8-K
Opus Genetics, Inc. (IRD)
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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): November 12, 2021
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<br><br> <br>Farmington Hills,<br> MI | 48335 | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code: (248) 681-9815
| N/A |
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(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 (see General Instruction A.2. below):
| ☐ | 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, $0.0001 par value | OCUP | Nasdaq Capital Market |
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 November 12, 2021, Ocuphire Pharma, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2021. A copy of this press release is furnished herewith as Exhibit 99.1 to this Current 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 November 15, 2021, 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 99.1 to this Current Report on Form 8-K (this “Report”).
The information in this Report, including Exhibit 99.1 hereto, is furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Securities 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.
This Report and Exhibit 99.1 hereto contain 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 99.1 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
| Exhibit<br><br> <br>Number | Exhibit Description |
|---|---|
| 99.1 | Press Release, dated November 12, 2021 |
| 99.2 | Corporate Presentation, dated November 15, 2021 |
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. | |
|---|---|
| By: | /s/ Mina Sooch |
| Mina Sooch | |
| Chief Executive Officer |
Date: November 15, 2021
Exhibit 99.1
Ocuphire Announces Financial Results for the Third Quarter 2021 and Provides Corporate Update
On Track to Initiate Additional Phase 3 FDA Registration Trials for Nyxol^®^ Eye Drops in Reversal of Mydriasis (RM) in 4Q21 and Presbyopia in 1H22
Three Clinical Trial Data Readouts Expected in Early 2022 for Nyxol in Night Vision Disturbance, RM, and RM for Pediatric Patients
Planned NDA Submission for Nyxol in Reversal of Mydriasis Indication in Late 2022
More Publications Supporting Novel Transcription Factor (Ref-1) Inhibitor, APX3330, Targeting Both Neovascularization and Inflammation in Retinal Diseases
Currently Recruiting for Phase 2 Trial Evaluating APX3330 for the
Treatment of Diabetic Retinopathy with Data Expected in 2H22
FARMINGTON HILLS, Mich., November 12, 2021 - Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of refractive and retinal eye disorders, today announced financial results for the third quarter of 2021 and provided a corporate update.
“The third quarter marked continued progress across our late-stage clinical programs and opportunities for multiple data presentations at major medical meetings,” said Mina Sooch, MBA, President and CEO of Ocuphire Pharma. “We have already achieved two successful clinical trials for Nyxol. In reversal of mydriasis (RM), we reported positive results in a Phase 3 trial and are on track to initiate the second Phase 3 trial before year end. In presbyopia, we reported positive results in a Phase 2 clinical trial. We are also delighted to see the early US regulatory approval of Allergan’s VUITY^TM^eye drops, the first pharmaceutical therapy for the large presbyopia market.”
“We are also very pleased to see a growing body of supportive research for our Phase 2 oral drug candidate, APX3330, which inhibits known pro-angiogenic and pro-inflammatory pathways. As a highly differentiated, first-in-class and orally-delivered therapy, we believe APX3330 will be an important source of potential value creation with the opportunity to broadly address the unmet global clinical need in diabetic retinopathy and treatment burden in other retinal diseases.”
“This week marks Ocuphire’s one-year anniversary of public trading on the Nasdaq and we are proud to have achieved so many important clinical and business milestones in that time. We thank our clinical trial participants and investigators for their continued support. Looking ahead, we believe 2022 is shaping up to be an even more exciting and catalyst-rich year to build significant value for our company and our shareholders, with cash on hand that provides runway into late 2022 to achieve these milestones.”
Key Anticipated Future Milestones
| • | Reversal of Mydriasis (RM): Initiate second<br> Phase 3 (MIRA-3) registration trial in subjects 12 and older and a small pediatric trial in subjects ages 3 to 11 (MIRA-4) in the fourth quarter of 2021 investigating Nyxol with results expected in early 2022; Planning to file NDA<br> submission with FDA for Nyxol in RM indication in late 2022 |
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| • | Presbyopia: Initiate Phase 3 program (VEGA-2)<br> in first half of 2022 investigating Nyxol and Low-Dose Pilocarpine (LDP) |
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| • | Night Vision Disturbances (NVD): Top-line data expected in early 2022 from Phase 3 (LYNX-1) registration trial investigating Nyxol |
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| • | Diabetic Retinopathy (DR) and Diabetic Macular Edema<br> (DME): Top-line data expected in the second half of 2022 for the randomized, well-controlled Phase 2 (ZETA-1) trial investigating APX3330 |
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Third Quarter and Recent Business Highlights
Presentations and Publications
| • | In November, clinical data on Nyxol^®^ and APX3330 were accepted for presentation at poster sessions at the American Academy of Ophthalmology (AAO) 2021 annual meeting to take place in New Orleans, November 12 – 15. In addition, Ocuphire presented new data on improvement in intermediate vision and Snellen equivalent<br> near vision at the Eyecelerator@AAO 2021 conference on November 11. Ocuphire was one of two companies presenting clinical data<br> for presbyopia at this meeting. |
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| • | In October, the Company announced the publication of a review article<br> within the Special Issue “Advances in Molecular Activity of Potential Drugs” of the International Journal of<br> Molecular Sciences, focused on how novel inhibitors of APE1/Ref-1 such as APX3330 may have the potential to improve disease outcomes for<br> retinal disease patients. The article underscores the role of the APE1/Ref-1 protein in pro-angiogenic pathways associated with neovascular eye disease including diabetic retinal diseases and age-related macular degeneration. It can be accessed online<br> at the following link: Inhibition of APE1/Ref-1 for Neovascular Eye Disease: From Biology to Therapy. |
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| • | In October, the Company announced the publication of a review article in<br> Cells titled “Potential<br><br> Therapeutic Candidates for Age-Related Macular Degeneration” noting the potential of APX3330 (referred to as “E3330”) for the treatment of<br> age-related macular degeneration (AMD). Because APE1/Ref-1 has been shown to contribute to retinal angiogenesis, the authors conclude that APE1/Ref-1 inhibitors such as APX3330 could inhibit the abnormal blood vessel formation seen in AMD<br> by reducing retinal endothelial cell proliferation, migration, and tube formation. The article can be accessed online at the following link: Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD). |
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| • | In October, Michael J. Allingham, MD, PhD presented at the 39^th^<br> Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) (Diabetic Retinopathy 1 Symposium), highlighting the favorable<br> safety and tolerability data for APX3330 in over 300 healthy volunteers and cancer/inflammation disease patients across 11 Phase 1 and Phase 2 studies. Also, Mina Sooch, CEO, presented APX3330 history and the design of the ongoing Phase 2<br> trial in DR at the OIS Retina Innovation Summit@ASRS. |
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| • | In July, the Company announced publication in the Journal of<br> Cellular Signaling featuring Ocuphire’s novel oral Ref-1 inhibitor APX3330 in Phase 2 trial for the treatment of retinal disease which<br> highlighted the favorable safety profile of APX3330 and its unique anti-angiogenic and anti-inflammatory mechanism of action properties relevant to a broad range of retinal diseases. |
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| • | In July, at the 2021 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting, Dr. Jay<br> S. Pepose, Medical Advisor and Board Director, presented papers featuring positive results for Nyxol in two studies: Phase 2 Presbyopia (VEGA-1) and Phase 3 Reversal of Mydriasis (MIRA-2). The Phase 3 MIRA-2 data presentation at ASCRS won the Best Paper of the Session. |
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| • | In July, Mina Sooch, CEO, participated in the presbyopia drug therapy<br> panel at the Eyecelerator@ASCRS 2021 held on July 22nd and in the Eye on Innovation panel at the Virtual Salon Series held on July<br> 28th. |
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Intellectual Property
| • | U.S. Patent and Trademark Office issued patent no. 11,160,770 “Compounds, compositions and methods for treating oxidative DNA damage disorders” which<br> provides protection for APX2009 and other APX pipeline candidates. |
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Third Quarter and Year-To-Date 2021 Financial Highlights
As of September 30, 2021, the Company had cash and cash equivalents of approximately $22.2 million. Net cash used in operating activities for the nine months ended September 30, 2021 was $13.7 million.
