8-K
Opus Genetics, Inc. (IRD)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): May 15, 2023
Ocuphire Pharma, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-34079 | 11-3516358 |
|---|---|---|
| (State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer Identification No.) |
37000 Grand River Avenue, Suite 120 Farmington Hills, MI 48335
(Address of principal executive offices and zip code)
248-957-9024
(Registrant’s telephone number including area code)
(Registrant’s former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered |
|---|---|---|
| Common Stock, par value $0.0001 per share | OCUP | NASDAQ |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging Growth Company ☐
If an emerging growth company, 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. ☐
| Item 2.02 | Results of Operations and Financial Condition. |
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On May 15, 2023, Ocuphire Pharma, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended March 31, 2023. A copy of this press release is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K (this “Report”) and is incorporated herein by reference.
In accordance with General Instruction B.2. of Form 8-K, the information in this Item 2.02, and Exhibit 99.1 hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any of the Company’s filings under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing, except as expressly set forth by specific reference in such a filing.
| Item 7.01 | Regulation FD Disclosure. |
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On May 15, 2023, the Company posted an updated corporate presentation to its website at https://ir.ocuphire.com/presentations, which the Company may use from time to time in communications or conferences. A copy of the corporate presentation is attached as Exhibit 99.2 to this Report.
The information in this Report, including Exhibit 99.2 hereto, is furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing. The Company’s submission of this Report shall not be deemed an admission as to the materiality of any information required to be disclosed solely to satisfy the requirements of Regulation FD.
Exhibit 99.2 hereto contains forward-looking statements within the meaning of the federal securities laws. These forward-looking statements are based on current expectations and are not guarantees of future performance. Further, the forward-looking statements are subject to the limitations listed in Exhibit 99.2 and in the other reports of the Company filed with the Securities and Exchange Commission, including that actual events or results may differ materially from those in the forward-looking statements.
| Item 9.01 | Financial Statements and Exhibits. |
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| (d) | Exhibits |
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| Exhibit<br><br> <br>Number | Exhibit Description |
| --- | --- |
| 99.1 | Press Release by Ocuphire Pharma, Inc., dated May 15, 2023 |
| 99.2 | Corporate Presentation, dated May 15, 2023 |
| 104 | Cover Page Interactive Data File (embedded within Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| OCUPHIRE PHARMA, INC. | ||
|---|---|---|
| Date: May 15, 2023 | By: | /s/ Richard J. Rodgers |
| | Richard J. Rodgers | |
| | Interim President and Chief Executive Officer |
Exhibit 99.1
Ocuphire Pharma Announces Financial Results for First Quarter 2023 and Provides Corporate Update
End-of-Phase 2 Meeting with FDA Anticipated in 2H 2023 to Confirm Phase 3 Regulatory Path for Oral APX3330 in Diabetic Retinopathy (DR)
PDUFA date for Nyxol First Indication in Reversal of Pharmacologically-Induced Mydriasis (RM) Set for September 28, 2023; Nyxol Development and Commercialization Funded by Viatris
Cash Balance of $39 Million Expected to Fund Operations into 2025
FARMINGTON HILLS, Mich., May 15, 2023 – Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing novel therapies for the treatment of unmet needs of patients with retinal and refractive eye disorders, today announced financial results for the first quarter ended March 31, 2023, and provided a corporate update.
“Ocuphire made significant progress across both our APX3330 and Nyxol programs throughout the first quarter,” said Rick Rodgers, Interim Chief Executive Officer. “Based on the efficacy and safety data from the ZETA-1 Phase 2 trial of APX3330, we are preparing for an End-of-Phase 2 meeting with the FDA to confirm Phase 3 registration endpoints and study parameters. If approved, APX3330 has the potential to be a non-invasive, oral, early intervention treatment for millions of DR patients at risk of progressing to vision-threatening complications. For Nyxol, we look forward to the September 2023 PDUFA date in its first indication in RM. With a strong cash position and our partner Viatris funding the Nyxol program, we are well positioned to advance both APX3330 and Nyxol programs.”
