APX3330

Acquisition creates a leading, clinical-stage company focused on the development of gene therapy treatments for rare inherited retinal degenerations New OPGx-LCA5 Phase 1/2 6-month data demonstrate safety and visual improvement in early onset retinal degeneration Additional clinical data in LCA5 pediatric patients and BEST1 patients is expected in 2H 2025 LYNX-2 Phase 3 trial of Phentolamine Ophthalmic Solution 0.75% in patients with dim light disturbances remains on track for top-line data in Q1 2025 VEGA-3 Phase 3 trial of Phentolamine Ophthalmic Solution 0.75% in presbyopia remains on track for top-line data in H1 2025 Company will seek a strategic partner to continue development of APX3330, an oral small-molecule inhibitor of Ref-1 for the treatment of non-proliferative diabetic retinopathy Projected cash runway extended into 2026 Conference call to discuss the acquisition to take place at 4:30 p.m. ET today FARMINGTON HILLS, Mich., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of patients with retinal and refractive eye disorders, today announced the all-stock acquisition of Opus Genetics, Inc., a clinical-stage gene therapy company for inherited retinal diseases (IRDs). The merger creates a transformative biotech company committed to being a leader in the development of gene therapies for the treatment of IRDs. In connection with the merger, the combined company will be renamed Opus Genetics, Inc., effective October 23, 2024, and will trade on Nasdaq under the ticker symbol “IRD” effective October 24, 2024. “Opus Genetics has created a compelling pipeline of transformative therapies for patients with inherited retinal diseases, with promising early data. This is an opportunity to advance these treatments quickly, with four major clinical milestones on the horizon in 2025 for the combined company,” said George Magrath, M.D., who will continue to serve as CEO of the combined company. “We are encouraged by the new LCA5 six-month proof-of-concept data showing visual improvement in three out of three patients with advanced disease and are excited to bring together a leadership team with deep expertise in the development of potentially groundbreaking gene therapies. We look forward to continuing our progress, creating value, and improving patient outcomes together.” Ben Yerxa, Ph.D., former President and CEO of Opus Genetics and President of the newly combined company, added, “With the Ocuphire team’s late-stage ophthalmic drug development and regulatory approval experience and resources, we believe we are well-positioned to accelerate our pipeline of potentially transformative gene therapies for inherited retinal diseases. We see this transaction as a win for patients with IRDs around the world, and we look forward to efficiently progressing our combined pipeline.” The combined company now has an expanded pipeline that includes multiple compelling assets from its adeno-associated virus (AAV)-based gene therapy portfolio, which is currently being developed for IRDs, as well as Phentolamine Ophthalmic Solution 0.75%, which is currently being evaluated in presbyopia and dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery. Due to the capital requirements and developmental timelines of APX3330, an oral small-molecule inhibitor of Ref-1 for the treatment of non-proliferative diabetic retinopathy, the company will seek a strategic partner to advance the clinical development of the late-stage diabetic retinopathy program and will redirect its existing resources towards the acquired gene therapy programs. The most advanced gene therapy candidate, OPGx-LCA5, is being developed to treat LCA5, an early-onset retinal degeneration, and an open-label, dose-escalation Phase 1/2 clinical trial is ongoing. The trial has shown early clinical proof-of-concept, with new six-month data demonstrating visual improvement in three out of three adult patients participating in the trial, each of whom has late-stage disease. Jean Bennett, M.D., Ph.D., scientific co-founder of Opus Genetics, commented, “This level of efficacy in patients with late-stage disease is exciting and supportive of the potential for a one-time treatment with OPGx-LCA5, which could have a transformative impact on individuals who have experienced devastating vision loss and for whom no alternative treatment options exist.” Enrollment of the first pediatric patients in the Phase 1/2 trial is expected in the first quarter of 2025, with the first data anticipated in the third quarter of 2025. As the program has received Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA), OPGx-LCA5 will be eligible to receive a priority review voucher upon biologics license application (BLA) approval. Dr. Bennett, Dr. Yerxa and Adrienne Graves, Ph.D., each of whom has served on the Board of Directors of Opus Genetics prior to the transaction, will join the Board of Directors of the combined company. Dr. Bennett is the scientific co-founder of Opus Genetics and former scientific founder of Spark Therapeutics. She was one of the first investigators to use viral vectors to deliver transgenes to specific cells in the retina and led the first team to demonstrate proof-of-principle of ocular gene therapy. Dr. Yerxa co-founded Opus Genetics and was the former CEO of the Foundation Fighting Blindness and oversaw the establishment of the Foundation Fighting Blindness’ Retinal Degeneration (RD) Fund. He has more than 30 years’ experience in biotechnology and ophthalmic drug development, translating promising research discoveries into clinical