Collaborations revenue was $0.5 million and $0.6 million for the three months and nine months ended September 30, 2021, respectively. Revenue during the periods was derived from the license agreements with Biosense Global, LLC and Processa Pharmaceuticals, Inc. related to certain technology transfers. There was no collaborations revenue recognized during the comparable prior year periods.
General and administrative expenses for the three months and nine months ended September 30, 2021 were $1.6 million and $6.7 million, respectively, compared to $0.6 million and $1.5 million for the comparable periods in 2020, respectively. The increases in the current periods were primarily attributable to administrative employee headcount, stock-based compensation, professional services, insurance, legal and settlement costs, and costs associated with operating as a public company subsequent to the reverse merger.
Research and development expenses for the three months and nine months ended September 30, 2021 were $3.1 million and $10.4 million, respectively, compared to $1.4 million and $2.3 million for the comparable periods in 2020, respectively. In the current periods, the increases were primarily attributable to new clinical trials and manufacturing activities for Nyxol and APX3330 as well as regulatory, preclinical and other development activities.
The loss from operations for the three and nine months ended September 30, 2021 was $4.2 million and $16.6 million, respectively, compared to $1.9 million and $5.9 million for the three and nine months ended September 30, 2020, respectively.
There was a non-cash expense of $33.8 million related to fair value change in warrant liabilities recorded for the nine months ended September 30, 2021 compared to a benefit of $0.2 million recorded for the nine months ended September 30, 2020 related to premium conversion derivatives. The reported losses also included non-cash stock-based compensation expense of $0.5 million and $1.4 million during the three and nine months ended September 30, 2021, respectively, and $0.6 million and $1.0 million during the three and nine months ended September 30, 2020, respectively.
For further details on Ocuphire’s financial results refer to the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, as 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 and commercializing therapies for the treatment of several eye disorders. Ocuphire’s pipeline currently includes two small-molecule product candidates targeting front and back of the eye indications. The company’s lead product candidate, Nyxol^®^ (0.75% phentolamine ophthalmic solution) Eye Drops, is a once-daily preservative-free eye drop formulation of phentolamine mesylate, a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size, and is being developed for several indications, including reversal of pharmacologically-induced mydriasis (RM), presbyopia and dim light or night vision disturbances (NVD), and has been studied in 9 clinical trials including the recently completed Phase 3 trial in RM and Phase 2 trial in presbyopia. Ocuphire reported positive topline data in March 2021 for MIRA-2, a Phase 3 FDA registration study for treatment of RM. Ocuphire also reported positive top-line data in June 2021 for VEGA-1, a Phase 2 trial for the treatment of presbyopia. Nyxol is also currently in Phase 3 clinical development for NVD. Ocuphire’s second product candidate, APX3330, is an oral tablet designed to inhibit angiogenesis and inflammation pathways relevant to retinal and choroidal vascular diseases, such as diabetic retinopathy (DR) and diabetic macular edema (DME) and has been studied in 11 Phase 1 and 2 trials. APX3330 is currently enrolling subjects in a Phase 2 clinical trial in subjects with DR/DME. As part of its strategy, Ocuphire will continue to explore opportunities to acquire additional ophthalmic assets and to seek strategic partners for late-stage development, regulatory preparation, and commercialization of drugs in key global markets. Please visit www.clinicaltrials.gov to learn more about Ocuphire’s completed Phase 2 trials, recently completed Phase 3 registration trial in RM (NCT04620213), recently completed Phase 2 trial in presbyopia (NCT04675151), ongoing Phase 3 registration trial in NVD (NCT04638660), and Phase 2 trial in DR/DME (NCT04692688). For more information, please 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 expected timing of our future clinical trials in RM, NVD, presbyopia, and DR/DME, and the extent of the Company’s cash runway. 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) the success and timing of commercialization of any 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 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.
Ocuphire Contacts
Mina Sooch, President & CEO
Ocuphire Pharma, Inc.
ir@ocuphire.com
www.ocuphire.com
Corey Davis, Ph.D.
LifeSci Advisors
cdavis@lifesciadvisors.com
Ocuphire Pharma, Inc.
Condensed Consolidated Balance Sheets
(in thousands, except share amounts and par value)
| December 31, | |||||
| 2020 | |||||
| Assets | |||||
| Current assets: | |||||
| Cash and cash equivalents | 22,250 | $ | 16,399 | ||
| Short-term investments | 383 | — | |||
| Prepaids and other assets | 560 | 1,269 | |||
| Total current assets | 23,193 | 17,668 | |||
| Property and equipment, net | 11 | 14 | |||
| Total assets | 23,204 | $ | 17,682 | ||
| Liabilities and stockholders’ equity (deficit) | |||||
| Current liabilities: | |||||
| Accounts payable | 1,434 | $ | 1,214 | ||
| Accrued expenses | 1,204 | 1,971 | |||
| Total current liabilities | 2,638 | 3,185 | |||
| Warrant liabilities | — | 27,964 | |||
| Total liabilities | 2,638 | 31,149 | |||
| Commitments and contingencies | |||||
| Stockholders’ equity (deficit) | |||||
| Preferred stock, par value 0.0001; 10,000,000 shares authorized as of September 30, 2021 and December 31, 2020;<br> no shares issued and outstanding at September 30, 2021 and December 31, 2020. | — | — | |||
| Common stock, par value 0.0001; 75,000,000 shares authorized as of September 30, 2021 and December 31, 2020;<br> 17,295,434 and 10,882,495 shares issued and outstanding at September 30, 2021 and December 31, 2020, respectively. | 2 | 1 | |||
| Additional paid-in-capital | 103,619 | 19,207 | |||
| Accumulated deficit | (83,055 | ) | (32,675 | ) | |
| Total stockholders’ equity (deficit) | 20,566 | (13,467 | ) | ||
| Total liabilities and stockholders’ equity (deficit) | 23,204 | $ | 17,682 |
All values are in US Dollars.
Ocuphire Pharma, Inc.
