Ranibizumab (Genentech)

First patient randomized into HELIOS-3, which along with HELIOS-2 form the basis of AXPAXLI’s registrational program in non-proliferative diabetic retinopathy (NPDR) HELIOS-2 and HELIOS-3 are global, complementary superiority trials using a novel ordinal diabetic retinopathy severity scale (DRSS) primary endpoint Targeting a broad diabetic retinopathy (DR) label by including patients with non-center-involved diabetic macular edema (non-CI-DME) BEDFORD, Mass., Nov. 24, 2025 (GLOBE NEWSWIRE) -- Ocular Therapeutix, Inc. (NASDAQ: OCUL, “Ocular”), an integrated biopharmaceutical company committed to redefining the retina experience, today announced that the first patient has been randomized in the HELIOS-3 Phase 3 registrational program for AXPAXLI (also known as OTX-TKI) for the treatment of non-proliferative diabetic retinopathy (NPDR). “Initiating the HELIOS registrational program marks a pivotal step toward redefining treatment for diabetic retinal disease. While there are more than 6 million NPDR patients in the U.S., fewer than 1% receive therapy today, due mostly to the burden of frequent injections in this working age population. AXPAXLI’s potential to deliver efficacy with attractive durability could help hundreds of thousands, if not millions more patients preserve vision,” said Pravin U. Dugel, MD, Executive Chairman, President and Chief Executive Officer of Ocular Therapeutix. “HELIOS-2 and HELIOS-3 are complementary superiority studies targeting a comprehensive and broad DR label. The HELIOS study designs reflect our intentional and strategic clinical philosophy: combining scientific rigor, outstanding clinical execution, and a focus on de-risking, with regulatory alignment to optimize the potential for success and a label that readily translates into broad adoptability. By aiming for a superiority-based DR label that spans the full continuum of disease – including NPDR and DME – we believe AXPAXLI could deliver a market opportunity that is not merely incremental, but transformative for patients, physicians, and payors around the world.” The HELIOS program is comprised of two complementary superiority studies, HELIOS-2 and HELIOS-3, designed to evaluate whether early AXPAXLI treatment, as infrequent as every 12 months, can meaningfully alter the course of non-proliferative diabetic retinopathy (NPDR). Ocular is targeting a broad diabetic retinopathy (DR) label with the HELIOS program by including patients with non-center-involved diabetic macular edema (non-CI-DME). The studies utilize a novel ordinal ≥2-step diabetic retinopathy severity score (DRSS) primary endpoint. HELIOS-2 is a superiority study comparing AXPAXLI dosed every 12 months to ranibizumab (0.3 mg), while HELIOS-3 compares 6- and 12-month dosing regimens of AXPAXLI to sham. The primary endpoint for each study is assessed at Week 52. Ocular has aligned with the FDA on the novel ordinal DRSS endpoint in its SPA agreement for HELIOS-2. “The HELIOS program has the potential to transform care for patients with diabetic retinal disease, and my patients are excited to participate in this study. Current DR treatments are burdensome and unsustainable – particularly for this working age population, unlike wet AMD – requiring numerous intravitreal injections every year. This limits treatment uptake, leaving many at risk for disease progression and irreversible vision loss,” commented Allen Hu, MD, Principal Investigator at Cumberland Valley Retina Consultants. “AXPAXLI shows significant promise to address the unmet need for an effective treatment with durable efficacy, based on the encouraging HELIOS-1 data. Given the rapid enrollment and outstanding execution of the SOL studies for AXPAXLI in wet AMD, I have full confidence that the Ocular clinical team will deliver another highly successful program in NPDR.” “The new ordinal ≥2-step DRSS endpoint Ocular has developed is an important and creative advancement for the retina field. This approach reflects real-world treatment goals, and I expect it will become the gold standard for DR trials going forward,” said Dilsher S. Dhoot, MD, of California Retina Consultants. “Unlike binary endpoints, this ordinal measure captures changes across the full DRSS spectrum, including improvement, stability, and progression. By allowing every patient to contribute to the primary analysis, it enables more efficient trials while generating clinically meaningful data. If the HELIOS trials are successful, I expect AXPAXLI will be widely adopted across diabetic retinal disease due to its potential for durable efficacy and low treatment burden, making it highly attractive to patients, physicians, and payors alike.” About AXPAXLIAXPAXLI™ (also known as OTX-TKI) is an