Key Anticipated Future Milestones
| • | APX3330: End of Phase<br> 2 meeting with FDA to confirm Phase 3 regulatory path for Oral APX3330 in DR (2H 2023) |
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| • | Nyxol: PDUFA date for Nyxol in RM. FDA approval in RM would trigger a $10 million milestone payment to Ocuphire (September 28, 2023) |
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| • | Nyxol: Topline<br> results from VEGA-2 Phase 3 pivotal trial of Nyxol in Presbyopia (Late 2023) |
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Recent Business Highlights
Clinical and Regulatory Updates
| • | In January 2023, the Company announced topline results from the ZETA-1 Phase 2 trial of oral APX3330 for the treatment of diabetic retinopathy (DR). Oral APX3330 achieved statistical<br> significance on a key pre-specified secondary endpoint of binocular ≥ 3-step worsening of DRSS and demonstrated favorable safety and tolerability. This binocular secondary endpoint is a potential Phase 3 registration endpoint. The Company<br> plans an End-of-Phase 2 FDA meeting in the second half of 2023 to formally confirm this endpoint and other clinical trial parameters. |
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| • | In February 2023, the Company announced that the FDA has accepted for review a New Drug<br> Application (NDA) for Nyxol^®^ in RM and set a PDUFA date of September 28, 2023. FDA approval in RM would trigger a $10<br> million milestone payment to Ocuphire. |
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| • | Topline results from the VEGA-2 Phase 3 pivotal trial of Nyxol in presbyopia are expected in late 2023. Nyxol clinical programs in presbyopia and dim light disturbances (DLD) continue to<br> progress as planned. |
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Presentations, Publications, and Conferences
| • | From January 2023 through May 2023, several papers, posters, and panel talks were presented at medical and industry conferences with updates on APX3330 in DR and Nyxol in RM, DLD and<br> presbyopia. Highlights include: |
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| • | Results from ZETA-1 Phase 2 trial of APX3330 in DR were presented for the first time to the medical community at the 20^th^ Angiogenesis, Exudation, and Degeneration<br> 2023 Meeting in February 2023. |
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| • | Results from LYNX-1 Phase 3 trial of Nyxol in DLD were presented for the first time to the medical community at the Association for Research in Vision and Ophthalmology (ARVO) Annual<br> Meeting in April 2023, and at the American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting in May 2023. |
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| • | Previously announced results from ZETA-1 Phase 2 trial of APX3330 in DR were presented to the medical community at the American Society of Cataract and Refractive<br> Surgery (ASCRS) Annual Meeting in May 2023. |
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Corporate
In April, Ocuphire announced the appointment of Rick Rodgers as Interim President and Chief Executive Officer. Mr. Rodgers is a seasoned operating executive with 20 years of experience in biopharmaceutical management.
First Quarter ended March 31, 2023 Financial Highlights
As of March 31, 2023, Ocuphire had cash and cash equivalents of approximately $39.0 million. The Company has no debt. Based on current projections, management believes the present cash on hand will be sufficient to fund operations into 2025.
License and collaborations revenue was $1.7 million for the three months ended March 31, 2023. There was no revenue recorded in the three months ended March 31, 2022. Revenue during the first quarter of 2023 was derived from the reimbursement of research and development services under the Nyxol License Agreement.
General and administrative expenses for the three months ended March 31, 2023 were $2.3 million, compared to $1.7 million for the three months ended March 31, 2022. The increase was primarily attributable to an increase in stock-based compensation, professional services fees, legal support, and business development activities, offset in part by a decrease in payroll and insurance costs on a net basis. General and administrative expenses included $0.5 million and $0.3 million in stock-based compensation expense during the three months ended March 31, 2023, and 2022, respectively.
Research and development expenses for the three months ended March 31, 2023 were $5.6 million, compared to $4.8 million for the three months ended March 31, 2022. The increase was primarily attributable to increased manufacturing activities for Nyxol and APX3330 period over period as well as increased payroll and consulting costs during the current period. Research and development expenses also included $0.3 million and $0.1 million in stock-based compensation expense during the three months ended March 31, 2023, and 2022, respectively.
The loss from operations for the quarter ended March 31, 2023 was $6.1 million, compared to $6.5 million for the quarter ended March 31, 2022.
Net loss for the quarter ended March 31, 2023 was $5.8 million or ($0.28) per share, compared to $6.6 million or ($0.35) per share for the quarter ended March 31, 2022.
For further details on Ocuphire’s financial results, refer to the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 to be filed with the Securities and Exchange Commission.
About Ocuphire Pharma
Ocuphire is a publicly traded (Nasdaq: OCUP), clinical-stage, ophthalmic biopharmaceutical company focused on developing novel therapies for the treatment of unmet needs of patients with retinal and refractive eye disorders.
Ocuphire’s lead product candidate targeting retinal (back-of-the-eye) indications APX3330, is a first-in-class, small molecule oral drug that blocks downstream pathways regulated by transcription factor Ref-1 – including those involving angiogenesis (VEGF) and inflammation (NFkB). These pathways are implicated across several ocular diseases, including diabetic retinopathy (DR), diabetic macular edema (DME), and age-related macular degeneration (AMD). Ocuphire recently announced topline data from the ZETA-1 Phase 2 trial in which APX3330 achieved statistical significance on a key pre-specified secondary endpoint of preventing clinically meaningful progression of DR after 24 weeks of daily treatment. APX3330 has also shown a favorable safety and tolerability profile in diabetic subjects (ZETA-1 trial) and in 11 previous clinical trials conducted in healthy, liver disease, and cancer subjects. An End-of-Phase 2 meeting with the FDA is planned for APX3330.