Condensed Consolidated Statements of Comprehensive Loss
(in thousands, except share and per share amounts)
(unaudited)
| For the Three Months Ended | For the Nine Months Ended | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| September 30, | September 30, | |||||||||||
| 2021 | 2020 | 2021 | 2020 | |||||||||
| Collaborations revenue | $ | 489 | $ | — | $ | 589 | $ | — | ||||
| Operating expenses: | ||||||||||||
| General and administrative | 1,595 | 565 | 6,707 | 1,508 | ||||||||
| Research and development | 3,126 | 1,383 | 10,437 | 2,311 | ||||||||
| Acquired in-process research and development | — | — | — | 2,126 | ||||||||
| Total operating expenses | 4,721 | 1,948 | 17,144 | 5,945 | ||||||||
| Loss from operations | (4,232 | ) | (1,948 | ) | (16,555 | ) | (5,945 | ) | ||||
| Interest expense | — | (179 | ) | — | (1,422 | ) | ||||||
| Fair value change of warrant liability and premium conversion derivatives | — | 879 | (33,829 | ) | 158 | |||||||
| Gain on note extinguishment | — | — | — | 1,260 | ||||||||
| Other income, net | 2 | — | 4 | 9 | ||||||||
| Loss before income taxes | (4,230 | ) | (1,248 | ) | (50,380 | ) | (5,940 | ) | ||||
| Benefit (provision) for income taxes | — | — | — | — | ||||||||
| Net loss | (4,230 | ) | (1,248 | ) | (50,380 | ) | (5,940 | ) | ||||
| Other comprehensive loss, net of tax | — | — | — | — | ||||||||
| Comprehensive loss | $ | (4,230 | ) | $ | (1,248 | ) | $ | (50,380 | ) | $ | (5,940 | ) |
| Net loss per share: | ||||||||||||
| Basic and diluted | $ | (0.25 | ) | $ | (0.33 | ) | $ | (3.64 | ) | $ | (1.61 | ) |
| Number of shares used in per share calculations: | ||||||||||||
| Basic and diluted | 16,925,006 | 3,743,907 | 13,841,067 | 3,678,840 |
Exhibit 99.2
Restore Vision & Clarity Ocuphire Corporate Presentation November 15, 2021 Mina Sooch CEO Exhibit 99.2
2 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 Ocuphire Pharma, Inc.’s (“Ocuphire” or the “Company”) product candidates and future milestones, including the potential for Nyxol to be a “best in class” presbyopia drop. 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) timing or ability for the company to achieve its targeted milestones; (ii) the success and timing of regulatory submissions and pre-clinical and clinical trials; (iii) regulatory requirements or developments; (iv) changes to clinical trial designs and regulatory pathways; (v) changes in capital resource requirements; (vi) risks related to the inability of the Company to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vii) legislative, regulatory, political and economic developments, and (viii) the effects of COVID-19 on clinical programs and business operations. 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 may not be reproduced or provided to any other person (other than your advisor) without our prior written consent. By accepting delivery of this presentation, you agree to the foregoing and agree to return this presentation and any documents related thereto and any copies thereof to us or to destroy the same if you do not make an investment in any securities. The information contain within this presentation shall not, except as hereinafter provided, without the prior written consent of the Company, be disclosed by you or your representatives in any manner whatsoever, in whole or in part, and shall not be used by you or your representatives other than for the purpose of evaluating the transaction described herein. By accepting delivery of this presentation you further acknowledge and agree aware of the restrictions imposed by the United States securities laws on the purchase or sale of securities by any person who has received material, nonpublic information from the issuer of the securities or any affiliate thereof and on the communication of such information to any other person when it is reasonably foreseeable that such other person is likely to purchase or sell such securities in reliance on such information for so long as the information remains material and non- public. 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. November 6, 2020
3 Late Clinical Stage Company Targeting Large, Unmet Ophthalmic Markets Significant Clinical Data andRegulatory Precedents Significant IP Portfolio and Small Molecule CMC Advantages Multiple Near-Term Data Catalysts with Capital Efficient Plan Nyxol eye drops target multiple chronic and acute front of the eye indications addressing large markets: Reversal of Mydriasis (RM), Presbyopia (P) & Dim Light / Night Vision Disturbances (NVD)APX3330 tablets target chronic back of the eye indications: Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME), a leading cause of blindness in diabetic patients Nyxol and APX3330 achieved promising clinical data over multiple Phase 1, 2, and 3 trialsNyxol with > 330 patients treated across 9 trialsAPX3330 with > 340 patients treated across 11 trialsFDA End of Phase 2 meeting guidance for Nyxol (all indications) in May 2020 US and global issued patents thru 2034 for both assets; new 2039 Nyxol patent issued for presbyopiaStable, small-molecule drugsNyxol = single-use, preservative-free eye dropAPX3330 = oral pill Initiated 4 late-stage trials (2 Phase 3, 2 Phase 2) with readouts expected in 2021-2022Reported positive P3 data in RM in 1Q21 with Nyxol NDA submission targeted late 2022Reported positive P2 data in Presbyopia in 2Q21 with plans to advance to P3 in 2022$22 million cash reported at the end of 3Q 2021 sufficient for operations through late 2022Analyst coverage by Cantor, Canaccord, Jones Trading, Alliance Global, Spartan, and Encode Ideas Ocuphire OpportunityA Late-Stage Clinical Ophthalmic Biotech (Nasdaq Symbol: OCUP) Nyxol® APX3330
4 Ocuphire Management TeamDecades of Biotech and Drug Development Experience Mina Sooch, MBA President & CEO and Founder Drey Coleman VP, Clinical Operations Amy Rabourn, CPA VP, Finance Charlie Hoffmann, MBA VP Corporate Developmentand Operations Mitch Brigell, PhDHead, Clinical Developmentand Strategy Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development Ronil Patel, MSSenior Director BD andMarket Strategy Chris Ernst Global Head, QA and Manufacturing Barbara Withers, PhDVP, Clinical and Regulatory Strategy
5 Large Unmet Opportunities for the Aging EyeDeveloping Drugs to Treat Front & Back of the Eye Diseases Source: GlobalData Market Research Report, 2020; Company Estimates for Market Size Front Back Nyxol® APX3330 Reversal of Mydriasis US Market~100M pupil dilations per year in U.S. Opportunity$325M- $1BPresbyopiaU.S. Prevalence: ~120M$9B - $18BNight Vision DisturbancesU.S. Prevalence: ~16M adults$2B - $4B $10+ to $20+B US Markets $4 to $10B US Markets Diabetic RetinopathyU.S. Prevalence:~ 7M US Market Opportunity $3B - $7BDiabetic Macular EdemaU.S. Prevalence: ~750K$1B - $3B
