Diabetic Retinopathy

Phase 2 data highlight consistent and sustained reductions in Intraocular Pressure (IOP), statistically significant (p<0.0001) through six months, with clinically meaningful reductions of 24-30% achieved with a single PAXTRAVA implant Generally well tolerated with no impact on corneal health observed Consistent durability of IOP reduction and implant bioresorption shows potential for repeat dosing without stacking of implants Expanded Focus on Retinal Disease Highlighted at the April 4th Eyecelerator BEDFORD, Mass., April 06, 2024 (GLOBE NEWSWIRE) -- Ocular Therapeutix, Inc. (NASDAQ:OCUL, “Ocular”, the “Company”), a biopharmaceutical company committed to enhancing people’s vision and quality of life through the development and commercialization of innovative therapies for wet age-related macular degeneration (wet AMD), diabetic retinopathy, and other diseases and conditions of the eye, today announced positive Phase 2 data for PAXTRAVA (travoprost intracameral implant or OTX-TIC) in patients with open-angle glaucoma or ocular hypertension (reported together as “glaucoma”, below) The data are being presented by Mark Gallardo, MD during the 2024 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting. “Ocular is very pleased to report positive six-month topline results for PAXTRAVA in the Phase 2 glaucoma study. We designed the Phase 2 clinical trial to evaluate PAXTRAVA over several time points that we believe are clinically meaningful, through six months. Observation of IOP reduction as early as the first follow-up visit, at 2 weeks, and demonstration of a 24-30% reduction in mean IOP through six months, with consistent and sustained reductions at each and every timepoint, are at the core of our enthusiasm for these results. That the majority of eyes (81.3%) treated with PAXTRAVA did not require additional IOP lowering therapy through six months further supports the strength of the data,” said Rabia Gurses Ozden, MD, Chief Medical Officer at Ocular Therapeutix. “As we incorporate these efficacy data, coupled with the expanded safety database, into our evaluation of next steps for the program, we thank all of the patients, caregivers and study sites who participated in this Phase 2 study.” Summary of Data and Findings: Efficacy: PAXTRAVA 26 µg single implant demonstrated consistent IOP control through 6 months: Statistically significant IOP changes from baseline were observed for each and every individual and mean diurnal measurement at Week 2 (M0.5), Week 6 (M1.5), and Week 12 (M3), as well as Months 4.5 and 6 (p<0.0001), although no formal statistical testing was prespecifiedClinically meaningful mean IOP reduction of ~24-30% from baseline observed over six monthsA majority (81.3%) of treated eyes did not require additional IOP-lowering therapy through 6 months indicating sustained and consistent treatment effects Safety: PAXTRAVA 26 µg was generally well-tolerated No impact on corneal endothelium was observed at 6 months following a single administrationMajority of adverse events (AEs) were mild in severity and generally resolved with topical medical treatment. Most ocular AEs within 3 days were deemed related to the injection procedure by the investigators. Post injection AEs observed (>3 days post injection procedure) were consistent with the travoprost label. One implant required removal (classified as a serious adverse event), most likely due to a peri-implantation bacterial infection, per investigatorConsistent bioresorption of the implant coupled with the durable effect seen in the trial suggests redosing would be possible, without the risk of stacking implants “I have dedicated my career to taking care of people with glaucoma and the evaluation of new therapies. I am enthusiastic about PAXTRAVA because of the positive, durable IOP reductions, accompanied by a good overall safety profile,” said Mark Gallardo, MD. Dr. Gallardo is a Study Investigator and Glaucoma Specialist at El Paso Eye Surgeons. He is an active principal investigator of innovative new treatments, having participated in more than 20 clinical trials over the last 7 years. “We were pleased to observe that PAXTRAVA generally stays in place at the site of implantation and maintains its form, that the majority of implants (64.5%) were significantly or fully bioresorbed at six months and that the implants were not observed to impact the surrounding corneal endothelium. Together, these features could address the compliance challenge of daily eyedrops and enable repeat dosing, without the risk of stacking, critical for the treatment of chronic disease. The totality of these features makes me optimistic about this product candidate.” The complete presentation (Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: Results from a Phase 2 Clinical Trial) will be available in the Scientific and Medical presentations section of the Company’s investor website. Phase 2 Study Overview: The PAXTRAVA Phase 2 study was designed as a randomized, parallel-group, controlled study to evaluate the safety and efficacy of PAXTRAVA in subjects with open-angle glaucoma (“OAG”) or ocular hypertension (“OHT”) and reported together as “glaucoma”, per above. Following a standard medication wash-out, patients were randomized 1:1:1 into one of three dosing groups (5 µg or 26 µg of PAXTRAVA or DURYSTA® (bimatoprost implant)), dosed in ‘the study eye’ and followed