Mydriasis

Eyenovia, Inc. and Betaliq, Inc. could potentially be heading toward a “reverse merger transaction” to form a new ophthalmic company, the companies recently announced. We’ll start with Eyenovia. Based in New York, the commercial-stage ophthalmic pharmaceutical technology company is developing a pipeline of micro-dosed treatments for front-and-back-of-eye diseases, including presbyopia, mydriasis, and myopia. On the regulatory side: The company’s Mydcombi (tropicaide and phenylephrine hydrochloride ophthalmic spray) 1% / 2.5% for inducing mydriasis was cleared by the FDA in 2023. The Optejet device is exclusively designed for ocular therapeutics as a way to dispense topical eye medications using Eyenovia’s Microdose Array Print (MAP) technology as a topical delivery system (similar to an inkjet printer). The process: Medication is dispensed horizontally in a mist to coat the surface of the cornea, with contact to the eye occurring at a low velocity to reduce ocular impact. The glaucoma-focused, clinical-stage pharmaceutical company—launched via a collaboration with Novaliq GmbH—is developing a portfolio of topical glaucoma treatments featuring a unique delivery system of its own. Eyenovia entered into a non-binding LOI with Betaliq to consider a reverse merger transaction to create a new ophthalmic company focused on the aforementioned proprietary technologies. Its proposed therapeutic focus: glaucoma. While both the Optejet and EyeSol platforms provide similar benefits for enhancing products’ ease of use and compliance with therapeutics, the companies also noted that—most importantly—EyeSol is compatible with the Optejet. Plus: EyeSol delivers a 10 microliters (µL) drop size that can be replicated in the Optejet device. There is, actually. Per the companies, the value for each—assuming zero cash (net of liabilities) at the closing of this potential merger—would be: For equity holders: As a result of this exchange ratio, the intent would be for Betaliq and Eyenovia equity holders to own an estimated 83.7% and 16.3% of the newly-combined company, respectively. Eyenovia CEO Michael Rowe stated that a potential merger is “in the best interests of our company, our team members, patients, and shareholders.” Similarly: Betaliq CEO Barry Butler emphasized the “significant opportunity in the eyecare space” that the joining of both technologies could represent for patients with glaucoma and other ocular diseases—not to mention opportunities for pipeline expansion. No exact timeframe has been shared so far. Even further: The deal will be contingent on a number of factors and definitive agreements from both sides. There are! Eyenovia plans to file for U.S. regulatory approval of a user-filled version of the Optejet, designed to operate with a number of topical ophthalmic liquids such as artificial tears and rewetting products. So on both fronts—this merger and the user-filled Optejet—stay tuned for news!

In October, Ocuphire Pharma acquired Opus Genetics, creating a leading, clinical-stage company focused on the development of gene therapy treatments for rare inherited retinal diseases (IRDs) The pro forma cash balance of the combined company was approximately $37 million as of September 30, 2024 (preliminary and unaudited), expected to extend runway into 2026 Four clinical data readouts expected in 2025 FARMINGTON HILLS, Mich., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage ophthalmic biotechnology company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and other ophthalmologic disorders, today announced financial results for the third quarter ended September 30, 2024 and provided a corporate update. “In October 2024, we acquired Opus Genetics with the goal of creating a leading gene therapy franchise to treat inherited retinal diseases,” said George Magrath, M.D., now CEO of Opus Genetics. “The transaction expanded our pipeline substantially, adding compelling gene therapy assets. The most advanced of these new candidates, LCA5, has generated positive six-month proof-of-concept data in patients with advanced disease. A second candidate, OPGx-BEST1 targets one of the largest IRD populations, and we’re excited to begin dosing patients next year. We continue to develop Phentolamine Ophthalmic Solution 0.75% in new indications, and this franchise is expected to provide meaningful potential cashflow in the future, if approved for the new indications. Our expected cash runway has been extended into 2026, through expected efficacy readouts from four clinical programs in 2025, including Phase 3 studies in two indications for Phentolamine Ophthalmic Solution 0.75% and two studies for the new gene therapy clinical assets.” Corporate Updates Acquisition of Opus Genetics On October 22, Ocuphire acquired Opus Genetics, Inc., a clinical-stage gene therapy company for inherited retinal diseases (IRDs), in an all-stock transaction. 