6 Product Candidate Indication Development Stage Anticipated Milestones Pre-clinical Phase 1 Phase 2 Phase 3 Ocuphire-Focused Development 0.75% Nyxol®Eye Drop Reversal of Mydriasis (RM) Positive Data Readout Initiated Phase 3 MIRA-2 trial 4Q20; Topline data reported in 1Q21 (n=185)Initiate Phase 3 MIRA-3 trial 2H21; Data expected in early 2022 (n=330)Initiate Pediatric trial 2H21;Data expected in early 2022 (n=20) 0.75% Nyxol® + Low- Dose 0.4% Pilocarpine Eye Drops Presbyopia (P) Positive Data Readout Initiated Phase 2 VEGA-1 trial 1Q21; Topline data reported in 2Q21 (n=150)Initiate Phase 3 program in 1H22 0.75% Nyxol®Eye Drop Dim Light or Night Vision Disturbances (NVD) Recruiting Initiated Phase 3 LYNX-1 trial 4Q20; Data expected in early 2022 (n=160) APX3330Oral Pill Diabetic Retinopathy (DR)/ Macular Edema (DME) Recruiting Initiated Phase 2 ZETA-1 trial Apr21; Data expected in 2H22 (n=100) Partnering- Focused Development APX2009 Intravitreal DME, Wet Age-Related Macular Degeneration (wAMD) Next steps: IND enabling studies (with partner funding) Ocuphire Pipeline & Upcoming MilestonesMultiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated over the Next Year Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution)
7 11Phase 1 & Phase 2 Trials >340Subjects Dosed Exposure in Humans365Days Patents to2034+ Extensive Development on Both Drug CandidatesWell-Controlled Phase 1, 2, and 3 Clinical Programs with MIRA-2 Data Leading the NDA Path NCE Development Pathway Studied in inflammation/hepatitis & cancer patients 9Phase 1, Phase 2,and Phase 3 Trials 330Subjects Dosed Exposure in Humans28Days Patents to2034+ 505(b)(2) Development Pathway Studied in multiple ocular refractive indications Nyxol APX3330
8 Nyxol® Phentolamine Mesylate Presbyopia RM Reversal of Mydriasis NVD Night Vision Disturbances P
9 Nyxol History & MOARationale for Differentiated Product Profile & 505(b)(2) Path Nyxol’s active ingredient, phentolamine mesylate (PM), is currently approved for 2 indicationsPheochromocytoma (60+ years ago, Regitine®) – intravenous injectionReversal of oral anesthesia (10+ years ago, OraVerse®) – intramuscular injection PM has been reformulated as a topical eye drop (Nyxol)Nyxol is a first-in-class non-selective α1 and α2 blocker product candidateMOA of relaxing the iris dilator muscle (α1)Redness is an on-target α1 effect on sclera vessels (transient, mild) Phentolamine Mesylate Dilates Blood Vessels (Vasodilation)α1: Smooth Muscle Blockade Reduces Pupil Sizeα1: Iris Dilator Blockade
10 Efficacy Data Improving Vision↓ Pupil Size (moderate miotic)↑ Contrast Sensitivity (night)↑ Near Visual Acuity (light/dark)↑ Distance Visual Acuity Safety Data No Systemic EffectsNo Changes in Blood Pressure No Changes in Heart RateTolerated Topical EffectsMild / Transient / Reversible Eye RednessIOP Unchanged or Decreased↓ Intraocular Pressure (IOP) at Normal Baseline Nyxol Product Candidate ProfileNovel Alpha 1/2 Blocker Eye Drop for Refractive Indications (505(b)(2) Pathway) Nyxol: 0.75% Phentolamine Ophthalmic Solution Preservative Free, EDTA Free, and Stable Chronic daily dosing of Nyxol at bedtime demonstratedno significant daytime redness and durability of effects for more than 24 hours
11 Nyxol® Phentolamine Mesylate NVD P Presbyopia RM Reversal of Mydriasis Night Vision Disturbances 0.4% +
12 Reversal of Mydriasis (RM) – Acute TreatmentAnnual Exams and Specialty Visits Involve Dilation to Monitor Eye Health At many annual eye exams and specialty visits, pupils are pharmacologically dilated, impairing vision for 6-24 hoursDilated eyes:heightened sensitivity to lightinability to focusreading, working, and driving are difficulthalos and glare The Problem ~100M eye exams / year in US No Current Commercially Available Treatments RM Source: GlobalData Market Research Report, 2020 I have to stay indoors. They say it only lasts a few hours, but it lasts all day, and it is very annoying.RM Patient, Age 51
13 Before After Reversal of Mydriasis (RM) – Acute TreatmentSingle Use Indication Leveraging a Precedent Approval Pathway Regulatory Precedent with Rev-Eyes (an alpha 1 blocker), approved by the FDA in 1990 but shortly thereafter discontinued (not for safety or efficacy reasons)Clinical Effect to potentially reduce pupil size and counteract the effect of mydriatic drugs (alpha agonists and cholinergic blockers) used to dilate the pupilConvenient and Stable eye drop given at the office that may allow vision to return to normal soonerTolerable with a minimal side effect profile (unlike cholinergic agonists such as pilocarpine) Nyxol’s Potential Differentiated Solution Seeking Treatment Findings Patients likely to request reversal of dilation1 80% Eye care providers likely to use reversal drops2 70% Source: 1.GlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (4-7 on a scale of 1-7) 2.GlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (6-10 on a scale of 0-10) RM
RM MIRA-2 Phase 3 Registration Design Completed Randomized, Double-Masked, Placebo-Controlled, Parallel, One-Day Trial MIRA-2 0.75% NyxolMydriatic Agent A, B, or C 12 USsites168target healthy subjects Nyxol drop(s)(2 drops study eye, 1 drop fellow eye) Mydriasis Time -1 HourPlaceboMydriatic Agent A, B, or C Placebo drop(s)(2 drops study eye, 1 drop fellow eye) TreatmentTime 0 (Max Dilation) Primary: % of subjects (study eye) returning to baseline (within0.2 mm) pupil diameter (PD) at 90 min Secondary:% of subjects returning to baseline at 30min, 1h, 2h, 3h, 4h, 6h, 24h (overall, by mydriatic agent, by iris color)Mean change in pupil diameter from mydriatic max at all timepoints (overall, by mydriatic agent, by iris color)Accommodation (Tropicamide/Paremyd)Safety and tolerability (redness) Endpoints Started and Completed Enrollment in 4Q20 – 185 Subjects Topline Results Expected in 1Q21 Reported in March 2021 Eligibility Screening Randomization 14 Mydriatic Agents 3:1:1 – 2.5% phenylephrine (alpha 1 agonist), 1% tropicamide (cholinergic blocker), Paremyd® (combination) 1:1 RM
15 Primary Endpoint: % of Subjects Study Eye Returning to Baseline PD at 90 Min Source: MIRA-2 Trial, mITT Population (same as Safety Population), *Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd) Nyxol Met the Primary & Secondary Endpoints at 90 Min; Additionally at 60 Min & All Subsequent Timepoints 2% 7% 11% 18% 30% 45% 3%1% 59% 0% 20% 40% 60% 80% 100% 0.5 Percent of Subjects (Study Eye) (%) 1 1.5 2 3 4 6Time Post-Treatment with Nyxol/Placebo (Hours) Placebo n=91 Nyxol n=94 p<0.000190% p<0.000149% p<0.0001 p<0.000180% p<0.000182% p<0.000128% 3 4 5 6 7 8 9 6 Mean Pupil Diameter (Study Eye) (mm) -1 0 0.5 1 1.5 2 3 4Time Post-Treatment with Nyxol/Placebo (Hours) Nyxol n=94 Placebo n=91 Max pupil dilation, Treatment Mydriatic p<0.0001 p<0.0001 p<0.0001 p<0.0001 Nyxol Reduced More Subjects to Baseline Pupil Diameter (PD)% of Subjects Returning to ≤ 0.2 mm of Baseline Nyxol Reduced PD Faster Across All Mydriatic Agents*Mean Pupil Diameter MIRA-2 Phase 3 Trial *Data include all three mydriatics (Phenylephrine, Tropicamide, Paremyd) p<0.0001p<0.0001 RM
16 3 4 5 6 7 8 9 6 24 Pupil Diameter of Study Eye (mm) -1 0 0.5 1 1.5 2 3 4Time Post-Treatment with Nyxol/Placebo (Hours) Tropicamide and Paremyd Nyxol (n=38) Placebo (n=36) 3 4 5 6 7 8 9 3 4 6 24 Pupil Diameter of Study Eye (mm) Time Post-Treatment with Nyxol/Placebo (Hours) Phenylephrine Nyxol n=56 Placebo n=55 Secondary Endpoint: Mean Pupil Diameter Over Time by Mydriatic AgentNyxol Reduced Pupil Diameter With All Mydriatic Agents; More Rapidly with Phenylephrine as Expected Source: mITT Population, MIRA-2 Trial, Standard Error bars are shown. Mydriatic Max pupil dilation, Treatment Max pupil dilation, Treatment Mydriatic MIRA-2 Phase 3 TrialNyxol More Rapidly Reduced PD in Subjects Across All 3 Mydriatic Agents Mean Pupil Diameter RM p<0.0001 p<0.0001p<0.0001-1 0 0.5 1 1.5 2 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001