for frequent assessments through the six month analysis point. Due to elevations in IOP observed in seven out of the 16 subjects enrolled in the PAXTRAVA 5 μg arm of the trial, the Company closed enrollment in this arm and continued with the PAXTRAVA 26 μg and DURYSTA arms of the trial. Safety and efficacy data presented at ASCRS and reported in this press release are based on the 26 µg dosing group, as a result. The enrolled subjects had a mean age of 65 years and had been previously treated with a mean of about 1.2 IOP-lowering agents prior to study entry. The treatment groups were well balanced for key demographics and baseline characteristics. The primary efficacy endpoints included measurement of changes in intraocular pressure (IOP) at three diurnal measurements (8 AM, 10AM and 4 PM) at weeks 2, 6, 12 and secondary endpoints included measurements at all other visits including 4.5 and 6 months. No formal statistical testing was prespecified in the clinical trial protocol or the statistical analysis plan. Other assessments included an evaluation of the need for additional IOP-lowering therapy, changes in endothelial count and central corneal thickness, as well as an evaluation of safety for the period. Summary of next steps: Seek an end-of-Phase 2 meeting with the FDA to finalize development plans for PAXTRAVA Phase 3 trials and move to a next generation, commercial injector that eases initiation of therapy. Strategic Focus on Retinal Disease Highlighted at the April 4th Eyecelerator@ASCRS Conference On Thursday, April 4th, Pravin Dugel, MD, Executive Chairman of Ocular Therapeutix presented at the Eyecelerator@ASCRS conference. “Ocular was very pleased to connect with the Eyecelerator community to share more about our strategic vision for Ocular as we transition to a retina-focused company”, said Dr. Dugel. “There are three important pillars related to our Phase 3 program for AXPAXLI™ for wet Age-related Macular Degeneration (wet AMD) that support our transformation to a leading retina company: promising clinical data, de-risking regulatory pathway, and an expansive market opportunity. With our expanded strategic and clinical team of recognized experts in place to strengthen the Company’s retinal expertise, I believe we are on a solid path to enrich and accelerate the AXPAXLI clinical program.” The complete presentation (Ocular Therapeutix, Evolving into a leading retina company) will be available in the Events and Presentations section of the Company’s investor website. About Ocular Therapeutix, Inc. Ocular Therapeutix, Inc. is a biopharmaceutical company committed to enhancing people’s vision and quality of life through the development and commercialization of innovative therapies for wet age-related macular degeneration (wet AMD), diabetic retinopathy, and other diseases and conditions of the eye. AXPAXLI™ (axitinib intravitreal implant, also known as OTX-TKI), Ocular’s product candidate for retinal disease, is based on its ELUTYX™ proprietary bioresorbable hydrogel-based formulation technology. AXPAXLI is currently in the first of two planned pivotal Phase 3 trials for wet AMD, the SOL-1 trial, and a Phase 1 clinical trial for the treatment of non-proliferative diabetic retinopathy. The clinical portfolio also includes PAXTRAVA™ (travoprost intracameral implant, also known as OTX-TIC), currently in a Phase 2 clinical trial for the treatment of primary open-angle glaucoma or ocular hypertension. Ocular’s expertise in the formulation, development and commercialization of innovative therapies and the ELUTYX platform supported the development and launch of its first commercial drug product, DEXTENZA®, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery and ocular itching associated with allergic conjunctivitis. ELUTYX is also the foundation for two other clinical-stage assets, OTX-CSI (cyclosporine intracanalicular insert) for the chronic treatment of dry eye disease and OTX-DED (dexamethasone intracanalicular insert) for the short-term treatment of the signs and symptoms of dry eye disease, as well as several preclinical programs. Follow us on our website, LinkedIn or X. DEXTENZA® is a registered trademark of Ocular Therapeutix, Inc. AXPAXLI™, PAXTRAVA™, and ELUTYX™ and Ocular Therapeutix™ are trademarks of Ocular Therapeutix, Inc. DURYSTA® is a registered trademark of Allergan, an AbbVie company. The travoprost label can be referenced using the accessdata.fda.gov site About DEXTENZA DEXTENZA is FDA-approved for the treatment of ocular inflammation and pain following ophthalmic surgery and ocular itching associated with allergic conjunctivitis. DEXTENZA is a corticosteroid intracanalicular insert placed in the punctum, a natural opening in the inner portion of the lower eyelid, and into the canaliculus, and is designed to deliver dexamethasone to the ocular surface for up to 30 days without preservatives. DEXTENZA resorbs and exits the nasolacrimal system without the need for removal. Please see full Prescribing and Safety Information at the DEXTENZA website. Forward-Looking Statements: Any statements in this press release about future expectations, plans, and prospects for the Company, including the development and regulatory status of the Company’s product candidates, including the timing, design, and enrollment of the Company’s pivotal trials of AXPAXLI (also called OTX-TKI) for the treatment of wet AMD; the Company’s