible for reporting the receipt, vesting, exercise of Options or other relevant fact and all matters relating to the purchase of Shares to the appropriate tax and other authorities. For Employees however, in case Options-related benefits are considered to be part of salary, RELIEF or the Affiliates will pay the social costs normally imputable to the employer and it will deduct if applicable the necessary payroll taxes (tax at source) from the employee’s salary. Wealth and / or similar taxes legally due during the holding period of the Options are to be paid by the Participant.

RELIEF will meet all reporting and withholding requirements that may be imposed on it under applicable Swiss tax and social security law. RELIEF does not guarantee the ultimate tax treatment of the Options with respect to taxation, time of taxation (issuance, vesting, buy-out, acceleration, exercise of Options, acquisition of Shares, sale of Shares, etc.), valuation or otherwise.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	8

To the extent RELIEF pays or is obliged to pay taxes, social security charges or social costs in connection with the grant, vesting, buy-out, acceleration or exercise of Options or the acquisition or ownership of Shares (whether such charges or costs are imputable to the Participant or to RELIEF), such taxes, charges and costs shall be reimbursed to it by the Participant and it may recover such taxes, charges and costs from the Participant in such manner as the Board deems necessary including: (i) deducting or offsetting any amount due by RELIEF to the Participant, including any compensation or remuneration; and/or (ii) requiring the Participant to account directly to RELIEF for such taxes, charges and costs and pay any amount due to RELIEF prior to the delivery of shares pursuant to an Option Exercise Notice.

For the purpose of taxes and social security reporting, the profit realized upon the exercise of an Option is calculated as:

a)	if the shares are held upon receipt (so called<br>exercise-and-hold), the closing share price of RELIEF on the SIX on the Exercise Date, less the Exercise Price; and
b)	if the shares are sold upon receipt (so called<br>exercise-and-sell), the realized share price less the exercise price.
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IV. SPECIAL PROVISIONS

A. Termination of Employment

1. Retirement

Upon the termination of employment, as a result of retirement on or after attainment of retirement age pursuant to the law or to a retirement plan of RELIEF or by mutual consent between RELIEF and the respective Participant, such Participant may, notwithstanding the provisions of section II./E., immediately exercise all of his or her Options from the date of termination of employment until twelve (12) months after the date of termination of employment.

2. Written Mutual Termination Agreement

Upon the termination of employment or mandate, as a result of a written mutual termination agreement between RELIEF and the respective Participant, which is explicitly approved by the Committee, the unvested Options will continue to vest. The Participant may, notwithstanding the provisions of section II./F., exercise his or her vested Options until six (6) months after the respective vesting dates.

3. Disability / Death

In the event of termination of employment or mandate as a result of disability (as defined below) or upon the death of a Participant, such Participant or his or her heirs respectively may, notwithstanding the provisions of section II./F., immediately exercise all of his or her Options from the date of termination of employment until twelve (12) months after the date of termination of employment. All Options which are not exercised within such period shall be terminated and thereby forfeited without any compensation becoming due and payable to the Participant or his or her heirs respectively.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	9

“Disability” shall mean the inability to engage in any substantial gainful activity by reason of a medically determinable physical or mental impairment which constitutes a permanent and total disability. The determination of whether a Participant has suffered a disability shall be made by the Board and be based upon such evidence as it deems necessary and appropriate in the relevant circumstances.

4. Termination / Resignation

Upon the termination of employment or mandate by RELIEF or any of its Affiliates or deselection by the shareholders or upon voluntary or involuntary resignation from employment or mandate by a Participant, such Participant may only exercise those Options relating to which the Vesting Period has already lapsed as of the date when either RELIEF or the relevant Affiliate or the Participant has given notice to terminate the employment or mandate (including date of deselection) (the “Notice Date”), irrespective of whether and when such employment relationship or mandate is actually terminated by such notice. The Participant may, notwithstanding the provisions of section II./F., exercise these Options until three (3) months after the Notice Date.