investigational, bioresorbable, intravitreal hydrogel incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties, being evaluated for the treatment of wet AMD, diabetic retinopathy, and other retinal diseases. About the HELIOS-2 StudyThe registrational Phase 3 HELIOS-2 trial is designed to evaluate the safety and efficacy of AXPAXLI in a multi-center, double-masked, randomized (1:1), parallel group study. This trial is a superiority study of AXPAXLI in approximately 432 subjects with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME). Eligible subjects are randomized to receive a single dose of AXPAXLI or a single dose of ranibizumab (0.3 mg) at Day 1. At Week 52, all subjects are re-dosed with their respective initial treatment of AXPAXLI or ranibizumab (0.3 mg). Subjects will be followed for safety until the end of Year 2. Throughout the study, subjects are assessed monthly. Trial subjects and designated study personnel will remain masked through the end of Year 2. The primary endpoint of HELIOS-2 is the ordinal DRSS 2-step change status at Week 52 from baseline (≥2-step improvement, ≥2-step worsening, less than 2-step change in either direction). The study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. About the HELIOS-3 StudyThe registrational Phase 3 HELIOS-3 trial is designed to evaluate the safety and efficacy of AXPAXLI in a multi-center, double-masked, randomized (1:1:1), three-arm study. This trial will be the second superiority study of AXPAXLI in approximately 930 subjects with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME). Subjects in the first arm receive a single dose of AXPAXLI at Day 1 and are re-dosed at Week 24. Subjects in the second arm receive a single dose of AXPAXLI at Day 1 and sham at Week 24. Subjects in the third arm receive sham at Day 1 and at Week 24, aligned with the AXPAXLI treatment arms for adequate masking. Throughout the study, subjects are assessed every 12 weeks. The primary endpoint of HELIOS-3 is the ordinal DRSS 2-step change status at Week 52 from baseline (≥2-step improvement, ≥2-step worsening, less than 2-step change in either direction). About Diabetic Eye DiseaseDiabetic eye disease is an increasingly prevalent global health concern, driven by the rapidly rising number of individuals diagnosed with diabetes each year. Diabetic retinopathy (DR) is the most common category of retinal diseases, affecting over an estimated 103 million people worldwide. DR is a progressive condition in which retinal blood vessels are damaged following a cascade of events triggered by chronically elevated levels of blood glucose. As many as half of all diabetic patients are expected to develop some form of DR in their lifetime. DR can progress from the non-proliferative (NPDR) stages to the proliferative (PDR) stage characterized by the growth of abnormal new blood vessels. Fewer than 1% of the 6.4 million NPDR patients in the U.S. receive treatment today, despite the availability of anti-VEGF therapies approved for the indication, largely due to the burden of frequent injections. Diabetic macular edema (DME) is also a leading cause of vision loss in the working-age population. DME, the result of an accumulation of fluid in the macula that can afflict patients with diabetes, can occur at any stage of DR. In patients with DME, blood vessels in the eyes leak and start to swell, which can cause vision loss or blindness. Anti-VEGF drugs are approved to treat DME, but these treatments typically require frequent intravitreal injections, placing a significant burden on patients and physicians alike. About Ocular Therapeutix, Inc.Ocular Therapeutix, Inc. is an integrated biopharmaceutical company committed to redefining the retina experience. AXPAXLI™ (also known as OTX-TKI), Ocular’s investigational product candidate for retinal disease, is an axitinib intravitreal hydrogel based on its ELUTYX™ proprietary bioresorbable hydrogel-based formulation technology. AXPAXLI is currently in Phase 3 clinical trials for wet age-related macular degeneration (wet AMD) and non-proliferative diabetic retinopathy (NPDR). Ocular’s pipeline also leverages the ELUTYX technology in its commercial product DEXTENZA®, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients and ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged two years or older, and in its investigational product candidate OTX-TIC, which is a travoprost intracameral hydrogel that has completed a Phase 2 clinical trial for the treatment of open-angle glaucoma or ocular hypertension. Ocular is currently evaluating next steps for the OTX-TIC program. Explore the Company’s new corporate branding and follow the Company on its website, LinkedIn, or X. DEXTENZA® is a registered trademark of Ocular Therapeutix, Inc. The