VEGF-C

EMERYVILLE, Calif., May 01, 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 announced that the U.S. Food and Drug Administration (FDA) has granted the Regenerative Medicine Advanced Therapy (RMAT) designation to 4D-150 for the treatment of diabetic macular edema (DME). “This milestone validates the potential of 4D-150 to address the significant unmet needs of patients with DME, a second large market retinal vascular disease indication after wet age-related macular degeneration (wet AMD),” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “The RMAT designation is based on the review of our results to-date from our ongoing 4D-150 SPECTRA DME study, underscoring the potential of 4D-150 to sustain visual acuity improvements while dramatically reducing treatment burden for patients. This designation in DME follows the RMAT designation granted for 4D-150 in wet AMD, and to our knowledge, 4D-150 is the first investigational medicine to be granted the designation in both indications. We look forward to continuing our ongoing collaboration with the FDA to advance 4D-150 into Phase 3 development with an aligned-upon single Phase 3 trial for approval in DME, combined with our two wet AMD 4FRONT Phase 3 clinical trials.” RMAT designation is part of the 21st Century Cures Act. The program was created to expedite the development and review of regenerative medicine therapies intended to treat, modify, reverse or cure a serious condition. Receiving RMAT designation offers sponsor companies all the benefits of the fast track and breakthrough therapy designation programs, allowing for early, close and frequent interactions with the FDA with the goal of expediting drug development. About 4D-150 4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection. 4D-150 utilizes our customized and evolved intravitreal vector, R100, which was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform. 4D-150 is being developed for wet AMD and DME, which both affect millions of patients globally, with the goal of freeing patients from burdensome injections while preserving vision. About DME DME, or diabetic macular edema, is a complication of diabetic retinopathy and is a highly prevalent disease with significant unmet medical need and poor treatment adherence. It is estimated that there are approximately one million individuals with DME in the U.S. according to published data. DME is characterized by inflammation and swelling in the macula due to leakage from blood vessels, which can lead to vision loss. DME is typically treated with intravitreal anti-VEGF agents administered approximately every 4-12 weeks, although patient compliance with therapy is poor and results in high unmet medical need. 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. Our 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. Our 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. Our 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 our 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 our 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 and market potential of 4DMT’s product candidates, as well as the plans, announcements, and related timing for the clinical development of and regulatory interactions regarding 4D-150. 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 November 13, 2024 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. Contacts: Media: Jenn Gordon dna Communications Media@4DMT.com Investors: Julian Pei Head of Investor Relations and Corporate Finance Investor.Relations@4DMT.com

ShORe Phase 3 topline results accelerated; trial did not meet primary endpoint of mean change in BCVA from baseline to week 52 Opthea and DFA Investors agreed to terminate both COAST and ShORe trials Opthea continues to consider impact of negative trial results under its Development Funding Agreement (DFA) and on the Company as a going concern MELBOURNE, Australia and PRINCETON, N.J. , March 31, 2025 (GLOBE NEWSWIRE) -- Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), today announced updates on its Phase 3 clinical program, including the termination of COAST (Combination of OPT-302 with Aflibercept Study) and accelerated topline results from its second Phase 3 trial ShORe (Study of OPT-302 in combination with Ranibizumab) in patients with wet AMD. ShORe Topline Results Following the negative results of the COAST Phase 3 trial announced on 24 March 2025 , Opthea determined that the most appropriate course of action for wet AMD patients, shareholders, and other stakeholders was to accelerate the ShORe trial topline data readout, including in consultation with its Development Funding Agreement investors (“ DFA Investors ”). The global ShORe Phase 3 trial evaluated the efficacy and safety of intravitreally administered 2 mg sozinibercept every four or eight weeks in combination with 0.5 mg ranibizumab every four