Any other Options, i.e. those Options relating to which the Vesting Period has not already lapsed as of the Notice Date (the “Unvested Options”), shall not be exercisable anymore, and accordingly, shall be terminated and thereby forfeited without any compensation becoming due and payable to the Participant.

If the termination of employment by RELIEF or any of its Affiliates affects a significant number of employees irrespective of such employees’ performance, e.g. in situations of collective or mass dismissals, when a business unit or division is sold, in restructuring or reorganization situations or in similar events, the Board may decide in its sole discretion that the Participants concerned may receive a compensation payment for the forfeited Options and / or that all or part of the Options of such Participants may, notwithstanding the provisions of section II./F., be exercised by such Participants within the period and according to the terms and conditions as defined by the Board.

5. Cause

Upon the termination of employment or mandate by RELIEF or any of its Affiliates for cause (as defined below), any and all Options, regardless of whether vested or unvested, shall not be exercisable anymore, and accordingly, shall be terminated and thereby forfeited with immediate effect without any compensation becoming due and payable to the Participant.

“Cause” shall mean any material act or omission, for which the Participant is responsible, and as a consequence of which employer cannot be reasonably in good faith expected to continue the employment or mandate, such as a breach of any material contractual or legal obligations due to willful misconduct or gross negligence, or if the Participant commits a serious crime or a serious act of dishonesty. In addition, Cause shall include any circumstances under which RELIEF or any of its Affiliates terminates an employment relationship for an important reason as set forth in art. 337 CO.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	10

B. Transfer / Leave of Absence

A transfer of a Participant from RELIEF or an Affiliate to RELIEF or another Affiliate, and a leave of absence, duly authorized in writing by RELIEF, for military service or sickness, or for any other purpose approved by the Board, provided the Participant’s right to reemployment is guaranteed either by statute or by contract, shall not be deemed a termination of employment for the purpose of the Plan. Where the employment, however, is terminated prior to the re-employment of the Participant, then the provisions of section IV./A. shall apply.

In the event of negative tax consequences of a transfer of a Participant from RELIEF or an Affiliate to RELIEF or another Affiliate in another tax jurisdiction, the Board may in its discretion and notwithstanding the provisions of section II./F., accelerate the time when any particular Option held by said Participant may be exercised.

C. Non-Transferability / No Hedging / Confidentiality / Data Protection

1. Transfer Restriction on Options

Without prior written approval of RELIEF and except in the case of death, a Participant shall neither in any way sell, assign, pledge, transfer or dispose in any manner of his or her right pursuant to the Plan, nor transfer by gift or subject to attachment, execution or other similar process.

If RELIEF agrees to a transfer of Options, RELIEF may impose additional conditions or amend the Plan for this specific Participant.

Swiss corporate law, stock exchange rules, insider regulations and other laws and regulations, as well as the articles of association or relevant internal guidelines of RELIEF restrict or may restrict or prohibit the acquisition of Shares by the Participant or the transfer or other disposal of Shares by the Participant and, therefore, prevent or restrict the exercise of Options by a Participant or the disposal of Shares acquired. Any restriction on the transfer of Shares in the articles of association of RELIEF shall equally restrict the acquisition of Shares by a Participant upon exercise of any Option.

2. No Hedging

Except as otherwise provided in the Plan, the Participant may not enter into any transactions having the economic effect of hedging, mitigating or otherwise shifting the risk of price movements of all or any part of his or her Options during the Vesting Period. Non-compliance with this obligation leads to immediate forfeiture without any compensation of any and all of a Participant’s Options relating to which the Vesting Period has not yet lapsed.

3. Confidentiality

This Plan and any related documents and agreements are trade secrets of RELIEF and shall be kept confidential. Any disclosure to third parties shall, unless required by law, only be permitted with written approval of the Board.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	11

4. Data Protection

A Participant hereby authorizes the Board to obtain, hold and process personal data or provide such persons, whether in Switzerland or abroad, as the Board considers necessary with any personal data relevant to the Plan (and the holding and processing of any personal data by any such person). The Participant agrees in particular that his or her personal data related to the Plan is transferred under appropriate confidentiality agreements to potential investors and certain service providers of RELIEF.