17 0.5 1 1.5 2 3 4 6 Placebo n=46 7% 4% 11% 15% 22% 35% 41% Nyxol n=49 2% 25% 43% 47% 71% 69% 88% 0% 20% 40% 60% 80% 100% Percent of Subjects (Study Eye) (%) Time Post-Treatment with Nyxol/Placebo (Hours) Placebo n=46 Nyxol n=49 Secondary Endpoint: % of Subjects Returning to Baseline PD by Iris Color Source: MIRA-2 Trial mITT Population,, Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd) Evidence of Efficacy in Subjects with Either Light or Dark Irides, with a More Vigorous Response in Light Irides 0% 20% 40% 60% 80% 100% P 0.5 1 1.5 2 3 4 6 Placebo n=45 0% 0% 2% 7% 13% 24% 49% Nyxol n=45 0% 31% 56% 71% 89% 96% 93% ercent of Subjects (Study Eye) (%) Time Post-Treatment with Nyxol/Placebo (Hours) Placebo n=45 Nyxol n=45 p<0.0001 p<0.0001 p<0.01 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.001 p<0.001p<0.001 p<0.01 p<0.0001 MIRA-2 Phase 3 TrialMore Subjects Returned to PD Baseline with Nyxol in Both Light and Dark IridesPercent of Subjects Returning to ≤ 0.2 mm of Baseline by Iris ColorLight Irides Dark Irides RM
18 Secondary Endpoint: Accommodation And Time Savings Nyxol Demonstrates a Faster Return to Baseline Accommodation and Shorter Dilation Time by 4-5 Hours Source: MIRA-2 CSR table #14.2.3.2.1. PP population is the per protocol population. Percent of Subjects with Unchanged Accommodation from Baseline (Tropicamide or Paremyd) Study Eye, PP population MIRA-2 Phase 3 Trial RM 16% 38% 66% 11% 77% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 2 6 Percent of Subjects (%) Time Post-Treatment with Nyxol/Placebo (Hours)Note: Worsening of accommodation was defined as an amplitude decrease of greater than 1 diopter Placebo (n=32) Nyxol (n=35) * p<0.05 60*% 1.8 2.8 3.6 3.4 1.4 2.9 2.3 6.3 5.1 7.2 7.5 4.8 6.1 5.8 2 3 4 5 6 7 8 Hours 0 1Placebo Nyxol Overall Mydriatic Agent Irides Color Study Eyen=185 Non-Study Eyen=185 Phenylephrinen=97 Tropicamiden=34 Dark Iridesn=81 Light Iridesn=84 Paremydn=34 Average Time to Return to ≤ 0.2 mm of Baseline PD Δt= 3.5 hrs t Δ = 3.2 hrs Δt= 3.4 hrs t Δ = 4.1 hrs t Δ = 3.6 hrs Δt= 2.3 hrs t Δ = 4.5 hrs
19 Summary of Positive MIRA-2 Phase 3 Results for Nyxol Eye Drops Met primary endpoint at 90 minutes with high statistical significance with 2 drops of NyxolMet all key secondary endpoints with high statistical significance Efficacy for all 3 mydriatic agents – phenylephrine, tropicamide, and Paremyd®Efficacy in both light and dark iris colorsEfficacy with only one Nyxol drop in non-study eye Favorable safety profileNo serious AEs, no drop-outs from AEs, no systemic AEs were observed in ≥ 5% of subjectsMild, transient conjunctival hyperemia reported in the first hour and declined steadily thereafter. Baseline mean of 0.7, the mean hyperemia score increased by approximately 1.0 unit on CCLRU scale mITT Population, MIRA-2 Trial Sustained Efficacy with a Favorable Safety Profile in Reversing Mydriasis with Nyxol Complete a second RM Phase 3 trial with increased subjects ~330 to also meet 24-hour safety population exposureComplete RM trial with 20 subjects ages 3 to 11 per pediatric planComplete registration batches with 1-year CMC stability and make commercial batches Path to Registration Submit NDA by Late 2022 Proposed IndicationThe treatment of pharmacologically induced mydriasis produced by adrenergic (e.g. phenylephrine) or parasympatholytic (e.g. tropicamide) agents, or a combination thereof. RM
20 Reversal of Mydriasis (RM) Market OpportunityWith No Commercially Available Treatment, Nyxol May Provide Significant Revenue Potential GlobalData market research reportVision Care Market Grows 2.4 Percent in 12-Months Ending September 2019. Vision Monday, January 20, 2020. 65% PatientsReport moderate to severe negative impact of dilated exams1 $5 - $20Price range surveyed for cash pay per patient with room for physician markup1 $325M - $1B+Estimated US RM Market Opportunity 100M+General and specialty eye exams per year1 Tropicamide Alone 52% Tropicamide and Phenylephrine 18% Phenylephrine Alone 16% Paremyd 9% Cyclopentolate 5% Physician’s Use of Mydriatic Agents1 $6B Eye Exam MarketExams, the third-largest category, grew faster than both prescription lenses and frames Use of phenylephrine, tropicamide, Paremyd®, or combinations of such comprise nearly 95% of dilating eye drops used by eyecare professionals.1 OptoMap: Retinal screening for those wanting to avoid dilations but not a replacement for full dilated eye exam $40-65 paid by patients RM
21 Nyxol® Phentolamine Mesylate NVD P Presbyopia RM Night Vision Disturbances Reversal of Mydriasis 0.4% +
22 2021: The Time for Presbyopia DropsHeadlines From Academia and Industry Articles Thru the Year with an Early First Approval Sources: Academic review articles, journals, and publications “The correction of presbyopia remains ophthalmology’s ‘Holy Grail’…”-OIS 10/29/2021 P
23 Presbyopia – Chronic OpportunityAging Population Drives Demand for Alternatives to Reading Glasses & Very Large Market Lens loses ability to change shape when viewing objects up close as we ageDependence on reading glasses for intermittent and prolonged useGrowing need for therapies that improve, rather than hinder, quality of life Source: GlobalData Market Research Report, 2020 The Problem P 120 MPatients No Currently Approved Drug Therapies Effectively everyone over 40 will have the problems with reading.Physician KOL Seeking Treatment Findings Patients requesting alternative to reading glasses 40% Patients would consider an eye drop alternative 69% ~$9-$18B Market OpportunityMarket Assumptions:Total patients - 120 million patients Price per month - $50+Patients considering eyedrops - ~50% Refills (Months) - 3 to 6
24 Presbyopia – Chronic OpportunityPupil Modulation Eye Drops May Replace Reading Glasses “Pin-hole” effect of Nyxol and low dose pilocarpine may improve near vision by enhancing depth of field as validated by other devices/therapiesMore durable combination of two miotics affecting different muscles (iris dilator and sphincter) involved in pupil size modulationTolerable use with minimal side effects expected with chronic evening use of Nyxol and daytime use of fractional concentration of pilocarpineThis would just become part of my daily routine for my eyes to be able to see things up close. How convenient is that?Presbyopic Patient, Age 49 Retinaeyedoctor.com, GlobalData Market Research Report, 2020 Nyxol’s Potential Differentiated Solution Large Pupil Pin-hole Pupil Near Far In focus In focus P
25 Product Profile: Nyxol ® + Low-Dose Pilocarpine (LDP) Combo Moderate Action on Iris Dilator and Iris Sphincter Muscles for Near Vision Improvement 0.4% 0.75%Nyxol 0.4% LDP Iris Dilator Muscle Inhibition Iris Sphincter Muscle Activation Phentolamine (alpha1/2 antagonist) approved non- ocular injectable indications decade(s) ago 505(b)(2)Novel MOA on iris dilator with 24+ hour durabilityModerate 1+mm pupil reductionNo daytime redness w/ chronic evening dosing NyxolWell-tolerated with no systemic effectsStable, preservative-free, single use vial Pilocarpine (cholinergic agonist) approved decades agoKnown MOA on sphincter muscle with potent miotic effects at approved doses (1%, 2%, 4%)Chronic daytime dosing of LDPLow concentration avoids known tolerability issues:headache and browacherednessaccommodative spasm causing loss of distance vision especially at night Source: 1) Nyxol® data from 8 completed trials; Pilocarpine Product label and Literature 1.5 to 2.5 mm PD reduction moves toward the pin-hole (2 to 2.5 mm, up to 3 mm) Daytime drop Evening drop P