Ocular Therapeutix logo, AXPAXLI™, ELUTYX™, and Ocular Therapeutix™ are trademarks of Ocular Therapeutix, Inc. Forward-Looking StatementsAny statements in this press release about future expectations, plans, and prospects for the Company, the development and regulatory status of the Company’s product candidates, the timing, design, enrollment, randomization, conduct and retention of subjects in the Company’s clinical trials, including the Company’s SOL-1 and SOL-R Phase 3 clinical trials of AXPAXLI (also known as OTX-TKI) for the treatment of wet AMD, and the Company’s HELIOS-2 and HELIOS-3 Phase 3 clinical trials of AXPAXLI for the treatment of NPDR; the Company’s plans to advance AXPAXLI, OTX-TIC, and its other product candidates; the potential utility or adoption, if approved, of any of the Company’s product candidates; and other statements containing the words “anticipate”, “believe”, “estimate”, “expect”, “intend”, “designed”, “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 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 any product or product candidate that receives regulatory approval; the ability to retain regulatory approval of any product or product candidate that receives regulatory approval; the initiation, design, timing, conduct and outcomes of ongoing and planned clinical trials, including the SOL-1 trial, the SOL-R trial, the planned SOL-X trial, the HELIOS-2 trial, and the HELIOS-3 trial; the risk that the FDA will not agree with the Company’s interpretation of the written agreements under the Special Protocol Assessments for AXPAXLI, including for the SOL-1 and HELIOS-2 trials; the risk that even though the FDA has agreed with the overall design of the SOL-1 and HELIOS-2 trials, the FDA may not find that the data generated by the applicable trial supports potential marketing approval; the risk that the FDA might not agree to the Company’s design, protocol, and statistical analysis plan of the SOL-R trial or the HELIOS-3 trial; the risk that the Company and the FDA may not agree on the registrational pathway for any of its product candidates; 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, whether preliminary or interim data from a clinical trial (including masked safety or masked rescue data from the Company’s SOL-1 trial or SOL-R trial) will be predictive of final data from such trial, or whether data from a clinical trial assessing a product candidate for one indication will be predictive of results in other indications; uncertainty as to whether data from the Company’s SOL-X trial will demonstrate clinically meaningful, long-term benefits; uncertainties regarding the potential commercial advantages and/or position of the Company’s product candidates; 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; 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 may 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. Investors & MediaOcular Therapeutix, Inc.Bill SlatteryVice President, Investor Relationsbslattery@ocutx.com

Entered strategic partnership with Otsuka Pharmaceutical Co., Ltd. for the development and commercialization of 4D-150 in the APAC region; to receive $85 million in upfront cash and expects to receive at least $50 million from cost sharing Announced positive long-term safety and efficacy data with 1.5 to 2 years of follow-up from the Phase 1/2 PRISM clinical trial in wet AMD Completed equity offering providing net proceeds of ~$93 million Announced up to $11 million equity investment from the Cystic Fibrosis Foundation to accelerate development of 4D-710 for cystic fibrosis into Phase 2 $372 million in cash, cash equivalents and marketable securities as of September 30, 2025, combined with upfront and expected cost sharing from Otsuka partnership and ~$93 million in net proceeds from equity offering, expected to fund currently planned operations into second half of 2028 EMERYVILLE, Calif., Nov. 10, 2025 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading late-stage biotechnology company advancing durable and disease-targeted therapeutics with potential to transform treatment paradigms and provide unprecedented benefits to patients, today reported Q3 2025 financial results, provided operational highlights and outlined expected upcoming milestones.  “In the third quarter, we made meaningful progress building upon and validating our business strategy focusing on 4D-150 and 4D-710,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “Our recently announced partnership with Otsuka, new data on 4D-150 in wet age-related macular degeneration, equity investment from the Cystic Fibrosis Foundation for advancement of 4D-710 and strengthened balance sheet position us well, with cash runway into 2H 2028, beyond primary readout for our two ongoing 4D-150 4FRONT Phase 3 trials in wet AMD, and provides for indication expansion in diabetic macular edema.” Recent Corporate Highlights Announced Exclusive License Agreement with Otsuka Pharmaceutical Co., Ltd. for Development and Commercialization of 4D-150 in Asia-Pacific Region: 4DMT to receive $85 million upfront cash payment and expects to receive at least $50 million of cost sharing from Otsuka over the next three years for development activities supporting global registration    The Company is eligible for up to $336 million in potential regulatory and commercial milestones and tiered double-digit royalties 4DMT retains full development and commercialization rights for 4D-150 outside the APAC region, including the U.S., Europe and Latin America Completed an Equity Offering with Approximately $93 Million of Net Proceeds: Proceeds to support planned operations into second half of 2028, which include planned 4D-150 Phase 3 clinical trial in diabetic macular edema (DME), and provide more than 12 months of expected cash runway beyond the expected 4FRONT-1 topline data Strengthened Leadership Team to Drive 4D-150 Program Execution Julie Clark, M.D., was promoted to Chief Medical Officer, bringing over 20 years of experience in retina and global clinical development, with a proven track record across 10 BLA-enabling studies, including six Phase 3 trials, with leadership roles in development and approvals of EYLEA®, JETREA®, BEOVU® and IZERVAY®  Liansheng Zhu, Ph.D., joined as SVP, Biometrics and Data Quality, bringing nearly two decades of global experience in late-stage and post-approval clinical development. His expertise includes biostatistics, statistical programming, data science and Health Economics and Outcomes Research. Dr. Zhu has led or contributed to multiple pivotal clinical trials and regulatory submissions resulting in efficient and successful U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals, including for LUCENTIS®, BEOVU® and IZERVAY®  Created Retina Leadership Advisory Board: Glenn P. Sblendorio – Former President and CEO of Iveric BioCal Roberts, M.D. – Former CEO of Lighthouse Guild, Former Chief Medical Officer of Bausch + Lomb, Clinical Professor of Ophthalmology at Weill Cornell Medical Center Wiley A. Chambers, M.D. – Former Director of the Division of Ophthalmology, Center for Drug Evaluation and Research at the FDA Recent Highlights and Expected Milestones for 4D-150 4D-150 for Wet AMD: 4FRONT Global Phase 3 Program: 4FRONT-1, North American Clinical Trial: Enrollment rate exceeds initial expectations, with over 200 patients randomized to date, and is on track to complete enrollment in Q1 2026, with 52-week topline data expected in H1 2027 4FRONT-2, Global Clinical Trial: Enrollment remains on track to be completed in H2 2026, with 52-week topline data expected in H2 2027  PRISM Phase 1/2 Clinical Trial: Announced positive long-term interim results (data cutoff: August 22, 2025)  4D-150 demonstrated consistent and durable benefit across all three patient cohorts as evidenced by maintenance of visual acuity, control of retinal anatomy and reduction of treatment burden at all time points with 1.5-2 years of follow-up Consistent dose response in favor of Phase 3 dose (3E10 vg/eye) continues to be demonstrated across all wet AMD cohorts studied 4D-150 continues to be well tolerated with no new safety or intraocular inflammation findings with up to 3.5 years of follow-up   4D-150 for DME: SPECTRA Clinical Trial: Presented positive 60-week results (data cutoff: May 3, 2025)   4D-150 continues to be well tolerated across all patients and dose levels, with no intraocular inflammation observed at any time point or dose levelFollowing the three loading doses of aflibercept, 3E10 vg/eye, the Phase 3 dose demonstrated strong signals of clinical activity, with sustained gain of BCVA of +9.7 letters and reduction of CST of -174 µm from baseline Supplemental injections: Phase 3 dose achieved 78% reduction in injection burden vs. projected on-label aflibercept 2mg Q8W Dose response observed for the Phase 3 dose vs. lower doses (58% fewer injections) Recent Highlights and Expected Milestones in 4D-710 Program 4D-710 for Cystic Fibrosis (CF) Lung Disease: Secured an equity investment from the CF Foundation of up to $11 million in two tranches, with the first tranche of $7.5 million received in October 2025 The funding will support:  Phase 1 Redosing and Phase 2 Cohort in AEROW clinical trial Phase 3 Readiness Interim safety and efficacy data from AEROW Phase 1 clinical trial expected by year-end 2025  Q3 2025 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $372 million as of September 30, 2025, as compared to $505 million as of December 31, 2024. The net decrease