plans to advance the development of AXPAXLI, PAXTRAVA and its other product candidates; the size of potential markets for its product candidates; the potential utility of any of the Company’s product candidates; the sufficiency of the Company’s cash resources; and other statements containing the words "anticipate”, "believe”, "estimate”, "expect”, "intend", "goal”, "may", "might”, "plan”, "predict”, "project”, "target”, "potential”, "will”, "would”, "could”, "should”, "continue”, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the timing and costs involved in commercializing DEXTENZA or any product or product candidate that receives regulatory approval; the ability to retain regulatory approval of DEXTENZA or any product or product candidate that receives regulatory approval; the initiation, design, timing, conduct and outcomes of clinical trials, including the SOL-1 trial, the planned SOL-2 trial and the Company’s other ongoing clinical trials; the risk that the FDA will not agree with the Company’s interpretation of the written agreement under Special Protocol Assessment for the SOL-1 trial; the risk that even though the FDA has agreed with the overall design of the SOL-1 trial, the FDA may not agree that the data generated by the SOL-1 trial supports potential marketing approval; uncertainty as to whether the data from earlier clinical trials will be predictive of the data of later clinical trials, particularly later clinical trials that have a different design or utilize a different formulation than the earlier trials; availability of data from clinical trials and expectations for regulatory submissions and approvals; the Company’s scientific approach and general development progress; uncertainties inherent in estimating the Company’s cash runway, future expenses and other financial results, including its ability to fund future operations, including clinical trials; the Company’s existing indebtedness and the ability of the Company’s creditors to accelerate the maturity of such indebtedness upon the occurrence of certain events of default; the Company’s ability to enter into strategic alliances or generate additional funding on a timely basis, on favorable terms, or at all; and other factors discussed in the “Risk Factors” section contained in the Company’s quarterly and annual reports on file with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. InvestorsOcular Therapeutix, Inc.Donald NotmanChief Financial Officerdnotman@ocutx.com Joyce AllaireLifeSci Advisorsjallaire@lifesciadvisors.com

NEW YORK, April 04, 2024 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced that it will present full results from the Phase 3 ARISE-HF study evaluating AT-001 (caficrestat) in Diabetic Cardiomyopathy (DbCM) in an oral presentation at the 2024 American College of Cardiology (ACC) Annual Scientific Session to take place April 6-8, 2024 in Atlanta, Georgia. The Company announced topline results from ARISE-HF in January 2024, demonstrating a strong trend in stabilizing cardiac functional capacity with AT-001 treatment, and a statistically significant difference in cardiac functional capacity in a prespecified subgroup of patients not receiving concomitant treatment with an SGLT2 or GLP-1 while preventing clinically significant worsening. The presentation at ACC will also include important data on progression to overt heart failure and other secondary outcome measures. AT-001 treatment prevented progression to overt heart failure in patients with DbCM as compared to placebo (p=0.0285). Detailed safety data will also be presented, demonstrating that AT-001 was safe and well tolerated in a large cohort of patients, providing proof of concept that the technology has overcome the selectivity and safety issues of “old” aldose reductase inhibitors. The oral presentation at ACC will be followed by simultaneous publication of the study results in the Journal of the American College of Cardiology Journal (JACC). ACC Presentation: A Selective Aldose Reductase Inhibitor (AT-001) For the Treatment of Diabetic Cardiomyopathy: Primary Results of the Phase 3 Randomized Controlled ARISE-HF Study James L. Januzzi Jr, Javed Butler, Stefano Del Prato, Justin A. Ezekowitz, Nasrien E. Ibrahim, Carolyn S.P. Lam, Gregory D. Lewis, Thomas H. Marwick, Riccardo Perfetti, Julio Rosenstock, Scott D. Solomon, W.H. Wilson Tang, Faiez Zannad on behalf of the ARISE-HF Investigators Monday, April 8, 2024, 8:30 – 9:45 am ET, Main Tent (Hall B1) JACC Publication: Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients with Diabetic Cardiomyopathy James L. Januzzi Jr, Javed Butler, Stefano Del Prato, Justin A. Ezekowitz, Nasrien E. Ibrahim, Carolyn S.P. Lam, Gregory D. Lewis, Thomas H. Marwick, Riccardo Perfetti, Julio Rosenstock, Scott D. Solomon, W.H. Wilson Tang, Faiez Zannad on behalf of the ARISE-HF Investigators Journal of the American College of Cardiology Published online April 8, 2024 About AT-001 (Caficrestat) AT-001 (caficrestat) is an investigational oral, novel, potent Aldose Reductase inhibitor in Phase 3 clinical development for the treatment of Diabetic Cardiomyopathy. The global ARISE-HF Phase 3 study evaluated the ability of AT-001 to improve or prevent worsening of disease, as measured by changes in cardiac functional capacity, in 675 patients with DbCM at high risk of progression to overt heart failure. The study demonstrated a positive