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 was renamed Opus Genetics, Inc., and began trading on Nasdaq under the ticker symbol “IRD,” effective as of October 24, 2024. As consideration for the Opus Acquisition, the Company issued 5,237,063 shares of its common stock and 14,145.374 shares of Series A Preferred Stock, each of which is convertible into 1,000 shares of common stock. As of November 7, 2024 there were 31,568,457 shares of the Company’s common stock outstanding. If the shares of Series A Preferred Stock were converted as of that date, there would be a total of 45,713,831 shares of common stock outstanding.As a combined company, we have an expanded pipeline that includes seven assets from our adeno-associated virus (AAV)-based gene therapy portfolio, each of them being developed for a specific IRD, 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.Our most advanced gene therapy candidate, OPGx-LCA5, is being developed to treat LCA5, an early-onset, severe hereditary retinal diseases. 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. Enrollment of the first pediatric patients is expected in the first quarter of 2025, with the first data anticipated in the third quarter of 2025.OPGx-BEST1 is in development for Bestrophin1-associated retinal disease. IND-enabling studies with OPGx-BEST1 have generated compelling proof-of-concept efficacy data and exhibited favorable safety. We anticipate filing a Clinical Trial Authorization (CTA) application in Germany in 2025 for commencement of a Phase 1/2 clinical trial. Phentolamine Ophthalmic Solution 0.75% Enrollment is ongoing in the LYNX-2 Phase 3 registration study evaluating Phentolamine Ophthalmic Solution 0.75% for the treatment of dim light disturbances under mesopic (low) light conditions following keratorefractive surgery. Top-line data are expected in the first quarter of 2025. The LYNX-2 trial is being conducted under conditions of a Special Protocol Assessment (SPA) with the FDA.The VEGA-3 Phase 3 trial evaluating Phentolamine Ophthalmic Solution 0.75% for the treatment of presbyopia is also enrolling patients. Top-line results are expected in the first half of 2025.The Phentolamine Ophthalmic Solution 0.75% development portfolio is being funded by Ocuphire’s partner in both indications (presbyopia and dim light vision disturbances). APX3330 The Company intends to seek a strategic partner to advance further late-stage development of APX330, its novel, oral REF-1 inhibitor for diabetic retinopathy (DR), given the development timelines and capital requirements. In the meantime, discussions remain ongoing with the FDA regarding the SPA for a Phase 3 program in DR. Financial Highlights for the Third Quarter Ended September 30, 2024 As of September 30, 2024, Ocuphire had cash and cash equivalents of $37 million. The pro forma cash balance of the combined company was approximately $37 million as of September 30, 2024 (preliminary and unaudited). Based on current projections, management believes that the cash on hand will be sufficient to fund operations into 2026. License and collaborations revenue was $3.9 million and $11.9 million for the three months ended September 30, 2024 and 2023, respectively. Revenue during both quarterly periods was derived from the License Agreement. Revenue for the three months ended September 30, 2024 was comprised largely of the reimbursement of research and development services. The decrease compared to the corresponding prior year period was largely due to the one-time achievement of a $10.0 million milestone attributed to the FDA’s approval of Phentolamine Ophthalmic Solution 0.75% for reversal of mydriasis in 2023. Revenue for the three months ended September 30, 2024 also included an earned royalty payment in the amount of $14,000 from the sales of RYZUMVI, indicated for the treatment of pharmacologically-induced mydriasis by our commercial partner. Until further notice, we