milestones and treatments. Dr. Graves is the former CEO of Santen Inc., and former chair of Iveric Bio, and currently serves as board chair for the RD Fund. The expected cash runway of the combined company has been extended into 2026, during which period the company anticipates clinical data readouts for pediatric patients in the OPGx-LCA5 Phase 1/2 trial, the initial patients of the OPGx-BEST1 Phase 1/2 trial, the LYNX-2 Phase 3 trial, and the VEGA-3 Phase 3 trial. The LYNX-2 Phase 3 trial in patients with decreased visual acuity under low light conditions following keratorefractive surgery and the VEGA-3 Phase 3 trial for presbyopia are actively enrolling, with top-line data expected in the first quarter and first half of 2025, respectively. Terms of the Acquisition In connection with the acquisition, Ocuphire issued 5.2 million shares of its common stock and 14.1 thousand shares of its convertible preferred stock to existing stockholders of Opus Genetics. The shares of convertible preferred stock will be convertible into shares of common stock, subject to stockholder approval at the company’s annual meeting of stockholders, to be held in April 2025. Following the issuances, pre-acquisition stockholders of Ocuphire will own approximately 58% of the combined company’s fully diluted capitalization, and pre-acquisition stockholders of Opus Genetics will own approximately 42% of the combined company’s fully diluted capitalization. Leerink Partners is serving as exclusive financial advisor to Ocuphire. Sidley Austin LLP is serving as legal counsel to Ocuphire. Smith Anderson is serving as legal counsel to Opus Genetics. Investor Conference Call Management will host a conference call and webcast with slides at 4:30 p.m. ET today to discuss the acquisition. Dial-in details are as follows: Investors dial 1-877-407-0792 International investors dial 1-201-689-8263 Conference ID 13749219 Call me™: Participants can use Guest dial-in #s above and be answered by an operator OR click the Call me™ link for instant telephone access to the event. The Call me™ link will be made active 15 minutes prior to scheduled start time. CALL ME LINK Webcast link: CLICK HERE An archive of the call will be available on the company’s corporate website for 90 days following the call. About the Company The company is a clinical-stage ophthalmic biopharmaceutical company developing therapies to treat patients with inherited retinal diseases (IRDs) and therapies to treat patients with other retinal and refractive disorders. The pipeline includes adeno-associated virus (AAV)-based gene therapies that address mutations in genes that cause different forms of bestrophinopathy, Leber congenital amaurosis (LCA) and retinitis pigmentosa. The company’s most advanced gene therapy program is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein and is currently being evaluated in a Phase 1/2 open-label, dose-escalation trial, with encouraging early data. The pipeline also includes Phentolamine Ophthalmic Solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist to reduce pupil size, and APX3330, a novel small-molecule inhibitor of Ref-1 to slow the progression of non-proliferative diabetic retinopathy. Phentolamine Ophthalmic Solution 0.75% is currently being evaluated in Phase 3 trials for presbyopia and dim (mesopic) light vision disturbances. Forward-Looking Statements This press release 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 expectations regarding our cash runway, data from and future enrollment for our clinical trials, our pipeline of additional indications, expectations of potential growth, and our expectations regarding integration following the acquisition of Opus Genetics, including with respect to the combination of their portfolio of clinical assets into our existing portfolio and our combined focus on gene therapy treatment. These forward-looking statements relate to us, our business prospects and our results of operations and are subject to certain risks and uncertainties posed by many factors and events that could cause our actual business, prospects and results of operations to differ materially from those anticipated by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those described under the heading “Risk Factors” included in Ocuphire’s Annual Report on Form 10-K. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “aim,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. We undertake no obligation to revise any forward-looking statements in order to reflect events or circumstances that might subsequently arise. These forward-looking statements are based upon our 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: The success and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; Regulatory requirements or developments; Changes to or unanticipated events in connection with clinical trial designs and regulatory pathways; Delays or difficulties in the enrollment of patients in clinical trials; Substantial competition and rapid technological change; Our development of sales and marketing infrastructure; Future revenue losses and profitability; Our relatively short operating history; Changes in capital resource requirements; Risks related to our inability to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; Domestic and worldwide legislative, regulatory, political and economic developments; Employee misconduct; Changes in market opportunities and acceptance; Reliance on third parties; Future, potential product liability and securities litigation; System failures, unplanned events, or cyber