in cash was primarily a result of cash used in operations. Based on our current operating plan, we estimate that our existing cash, cash equivalents and marketable securities, and expected payments under our collaboration agreement with Otsuka, together with the net proceeds from the November 2025 equity offering, will be sufficient to fund our operating expenses and capital expenditure requirements at least into the second half of 2028. R&D Expenses: Research and development expenses were $49.4 million for the third quarter of 2025, as compared to $38.5 million for the third quarter of 2024. This increase was primarily driven by the Phase 3 clinical trials of 4D-150 in wet AMD. G&A Expenses: General and administrative expenses were $11.8 million for the third quarter of 2025, as compared to $12.7 million for the third quarter of 2024. The decrease was primarily due to decreased headcount of general and administrative personnel. Net Loss: Net loss was $56.9 million for the third quarter of 2025, as compared to net loss of $43.8 million for the third quarter of 2024. About 4DMT 4DMT is a leading late-stage biotechnology company advancing durable and disease-targeted therapeutics with potential to transform treatment paradigms and provide unprecedented benefits to patients. The Company’s lead product candidate 4D-150 is designed to be a backbone therapy forming the foundation of treatment of blinding retinal vascular diseases by providing multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) with a single, safe, intravitreal injection, which substantially reduces the treatment burden associated with current bolus injections. The Company’s lead indication for 4D-150 is wet age-related macular degeneration, which is currently in Phase 3 development, and second indication is diabetic macular edema. The Company’s second product candidate is 4D-710, which is the first known genetic medicine to demonstrate successful delivery and expression of the CFTR transgene in the lungs of people with cystic fibrosis after aerosol delivery. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.   All of the Company’s product candidates are in clinical or preclinical development and have not yet been approved for marketing by the U.S. Food and Drug Administration or any other regulatory authority. No representation is made as to the safety or effectiveness of the Company’s product candidates for the therapeutic uses for which they are being studied.  Learn more at www.4DMT.com and follow us on LinkedIn. Forward-Looking Statements: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the therapeutic potential and clinical benefits of, as well as the plans, announcements and related timing for the clinical development of our product candidates, the potential benefits of the strategic partnership with Otsuka, the amount of any potential cost sharing or milestone payments pursuant to the Company’s agreement with Otsuka, the Company’s use of proceeds, the potential benefits of the investment from and collaboration with the CF Foundation, the potential additional second tranche funding from the CF Foundation and statements regarding our financial performance, results of operations and anticipated cash runway. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics’ most recent Quarterly Report on Form 10-Q filed on or about the date hereof, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent 4D Molecular Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.  4D Molecular Therapeutics, Inc.Statements of Operations(Unaudited)(in thousands, except share and per share amounts) Three months endedSeptember 30, Nine months endedSeptember 30, 2025 2024 2025 2024 Revenue: Collaboration and license revenue $90 $3 $119 $36 Operating expenses: Research and development 49,438 38,484 138,088 98,212 General and administrative 11,837 12,651 36,293 33,548 Total operating expenses 61,275 51,135 174,381 131,760 Loss from operations (61,185) (51,132) (174,262) (131,724)Other income, net 4,309 7,289 14,756 20,527 Net loss $(56,876) $(43,843) $(159,506) $(111,197)Net loss per share, basic and diluted $(1.01) $(0.79) $(2.85) $(2.08)Weighted-average shares outstanding used in computing net loss per share, basic and diluted 56,126,330 55,554,476 55,933,890 53,377,712 4D Molecular Therapeutics, Inc.Balance Sheet Data(Unaudited)(in thousands) September 30,2025 December 31,2024 Cash, cash equivalents and marketable securities $372,228 $505,460 Total assets 423,982 560,384 Total liabilities 54,999 49,778 Accumulated deficit (735,701) (576,195)Total stockholders’ equity 368,983 510,606 Contacts: Media: Jenn Gordondna CommunicationsMedia@4DMT.com Investors: Julian PeiHead of Investor Relations and Strategic FinanceInvestor.Relations@4DMT.com