will report earned RYZUMVI royalties as a component of revenue listed in the Income Statement. General and administrative expenses for the three months ended September 30, 2024 were $2.9 million compared to $2.1 million for the three months ended September 30, 2023. The increase period over period was primarily attributable to personnel-related costs, stock-based compensation, legal support costs and business development costs. These were offset in part by a reduction in non-legal professional service costs. General and administrative expenses included the following noncash items: $0.5 million and $0.3 million in stock-based compensation expense during both three months ended September 30, 2024 and 2023, respectively. Research and development expenses for the three months ended September 30, 2024 were $9.0 million compared to $3.5 million for the three months ended September 30, 2023. The increase in the current period was primarily attributable to increased clinical costs related to the APX3330 development program and other research and development activities period over period, drug manufacturing costs and toxicology service costs related to APX3330, increased payroll related costs and regulatory and operating related expenses. Pursuant to the License Agreement, our budgeted research and development expenses related to the development of Phentolamine Ophthalmic Solution 0.75%, are fully reimbursed by our development partner. Research and development expenses also included $0.2 million in stock-based compensation expense during each of the three-month periods ended September 30, 2024 and 2023. Net loss for the quarter ended September 30, 2024, was $7.5 million or $(0.29) per basic and diluted share as compared to net income of $5.6 million or $0.26 and $0.25 per basic and diluted share, respectively, for the third quarter of 2023. For further details on our financial results, including results for the nine-month period ended September 30, 2024, please refer to our Quarterly Report on Form 10-Q to be filed with the Securities and Exchange Commission. About Opus Genetics Opus Genetics is a clinical-stage ophthalmic biotechnology company developing gene therapies to treat patients with inherited retinal diseases (IRDs) and therapies to treat patients with other ophthalmologic 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. BEST1 gene therapy is designed to address mutations in the BEST1 gene, which is associated with retinal degeneration; A Phase 1/2 study will be initiated in 2025. 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. For more information, please visit www.opusgtx.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 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 our product candidates and our preclinical programs;Domestic and worldwide legislative, regulatory, political and economic developments;Employee misconduct;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; andObtaining 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 CorporateInvestor RelationsNirav Jhaveri, MBACFOir@opusgtx.comCorey Davis, Ph.D.LifeSci Advisorscdavis@lifesciadvisors.com Ocuphire Pharma, Inc.Condensed Balance Sheets(in thousands, except share amounts and par value) As of September30, December31, 2024 2023 Assets (unaudited) Current assets: Cash and cash equivalents $36,632 $50,501 Accounts receivable 1,857 926 Contract assets and unbilled receivables 1,468 1,407 Prepaids and other assets 429 1,099 Short-term investments 3 15 Total current assets 40,389 53,948 Property and equipment, net — — Total assets $40,389 $53,948 Liabilities and stockholders’ equity Current liabilities: Accounts payable $844 $2,153 Accrued expenses 5,171 1,815 Derivative liability 74 74 Total current liabilities 6,089 4,042 Total liabilities 6,089 4,042 Commitments and contingencies Stockholders’ equity: Preferred stock, par value $0.0001; 10,000,000 shares authorized as of September 30, 2024 and December 31, 2023; no shares issued and outstanding at September 30, 2024 and December 31, 2023. — — Common stock, par value $0.0001; 125,000,000 and 75,000,000 shares authorized as of September 30, 2024 and December 31, 2023, respectively; 26,198,444 and 23,977,491 shares issued and outstanding at September 30, 2024 and December 31, 2023, respectively. 