Ocuphire has a partnership with Viatris, Inc. to develop and commercialize Nyxol^®^ eye drops as a preservative-free eye drop formulation of phentolamine mesylate, a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size by uniquely blocking the alpha-1 receptors found only on the iris dilator muscle without affecting the ciliary muscle. Nyxol has been studied in a total of 12 clinical trials (3 Phase 1, 5 Phase 2, 4 Phase 3) across three indications, including single-use for reversal of pharmacologically-induced mydriasis (RM), and once-daily for treatment of presbyopia and dim light (night) vision disturbances (DLD), pending regulatory approvals. Nyxol’s NDA under the 505(b)(2) pathway for the first indication, RM, has been accepted with a PDUFA date assigned of September 28, 2023. Nyxol is currently in Phase 3 for presbyopia and DLD.
For more information, visit www.ocuphire.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the timing and success of identifying a permanent CEO, the potential receipt of regulatory approval for Nyxol for the treatment of RM, expected financial results for the quarter ended March 31, 2023, the ability to fund operations into 2025, the occurrence and timing of an End-of-Phase 2 meeting with the FDA, the ability of Viatris to execute successful US and global launches of Nyxol, and the ability to determine a path to registration for APX3330. These forward-looking statements are based upon Ocuphire’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market opportunities, (viii) the effects of COVID-19 on clinical programs and business operations; (ix) risks that the Nyxol partnership may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; (x) the success and timing of commercialization of any of Ocuphire’s product candidates; and (xi) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and may be filed by Ocuphire from time to time with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Ocuphire undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contacts
| Corporate | Investor Relations | |
|---|---|---|
| Rick Rodgers<br><br> <br>Interim President & CEO<br><br> <br>ir@ocuphire.com | Corey Davis, Ph.D.<br><br> <br>LifeSci Advisors<br><br> <br>cdavis@lifesciadvisors.com | Bret Shapiro<br><br> <br>CoreIR<br><br> <br>brets@coreir.com |
Ocuphire Pharma, Inc.
Condensed Balance Sheets
(in thousands, except share amounts and par value)
| December<br><br> <br>31,<br><br> <br>2022 | |||||
| Assets | |||||
| Current assets: | |||||
| Cash and cash equivalents | 38,988 | $ | 42,634 | ||
| Accounts receivable | 2,834 | 1,298 | |||
| Contract asset | 2,467 | 3,552 | |||
| Prepaids and other current assets | 1,088 | 1,453 | |||
| Short-term investments | 22 | 49 | |||
| Total current assets | 45,399 | 48,986 | |||
| Property and equipment, net | 5 | 6 | |||
| Total assets | 45,404 | $ | 48,992 | ||
| Liabilities and stockholders’ equity | |||||
| Current liabilities: | |||||
| Accounts payable | 2,221 | $ | 1,069 | ||
| Accrued expenses | 1,933 | 1,684 | |||
| Total current liabilities | 4,154 | 2,753 | |||
| Warrant liabilities | — | — | |||
| Total liabilities | 4,154 | 2,753 | |||
| Commitments and contingencies | |||||
| Stockholders’ equity | |||||
| Preferred stock, par value 0.0001; 10,000,000 shares authorized as of March 31, 2023 and December 31, 2022; no shares<br> issued and outstanding at March 31, 2023 and December 31, 2022. | — | — | |||
| Common stock, par value 0.0001; 75,000,000 shares authorized as of March 31, 2023 and December 31, 2022; 20,947,830<br> and 20,861,315 shares issued and outstanding at March 31, 2023 and December 31, 2022, respectively. | 2 | 2 | |||
| Additional paid-in capital | 118,519 | 117,717 | |||
| Accumulated deficit | (77,271 | ) | (71,480 | ) | |
| Total stockholders’ equity | 41,250 | 46,239 | |||
| Total liabilities and stockholders’ equity | 45,404 | $ | 48,992 |
All values are in US Dollars.
Ocuphire Pharma, Inc.