26 Presbyopia VEGA-1 Phase 2 DesignRandomized, Double-Masked, Placebo-Controlled, Multi-Center One-Week Trial Clinical trial NCT#04675151. DCNVA = distance-corrected near visual acuity . BCDVA = best corrected distance visual acuity Endpoints Primary: % of subjects with ≥ 3 lines of improvement in distance- corrected near visual acuity comparing Nyxol + LDP vs placebo alone at 1 hourSecondary:% of subjects with ≥ 2 and ≥ 3 lines gained at time points from 30 min to 6 hours in photopic lighting comparing Nyxol + LDP vs placebo, Nyxol alone, and LDP aloneNo loss of distance visionPupil diameter at time pointsSafety and tolerability (redness) Visit 1 VEGA-1 Randomization 4 arms 0.75% Nyxol Placebo 17 US sites150presbyopic patients Visit 2(3 – 6 Days Later) Treatment Arms Nyxol + LDP LDP Drop Nyxol Baseline Nyxol Alone No Treatment Nyxol Baseline LDP Alone LDP Drop Placebo Baseline Placebo Alone No Treatment Placebo BaselineScreening Evening Dosing (3-4 doses) Males or females ≥ 40 and ≤ 64 years of ageBCDVA of 0.0 LogMAR(20/20 Snellen equivalent) or better in each eye under photopic conditionsDCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse in photopic conditions in each eye & binocularly Eligibility Criteria P Phase 2 Enrollment Completed Feb to May 2021 – 150 SubjectsReported Topline Results End of 2Q21
27 79% 90%80%70%60%50%40%30%20%10%0% Percent of Subjects (%) Secondary Endpoint: Percent of Subjects with ≥ 10 Letters DCNVA Improvement from Baseline Binocular (PP Population) 1Time (Hours)Placebo (n=43) Nyxol+LDP (n=43) Primary Endpoint: % of Subjects ≥ 15 Letter Gain in Photopic DCNVA at 1 HourPrimary Endpoint Was Significantly Met for Nyxol + LDP Gaining ≥ 15 Letters Near Vision VEGA-1 Phase 2 Trial 61% 28% 90%80%70%60%50%40%30%20%10%0% Percent of Subjetcts (%) Primary Endpoint: Percent of Subjects with ≥ 15 Letters DCNVA Improvement from Baseline Binocular (PP Population) 1Time (Hours)Placebo (n=43) Nyxol+LDP (n=43) p=0.003 33%Placebo Adjusted Responders p=0.006 49% 30% PlaceboAdjusted Responder s Source: VEGA-1 TLR Table 14.2.1.2 %of Subjects With Improvement From Baseline in Photopic DCNVA by Time Point (PP Population). 15 letters is 3 lines and 10 letters is 2 lines. Note: PP population differs from mITT by only one subject; results were essentially identical. P
28 Efficacy Endpoints: % of Subjects ≥ 15 Letter DCNVA Gain Across TimepointsNyxol + LDP had Strong Response with ≥ 15 Letter Near Gain from 30 Minutes to 6 Hours Source: VEGA-1 TLR Table 14.2.1.2 Percent of Subjects with Improvement From Baseline in Photopic DCNVA by Time Point (PP Population). 15 letters is 3 lines. Percent of Subjects (%) VEGA-1 Phase 2 Trial Percent of Subjects with ≥ 15 Letters Binocular Photopic DCNVA Improvement from Baseline70% p=<0.0001 Durable benefitp=<0.0001 p=0.003 63% over 6 hours61% 61%60%Nyxol alone effect(~12 hr data) p=0.02 p=0.0250% 47% 47%p=0.0640% p=0.09 37%33%30% 28%21% 21% 19%20% 16% 14% 16%10%0%0 0.5 1 2 3 4 6Primary EndpointRapid onset Time (Hours)of efficacy Placebo (n=43) Nyxol+LDP (n=43) P
29 2nd Endpoint: % of Subjects ≥ 15 Letter Gain In Near & < 5 Letter Loss In Distance Source: VEGA-1 TLR Table 14.2.2.2 Percent of Subjects with >= 15 Letters of Improvement in Photopic DCNVA and < 5 Letters of Loss in Photopic Binocular BCDVA by Time Point (PP Population) Phase 3 Approval Endpoint Confirmed Greater Efficacy of Combo over Components at Multiple Timepoints 14% 14% 61% 61% 63% 33% 26% 42% 10%0% 20% 30% 40% 50% 60% 70% 0.5 1 2 Percent of Subjects (%) Percent of Subjects with 15 Letter Improvement in DCNVA and < 5 Letter Loss in BCDVA Binocular Placebo (n=43) Time (Hours)Nyxol+LDP (n=43) Nyxol (n=30) LDP (n=31) p=<0.0001 p=0.03 p=0.0130% p=0.008 p=0.00428% p=0.06 39% p=<0.0001 p=0.2 p=0.000920% Statistics Compared to Nyxol+LDP arm Powered for comparison to placebo whereas comparison to component arms were designed to inform the Phase 3 sample size VEGA-1 Phase 2 Trial P Even with a small sample size, combination arm provided statistically meaningful results at 30 min and 2 hours vs. LDP and Nyxol alone arms
30 Secondary Endpoint: Mean Pupil Diameter Over Time Source: VEGA-1 TLR Table 14.2.12.1 Observed Values and Change from Baseline in Photopic Pupil Diameter by Time Point (PP Population) 4.3 4.5 4.4 4.3 4.2 3.2 2.4 2.1 2.3 2.5 2.7 2.9 4.8 3.1 3.2 3.2 3.4 3.3 3.3 4.4 4.3 3.0 2.5 2.7 3.1 3.3 1.0 2.0 3.0 4.0 5.0 -1 0 1 2 3 4 5 6 Mean
Pupil Diameter \(mm\) Best Eye Mean Pupil Diameter Time \(Hours\)Placebo \(n=43\) Nyxol+LDP \(n=43\) Nyxol \(n=30\) LDP \(n=31\) \*\*\* 4.5 \*\*\* \*\*\* \*\*\*\*\*\* \*\*\* \*\*\* \*\* \*\*\* \*\*\* \*\* \*\*\* 4.4 \*\*\* 4.4 \*\*\* 3.3\*\*\* \*\*\* 4.6 \*\* \*\*\* 3.6 Daily
Evening Nyxol Dosing 12 hr minimum interval to Time 0 Baseline \*\*\*\*\*\* Nyxol+LDP arm statistically significant compared to all arms \*\*p<0.01\*\*\*p<0.0001 Achieved Pupil Size ~2mm in Nyxol+LDP Consistent with 3-line
Improvement in Near VisionVEGA-1 Phase 2 Trial P
31 Secondary Endpoint: Safety FindingsNyxol + LDP Combination Was Well Tolerated with a Favorable Safety Profile Source: VEGA-1 Study Results (Safety Population, n=150); Only a single subject difference between mITT (n=148) and PP population (n=147) No serious AEs, almost all AEs were mild0% headaches or brow aches reported for Nyxol+LDP arm ≤ 5% mild, transient conjunctival hyperemia AEs in Nyxol+LDP armNo change in distance vision for Nyxol + LDP arm0% had ≤ 5 letter distance loss in photopic lightingOnly 5% distance loss in mesopic lightingNo change in IOP Conjunctival Hyperemia CCLRU Scale Nyxol + LDP and LDP aloneOnly transient 0.5 point mean increase P
32 Product Attributes* Nyxol+LDP compared to VUITYTM Efficacy (all time-points) ✓+ Safety: Maintain Distance Vision (especially at night) ✓+ Safety: Tolerability (no headaches) ✓+ Durability (at least 6 hours) ✓+ Fast Onset (within 30 mins) ✓+ Convenience (daily drops) ✓ Tunable Pupil Modulation ✓+ ASCRS (July 2021) Abstract# 76645 (Phase 2) and 74336 (Phase 3) and VUITYTM Label✓+- Indicates better compared to Vuity- Indicates comparable to Allergan/AbbVie based on Phase 3 BID dosing (NCT04983589) Potential ‘Best in Class’ Presbyopia DropNyxol+LDP Combination Data Outperforms in Efficacy, Safety, Durability and Onset P Nyxol’s Potential Differentiated Solution
33 Presbyopia Eye Drops Competitive Landscape Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020 Validation of Pupil Modulating Drops Achieving Pin-Hole Effect & Efficacy, Many with Pilocarpine Pupil modulation MOA Combination drugs Soften lens MOA Phase 3 Phase 2 Phase 1 Allergan (VUITYTM;1.25% pilo) Orasis (CSF-1;Low dose pilo) Ocuphire (0.75% Nyxol+ 0.4% pilo) carbachol) Other Cholinergic Agonists*Visus (Brimochol®; brimonidine + Cholinergic Agonist* (pilocarpine) Lenz (PRX-100;aceclidine) Eyenovia (MicroLine; 1 or 2% pilo) Novartis (EV-06) Alpha Antagonist & pilocarpine* P NDA *act on sphincter and ciliary muscles in dose- dependent manner Ocuphire is differentiated by using both the dilator and sphincter muscles moderately to reach a pin-hole pupil size Next Steps: Advance into Phase 3 Presbyopia Registration Trials in 1H 2022 Towards a Potential NDA Filing in 2023