3 2 Additional paid-in capital 138,160 131,370 Accumulated deficit (103,863) (81,466)Total stockholders’ equity 34,300 49,906 Total liabilities and stockholders’ equity $40,389 $53,948 Ocuphire Pharma, Inc.Condensed Statements of Comprehensive Loss(in thousands, except share and per share amounts)(Unaudited) For the Three Months EndedSeptember 30, For the Nine Months EndedSeptember 30, 2024 2023 2024 2023 License and collaborations revenue $3,867 $11,935 $6,690 $17,358 Operating expenses: General and administrative 2,894 2,055 10,918 8,680 Research and development 8,982 3,494 19,817 13,812 Total operating expenses 11,876 5,549 30,735 22,492 (Loss) income from operations (8,009) 6,386 (24,045) (5,134)Financing costs — (1,328) — (1,328)Fair value change in derivative liability — 61 — 61 Other income, net 483 456 1,648 1,224 (Loss) income before income taxes (7,526) 5,575 (22,397) (5,177)Provision for income taxes — (14) — (14)Net (loss) income (7,526) 5,561 (22,397) (5,191)Other comprehensive (loss) income, net of tax — — — — Comprehensive (loss) income $(7,526) $5,561 $(22,397) $(5,191)Net (loss) income per share: Basic $(0.29) $0.26 $(0.88) $(0.25)Diluted $(0.29) $0.25 $(0.88) $(0.25)Number of shares used in per share calculations: Basic 26,145,080 21,446,648 25,501,117 21,117,211 Diluted 26,145,080 22,405,995 25,501,117 21,117,211

Publication in the Journal of Ocular Pharmacology and Therapeutics highlights the ability of the Optejet to achieve a therapeutic dose of medication with far less exposure to harmful preservatives Additional presentation at the American Academy of Optometry summarizes a Phase 4 study of Mydcombi demonstrating that clinically relevant mydriasis can be achieved with a half-dose per eye NEW YORK, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Eyenovia, Inc. (NASDAQ: EYEN), an ophthalmic technology company, today announced a publication in the Journal of Ocular Pharmacology and Therapeutics as well as an upcoming presentation at the American Academy of Optometry’s “Academy 2024 Indianapolis” Annual Meeting. Publication in the Journal of Ocular Pharmacology and Therapeutics The peer-reviewed paper highlights the ability of Eyenovia’s proprietary Optejet dispenser to deliver a therapeutic dose of latanoprost with far less exposure to the preservative benzalkonium chloride (BAK) than traditional eye drops. BAK, in larger volumes, can cause unwanted side effects, including cytotoxicity, cytoplasmic shrinkage, and loss of cell-cell contact, and expression of chemokine (C-C motif) ligand 2 and interleukin-6 (markers of inflammation). In contrast, this in-vitro study of latanoprost plus BAK delivered in the same amount by the Optejet dispenser (8 microliters) avoided the cytotoxicity associated with larger volumes found in eye drops and was similar to no treatment controls and BAK-free latanoprost drops. “We have shown in prior studies the ability of the Optejet dispenser to achieve a therapeutic dose of medication with approximately 80% less volume and exposure to harmful preservatives than traditional eye drops,” stated Michael Rowe, Chief Executive Officer of Eyenovia. “The implication here is that preserved medications may not need to be reformulated to get many of the benefits of non-preserved products if delivered with the Optejet. We believe this creates potential opportunities for the Optejet to improve the administration of topical ocular therapeutics well beyond our own development pipeline.” Presentation at the American Academy of Optometry’s “Academy 2024” Eyenovia also announced today an upcoming presentation at the American Academy of Optometry’s “Academy 2024 Indianapolis,” which is being held November 6-9, in Indianapolis, IN. The presentation details the results of an open-label Phase 4 study of 1% tropicamide and 2.5% phenylephrine ophthalmic metered spray, similar to Mydcombi, Eyenovia’s commercially available product for inducing mydriasis. Twenty-nine subjects completed the study and administered one spray. Baseline pupil diameter (PD) for all eyes was 2.74±0.48 mm. Mean change in PD from baseline to 30 minutes was 3.69±1.25 mm. At 30 minutes post-dosing, mean PD was 6.42±1.25 mm, with 67% and 43% of eyes dilated to ≥ 6mm and 7mm, respectively. The majority of patients returned to functional vision (PD ≤ 5 mm) as early as 3.5 hours post-instillation, with 93% reaching that point by six hours. Safety outcomes were favorable, as only mild adverse events were reported (dry eye and mild instillation site pain) all of which resolved