Condensed Statements of Comprehensive Loss
(in thousands, except share and per share amounts)
(Unaudited)
| Three Months Ended | ||||||
|---|---|---|---|---|---|---|
| March 31, | ||||||
| 2023 | 2022 | |||||
| License and collaborations revenue | $ | 1,749 | $ | — | ||
| Operating expenses: | ||||||
| General and administrative | 2,285 | 1,736 | ||||
| Research and development | 5,595 | 4,772 | ||||
| Total operating expenses | 7,880 | 6,508 | ||||
| Loss from operations | (6,131 | ) | (6,508 | ) | ||
| Interest expense | — | (5 | ) | |||
| Fair value change in warrant liabilities | — | — | ||||
| Other income (expense), net | 340 | (82 | ) | |||
| Loss before income taxes | (5,791 | ) | (6,595 | ) | ||
| Benefit (provision) for income taxes | — | — | ||||
| Net loss | (5,791 | ) | (6,595 | ) | ||
| Other comprehensive loss, net of tax | — | — | ||||
| Comprehensive loss | $ | (5,791 | ) | $ | (6,595 | ) |
| Net loss per share: | ||||||
| Basic and diluted | $ | (0.28 | ) | $ | (0.35 | ) |
| Number of shares used in per share calculations: | ||||||
| Basic and diluted | 20,939,607 | 18,888,471 |
Exhibit 99.2
Ocuphire Corporate Presentation May 2023
Disclosures and Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the success and timing of planned regulatory filings and approvals, pre-commercial activities, commercialization strategy and timelines, business strategy, product labels, cash runway, scalability, future clinical trials in presbyopia (P), dim light/night vision disturbance (DLD) and diabetic retinopathy (DR) / diabetic macular edema (DME), including the potential for Nyxol to be a “best in class” presbyopia drop, and timing of planned future clinical trials for APX3330, timing and occurrence of an End-of-Phase 2 meeting with the FDA, the potential of a Phase 3 registration path for APX3330, the success and timing of planned regulatory filings, business strategy, cash runway, scalability, the potential for APX3330 to be the first line of therapy for DR patients, and the potential market opportunity for the slowing of DR progression. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success, costs, and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market opportunities, (viii) risks that the partnership with Viatris may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; (ix) the success and timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s product candidates and (x) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and may be filed by the Company from time to time with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. The Company makes no representation or warranty, express or implied, as to the accuracy or completeness of the information contained in or incorporated by reference into this presentation. Nothing contained in or incorporated by reference into this presentation is, or shall be relied upon as, a promise or representation by the Company as to the past or future. The Company assumes no responsibility for the accuracy or completeness of any such information. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. 2
Corporate Highlights Two Lead Clinical-Stage Novel Drugs Addressing Multiple Large Ophthalmology Markets with Limited to No Competition & Extensive Patent Portfolio Global License Agreement with Viatris to Fund the Development and Commercialization of Nyxol for All Indications Strong Financial Position to Advance APX 3330 and Nyxol Clinical Programs into 2025 Nyxol for RM Indication PDUFA Date on September 28, 2023 APX3330 – Paradigm Changing Oral Tablet for 8 million DR patients; Moving into Phase 3 APX3330 oral tablets Diabetic Retinopathy/Diabetic Macular Edema (DR/DME) Nyxol eyedrops Reversal of Mydriasis (RM) – eye dilation Presbyopia (P) – age-related blurry near vision Dim Light or Night Vision Disturbances (DLD) 3
Product Candidate Indication Pre-clinical Phase 1 Phase 2 Phase 3 Regulatory Approval Upcoming Milestones APX3330 Oral Pill Diabetic Retinopathy (DR)/ Macular Edema (DME) EOP2 Mtg 2H 2023 to Advance to Phase 3 Nyxol® Eye Drop Reversal of Mydriasis (RM) PDUFA Date Sep 28, 2023 Nyxol® Eye Drop Presbyopia (P) VEGA-2 Phase 3 Topline Data Late 2023 Nyxol® + 0.4% Low Dose Pilocarpine (LDP) Eye Drops Nyxol® + 0.4% Low Dose Pilocarpine (LDP) Eye Drops Nyxol® Eye Drop Dim Light or Night Vision Disturbances (DLD) LYNX-2 2nd Phase 3 trial (n=150+) Ocuphire Pipeline Partnered with Viatris Partnered with Viatris Partnered with Viatris EOP2 Meeting PDUFA Sept 28, 2023 Ph3 Initiated 4
Global Partnership with Viatris for Nyxol Viatris Has Selected Nyxol to be a Key Element of its Global Eye Care Division Fully funded development and commercialization costs for all 3 Nyxol indications Partner for Nyxol global commercialization Allows Ocuphire to focus on APX3330 development Strengthens cash position into 2025 $35 million upfront Funding for potentially all R&D and commercialization for all 3 indications globally $130 million in regulatory and sales milestones First potential $10 million milestone payment on FDA approval in RM Tiered double digit royalties through 2040 5