D. Forfeiture Provisions

Any and all options (whether vested or not), shall lapse and become null and void immediately if

a)	the Participant breaches a non-compete obligation in the employment or<br>mandate agreement between the Participant and RELIEF or any Affiliates;
b)	the Participant induces, solicits, or encourages any Employee to join any other business that competes with<br>RELIEF;
---	---
c)	the Participant directly or indirectly uses, discloses or disseminates to any other person or entity, or<br>otherwise employs any confidential information in breach of a confidentiality obligation owed to RELIEF or any Affiliates; or
---	---
d)	the Participant commits a criminal act against RELIEF or any Affiliates.
---	---

The Board may waive any of these conditions in its sole discretion.

E. No Right of Continued Employment

Neither the establishment of the Plan, nor the granting of Options, nor the payment of any benefits nor any action of RELIEF or of the Board, the Committee, the Administrator or any other body of RELIEF or an Affiliate shall be held or construed to confer upon any Participant any right (legal or otherwise) to be continued in the employ of RELIEF or its Affiliates. Each company expressly reserves the right to discharge any Employee whenever the interests of any such company as determined in its sole discretion may so require, without liability to such company or the Board, the Committee, the Administrator or any other body of RELIEF or an Affiliate, except as to any rights which may be expressly conferred upon such Employee under the Plan.

F. No Right of Continued Option Grant

Neither the establishment of the Plan nor the granting of Options, nor the payment of any benefits nor any action of RELIEF or of the Board, the Committee, the Administrator or any other body of RELIEF or an Affiliate shall be held or construed to confer upon any Participant any right (legal or otherwise) to the continued grant of Options. The granting of Options shall constitute voluntary contributions, even where repeatedly made. In this regard, RELIEF expressly reserves the right to discontinue any such Option grants at any time without notice.

G. Investment Opportunity

The benefits received by a Participant under the Plan are not a constituent part of the Participant’s salary, remuneration or compensation, but are considered to be an investment opportunity offered by RELIEF to selected Employees that can be rejected by a Participant at any time.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	12

H. Recapitalization of RELIEF or Extraordinary Dividends

In the event that the shareholders of RELIEF or the Board or any other competent body of RELIEF shall decide upon any stock dividend, extraordinary cash dividend, recapitalization, variation in the share capital including a split or reverse split of the Shares, reorganization, merger, consolidation, split-up, spin-off, combination, exchange of shares, options or rights offering to purchase Shares at a price substantially below fair market value (as defined below), or other similar corporate events affect the Shares such that an adjustment is required in order to preserve the benefits or potential benefits intended to be made available under the Plan, then the Board shall accordingly, at its discretion, adjust any and all of the number and kind of Shares which thereafter may be optioned under the Plan, the number and kind of Shares subject to outstanding Options and / or the exercise price with respect to any Option and / or, if deemed appropriate, make provision for a cash payment to a Participant who has outstanding Options.

The “Fair Market Value” of Shares shall mean, as of any relevant date, the average of the highest and the lowest price quoted for a Share trading on the SIX Swiss Exchange on the relevant day or, if there shall be no reported sale for such date, on the next preceding date for which a sale was reported; provided that no Fair Market Value can be determined for any date, the Fair Market Value shall be determined by the Board by whatever means or method as the Board, in the good faith exercise of its discretion, shall at such time deem appropriate.

I. Change in Control / Liquidation / Transfer Event / Restructuring

In the case of the liquidation of RELIEF or a change in control (as defined below) of RELIEF, the Board may, at its discretion, accelerate the vesting so that the Options will become immediately exercisable before the occurrence of a change in control (as defined below) or a transfer event (as defined below). In such case, the Participant shall receive the intrinsic value of the Options, such value being the difference between the real value (as defined herein below) of the Shares and the exercise price. The decision of the Board is fully discretionary.

A “Change in Control” shall be deemed to occur where:

a)	any person or any group of persons directly or indirectly purchases or otherwise becomes the beneficial owner<br>or has the right to acquire such beneficial ownership (whether or not such right is exercisable immediately, with the passage of time, or subject to any condition) of voting securities representing more than 50% of the combined voting power of all<br>outstanding voting securities of RELIEF; or
b)	the shareholders of RELIEF approve an agreement to merge or consolidate RELIEF with or into another corporation<br>(and such other corporation also approves such agreement) as a result of which less than 50 % of the outstanding voting securities of the surviving or resulting entity are or will be owned by the former stockholders of RELIEF; or<br>
---	---
c)	the shareholders of RELIEF approve the sale of all or substantially all of RELIEF’s business and / or<br>assets to a person or entity which is not a wholly-owned subsidiary of RELIEF.
---	---
Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	13
---	---

The “Real Value” of the Shares shall mean the following:

a)	If a Change in Control as defined in section IV./I. a) occurs: the price paid by the party acquiring the Shares<br>or, if the acquiring party is obliged to make a take-over bid under the applicable laws and regulations, the price offered in such take-over bid.
b)	If a Change in Control as defined in section IV./I. b) occurs: the valuation of the Shares contained in the<br>merger agreement.
---	---
c)	Under all other sections of the Plan (including section IV./I. c) as well as in section IV./I. a) and b) if the<br>valuation of the Shares according to section (a) and (b) above is bona fide not possible): the Fair Market Value according to section IV./H. on the relevant day.
---	---

Alternatively, in particular if RELIEF will be dissolved and if the business of RELIEF will be integrated into another company as a result of the Change in Control, the Board may, at its discretion, decide to adjust the Options in the sense that the Participants may exercise the Options with respect to shares of such other company rather than with respect to Shares of RELIEF. When doing so, the Board shall adjust the parameters of the Options so that the value of the Options will be maintained to the fullest extent possible.

If a Participant’s employment terminates because of a transfer event (as defined below) the Board may, at its discretion, accelerate the vesting date for part or all of the unvested Options and/or to relax any provisions relating to forfeiture. The Board will determine when and whether a transfer event has occurred.

A “Transfer Event” shall be deemed to occur where:

a)	the company employing the Participant ceases to be an Affiliate; or
b)	an undertaking or part of an undertaking in which the Participant is employed is transferred or sold to a<br>person or entity other than RELIEF or an Affiliate.
---	---

If the Board decides on a restructuring of RELIEF, the Participants may be required to swap their Options against equivalent options on the shares of such other company as the Board may decide. The decision of the Board is fully discretionary. Such option swap shall not lead, to the fullest extent possible, to a dilution of the benefits acquired by a Participant under the Plan previous to such restructuring.

J. U.S. Selling Restrictions

The Options and the Shares acquired upon exercise of the Options have not been and will not be registered under the U.S. Securities Act of 1933 (the “Securities Act”) and may not be offered, sold or otherwise delivered within the United States or to, or for the account or benefit of, U.S. Persons (as defined in Regulation S under the Securities Act), except in certain transactions exempt from the registration requirements of the Securities Act. With respect to any Participant resident in the United States,

a)	such Participant will either (i) be granted Options under Rule 701 under the Securities Act or<br>(ii) be required to represent at the time of grant and the time of exercise of the Options that he or she is an “accredited investor” within the meaning of Rule 501 (a) of Regulation D under the Securities Act and is acquiring the<br>Options and / or the Shares for his or her own account and to make such other representations as may be appropriate to establish the availability of an exemption from registration under the Securities Act; and
Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	14
---	---
b)	such Participant will agree that it will not reoffer or resell any Shares, except in accordance with Regulation<br>S under the Securities Act (such as a market transaction on the SIX Swiss Exchange).
---	---

V. CONSENT TO TERMS AND CONDITIONS OF THE PLAN

By accepting grants and / or offerings and / or any other benefits under this Plan, a Participant fully agrees to the terms and conditions of this Plan.