without intervention. “We conducted this study to address questions from doctors about modulating dosing for patients who may benefit from a lower dose of tropicamide or phenylephrine,” stated Dr. Julie Whitcomb, Senior Director of Medical Affairs at Eyenovia. “What we found in this study was that a half dose may also provide clinically relevant pupil dilation, was well-tolerated, and had a desirable shorter duration of effect.” Presentation details: Title:An Open Label, Phase 4 Study of the Safety and Efficacy of Fixed Combination Tropicamide 1% and Phenylephrine 2.5% Ophthalmic Spray (MydCombi®)Poster:#109, Exhibit Hall HPresenter:Dr. Josianne Manasse, OD, SUNY College of OptometryDate/time:Friday, November 8th, 1:00-3:00pm For additional information on the Expo: https://aaopt.org/meetings/academy-2024-indianapolis/ About Eyenovia, Inc. Eyenovia, Inc. (NASDAQ: EYEN) is an ophthalmic technology company developing a pipeline of advanced products based on its Optejet platform. Eyenovia is currently focused on the commercialization of Mydcombi® for mydriasis, clobetasol propionate ophthalmic suspension, 0.05% for post-surgical pain and inflammation, as well as the ongoing late-stage development of medications in the Optejet device for pediatric progressive myopia as well as out-licensing for additional indications. For more information, visit Eyenovia.com. The Eyenovia Corporate Information slide deck may be found at ir.eyenovia.com/events-and-presentations. PLEASE GO TO MYDCOMBI.COM FOR IMPORTANT SAFETY INFORMATION for MYDCOMBI™ (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1%/2.5% PLEASE GO TO CLOBETASOLBID.COM FOR IMPORTANT SAFETY INFORMATION for Clobetasol Propionate Ophthalmic Suspension 0.05% Forward-Looking StatementsExcept for historical information, all the statements, expectations and assumptions contained in this press release are forward-looking statements. Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations, strategies, predictions or any other statements relating to our future activities or other future events or conditions, including the timing and scale of acceptance and use of our approved products. These statements are based on current expectations, estimates and projections about our business based, in part, on assumptions made by management. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Therefore, actual outcomes and results may, and in some cases are likely to, differ materially from what is expressed or forecasted in the forward-looking statements due to numerous factors discussed from time to time in documents which we file with the U.S. Securities and Exchange Commission. In addition, such statements could be affected by risks and uncertainties related to, among other things: risks of our clinical trials, including, but not limited to, the costs, design, initiation and enrollment, timing, progress and results of such trials; the timing of, and our ability to submit applications for, obtaining and maintaining regulatory approvals for our products and product candidates; the potential advantages of our products, product candidates and platform technology; the rate and degree of market acceptance and clinical utility of our products and product candidates; our estimates regarding the potential market opportunity for our products and product candidates; reliance on third parties to develop and commercialize our products and product candidates; the ability of us and our partners to timely develop, implement and maintain manufacturing, commercialization and marketing capabilities and strategies for our products and product candidates; intellectual property risks; changes in legal, regulatory, legislative and geopolitical environments in the markets in which we operate and the impact of these changes on our ability to obtain regulatory approval for our products and product candidates; and our competitive position. Any forward-looking statements speak only as of the date on which they are made, and except as may be required under applicable securities laws, Eyenovia does not undertake any obligation to update any forward-looking statements. Eyenovia Contact:Eyenovia, Inc.Andy Jones Chief Financial Officerajones@eyenovia.comEyenovia Investor Contact:Eric RibnerLifeSci Advisors, LLCeric@lifesciadvisors.com(646) 751-4363Eyenovia Media Contact:Eyenovia, Inc.Norbert LoweVice President, Commercial Operationsnlowe@eyenovia.com