6 APX3330 ORAL TABLET DR Diabetic Retinopathy DME Diabetic Macular Edema “ ” “I could lose my hearing, I could lose talking but…. It’s frightening to lose my eyesight.” Patient Diagnosed with DR
Diabetic Retinopathy At a Glance Larger Disease to Manage with Growing Diabetes There are 8M adults in the U.S. with DR1 DR is the leading cause of blindness among working-age adults DR/DME affects about 1 in 4 people with type 1 and type 2 diabetes Majority of patients with mild to moderate DR are not treated with anti- VEGF due to injection fear and burden $13B (2020) Global Intravitreal Injection Revenues 7 American Diabetes Association; International Diabetes Federation; Healthline
DRSS Predicts Vision-Threatening Complications (PDR/DME) 8 Early treatment diabetic retinopathy study research group. ophthalmology. 1991;98(5 suppl):823-33. Diabetes control and complications trial research group. N Engl J Med. 1993;329(14):997-86. Fathy C, Patel S, Sternberg P Jr, Kohanim S. Disparities in adherence to screening guidelines for diabetic retinopathy in the United States: a comprehensive review and guide for future directions. Semin Ophthalmol. 2016;31(4):364–377. doi: 10.3109/08820538.2016.1154170 Early screening and treatment for DR can reduce vision loss by up to 94% 1 Year Follow-up 3 Year Follow-up 5 Year Follow-up Percentage of Eyes that Worsen to PDR Regardless of severity, all eyes worsen over time
Broad Opportunities to Treat Retinal Diseases with APX3330 Source:1. American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; 2. Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918 3. Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 4. Estimates are provided by the National Eye Institute, FactSheet, Global Data, and Research and Markets. Estimated values are rounded. 5. Estimated prevalence in the U.S.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion 9 Diabetic Retinopathy PDR(DRSS >60) Moderate to Severe NPDR (DRSS 43-53) Mild NPDR 34 Million Diabetics in US 10M 6M 1M 1M ~8M+DR Patients Anti-VEGF treatments APX3330 APX3330 / APX2009 / APX2014 (Local Delivery) US Market Opportunity Addressable Market Potential First Oral Rx for Retina Diseases with Multi-Billion Revenue Opportunity APX3330 ~$10B+ Market Revenues DME 1M Wet AMD 2M Dry AMD 10M+ GA 1M Inflammatory component is common across these retina indications as well & potentially addressable by MOA of Ref-1
APX3330 Profile Overview Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data from 12 Completed Trials Novel MOA for Treating Retina ↓ Inflammation ↓ Abnormal Angiogenesis Good Patient Compliance in ZETA-1 with Convenient Oral Dosing APX3330 Demonstrated Slowing of Progression of Diabetic Retinopathy Over 350 Subjects (Healthy, Liver, Cancer, Diabetic) treated with Several Subjects Systemically Dosed ~1 Year and Others at 24-Wks Few Systemic AEs Across All Doses (120mg-720mg) < 5% Mild Skin Rash/Pruritis (reversible) < 5% Mild Diarrhea No Treatment-Related Organ Toxicity Minimal Ocular Side Effects* APX3330: Well-tolerated Oral Dose up to 600 mg/day | Twice Daily Dosing MOA and Efficacy Signals in DR Favorable Safety Profile 10 Source: ZETA-1 Clinical Trial *1 subject had vision blur thought to be related by investigator in ZETA-1
Sources: Logsdon et al (2018), Li et al (2014). APX3330 Ref-1 Inhibition – Decreases Abnormal Angiogenesis Ref-1 Involved in Multiple Key Pathways that Contribute to DR and DME Mechanism of Action – Ref-1 Inhibition Hypoxia Ref-1 HIF-1α VEGF (Signaling Cascade) Inflammation Ref-1 NF-κB Other Growth Factors (Signaling Cascade) TNF-α Chemokines Neovascularization Lucentis® EYLEA® Anti-VEGF Steroids APX3330 Ref-1 (reduction-oxidation effector factor-1), a novel target for retinal diseases, is a transcription factor regulator of angiogenesis (VEGF) and inflammation (NFkB) Unique dual MOA decreases abnormal angiogenesis and inflammation Anti-VEGF injections do not target inflammation Previously developed by Eisai for hepatic inflammatory indications and by Apexian for solid tumors in 11 Phase 1 and 2 trials Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety 11
Primary: % subjects with ≥ 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale1) at week 24 Secondary: DRSS worsening ≥1, ≥2, ≥3*, ≥4* DRSS worsening ≥1, ≥2, ≥3*, ≥4* Progression to vision threatening complications Central subfield thickness (CST) Best Corrected Distance Visual Acuity (BCDVA) Rescue subjects DME fellow eye status Safety and tolerability Exploratory: Labs/PK *Potential Phase 3 approvable endpoints ZETA-1 Phase 2 Design – APX 3330 in DR Randomized, Double-masked, Placebo-controlled 24-week Trial (Similar to Eylea P3 DR trial) Endpoints 25 US sites N = 90-100 participants with moderately severe to severe NPDR or mild PDR (DRSS 47, 53, 61) Key inclusion: ≥ 18 years of age DRSS 47, 53, or 61 Noncentral DME permitted ETDRS BCVA ≥ 60 letters (20/63) Key exclusion: OCT CST >320 µm2 Center involved DME allowed in fellow eye Anti-VEGF within past 6 months3 HbA1c ≥ 12.0% Eligibility Criteria 103 subjects enrolled (FPFV Apr 2021 to LPLV Aug 2022) Topline announced in early 2023 1:1 By Central Reading Center Center-Involved DME in Fellow Eye is Acceptable Includes Systemic or IVT VEGF www.clinicaltrials.gov (NCT04692688); Eylea® is registered trademark of Regeneron NPDR = non-proliferative diabetic retinopathy PDR = proliferative diabetic retinopathy 12 Week 0 Week 12 Week 24 Week 4 Primary Endpoint APX3330 600mg/day (BID) Placebo BID Randomization