incidents; The substantial number of shares subject to potential issuance associated with our equity line of credit arrangement; Risks that our partnership or other licensing arrangements, may not facilitate the commercialization or market acceptance of our product candidates; Future fluctuations in the market price of our common stock; Our ability to realize the expected benefits of the acquisition of Opus Genetics; Our ability to execute clinical programs for gene therapies successfully and changes in expected commercial value we predict from the development of gene therapies; The success and timing of commercialization of any of our product candidates; and Obtaining and maintaining our intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive. Readers are urged to carefully review and consider the various disclosures made by us in this report and in our other reports filed with the Securities and Exchange Commission that advise interested parties of the risks and factors that may affect our business. All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake 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 Nirav Jhaveri, M.B.A. CFO ir@ocuphire.com Corey Davis, Ph.D. LifeSci Advisors cdavis@lifesciadvisors.com

Top-line data from VEGA-3 Phase 3 trial expected in first half of 2025 Top-line data from LYNX-2 Phase 3 trial in patients with decreased visual acuity under low light conditions following keratorefractive surgery expected in first quarter of 2025 FARMINGTON HILLS, Mich., Sept. 05, 2024 (GLOBE NEWSWIRE) -- Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing small-molecule therapies for the treatment of patients with retinal and refractive eye disorders, today announced that the VEGA-3 Phase 3 clinical trial evaluating Phentolamine Ophthalmic Solution 0.75% for presbyopia has dosed its first participants. Presbyopia, the gradual loss of ability to focus on near objects, typically becomes noticeable in the early to mid-40s. This progressive and ubiquitous condition leads to the widespread use of reading glasses or bifocals. Phentolamine Ophthalmic Solution 0.75% is being developed to provide a non-invasive, convenient alternative to traditional corrective measures. “Our goal is to provide a safe, long-lasting, effective solution that restores near vision and enhances overall visual performance in people with presbyopia, under both daytime and nighttime conditions,” said George Magrath, M.D., M.B.A., M.S., Ocuphire’s Chief Executive Officer. “We are pleased to begin the VEGA-3 trial, building on the positive results generated in our prior presbyopia studies, which have shown a rapid onset of action, favorable safety profile, and sustained duration of effect that are promising at this stage.” Ocuphire anticipates using data obtained from the VEGA-3 trial demonstrating the efficacy and safety of Phentolamine Ophthalmic Solution 0.75% as a potential treatment for presbyopia to support a supplemental New Drug Application with the U.S. Food and Drug Administration (the “FDA”). Dr. Magrath continued, “We are also excited about the continued enrollment in the LYNX-2 trial. Our top-line data for LYNX-2 are expected in the first quarter of 2025, assuming enrollment continues at the current rate. I’m very proud of the work our team and partners have put into the execution of this study.” VEGA-3 Phase 3 Pivotal Trial Design VEGA-3 is a randomized, double-masked, placebo-controlled, multi-center, Phase 3 clinical trial evaluating Phentolamine Ophthalmic Solution 0.75% in 545 participants with presbyopia. Participants are randomized 3:2 to receive one drop of Phentolamine Ophthalmic Solution 0.75% or placebo each evening. The primary endpoint is the percentage of participants with 15-letter improvement in photopic binocular distance-corrected near visual acuity (“DCNVA”) on the eighth day following their first visit. The improvement in binocular DCNVA for each participant will be relative to their own baseline value. Participants will be followed a total of 48 weeks to collect chronic safety data. Recruitment will take place at up to 40 investigational sites in the U.S. For more information on the trial design and endpoints, please refer to www.ClinicalTrials.gov (NCT06542497). Top Line Data from LYNX-2 Phase 3 Study Expected Q1 2025 The LYNX-2 Phase 3 trial is a randomized, double-masked, placebo-controlled Phase 3 registration trial designed to evaluate the safety and efficacy of Phentolamine Ophthalmic Solution 0.75% compared to placebo in participants who underwent keratorefractive surgery and then reported glare, halos or starbursts and demonstrated low contrast visual acuity under mesopic (low) light conditions. The LYNX-2 trial is being conducted under conditions of a Special Protocol Assessment (SPA) with the FDA. The trial is expected to enroll 200 participants. The primary endpoint, agreed with the FDA under the SPA, will be a gain of 3 lines (or 15 letters) or more of distance vision improvement on a low contrast chart in low light conditions after 15 days of dosing. Top line data are expected in the first quarter of 2025. Additional information about the LYNX-2 Phase 3 trial can be found at www.ClinicalTrials.gov (NCT06349759). There are currently no FDA-approved treatments for visual disturbances under low light conditions. With a mechanism of action that moderately reduces pupil size without the increased risks of retinal tears or detachment associated with parasympathomimetic miotics that engage the ciliary muscle, Phentolamine Ophthalmic Solution 0.75% eye drops have