34 Nyxol® Phentolamine Mesylate NVD P Presbyopia RM Night Vision Disturbances Reversal of Mydriasis 0.4% +
35 Moderate-to-Severe NVDs US Patients Night Myopia 10.8M Cortical Cataracts 4.1M Post-LASIK 500k Post-IOL Implant 300k Total ~16M Night Vision Disturbances (NVD) – Chronic OpportunityImperfections in the Eye Affect Night Vision in Millions Peripheral imperfections scatter light when pupils enlarge in dim light, causing halos, starbursts, and glare that impair visionThe imperfections may be caused by LASIK surgery, IOL implants, certain types of cataracts (cortical), and natural reasons (especially with age)Symptoms cannot be properly corrected by any type of lens (reading glasses, contact lenses) or surgical procedures Source: GlobalData Market Research Report, 2020 The Problem No Currently Approved Therapies NVD I’m no longer comfortable driving at night, especially with my son in the car. I have a hard time playing beach volleyball in the evenings due to the bright lights at the courts.Post-LASIK, Age 42
36 Night Vision Disturbances (NVD) – Chronic OpportunityPeripheral Optical Imperfections Allowing Pupil Modulation as a Solution Moderate Decrease in Pupil Size for scattered light gets blocked by the irisClinical Effect to potentially improve low contrast night vision as seen in trialsTolerable with a minimal side effect profileConvenient and Durable with chronic once-daily evening dose Nyxol’s Potential Differentiated Solution After Before Once there is a drug and a category, that’s when they start looking for the disease.Physician KOL Seeking Treatment Findings Patients willing to try a new eye drop treatment 67% Patients avoiding driving at night 25% NVD
37 NVD LYNX-1 Phase 3 Registration DesignOngoing Randomized, Double-Masked, Placebo-Controlled Two-Week Trial LYNX-1 Endpoints Primary: % of subjects with≥ 3 lines of improvement in mesopic low contrast best- corrected distance visual acuity (Day 8)Secondary (Days 8 & 15):Pupil diameterVisual acuity measures (distance and near)Safety and tolerability (redness) Eligibility Screening Randomization 1:1 0.75% Nyxoldaily evening dose (14 days) daily evening dose (14 days) Placebo 20 US sites~160 patients with NVD Phase 3 Initiated in Late 4Q20 Top Line Expected Early 2022 NVD
38 -0.07-2% -0.05-0.5% -0.11-1% -0.99-20% -1.00-21% -0.88-19% -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 Day
8 Day 15 Day 16 Pupil Diameter Change from Baseline ANCOVA \(mm and %\) Placebo \(n = 20\) 14-day Daily Evening Dosing, Last Dose on Day 14 ORION-1 Phase 2 Trial Nyxol Demonstrated Clinical Effect in NVDKey Endpoints Observed
in Multiple Phase 2 Trials Source: NYXG-201 Durable > 24-hour Pupil Modulation EffectPupil Diameter Change from Baseline in Mesopic Conditions \(Study Eye\)Baseline Pupil Diameter: Placebo 4.6mm, Nyxol 4.7mm Percent of Subject
Eyes NYX-SNV Phase 2 Trial Improved Low Contrast Distance Visual Acuity\*% of Eyes with Mesopic Low Contrast Visual Acuity Improvement80% p=0.02969% Placebo n=16Nyxol n=3260%p=0.0440% 34%31% p=0.1619%20%6%0%0%≥ 1 line ≥ 2 lines ≥ 3
linesSource NYX-SNV \*NYX-SNV trial was small and not designed for a statistical 3-line improvement in low-contrast visual acuity; the ~20% effect was used for powering and sizing of Phase 3 trial p = 0.0002 1% Nyxol \(n = 19\)p =
0.0001 p = 0.0004 NVD
39 APX3330 APX3330 DR Diabetic Retinopathy DME Diabetic Macular Edema wAMD Wet Age-Related Macular Degeneration
40 Large, Unmet Need in Diabetic Eye Diseases (US) DR ~7.7M Patients DME ~750K Patients Diabetic Retinopathy & Macular EdemaNon-Injectable Alternative Therapies are Needed For Earlier Stages of Disease Diabetic retinopathy (DR) and diabetic macular edema (DME) are a leading cause of vision loss worldwideDiabetes damages small blood vessels within the eye causing leakage, oxygen starvation, and abnormal vessel growthDR patients are not routinely treated with approved injectable anti-VEGF drugsDR progresses resulting in vision lossCurrent treatment for DME are not satisfactory25% non-responders50% partial responders to anti-VEGF drugs Sources: Global Market Insights Report 2019-2025, Market Watch 2019 Report, Gene.com Retinal Diseases Fact Sheet The Problem Limited Retina Treatment Options for Diabetics DR DME DR DME
41 APX3330 History and Ref-1 Inhibition MechanismRef-1 Involved in Multiple Key Pathways that Contribute to Diabetic Retinopathy 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-αChemokines Neovascularization Lucentis® EYLEA® Anti-VEGF Steroids APX3330 Logsdon et al (2018), Li et al (2014). Ref-1 (reduction-oxidation effector factor-1) is a novel target discovered by Dr. Mark R. Kelley at Indiana University School of MedicineAPX3330 is a small molecule oral drug candidate and a first-in-class inhibitor of Ref-1APX3330 previously developed by Eisai for multiple hepatic inflammatory indications and later by Apexian for advanced solid tumors– Similar oncology origin as approved anti-VEGFsMOA uniquely decreases both abnormal angiogenesis and inflammation by blocking pathways downstream of Ref-1 DR DME
42 APX3330 Down-Regulates VEGF Protein and Anti-Inflammatory Cytokines In Vivo and In Vitro Evidence of APX Dual Pathway Mechanism of Action Treatment of APX3330 (10mg/kg, oral gavage) in rats with type 1 diabetes and induced stroke shows a significant decrease of VEGF signaling.Increased VEGF is a hallmark of uncontrolled neovascularization and inflammation in diabetic retinopathies; current approved treatments successfully decrease VEGF levels in the eye. Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315 In vitro APX3330 suppresses pro-inflammatory cytokines in LPS stimulated murine macrophage cell lines known to be involved in macular degeneration: TNF-α is a potent cytokine that enhances secretion of VEGF-A and VEGF-B by human choroidal fibroblast cells. J Cell Physiol. 2011Genetic ablation of IL-6 led to significant suppression of AMD (murine CNV model). Am J Pathol. 2007 APX3330 Reduces VEGF Protein in the Brain of Preclinical Models APX3330 Reduces Pro-inflammatory Cytokinesin Murine Cell Lines Involved in Macular Degeneration DR DME
43 Preclinical Data: Oral APX3330 Blocks NeovascularizationLesion Volume Decrease with Oral APX3330 in Murine Laser CNV Model Similar to EYLEA® Data Silva et al. Oral APX3330 treatment reduces L-CNV lesions in preclinical mouse model and confirms Phase 2 DR/DME clinical dose with sufficient distribution to human retina using PBPK modeling. Presented at the ARVO 2021 Annual MeetingPublished data on EYLEA -44% EYLEA L-CNV Mouse Retina Model APX3330Lesion Size and Corresponding Fluorescent Stains in L-CNV Models Treated with APX3330 at 25 mg/kg oral gavageVehicle 25 mg/kg 50 mg/kg APX3330 Gavage OCTLesion Volume-55%Silva et al, 2021 L-CNV Mouse Retina Model DR DME
44 Apexian preclinical dataEisai preclinical dataSilva et al. Oral APX3330 treatment reduces L-CNV lesions in preclinical mouse model and confirms Phase 2 DR/DME clinical dose with sufficient distribution to human retina using PBPK modeling. Presented at the ARVO 2021 Annual Meeting Phase 1 PK Clinical Data Human Drug Exposure Multiple Times Higher than Mouse Efficacious LevelsHuman Pharmacokinetics of APX3330 at 120 mg/dayHuman 120 mg/dayMice 25 mg/kgSource: Eisai/Apexian Human PK data Human Mouse Rat 10 mg/kg APX3330 oral gavage measured in rat eye2 300 mg BID (600 mg/day total)Established PBPK model predicts APX3330 reaches sufficient human retinal concentrations3 25 mg/kg APX3330 oral gavage measured in mouse retina1 Phase 1/2 Clinical Trials: PK Data Supporting the ZETA-1 TrialAPX3330 is Bioavailable and Reaches the Retina via Oral Administration Does oral administration of APX3330 reach the retina in sufficient concentration? DR DME