Change in DRSS is Regulatory Approval Endpoint for DR Local Drugs (Intravitreal Injections) Systemic Drugs Precedent approvable endpoint for locally- delivered drugs (Non-Systemic) in DR: ≥ 2-step DRSS improvement in study eye Aflibercept (PANORAMA trial) Ranibizumab (RISE/RIDE/DRCR trials) Potential approvable endpoints for systemic drug in DR (to be confirmed at the EOP2 FDA meeting) include: ≥ 3-step binocular DRSS improvement ≥ 3-step binocular DRSS worsening End-of-Phase 2 meeting with FDA to align on binocular ≥ 3-step DRSS worsening (i.e., sum of right and left eye change in DRSS) as an acceptable primary endpoint for registration. This endpoint is distinct from historical anti-VEGF IVT precedent due to different delivery FDA accepts improvement OR worsening (prevention of progression)1 of the disease AND DRSS is an established surrogate endpoint for DR 13 Nair P, Aiello LP, Gardner TW, Jampol LM, Ferris FL III. Report From the NEI/FDA Diabetic Retinopathy Clinical Trial Design and Endpoints Workshop. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5127-5142. doi: 10.1167/iovs.16-20356. PMID: 27699406; PMCID: PMC6016432. Source: ZETA-1 Clinical trial; Eylea® is registered trademark of Regeneron; Lucentis® is registered trademark of Roche/Genentech
Source: ZETA-1 Clinical Trial Key Visual Metrics APX3330 n=51 Placebo n=52 Total n=103 BCVA Study Eye Letters (mean) 81 78 80 (20/25 Snellen) BCVA Fellow Eye Letters (mean) 76 77 77 (20/32 Snellen) OCT CST Study Eye (µm) 270 271 271 OCT CST Fellow Eye (µm) 292 286 289 Intraretinal Fluid in the Center of SE Y – 21 N – 26 Y – 12 N – 31 Y – 33 N – 57 Intraretinal Fluid at the Foveal Center of SE Y – 1 N – 20 Y – 1 N – 41 Y – 2 N – 61 Intraocular Pressure in Study Eye (mmHg) 15 16 15 APX3330 n=51 Placebo n=52 DRSS Score – Study Eye 47 (Moderately severe to severe NPDR) 22 (43%) 18 (35%) 53 (Moderately severe to severe NPDR) 25 (49%) 28 (54%) 61 (Mild proliferative diabetic retinopathy) 4 (8%) 6 (12%) DRSS Score – Fellow Eye 43 or Lower (Mild to moderate NDPR or better) 14 (31%) 12 (24%) 47 (Moderately severe to severe NPDR) 13 (29%) 19 (39%) 53 (Moderately severe to severe NPDR) 12 (27%) 9 (19%) 61 (Mild proliferative diabetic retinopathy) 1 (2%) 4 (8%) 65 or Higher (Moderate to severe prolif. DR) 5 (11%) 5 (10%) Good Visual Acuity Fluid Below 320µm Note: 15 fellow eyes were CST>320 microns (center-involved DME eyes) ZETA-1: Baseline Characteristics - Well-Balanced Across Arms 14 DRSS Scores
ZETA-1: % of Subjects with Binocular Improvement/Worsening in DRSS at Wk 24 APX3330 Demonstrated Statistical Efficacy on Potential Phase 3 Registration Endpoint p=0.12 8% p=0.04 16% 18% 35% 33% 33% 20% 6% p=0.18 2% 0% 0% 11% 36% 36% 29% 18% 11% 9% 0% 5% 10% 15% 20% 25% 30% 35% 40% ≥ 4 Steps Worsening ≥ 3 Steps Worsening ≥ 2 Steps Worsening ≥ 1 Steps Worsening No Change ≥ 1 Step ≥ 2 Step ≥ 3 Step ≥ 4 Step Improvement Improvement Improvement Improvement Percent of Subjects (%) Percent of Subjects With Binocular Improvement or Worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 Steps From Baseline (mITT-LOCF) Placebo (n=49) APX3330 (n=45) 15 Source: ZETA-1 Clinical Trial
ZETA-1: Percent of Subjects With Binocular ≥ 3-Step Worsening in DRSS Primary Endpoint for Planned Phase 3 Demonstrates Prevention of Progression 12% 16% 0% 5% 10% 15% 20% Week 12 Week 24 Percent of Subjects (%) Visit Placebo (N=49) APX3330 (N=46) n=49 0% n=45 0% n=45 n=49 p=0.04 p=0.07 Percent of Subjects With Worsening in DRSS of ≥3 Steps From Baseline by Visit Binocular Eyes (mITT-LOCF) Based on extrapolation from ZETA-1 and Rise/Ride extension trials1, estimated ~25% of untreated patients may progress by ≥ 3 steps in binocular DRSS over 1 year 5% 19% 0% 5% 10% 15% 20% 25% Placebo (n=43) APX3330 (n=40) Treatment Group % of Subjects p=0.07 BCVA data shows function followed structure with fewer APX3330 treated subjects losing visual acuity compared to placebo at week 24 Percentage of Subjects with ≥ 5 Letters of BCVA Lost at Week 24 (Safety Population) 16 Source: ZETA-1 Clinical Trial Sun JK, Evidence for DR Progression and Regression from Clinical Trials. Presented at NDI/FDA DR Clinical Trials Design and Endpoints Workshop, June 26, 2015. Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting Note: Large “N” indicates total number of participants within each arm for the mITT-LOCF population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm.
