Nonproliferative diabetic retinopathy

88% of EYLEA HD patients had a last assigned dosing interval of ≥12 weeks at week 156, while sustaining visual and anatomic improvements achieved in the first 96 weeks, in this extension study of the Phase 3 PHOTON trial presented at AAO Patients switched to EYLEA HD experienced substantially slower fluid reaccumulation, as compared to their previous rate of fluid reaccumulation with EYLEA® (aflibercept) Injection 2 mg The consistent achievement of much longer dosing intervals with EYLEA HD – together with the notably slower fluid reaccumulation observed following switch to EYLEA HD – supports the longer duration of action of EYLEA HD versus EYLEA Safety data remains consistent with the known EYLEA HD and EYLEA safety profiles Oct. 18, 2024 -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive three-year (156-week) data for EYLEA HD® (aflibercept) Injection 8 mg from an extension study of the Phase 3 PHOTON trial in patients with diabetic macular edema (DME). At three years, the longer-term data showed the vast majority of EYLEA HD patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year, while achieving substantially longer treatment intervals than have been previously demonstrated. Notably, patients switched to EYLEA HD experienced substantially slower fluid reaccumulation following their first EYLEA HD dose. The achievement of much longer dosing intervals with EYLEA HD – together with the notably slower fluid reaccumulation – supports the longer duration of action of EYLEA HD. The results were presented today in a late-breaking session at the American Academy of Ophthalmology (AAO) Annual meeting. “Many patients with diabetic eye disease are of working age and often have to juggle a high burden of healthcare appointments and treatments alongside job and family commitments. These latest three-year results from the Phase 3 PHOTON trial continue to demonstrate that EYLEA HD can safely provide meaningful and lasting vision and anatomical benefits for people living with diabetic macular edema – with as few as three or four injections per year,” said Diana V. Do, M.D., Professor of Ophthalmology and Vice Chair for Clinical Affairs at the Byers Eye Institute, Stanford University and a trial investigator. “Over the last year, EYLEA HD has made an impact on how diabetic eye disease is managed among retina specialists, and these longer-term results reinforce confidence in initiating patients on EYLEA HD as a first-line treatment.” In PHOTON, EYLEA HD patients were initially randomized at baseline to either 12- or 16-week dosing intervals (after three initial monthly doses). If pre-specified criteria were met, dosing intervals could be shortened throughout the trial or extended in the second and third year. As previously presented, 89% of all EYLEA HD patients completing week 96 maintained ≥12-week dosing intervals. Patients could then participate in an optional extension study for an additional 60 weeks. Of the EYLEA HD patients (n=152) who completed the full 156 weeks of treatment: 88% were assigned a dosing interval of ≥12 weeks, and 48% were assigned a dosing interval of ≥20 weeks, at the end of three years of treatment. Vision gains and anatomical improvements achieved through year two in PHOTON were sustained through year three in the extension study. Patients in the PHOTON comparator arm received EYLEA® (aflibercept) Injection 2 mg as a fixed 8-week dosing regimen (after five initial monthly doses) for 96 weeks. These patients were then able to enter the extension study at week 96 and switch to a 12-week dosing interval with EYLEA HD. Of these patients who completed the extension study (n=58), 83% had a last assigned dosing interval ≥12 weeks at the end of the study (week 156), while mean visual and anatomic improvements achieved with EYLEA in the first 96 weeks were sustained following the switch to longer dosing intervals with EYLEA HD. Notably, patients synchronously switched to the EYLEA HD dose experienced substantially slower fluid reaccumulation following their first dose – as compared to their previous rate of fluid reaccumulation while on EYLEA treatment. The consistent achievement of much longer dosing intervals with EYLEA HD – together with the notably slower fluid reaccumulation observed following switch to EYLEA HD – support the longer duration of action of EYLEA HD versus EYLEA. In the extension study, the safety profile of EYLEA HD (n=265) continued to be similar to EYLEA through three years and remained generally consistent with the known safety profile of EYLEA HD in its pivotal trials. Ocular treatment emergent adverse events (TEAEs) occurring in ≥4% of all patients included cataract, vitreous floaters, and diabetic retinal edema. There were no cases of occlusive retinal vasculitis. The rate of intraocular inflammation was 1.4% for the patients that switched from EYLEA to EYLEA HD, and 1.5% for the EYLEA HD patients randomized at baseline. Anti-platelet trialists' collaboration-defined arterial thromboembolic TEAEs occurred in 7% of patients in both groups. EYLEA HD (known as Eylea™ 8 mg in the European Union and Japan) is being jointly developed by Regeneron and Bayer AG. In the U.S., Regeneron maintains exclusive rights to EYLEA and EYLEA HD. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of EYLEA and EYLEA HD. PULSAR in wet age-related macular degeneration and PHOTON in DME/diabetic retinopathy (DR) are double-masked, active-controlled pivotal trials that were conducted in multiple centers globally. In both trials, patients were randomized into 3 treatment groups to receive either: EYLEA HD every 12 weeks, EYLEA HD every 16 weeks, or EYLEA every 8 weeks. The lead sponsors of the trials were Bayer for PULSAR and Regeneron for PHOTON. Patients treated with EYLEA HD in both trials had 3 initial monthly doses, and patients treated with EYLEA received 3 initial doses in PULSAR and 5 in PHOTON. In the first year, patients in the EYLEA HD groups could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Intervals could not be extended until the second year of the study. Patients in all EYLEA groups maintained a fixed 8-week dosing regimen throughout their participation in the two-year trials. In both studies, there was an optional extension study starting at week 96, with all participating patients receiving EYLEA HD through week 156. Patients initially randomized to EYLEA in PHOTON, were switched to EYLEA HD at the start of the extension study and immediately assigned to a 12-week dosing interval. Dosing intervals for all patients in the extension study could be shortened or extended by 2-week increments if protocol-defined criteria were met, with a minimum dosing interval of every 8 weeks and a maximum dosing interval of every 24 weeks. DR is an eye disease characterized by microvascular damage to the blood vessels in the retina often caused by poor blood sugar control in people with diabetes. The disease generally starts as nonproliferative diabetic retinopathy (NPDR) and often has no warning signs or symptoms. NPDR may progress to proliferative diabetic retinopathy (PDR), a stage of the disease in which abnormal blood vessels grow onto the surface of the retina and into the vitreous cavity, potentially causing severe vision loss. DME can occur at any stage of DR as the blood vessels in the retina become increasingly fragile and leak fluid, potentially causing visual impairment. In the U.S., approximately 1.5 million adults are diagnosed with DME, while approximately 6 million people have DR without DME. At Regeneron, we relentlessly pursue groundbreaking innovations in eye care science to help maintain the eye health of the millions of Americans impacted by vision-threatening conditions. Over a decade ago, our breakthrough scientific research resulted in the development of EYLEA, a vascular endothelial growth factor (VEGF) inhibitor designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels in the eye. EYLEA has since brought fundamental change to the retinal disease treatment landscape and is supported by a robust body of research that includes eight pivotal Phase 3 trials, 12 years of real-world experience, and more than 80 million EYLEA injections globally. Regeneron continues to advance our anti-angiogenesis expertise with new solutions with the aim of offering optimal flexibility for a broad group of patients and eye care professionals. This includes EYLEA HD, which has been developed with the aim of extending the time between injections, while maintaining the vision gains, anatomic benefits and safety previously observed with EYLEA. Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. 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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

Google announced it is licensing its AI model focused on detecting diabetic retinopathy to partners in Thailand and India, two countries the tech giant says have a shortage of eye specialists. Google Research teams partnered with foundational research partners Aravind Eye Hospital in India and Rajavithi Hospital in Thailand nearly a decade ago to research whether AI could be used to help reduce preventable blindness caused by diabetic retinopathy. Today, the company announced it is partnering with healthcare providers and health-tech partners across the countries to distribute the developed AI-enabled diabetic retinopathy model to improve access to eyesight-saving care. Google's newly announced partners include India-based medical equipment manufacturer Forus Health, nonprofit ophthalmic manufacturing company AuroLab and Thailand-based AI-enabled medical imaging technology company Perceptra. "We’ve also been working with the Thai Ministry of Public Health’s Department of Medical Services (DMS), which is responsible for the country’s diabetic retinopathy screening program, on implementation research and cost-effectiveness analysis. This collaboration is bringing our AI into Thailand’s National Innovation program and will pave the way for a partnership between Perceptra and DMS to apply the diabetic retinopathy AI model in public sector hospitals and help deliver impact at population scale," Google wrote in a blog post. The partners will work toward receiving local regulatory approvals to ensure clinical systems in both countries have access to the AI model, The organizations have also set a goal to deliver six million AI-enabled screenings to communities in need at no cost to patients over the next decade. THE LARGER TREND In a study published in the Indian Journal of Ophthalmology, researchers stated that the number of people with diabetic retinopathy globally will increase from 126.6 million in 2010 to 191 million by 2030, with vision-threatening diabetic retinopathy rising from 37.3 million to 56.3 million. In 2022, a study published out of Thailand in The Lancet revealed that deep learning algorithms could diabetic retinopathy in patients with diabetes on par with community specialists. Researchers discovered that the deep-learning system could detect vision-threatening diabetic retinopathy with 94.7% accuracy, 91.4% sensitivity and 95.4% specificity. This was compared to the retina specialist over-readers, who performed with an accuracy of 93.5%, a sensitivity of 84.8% and a specificity of 95.5%. In 2019, Alphabet's life science subsidiary Verily unveiled real-world clinical use for its machine learning algorithm to screen for diabetes-related conditions, including diabetic retinopathy and diabetic macular edema. The tool was first rolled out in India and aimed at helping with the shortage of doctors worldwide.