45 APX3330 Product Candidate Profile for Multiple Retinal IndicationsFirst-in-Class Ref-1 Inhibitor with Favorable Human Safety Data for Retinal Indications Expected Efficacy Data Improving Eye Health in Diabetics↓ Inflammation↓ Abnormal AngiogenesisEnhance Compliance & ExposureOral pill may reduce the burden of frequent anti-VEGF injections Safety Data Few Systemic Adverse Effects< 5% Mild Gastrointestinal (diarrhea)< 5% Mild Skin Rash (reversible)Lack of Significant Acute Neurologic, Cardiovascular, Liver, or Pulmonary toxicityNo Ocular EffectsNo observed ocular AEs APX3330: Well-tolerated Oral Dose up to 600mg/day Twice a day dosing of APX3330 being developed to provide steady state effectiveness with a tolerable chronic safety profile DR DME
46 DR/DME ZETA-1 Phase 2b DesignOngoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar to Eylea Pivotal P3 DR Trial) NPDR = non-proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema) PDR = proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema) ZETA-1 Eligibility Screening Randomization 1:1 APX3330 600mgTwice daily oral dose (24 weeks) Twice daily oral dose (24 weeks) Placebo 20 US sites~100 patients with moderate- to-severe NPDR and mild PDR Primary: % of subjects with a ≥2 step improvement on the DRSS (DiabeticRetinopathy Severity Scale) score at week 24Secondary:Central subfield thickness (CST)BCDVA (ETDRS)DRSS change at week 12Rescue subjectsSafety and tolerabilityExploratory:Labs / PK Endpoints Phase 2b Start Initiated in April 2021 Top Line Expected in 2H22 DR DME
47 Innovative Approach for Retinal Diseases with APX PlatformAPX3330 May Treat Patients Across the Spectrum of Retinal Diseases Potential First Oral Rx for Retina DiseasesFirst-line earlier intervention for the diabetic eyeAdd-on therapy to current anti-VEGF treatmentsProven Novel MechanismMay decrease both inflammation and angiogenesisConvenient Daily RegimentFavorable Oral Safety ProfileAs seen in 11 completed Phase 1 and Phase 2 clinical trialsImprove Patient CompliancePotentially alleviate the frequent burden of injections Potential Differentiated Solution DR DME Wet AMD Dry AMD RVO GA APX3330 Current anti-VEGF treatments APX2009 APX2014 APX3330(Local Delivery) DR DME
48 Boards and Milestones
49 Ed Holland, MDLoyola University Chicago Jay Pepose, MD, PhD UCLA Thomas Samuelson, MD University of Minnesota Paul Karpecki, OD Indiana University Eliot Lazar, MDGeorgetown University Marguerite McDonald, MD Columbia University David Boyer, MD Chicago Medical School Gerald Horn, MD University of IllinoisCo-Founder Ocularis/Nyxol Past MAB Member Mark Kelley, PhD Indiana UniversityCo-Founder Apexian/APX3330 Ocuphire's World-Class Medical Advisory BoardFortunate for the Insights of Leading KOLs & Drug Candidate Co-Founders elCON Medical Michael Allingham, MD, PhD University of North Carolina Peter Kaiser, MD Harvard Medical School Jeffrey Heier, MD Boston University Y. Ralph Chu, MD Northwestern University Douglas Devries, OD University of Nevada David Brown, MD Baylor University Richard Lindstrom, MD University of Minnesota
50 Ocuphire Board of DirectorsSeasoned Directors with Decades of Drug Development, M&A/Financings, and Ophthalmology Sean Ainsworth, MBALead Independent Director,Board Director James Manuso, PhD/MBABoard Director Jay Pepose, MD, PhDBoard Director Richard Rodgers, MBABoard Director Susan Benton, MBABoard Director Cam Gallagher, MBAChair, Board Director Mina Sooch, MBA Vice-Chair, Board DirectorPresident & CEO
51 2021 to 2022 Ocuphire Cadence of MilestonesMultiple Data Catalysts On Path To NDA(s) Ongoing Partnering Discussions with Leading Ophthalmic Companies (including European and Asian Players) 2021 2022 Report Phase 3 Data for NVD Report 2nd Phase 3 Data for RM Report Pediatric Data in RM Submit Nyxol NDA for RM Report Phase 2 Data for DR/DME Initiate Two Phase 3 Presbyopia Trials Report Positive Phase 3 Data for RM (MIRA-2) Report Positive Phase 2 Data for Presbyopia (VEGA-1) New Patent Claims for Presbyopia ASCRS 2021 Presentation for MIRA-2 & VEGA-1 Manufacture 3xRegistration Batches for Nyxol Blow-Fill-Seal (BFS) Eye Drops Initiate 2nd Phase 3 RM and Pediatric RM trial Initiate Phase 3 Chronic Safety Trial Early 2022
52 Recent FDA Ophthalmology Drug ApprovalsFDA Record Number of Drugs Approved for Front and Back of the Eye in 2021 Source: Company websites, 2020 10K annual reports, Q2 2021 quarterly reports Company Drug Indication Date Status Cyclosporine Topical Opthalmic Emulision Severe Vernal Keratoconjunctivits June 2021 New Product Approval OC-01 Nasal Spray Dry Eye Disease October 2021 New Product Approval DextenzTM Ocular Itching Associated with Allergic Conjunctivitis October 2021 sNDAApproved XipereTM Macular Edema associated with Uveitis October 2021 New Product Approval MydCombiTM Fixed combination mydriatic microdose system October 2021 CRL, now drug/device classifcaiton SusvimoTM Wet-AMD October 2021 New Product Approval Vuity TM Presbyopia October 2021(10-29-21) Approved Two months inadvance
53 OCUP – Market SnapshotSufficient Cash Runway Through 2022 Source: FactSet Ticker OCUP Price $4.02 Close on 11-1-21 Market Cap ~$70 M As of 11-1-21 Common Shares Outstanding 17.3 M As of 9-30-21 Cash $22.2 M As of 9-30-21 Cash Runway Sufficient through 2022 Guidance as of 9-30-21 Average Daily Volume ~200 K As of 11-1-21 Short Interest ~445K; <3% of Float As of 11-1-21 Research Analyst - Institutional Coverage on OCUP James Molloy Alliance Global Partners John Newman Canaccord Genuity Kristen Kluska Cantor Fitzgerald Prakhar Agrawal Jones Trading
Restore Vision & Clarity www.ocuphire.com ir@ocuphire.com
55 Appendix
56 NVD Endpoint: 5% Low Contrast Visual Acuity (LCVA) ChartFDA Accepted Endpoint for Contrast Sensitivity Assessment Precision Vision Before Treatment* 3 Lines Improvement Illustration Primary Endpoint of Nyxol LYNX-1 TrialPercent of subjects with ≥ 3 lines of improvement in mesopic low contrast best-corrected distance visual acuity(7 days) * Inclusion Criteria includes subjects with baseline mesopic LCVA of 20/100 or worse
57 DRSSScore 1(10) 2(20) 3(35) 4(43) 5, 6(47, 53) 7 – 13 (60 , 61, 65, 71, 75,85,90) Description DR Absent Micro- aneurysm only Mild NPDR Moderate NPDR Moderately Severe NPDR PMod DR – Mild, erate, and Severe Retinal Image Healthy blood vessels with no bulges Small bulges in blood vessel walls as well as other signs in the retina More changes in the blood vessels in the retina and small spots of blood can become more visible More blood vessels in larger areas of the retina show changes Many of the blood vessels in the retina show visible changes Incr of n bl eased growth ew, damaged ood vessels DR/DME Endpoint: Diabetic Retinopathy Severity Scale (DRSS)FDA Accepted Endpoint for DR (EYLEA® in PANORAMA Pivotal Trial) EYLEA Product Pamphlet ® Patientsincluded in the ZETA-1 Trial Primary Endpoint of APX3330ZETA-1 TrialPercent of patients with a ≥ 2 step improvement on the DRSS score at week 24 A 13-point Scale Outlining the Various Stages of Diabetic Retinopathy