weeks, as per label, versus 0.5 mg ranibizumab monotherapy. The trial did not meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52. In wet AMD patients with minimally classic and occult lesions, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=301) or every eight weeks (n=301) achieved a mean change in BCVA of 13.3 or 12.9 letters from baseline to week 52, respectively, versus 14.2 letters with ranibizumab monotherapy (n=299, p-values of 0.35 and 0.19 respectively). In the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=328) or every eight weeks (n=326) achieved a mean change in BCVA of 13.3 and 12.6 letters from baseline to week 52, respectively, versus 14.3 letters with ranibizumab monotherapy (n=331 p-values of 0.32 and 0.09 respectively). Sozinibercept combination therapy was well tolerated. “We are disappointed that COAST and ShORe did not demonstrate the improvements in vision with sozinibercept combination therapy compared to standard of care that we had hoped for,” said Frederic Guerard , PharmD, Chief Executive Officer of Opthea . “We are grateful to all patients, clinical investigators and their staff around the world who participated in the sozinibercept Phase 3 clinical program, and for their contributions in investigating new treatments for wet AMD.” “As previously disclosed, the Company has certain obligations under the DFA. In light of the Phase 3 clinical trial results, the Company and the DFA Investors will continue to discuss this matter in good faith, and we will provide updates on this matter in the future,” Dr. Guerard concluded. Corporate Updates Following the negative results of the COAST and ShORe trials, Opthea and the DFA Investors agreed to discontinue the development of sozinibercept in wet AMD with immediate effect, and that this decision did not constitute a termination event under the DFA resulting in any amount payable by Opthea . It remains possible that under the DFA, in certain circumstances upon or following termination of the DFA, Opthea could become required to pay a multiple of the amount funded by the DFA Investors that would have a material adverse impact on the solvency of the Company. As previously disclosed, termination can be triggered by a range of events, including, among other things, Opthea’s insolvency, in which case Opthea will be obligated to pay a multiple of the amounts funded by the DFA Investors . Opthea continues active discussions with the DFA Investors , pursuant to and as required under the DFA, to explore possible options to deliver the best outcome for the Company and its shareholders. A copy of the DFA is included as Exhibit 4.19 to Opthea’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission on August 30, 2024 . Opthea estimates it will have unaudited cash and cash equivalents of US$100M at the end of March 2025 . In light of these matters, there remains material uncertainty as to Opthea's ability to continue as a going concern.1 As noted above, discussions with the DFA Investors are ongoing and Opthea cannot be certain as to the outcome of those discussions or when that outcome may become known. Opthea is currently relying on the "safe harbour" provisions in section 588GA of the Corporations Act 2001 (Cth). Trading in Opthea’s listed securities will be suspended by ASX under ASX Listing Rule 17.3 until Opthea is in a position to provide an announcement to the market providing more clarity on these issues and the impact on Opthea’s financial position. Authorized for release to ASX by The Board of Directors. Forward-Looking Statements This ASX announcement contains certain forward-looking statements, including within the meaning of the US Private Securities Litigation Reform Act of 1995. The words “expect”, “believe”, “should”, “could”, “may”, “will”, “plan” and other similar expressions are intended to identify forward-looking statements. Forward-looking statements in this ASX announcement include statements regarding possible outcomes in connection with the DFA and Opthea’s ability to continue as a going concern. Forward-looking statements, opinions and estimates provided in this ASX announcement are based on assumptions and contingencies which are subject to change without notice, as are statements about market and industry trends, which are based on interpretations of current conditions. Forward-looking statements are provided as a general guide only and should not be relied upon as an indication or guarantee of future performance. They involve known and unknown risks and uncertainties and other factors, many of which are beyond the control of Opthea and its directors and management and may involve significant elements of subjective judgment and assumptions as to future events that may or may not be correct. These statements may be affected by a range of variables which could cause actual results or trends to differ materially, including but not limited to future capital requirements, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, clinical research organization and labor costs, intellectual property protections, and other factors that are of a general nature which may affect the future operating and financial performance of the Company including risk factors set forth in Opthea’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission (the “SEC”) on August 30, 2024 , and other future filings with the SEC . Actual results, performance or achievements may vary materially from any projections and forward-looking statements and the assumptions on which those statements are based. Subject to any continuing obligations under applicable law or any relevant ASX listing rules, Opthea disclaims any obligation or undertaking to provide any updates or revisions to any forward-looking statements in this ASX announcement to reflect any change in expectations in relation to any forward-looking statements or any change in events, conditions or circumstances on which any such statement is based, except as otherwise required by applicable law. Investor Inquiries PJ Kelleher LifeSci Advisors , LLC Email: pkelleher@lifesciadvisors.comPhone: 617-430-7579 Join our email database to receive program updates: Email: info@opthea.com Web: www.opthea.com Source: Opthea Limited [1] Investors should refer also to the 'going concern' statements contained in Note 2 to Opthea's Condensed Consolidated Financial Statements for the half year ended 31 December 2024 released on 28 February 2025 . Source: Opthea Limited

iStock, White Bear Studio The Eylea franchise was in need of a win after an appellate court last week denied the pharma’s bid to block Amgen’s biosimilar from the U.S. Two investigational eye therapies, from Opthea Limited and UNITY Biotechnology, were unable to unseat Regeneron ’s blockbuster anti-VEGF therapy Eylea on Monday as the standard of care in two different ophthalmic indications. The news comes as Regeneron last week lost its court appeal to prevent Amgen’s biosimilar Pavblu from entering the U.S. market. In a March 15 note to investors, BMO Capital Markets analysts said the failed appeal “reads as a modest negative to Regeneron” and compounds the existing risk to its Eylea franchise. Presenting topline data from the Phase III COAST study, Australian biotech Opthea revealed that its investigational VEGF blocker sozinibercept failed to significantly outperform Eylea at improving vision in patients with wet age-related macular degeneration (AMD). At 52 weeks, best-corrected visual acuity (BCVA) in those treated with sozinibercept improved by 12.8 letters on average from baseline, while mean improvement in Eylea counterparts was 13.7 letters. Like Eylea, sozinibercept is designed to be injected into the eye and also works by binding VEGF, a protein involved in the formation of new blood vessels. Uniquely, however, sozinibercept targets the VEGF-C and VEGF-D subtypes (Eylea binds to VEGF-A and placental growth factor), which according to Opthea is highly expressed in patients receiving the standard VEGF-A therapies, in turn leading to leaky blood vessels that could ultimately also harm vision. Sozinibercept is Opthea’s only clinical candidate , and wet AMD is its most advanced indication. Monday’s Phase III stumble thus presents a financial problem for the biotech, which in its news release revealed that it “has been assessing its rights and obligations” to investors. Opthea could be on the hook for certain payments that “would have a material adverse impact on the solvency of the company,” it wrote. The biotech is in “active discussions” with its investors, trying to determine “whether there is a pathway that represents the best outcome for the company and its shareholders,” according to Monday’s release. Opthea has yet to reach a decision but is mulling over terminating the COAST trial or unmasking a separate wet AMD trial. Also on Monday, California-based UNITY Biotechnology announced that its investigational eye injection UBX1325 likewise fell to Eylea in patients with diabetic macular edema. Topline data from the Phase IIb ASPIRE study showed that UBX1325 improved visual acuity by more than five letters at 24 and 36 weeks versus baseline. These gains, according to UNITY, were “non-inferior” to Eylea at almost all time points through 36 weeks except at the average of weeks 20 and 24. At this time point, UBX1325 showed non-inferiority at an 88% confidence interval—just shy of the 90% prespecified threshold for the study’s primary endpoint. Despite missing its target, UNITY CEO Anirvan Ghosh sang an optimistic tune in a statement on Monday, noting that UBX1325 “showed robust vision improvements in a difficult to treat patient population.” The biotech will continue to advance the candidate into late-stage studies.