APX3330 SAEs: Dyskinesia, TIA, Chest pain Placebo SAEs: Vertigo, Asthenia, Multiple organ dysfunction, Bradycardia, CAD AEs → Withdrawal APX3330: Presyncope, Dyspnea; Placebo: DME (both eyes) *Preferred Term within Organ Class ZETA-1: Treatment Emergent Adverse Events Oral APX3330 Showed a Favorable Safety Profile Consistent with Prior Trials APX3330 (n=51) Placebo (n=52) Total (n=103) Total AEs 91 120 211 # of Subjects with AEs 29 (57%) 35 (67%) 64 (62%) Treatment Related AEs 14 (45%) 17 (55%) 31 (30%) Serious AEs 3 (3%) 11 (9%) 14 (7%) Subjects Withdrawals Due to AEs 2 (4%) 1 (2%) 3 (3%) Deaths 0 (0%) 1 (2%) 1 (1%) AEs in >5% of Subjects* Diabetic Retinal Edema 2 (4%) 5 (10%) 7 (7%) Diabetic Retinopathy 1 (2%) 6 (12%) 7 (7%) Vitreous detachment 0 (0%) 3 (6%) 3 (3%) Cataract 3 (6%) 1 (2%) 4 (4%) Pruritus 6 (12%) 1 (2%) 7 (7%) Rash 3 (6%) 1 (2%) 4 (4%) COVID-19 1 (2%) 5 (10%) 6 (6%) APX3330 Safety Profile: Limited AEs, most mild in severity AEs similar to or less than placebo (except for pruritis/rash) Few serious treatment-related AEs, all unrelated to study medication No ocular AEs other than expected DR progression No effect on clinical labs No adverse effects on heart, kidney, liver, CNS, GI No effect on vital signs (HR, BP) Patients continued routine medications to manage their diabetes comorbidities | Eye disorders | 17
APX3330 - Phase 2 Summary and Next Steps APX3330 is the most advanced oral program in development for diabetic eye disease APX3330 demonstrated favorable safety with compelling potential to slow progression of diabetic retinopathy ZETA-1 statistically significant results on potential Phase 3 registration endpoint: 0% APX3330-treated patients had a binocular ≥ 3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients (p=0.04) ZETA-1 Summary Further analysis of ZETA-1 Phase 2 data, including insights for Phase 3 trial design Prepare for EOP2 FDA meeting in 2H 2023 to formally confirm Phase 3 design and endpoints Advance APX3330 into Phase 3 program APX3330 Next Steps To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients Our Goals for Patients 18
19 Reversal of Mydriasis (RM) P DLD Presbyopia Dim Light or Night Vision Disturbances (DLD) Nyxol as a Single Drop Nyxol with LDP Adjunctive Therapy 1 0.4% 2 RM RM NYXOL® EYE DROPS THREE INDICATIONS NEW PARTNERSHIP WITH VIATRIS
Decreases pupil size (moderately) without affecting the iris sphincter or ciliary muscles Allows for 3 indications: RM, Presbyopia and DLD 505(b)(2) Regulatory Pathway Supported by Prior Phentolamine Approvals in non-ophthalmic Indications Nyxol’s Differentiated MOA as an Alpha-1 Blocker No Engagement of Ciliary Muscle, No Headaches and Lower Risk of Retinal Detachment Phentolamine is the Active Ingredient in Nyxol: a non-selective α1 Antagonist Phentolamine blocks α1 receptors on the Iris Dilator Muscle up to 24 hours 20 Company websites. Illustration for educational purposes
*Trend toward statistical significance even in smaller POS arm from time 0 to time 6 hours (n=30); larger sample size for all arms planned in Phase 3 program Primary Endpoint Efficacy Data Key Secondary Endpoint(s) Safety & Tolerability Return to baseline pupil diameter at 90 minutes after dilation Met Phase 3 primary endpoint MIRA-3: 58% Nyxol vs. 6% placebo MIRA-2: 49% Nyxol vs. 7% placebo (p<0.0001) MIRA-4: 64% Nyxol vs. 25% placebo Efficacy across all mydriatic agents, iris color, 1 or 2 drops, and all ages (3-80) No headaches No blurry vision ~5% mild redness No change in IOP No SAEs Most AEs were mild ≥3 line gain in near vision with loss of no more than 1 line in distance vision Met planned Phase 3 primary endpoint VEGA-1: 29% Nyxol vs.12% placebo at 12 hrs post-Nyxol dose (p=0.02) Durable near vision (18 hrs) Optimal pupil size Pupillary light reflex Met Phase 2 primary endpoint Met planned Phase 3 primary endpoint VEGA-1: 61% combo post-LDP dose (30 min) + post-Nyxol dose (12 hrs) vs. 14% placebo (p<0.0001) Durable near vision gain Optimal pupil size Pupillary light reflex ≥3 lines (eye test) of improvement in mesopic low contrast best-corrected distance visual acuity (mLCVA) Met Phase 3 primary endpoint LYNX-1: 13% Nyxol vs. 3% placebo at Day 8 (p<0.05) and 21% in Nyxol vs.3% placebo at Day 15 (p<0.01) Improvement visual acuity measures (distance and near) in dim light conditions Summary of Nyxol Trial Results Comprehensive Body of Clinical Data Supporting Efficacy and Safety Across 3 Indications RM P: Nyxol DLD 21 Indication RM Presbyopia (Nyxol Alone) Presbyopia (Nyxol + LDP) DLD
