First Patient Enrolled in LYNX-2 Phase 3 Study Evaluating Phentolamine Ophthalmic Solution 0.75% (PS) for the Treatment of Decreased Visual Acuity Under Low Light Conditions Following Keratorefractive Surgery

LYNX-2 Follows SPA Agreement with FDA

Development of PS is Funded by Ocuphire’s Partner Viatris

FARMINGTON HILLS, Mich., April 11, 2024 (GLOBE NEWSWIRE) -- Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage biopharmaceutical company focused on developing novel therapies for the treatment of unmet needs of patients with retinal and refractive eye disorders, today announced the enrollment of the first subject in the LYNX-2 Phase 3 registration study evaluating Phentolamine Ophthalmic Solution 0.75% (PS) for the treatment of decreased visual acuity under low (mesopic) light conditions following keratorefractive surgery.

The LYNX-2 trial is being conducted under conditions of a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). As previously announced, Ocuphire received written agreement from the FDA that the clinical trial protocol and planned statistical analysis of the LYNX-2 Phase 3 trial would adequately address objectives supporting regulatory submission and a potential future marketing application in this indication.

“We are pleased to begin enrollment in the LYNX-2 study of PS,” said George Magrath, M.D., M.B.A., M.S., CEO of Ocuphire. “If our registration program meets expectations, and PS is subsequently approved by the FDA, it could potentially be the first commercial treatment for patients who have undergone LASIK surgery and experience low light visual disturbances. We believe that PS is a product with broad potential applications in ophthalmology. Having already received approval for RYZUMVI™ to treat pharmacologically-induced mydriasis, our partner Viatris, Inc. (Viatris) now has the opportunity to create further value as it pursues additional indications for PS, which also include presbyopia.”

Vision disturbances under low light conditions are characterized by peripheral corneal imperfections (aberrations) that result in unfocused light when the pupil dilates under low light conditions. Patients experience decreased low contrast visual acuity as well as glare, halos and starbursts. Patients undergoing keratorefractive surgery (including LASIK, PRK, SMILE, and RK) have been identified as one of the major sub-populations affected, the others being those who have night myopia (naturally occurring), non-central cortical cataracts, keratoconus or post-multifocal or extended depth of focus intraocular lens (IOL) implantation.

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, PS eye drops have the potential to be a treatment option that could improve patients’ ability to see and function in low light. The previous LYNX-1 Phase 3 study evaluating PS successfully met its primary endpoint, with 13% of subjects gaining 15 or more ETDRS letters of mesopic low contrast distance visual acuity at Day 8 vs. 3% on placebo (p<0.05). PS is manufactured as a preservative-free eye drop, which potentially allows for continued use while avoiding the common side effects of preservatives, such as ocular surface damage, eye irritation and tear film instability. For more information about the prior LYNX-1 Phase 3 study evaluating PS, please visit https://www.ocuphire.com/news-media/press-releases/detail/374/ocuphire-announces-positive-topline-results-from-lynx-1.

Jay Pepose, M.D., PhD., Chief Medical Advisor at Ocuphire, commented, “Low light vision disturbances are characterized by difficulty in distinguishing objects with subtle differences in contrast, such as a pedestrian in a crosswalk at dusk or on a rainy day under low light conditions. This represents a significant, yet often overlooked sequela of LASIK or other forms of keratorefractive surgery. Despite the success and popularity of LASIK for vision correction, a subset of patients find themselves grappling with these low light or night-time vision challenges, for which there has been no specific, targeted treatment available. If approved, PS offers the potential to enhance visual performance in low light conditions and restore a sense of normalcy and confidence in these patients.”

Ocuphire has a global license agreement with Viatris to co-develop and commercialize PS for the reversal of mydriasis, presbyopia and low light vision disturbances. Under the terms of this agreement, the two companies agreed to co-develop the product for each of these conditions, with Viatris providing funding for development of these programs. Further, Ocuphire is eligible to receive specified regulatory or net sales milestone payments associated with these indications as well as royalties on commercial sales. In September 2023, Ocuphire met the $10 million milestone payment requirements attributed to the FDA’s approval of PS for reversal of mydriasis.

LYNX-2 Design

LYNX-2 is a randomized, double-masked, placebo-controlled Phase 3 registration study designed to evaluate the safety and efficacy of PS compared to placebo in subjects who underwent keratorefractive surgery and then reported decreased visual acuity under low light conditions. The trial is expected to enroll 200 subjects. 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. Additional information about the Phase 3 trial can be found at www.clinicaltrials.gov.

About Ocuphire Pharma

Ocuphire is a clinical-stage ophthalmic biopharmaceutical company focused on developing novel therapies for the treatment of unmet needs of patients with retinal and refractive eye disorders.

Ocuphire’s lead retinal product candidate, APX3330, is an oral small-molecule inhibitor of Ref-1 (reduction oxidation effector factor-1 protein) for the treatment of non-proliferative diabetic retinopathy (NPDR). Ref-1 is a regulator of the transcription factors HIF-1α and NF-κB. Inhibiting REF-1 reduces levels of vascular endothelial growth factor (VEGF) and inflammatory cytokines which are known to play key roles in ocular angiogenesis and inflammation. APX3330 is an oral tablet to be administered twice per day for the treatment of diabetic retinopathy (DR). A Phase 2 study in subjects with DR and an End-of-Phase 2 meeting have recently been completed, and a SPA is planned to be submitted.

In addition, Ocuphire has a partnership with Viatris to develop and commercialize Phentolamine Ophthalmic Solution 0.75% (PS), a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. PS was approved by the FDA for the treatment for pharmacologically-induced mydriasis under the brand name RYZUMVI™ in September 2023. As discussed above, PS is also in Phase 3 clinical development for the treatment of presbyopia and for the treatment of decreased visual acuity under low light (mesopic) conditions after keratorefractive surgery.

Ocuphire is also developing APX2009 and APX2014, second-generation analogs of APX3330. These programs are being evaluated for treating other retinal diseases such as age-related macular degeneration and geographic atrophy. 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 applications of PS in ophthalmology, the registration program for PS, the LYNX-2 Phase 3 registration study, the benefits, uses and side effects of PS treatment, ongoing discussions with the FDA regarding various of our drug products, and continued drug development under our agreement with Viatris.

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,” “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 with Viatris, or our 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; and
• Obtaining 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 SEC 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.

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