By accepting grants or any other benefits under this Plan, a Participant is aware of and agrees that:

a)	RELIEF or any Affiliate may furnish to RELIEF or any third party such personal information and data as may be<br>required or deemed appropriate by RELIEF to facilitate the implementation, administration or management of the Plan;
b)	RELIEF or any Affiliate may transfer personal data to any place outside the country in which such Participant<br>works as RELIEF shall consider necessary for purposes related to such Participant’s participation in the Plan. Such transfer may also be made to a country outside the EU, in particular to the United States; and
---	---
c)	the future value of the Shares underlying the Options is unknown and cannot be predicted and that if the Shares<br>underlying the Options do not increase in value, the Options will have a lower value than today or even no value at the end of the Vesting Period and / or the Exercise Period.
---	---

VI. AMENDMENT / APPLICABLE LAW AND JURISDICTION

A.Amendments to or Cancellation of the Equity Awards Program / Sub-Plans

The Board may, in its sole discretion, suspend or terminate the Plan, reconstitute the Plan in whole or in part, or revise the Plan in any respect whatsoever, except that no change shall be made in the terms of any prior grant of Options which would materially decrease the benefits under this Plan without the members of the Board and Employees’ consent, unless such change is required to comply with applicable law. Notwithstanding the foregoing and the following provisions, any terms and provisions of the Plan relating to the exercise price and the number and class of securities issuable shall be subject to appropriate adjustment in the event of any recapitalization, merger, consolidation, disposition of property or stock, separation, reorganization, stock dividend, issuance rights, combination or split-up or exchange of shares, or the like.

With respect to Participants, if any, who reside or work outside Switzerland, the Board may, in its sole discretion, amend the terms of the Plan with respect to such Participants or establish one or more sub-plans in order to conform such terms with the provisions of local law and / or to permit such Participants to benefit from favorable local tax and / or social security regimes. The Board reserves the right to make any amendments to the Plan if, in the sole discretion of the Board, such amendments become necessary or advisable as a result of changes in law or regulation, to prevent any Option from becoming subject to the provisions of Section 409A or Section 457A of the U.S. Internal Revenue Code of 1986, as amended from time to time, or to avoid the imposition of any additional tax under Section 409A or Section 457A.

Stock Option Plan 2021, RELIEF THERAPEUTICS Holding Ltd.	15

B. Compliance with Articles of Association / Severability

Any provision of the Plan shall be understood and interpreted in full compliance with the RELIEF’s articles of association and with applicable laws.

The invalidity or non-enforceability of any one or more provisions contained in the Plan will not affect the validity or enforceability of the Plan, which will remain in full force and effect.

C. Applicable Law

The Plan and any related document shall be governed by and construed in accordance with the laws of Switzerland.

D. Jurisdiction

Unless the courts at the place where the Participant habitually carries out his or her work have mandatory jurisdiction according to the law in that place, any disputes arising under or in connection with the Plan shall be resolved exclusively by the competent courts located at the domicile of RELIEF, Switzerland.

VII. EFFECTIVE DATE

This Plan is approved by the Board and shall be effective as of August 24, 2021.

Raghuram Selvaraju
Chairman of the Board of Directors
Jack Weinstein
Chief Financial Officer
Jeremy Meinen
VP Finance
Annex 1: Option Grant Agreement	16
---	---

APPENDIX 1: OPTION GRANT AGREEMENT

(Capitalized terms shall have the same meaning as defined in the Stock Option Plan (the “Plan”))

RELIEF THERAPEUTICS Holding Ltd.

STOCK OPTION PLAN 2021

Dear [•]

We are pleased to inform you that pursuant to the RELIEF Stock Option Plan (“Plan”), subject to the terms and conditions of the Plan including the country specific addendum, if any, and this Option Grant Agreement, RELIEF hereby grants you

[number] (in words [•])Options

which entitle you, upon the terms and conditions contained herein and in the Plan, to buy an equal number of Shares of Relief.