Phase 2 Phase 1 Ocuphire Nyxol + 0.4% pilo Visus Brimochol® (carbachol + brim) Other Cholinergic Agonists* Cholinergic Agonist* (pilocarpine) Lenz Aceclidine; Aceclidine + brim Eyenovia MicroLine (2% pilo) Alpha Antagonist & low dose pilocarpine* Alpha Antagonist NDA Allergan VUITYTM; (1.25% pilo) Orasis CSF-1 (Low dose pilo) Phase 3 Nyxol’s potential differentiation: New MOA class (iris dilator muscle inhibitor) Favorable safety and tolerability (e.g.: no headaches, no accommodative spasm, no risk of retinal detachment) 24-hour durability Broad range of patients including high myopes Improvement in night vision disturbances Nyxol+LDP may offer added efficacy and tunability Ocuphire Nyxol (0.75% phentolamine) Pupil modulation MOA Combination drugs Lens softening MOA X Novartis EV-006 Lens Softening * acts on sphincter and ciliary muscles in dose- dependent manner 22 Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020 A New, Differentiated MOA and Combination Therapy Offers Tunability
Corporate Highlights Two Lead Clinical-Stage Novel Drugs Addressing Multiple Large Ophthalmology Markets with Limited to No Competition & Extensive Patent Portfolio Global License Agreement with Viatris to Fully Fund the Development and Commercialization of Nyxol for All Indications Strong Financial Position to Advance APX and Nyxol Clinical Programs into 2025 Nyxol for RM Indication PDUFA Date on September 28, 2023 APX3330 – Paradigm changing oral for 8 million DR patients; Moving into Phase 3 APX3330 oral tablets Diabetic Retinopathy/Diabetic Macular Edema (DR/DME) Nyxol eyedrops Reversal of Mydriasis (RM) – eye dilation Presbyopia (P) – age-related blurry near vision Dim Light or Night Vision Disturbances (DLD) 23
Restore Vision & Clarity www.ocuphire.com ir@ocuphire.com Ocuphire Pharma Appendix: Team and Nyxol Data 24
25 Drey ColemanVP, Clinical Operations Amy Rabourn, CPA SVP, Finance Charlie Hoffmann, MBA SVP, Corporate Development Mitch Brigell, PhD Head, Clinical Development and Strategy Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development Ronil Patel, MS SVP, Operations and BD Chris Ernst Global Head, QA and Manufacturing Barbara Withers, PhDVP, Clinical and Regulatory Strategy Bindu Manne Head, Market Development and Commercialization Laura Gambino Director, Project Management Richard Rodgers, MBA Interim CEO Management Team with Decades of Drug Development Experience
Ocuphire's World-Class Medical Advisory Board Chief Medical Advisor, Ocuphire Refractive Specialist Jay Pepose, MD, PhD UCLA School of Medicine Refractive Specialist Y. Ralph Chu, MD Northwestern University Refractive Specialist Zaina Al-Mohtaseb, MD Baylor College of Medicine Refractive Specialist James Katz, MD University of Illinois Refractive Specialist Marguerite McDonald, MD Columbia University Refractive Specialist Mitch Jackson, MD University of Chicago Refractive/ Glaucoma Specialist Thomas Samuelson, MD University of Minnesota Refractive/Glaucoma Specialist Inder Paul Singh, MD The Chicago Medical School Eliot Lazar, MD Georgetown University elCON Medical Retinal Specialist Peter Kaiser, MD Harvard Medical School Retinal Specialist David Lally, MD Vanderbilt University Retinal Specialist Michael Allingham, MD, PhD University of North Carolina Retinal Specialist David Boyer, MD Chicago Medical School Retinal Specialist David Brown, MD Baylor University Retinal Specialist Jeffrey Heier, MD Boston University Retinal Specialist Anat Lowenstein, MD, PhD The Hebrew University Retinal Specialist Caroline Baumal, MD University of Toronto Medical School Optometry Douglas Devries, OD University of Nevada Optometry Paul Karpecki, OD Indiana University Optometry Justin Schweitzer, OD Pacific University College of Optometry Optometry Selina McGee, OD Northeastern State University Optometry Leslie O’Dell, OD Salus University Co-Founder Apexian/APX3330 Mark Kelley, PhD Indiana University 26
Ocuphire Board of Directors Seasoned Directors with Decades of Drug Development, M&A/Financings, and Ophthalmology 27 Sean Ainsworth, MBA Lead Independent Director, Board Director Jay Pepose, MD, PhD Board Director Cam Gallagher, MBA Chair, Board Director Mina Sooch, MBA Board Director Susan Benton, MBA Board Director James Manuso, PhD/MBA Board Director Richard Rodgers, MBA Interim President & CEO Board Director