the potential to be a treatment option that could improve patients’ ability to see and function in low light following keratorefractive surgery. Ocuphire is responsible for managing the VEGA-3 and LYNX-2 trials. Under the terms of the License Agreement, Ocuphire’s partner will reimburse Ocuphire for agreed-to budgeted costs related to the development of Phentolamine Ophthalmic Solution 0.75% through FDA approval, and then share costs above an agreed upon threshold amount. About Phentolamine Ophthalmic Solution 0.75% Phentolamine Ophthalmic Solution 0.75%, Ocuphire’s late-stage product candidate, is a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. It works by uniquely blocking the alpha-1 receptors found on the radial iris dilator muscles, which are activated by the alpha-1 adrenergic receptors, without affecting the ciliary muscle. Phentolamine Ophthalmic Solution 0.75% is being developed for presbyopia and dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery. Phase 2 and Phase 3 trials for the use of Phentolamine Ophthalmic Solution 0.75% to treat presbyopia have met their primary endpoints. About Presbyopia As the eye ages, the ability to focus for reading and other tasks that require clear vision at near distances decreases. Presbyopia patients experience blurred near vision, difficulty seeing in dim light and eye strain. It is estimated that 128 million Americans, and over 2 billion people worldwide, have presbyopia, and this number is expected to grow as the population ages. About Dim Light Disturbances after Keratorefractive Surgery Decreased visual acuity under low light conditions (“DLD”) is characterized by peripheral corneal imperfections (aberrations) that result in unfocused light when the pupil dilates under low light conditions. Patients with DLD experience decreased low contrast visual acuity as well as glare, halos, and starbursts. About Ocuphire Pharma Ocuphire Pharma, Inc. (Nasdaq: OCUP) is a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing novel therapies for the treatment of patients with retinal and refractive eye disorders. Ocuphire’s lead product candidate, APX3330, a novel small-molecule inhibitor of Ref-1 (reduction oxidation effector factor-1 protein), is in development for diabetic retinopathy. In addition, Ocuphire’s late-stage product candidate Phentolamine Ophthalmic Solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size, is being developed for presbyopia and DLD. For more information, please visit www.ocuphire.com. Forward Looking Statements This press release 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 efficacy and safety of Phentolamine Ophthalmic Solution 0.75% in the treatment of presbyopia and dim (mesopic) light vision disturbances, logistical details regarding the VEGA-3 Phase 3 clinical trial, our plan to submit a New Drug Application based on the results of the upcoming VEGA-3 Phase 3 clinical trial, expectations about when data will be available from the LYNX-2 Phase 3 trial, and continued drug development and marketing under our partnership agreement. These forward-looking statements relate to us, our business prospects and our results of operations and are subject to certain risks and uncertainties posed by many factors and events that could cause our actual business, prospects and results of operations to differ materially from those anticipated by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those described under the heading “Risk Factors” included in our Annual Report on Form 10-K. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “aim,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. We undertake no obligation to revise any forward-looking statements in order to reflect events or circumstances that might subsequently arise. 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: The success and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts;Regulatory requirements or developments;Changes to or unanticipated events in connection with clinical trial designs and regulatory pathways;Delays or difficulties in the enrollment of patients in clinical trials;Substantial competition and rapid technological change;Our development of sales and marketing infrastructure;Future revenue losses and profitability;Our relatively short operating history;Changes in capital resource requirements;Risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs;Domestic and worldwide legislative, regulatory, political and economic developments;Employee misconduct;Changes in market opportunities and acceptance;Reliance on third parties;Future, potential product liability and securities litigation;System failures, unplanned events, or cyber incidents;The substantial number of shares subject to potential issuance associated with our equity line of credit arrangement;Risks that our partnership or other licensing arrangements, may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates;Future fluctuations in the market price of our common stock;The success and timing of commercialization of any of Ocuphire’s product candidates; andObtaining and maintaining 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. Readers are urged to carefully review and consider the various disclosures made by us in this report and in our other reports filed with the Securities and Exchange Commission that advise interested parties of the risks and factors that may affect our business. 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 Nirav Jhaveri M.B.A.CFOir@ocuphire.com Corey Davis, Ph.D. LifeSci Advisors cdavis@lifesciadvisors.com