Grant Date:
Exercise Price per one (1) Option:	CHF
Option Term:	Maximum 8 years; from Grant Date to end of Exercise Period
Vesting Period:	for [number 1/3] Options: Grant Date – [Day/Month] 2022<br><br><br>for [number 1/3] Options: Grant Date – [Day/Month] 2023<br><br><br>for [number 1/3] Options: Grant Date – [Day/Month] 2024
Exercise Period:	for [number 1/3] Options: [Day/Month] 2022 – [Day/Month] 2027<br><br><br>for [number 1/3] Options: [Day/Month] 2023 – [Day/Month] 2028<br><br><br>for [number 1/3] Options: [Day/Month] 2024 – [Day/Month] 2029

Subject to other limitations set forth in the Plan, the Options may be exercised, in whole or in part, at any time during the Exercise Period. Options which are not exercised during the Exercise Period shall expire without any compensation being payable.

Annex 2: Option Exercise Notice	17

By countersigning and returning this Option Grant Agreement, I understand and agree that:

•	the Options are subject to a Vesting Period as outlined above, during which they cannot be exercised and during<br>which I may lose the Options upon occurrence of certain circumstances as specified in the Plan without being entitled to any compensation;
•	the Options cannot be sold, transferred, given, assigned, pledged or otherwise encumbered or divested of whether<br>voluntarily or by operation of law, except by will or by provisions of inheritance law;
---	---
•	neither the establishment of the Plan, nor the granting of Options, nor the payment of any benefits, nor any<br>action of RELIEF or of the Board, the Committee, the Administrator or any other body of RELIEF or an Affiliate shall be held or construed to confer upon me any right (legal or otherwise) to be continued in the employ of RELIEF or any of its<br>Affiliates or any right to the continued granting of Options;
---	---
•	the granting of Options shall constitute a discretionary and voluntary contribution (art. 322d CO), even where<br>repeatedly made and that RELIEF and any of its Affiliates expressly reserve the right to discontinue any such Option grants at any time without notice;
---	---
•	the benefits received under the Plan are not a constituent part of my salary, remuneration or compensation, but<br>are considered to be an investment opportunity offered by RELIEF to selected Employees that can be rejected by me. Accordingly, the benefits offered under the Plan and this Option Grant Agreement are not to be taken into account for purposes of<br>calculating any severance, resignation, redundancy, or end of service payments, or any bonuses, long-service awards, pension or retirement benefits or similar payments;
---	---
•	RELIEF or any Affiliate may furnish to RELIEF or any third party such personal information and data as may be<br>required or deemed appropriate by RELIEF to facilitate the implementation, administration or management of the Plan. I also consent to the transfer of my personal data to any place outside the country in which I work as RELIEF shall consider<br>necessary for purposes related to my participation in the Plan;
---	---
•	benefits realized from the Options offered under the Plan are generally considered taxable income at the time of<br>grant and / or vesting and / or exercise of the Options. It is understood that the correct declaration of the taxable income is solely my responsibility. I agree to the deduction of the employee’s share in the social security contributions from<br>any relevant payment, if and to the extent applicable;
---	---
•	the grant and / or the exercise of the Options and / or the sale of the Shares acquired upon the exercise of the<br>Options may trigger notification obligations for my part under applicable stock exchange rules and regulations and I agree to comply with such rules and regulations;
---	---
•	the future value of the Shares underlying the Options is unknown and cannot be predicted and that if the Shares<br>underlying the Options do not increase in value, the Options will have a lower value than today or even no value at the end of the Vesting Period and / or the Exercise Period.
---	---
•	unless the courts at the place where I habitually carry out my work have mandatory jurisdiction according to the<br>law in that place, any disputes arising under or in connection with the Plan shall be resolved exclusively by the competent courts located at the domicile of RELIEF, Switzerland.
---	---
Annex 2: Option Exercise Notice	18
---	---
•	I confirm that I have reviewed the Plan rules and this Option Grant Agreement and I herewith agree to all terms<br>and conditions of the Plan and this Option Grant Agreement.
---	---

Please indicate to which address any future correspondence should be sent (check one):

☐	Internal RELIEF address	☐	Private address as follows:

By choosing an address, you acknowledge and agree that until further notice from you – which may be given at any time – any correspondence under the Plan will be sent to the address stated above.