impact of AT-001 treatment, which was statistically significant in a prespecified subgroup of patients not on concomitant treatment with an SGLT2 or GLP-1 inhibitor. AT-001 has been previously studied in a Phase 1/2 study in approximately 120 patients with type 2 diabetes, a subset of which had DbCM. About Applied Therapeutics Applied Therapeutics is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need. The Company’s lead drug candidate, govorestat, is a novel central nervous system penetrant Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare metabolic diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. The Company is also developing AT-001, a novel potent ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. The preclinical pipeline also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of Diabetic retinopathy. To learn more, please visit www.appliedtherapeutics.com and follow the company on Twitter @Applied_Tx. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding the strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” “predicts” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, (i) our plans to develop, market and commercialize our product candidates, (ii) the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and our research and development programs, (iii) our ability to take advantage of expedited regulatory pathways for any of our product candidates, (iv) our estimates regarding expenses, future revenue, capital requirements and needs for additional financing, (v) our ability to successfully acquire or license additional product candidates on reasonable terms and advance product candidates into, and successfully complete, clinical studies, (vi) our ability to maintain and establish collaborations or obtain additional funding, (vii) our ability to obtain and timing of regulatory approval of our current and future product candidates, (viii) the anticipated indications for our product candidates, if approved, (ix) our expectations regarding the potential market size and the rate and degree of market acceptance of such product candidates, (x) our ability to fund our working capital requirements and expectations regarding the sufficiency of our capital resources, (xi) the implementation of our business model and strategic plans for our business and product candidates, (xii) our intellectual property position and the duration of our patent rights, (xiii) developments or disputes concerning our intellectual property or other proprietary rights, (xiv) our expectations regarding government and third-party payor coverage and reimbursement, (xv) our ability to compete in the markets we serve, (xvi) the impact of government laws and regulations and liabilities thereunder, (xvii) developments relating to our competitors and our industry, (xviii) our ability to achieve the anticipated benefits from the agreements entered into in connection with our partnership with Advanz Pharma and (xix) other factors that may impact our financial results. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. Factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Contacts Investors:Maeve Conneighton (212) 600-1902 orappliedtherapeutics@argotpartners.com Media:media@appliedtherapeutics.com

ZUG, Switzerland and BOSTON, April 04, 2024 (GLOBE NEWSWIRE) -- Oculis Holding AG (Nasdaq: OCS) (“Oculis”), a global biopharmaceutical company purposefully driven to save sight and improve eye care, today announced that Oculis’s management will be attending and presenting at the following upcoming investor conferences: Needham Annual Virtual Healthcare ConferenceFormat: Corporate presentation Presenter: Riad Sherif, MD, Chief Executive OfficerPresentation date and time: April 11, 2024 at 8:00 am EDT Location: VirtualWebcast: here Van Lanschot Kempen Life Sciences ConferenceDate: April 16-17, 2024Location: Amsterdam, the Netherlands The Company will be available for one-on-one meetings during the conferences. Interested investors should contact their respective representative to request meetings. About Oculis Oculis (Nasdaq: OCS) is a global biopharmaceutical company purposefully driven to save sight and improve eye care. Oculis’s highly differentiated clinical-stage pipeline comprises multiple innovative product candidates in development for eye diseases of high unmet need. It includes OCS-01 eye drops, a topical candidate in Phase 3 development for diabetic macular edema (DME) and inflammation and pain following ocular surgery; OCS-02 eye drops, a topical biologic candidate in Phase 2 development for dry eye disease (DED) and uveitis; and OCS-05, a disease modifying candidate for acute optic neuritis (AON) and other neuro-ophthalmic disorders, such as glaucoma, diabetic retinopathy, geographic atrophy, and neurotrophic keratitis. The first in-patient, proof-of-concept trial with OCS-05 is currently ongoing in France. Headquartered in Switzerland and with operations in the US, Oculis’s goal is to deliver life-changing eye treatments to patients worldwide. The company is led by an experienced management team with a successful track record in the pharmaceutical industry, supported by leading international healthcare investors. For more information, please visit: www.oculis.com Oculis ContactsMs. Sylvia Cheung, CFOsylvia.cheung@oculis.com Investor & Media Relations LifeSci AdvisorsCorey Davis, Ph.D.cdavis@lifesciadvisors.com1-212-915-2577