Please return the original signed copy of this Option Grant Agreement to:

RELIEF THERAPEUTICS Holding Ltd.

Attn. Finance Department

avenue de Sécheron 15

1202 Genève

on or before [DATE] at the latest.

IMPORTANTNOTICE:

In the event that you fail to deliver this fully executed Option Grant Agreement to RELIEF on or before the date specified above, RELIEF may assume that you do not accept the granting of Options under the Plan. AS A RESULT, THE GRANTING OF OPTIONS UNDER THIS OPTION GRANT AGREEMENT SHALL BE DEEMED FORFEITED AND RELIEF WILL HAVE NO FURTHER OBLIGATIONS UNDER THE PLAN AND THIS OPTIONGRANT AGREEMENT.

RELIEF THERAPEUTICS Holding Ltd.:
	signature
place, date	signatory name
Accepted and agreed:
	signature
place, date	employee name
Annex 2: Option Exercise Notice	19
---	---

APPENDIX 2: OPTION EXERCISE NOTICE

(Capitalized terms shall have the same meaning as defined in the Stock Option Plan (the “Plan”))

RELIEF THERAPEUTICS HOLDING Ltd.

STOCK OPTION PLAN 2021

To:

RELIEF THERAPEUTICS Holding Ltd.

Attn. Finance Department

avenue de Sécheron 15

1202 Genève

From:

insert name and address

I hereby exercise my vested Options in accordance with and under the terms and conditions of the Plan and my Option Grant Agreement, as follows:

Number of Options exercised in total:	Options
Exercise Price per Option:	CHF
Grant Date:

I confirm that I have paid to RELIEF the full Exercise price of the Options in the amount of total CHF .

I hereby instruct and authorize each of RELIEF to execute any transaction relating to the exercise of my Options in my name and on my behalf and account.

I declare that once I have received any Shares under the Plan, I will treat such Shares as my legal and economic property and not on a fiduciary basis or otherwise for any third party.

Participant:

Place, date	Signature

EX-12.1

Exhibit 12.1

Certification by the Principal Executive Officer pursuant to

Securities Exchange Act Rules 13a-14(a) and 15d-14(a)

as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

I, Jack Weinstein, certify that:

1.	I have reviewed this annual report on Form 20-F of RELIEF THERAPEUTICS<br>Holding SA (the “Company”).
2.	Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a<br>material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
---	---
3.	Based on my knowledge, the financial statements, and other financial information included in this report,<br>fairly present in all material respects the financial condition, results of operations and cash flows of the Company as of, and for, the periods presented in this report;
---	---
4.	The Company’s other certifying officer and I are responsible for establishing and maintaining disclosure<br>controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the Company and have:
---	---
a.	Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be<br>designed under our supervision, to ensure that material information relating to the Company, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being<br>prepared;
---	---
b.	Designed such internal control over financial reporting, or caused such internal control over financial<br>reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting<br>principles;
---	---
c.	Evaluated the effectiveness of the Company’s disclosure controls and procedures and presented in this<br>report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
---	---
d.	Disclosed in this report any change in the Company’s internal control over financial reporting that<br>occurred during the period covered by the annual report that has materially affected, or is reasonably likely to materially affect, the Company’s internal control over financial reporting; and
---	---
5.	The Company’s other certifying officer and I have disclosed, based on our most recent evaluation of<br>internal control over financial reporting, to the Company’s auditors and the audit committee of the Company’s board of directors (or persons performing the equivalent functions):
---	---
a.	All significant deficiencies and material weaknesses in the design or operation of internal control over<br>financial reporting which are reasonably likely to adversely affect the Company’s ability to record, process, summarize and report financial information; and
---	---
b.	Any fraud, whether or not material, that involves management or other employees who have a significant role in<br>the Company’s internal control over financial reporting.
---	---

Date: May 12, 2023

By:	/s/ Jack Weinstein
	Jack Weinstein
	Chief Executive Officer
	(Principal Executive Officer)

EX-12.2

Exhibit 12.2

Certification by the Principal Financial Officer pursuant to

Securities Exchange Act Rules 13a-14(a) and 15d-14(a)

as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

I, Jeremy Meinen, certify that:

1.	I have reviewed this annual report on Form 20-F of RELIEF THERAPEUTICS<br>Holding SA (the “Company”).
2.	Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a<br>material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
---	---
3.	Based on my knowledge, the financial statements, and other financial information included in this report,<br>fairly present in all material respects the financial condition, results of operations and cash flows of the Company as of, and for, the periods presented in this report;
---	---
4.	The Company’s other certifying officer and I are responsible for establishing and maintaining disclosure<br>controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the Company and have:
---	---
a.	Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be<br>designed under our supervision, to ensure that material information relating to the Company, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being<br>prepared;
---	---
b.	Designed such internal control over financial reporting, or caused such internal control over financial<br>reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting<br>principles;
---	---
c.	Evaluated the effectiveness of the Company’s disclosure controls and procedures and presented in this<br>report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
---	---
d.	Disclosed in this report any change in the Company’s internal control over financial reporting that<br>occurred during the period covered by the annual report that has materially affected, or is reasonably likely to materially affect, the Company’s internal control over financial reporting; and
---	---
5.	The Company’s other certifying officer and I have disclosed, based on our most recent evaluation of<br>internal control over financial reporting, to the Company’s auditors and the audit committee of the Company’s board of directors (or persons performing the equivalent functions):
---	---
a.	All significant deficiencies and material weaknesses in the design or operation of internal control over<br>financial reporting which are reasonably likely to adversely affect the Company’s ability to record, process, summarize and report financial information; and
---	---
b.	Any fraud, whether or not material, that involves management or other employees who have a significant role in<br>the Company’s internal control over financial reporting.
---	---

Date: May 12, 2023

By:	/s/ Jeremy Meinen
	Jeremy Meinen
	Chief Financial Officer
	(Principal Financial Officer)

EX-13.1

Exhibit 13.1

Certification of the Principal Executive Officer pursuant to

18 U.S.C. Section 1350, as adopted pursuant to

Section 906 of the Sarbanes-Oxley Act of 2002

CERTIFICATIONS

In connection with the annual report of RELIEF THERAPEUTICS Holding SA (the “Company”) on Form 20-F for the fiscal year ended December 31, 2022 filed with the Securities and Exchange Commission on the date hereof (the “Report”), I, Jack Weinstein, Chief Executive Officer of the Company, certify, pursuant to 18 U.S.C. §1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:

1.	The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act<br>of 1934, as amended; and
2.	The information contained in the Report fairly presents, in all material respects, the financial condition and<br>results of operations of the Company.
---	---

Date: May 12, 2023

By:	/s/ Jack Weinstein
	Jack Weinstein
	Chief Executive Officer
	(Principal Executive Officer)

EX-13.2

Exhibit 13.2

Certification of the Principal Financial Officer pursuant to

18 U.S.C. Section 1350, as adopted pursuant to

Section 906 of the Sarbanes-Oxley Act of 2002

CERTIFICATIONS

In connection with the annual report of RELIEF THERAPEUTICS Holding SA (the “Company”) on Form 20-F for the fiscal year ended December 31, 2022 filed with the Securities and Exchange Commission on the date hereof (the “Report”), I, Jeremy Meinen, Chief Financial Officer of the Company, certify, pursuant to 18 U.S.C. §1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:

1.	The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act<br>of 1934, as amended; and
2.	The information contained in the Report fairly presents, in all material respects, the financial condition and<br>results of operations of the Company.
---	---

Date: May 12, 2023

By:	/s/ Jeremy Meinen
	Jeremy Meinen
	Chief Financial Officer
	(Principal Financial Officer)