VEGF-C inhibitors(Vascular endothelial growth factor C inhibitors), VEGF-D inhibitors(Vascular endothelial growth factor D inhibitors), VEGFR3 modulators(Vascular endothelial growth factor receptor 3 modulators)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Lymphangioleiomyomatosis

Inactive Indication

Diabetic macular oedemaNeovascularization, PathologicWet age-related macular degeneration+ [1]

Originator Organization

Ceryvyn Therapeutics Ltd.

Active Organization

Ceryvyn Therapeutics Ltd.

Inactive Organization-

License Organization

Ceryvyn Therapeutics Ltd.

Launch Therapeutics, Inc.

Drug Highest PhasePreclinical

First Approval Date-

RegulationFast Track (United States)

Structure/Sequence

Sequence Code 9733459

Source: *****

Clinical Trials associated with Sozinibercept

NCT04757610

/ TerminatedPhase 3

A Phase 3, Multicentre, Double-masked, Randomised Study to Evaluate the Efficacy and Safety of Intravitreal OPT-302 in Combination With Ranibizumab, Compared With Ranibizumab Alone, in Participants With nAMD

A 2-year, phase 3, multicentre, randomised, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at Week 52.

Start Date12 Mar 2021

Sponsor / Collaborator

Ceryvyn Therapeutics Ltd.

NCT04757636

/ TerminatedPhase 3

A Phase 3, Multicentre, Double-masked, Randomised Study to Evaluate the Efficacy and Safety of Intravitreal OPT-302 in Combination With Aflibercept, Compared With Aflibercept Alone, in Participants With nAMD

A 2-year phase 3, multicentre, randomised, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at Week 52.

Start Date12 Mar 2021

Sponsor / Collaborator

Ceryvyn Therapeutics Ltd.

NCT03397264

/ CompletedPhase 1/2

Phase 1b/2a Study of OPT-302 in Combination With Aflibercept for Persistent Central-involved Diabetic Macular Edema

A two part, multi-center study consisting of a Phase 1b open label, sequential dose escalation followed by a Phase 2a randomized, double-masked, dose expansion evaluating OPT-302 in combination with aflibercept in participants with persistent central-involved Diabetic Macular Edema.

Start Date16 Jan 2018

Sponsor / Collaborator

Ceryvyn Therapeutics Ltd.

100 Clinical Results associated with Sozinibercept

100 Translational Medicine associated with Sozinibercept

100 Patents (Medical) associated with Sozinibercept

Literatures (Medical) associated with Sozinibercept

01 Dec 2025·EYE

Novel targets beyond vascular endothelial growth factor-A inhibition: improving vision with neovascular age-related macular degeneration treatment

Review

Author: Han, John J ; Leitch, Ian M ; Regillo, Carl ; Baldwin, Megan E ; Wong, Tien Y ; Weng, Christina Y ; Khanani, Arshad M ; Bakri, Sophie J

The primary goal in the management of neovascular age-related macular degeneration (nAMD) is to optimise visual acuity outcomes for patients. Landmark clinical trials have demonstrated improved visual outcomes with standard-of-care vascular endothelial growth factor (VEGF) inhibitors, principally targeting a single ligand (VEGF-A). However, in the real-world setting, not all patients attain optimal visual outcomes with these monotherapies. The role of the VEGF-A and VEGF receptor (VEGFR)-2 axis in angiogenesis and vascular permeability is well characterised, but other VEGF family members, including VEGF-C and VEGF-D, which activate VEGFR-2 and VEGFR-3, have also been implicated in nAMD pathogenesis. This may explain the heterogeneous responses observed with current therapies that primarily inhibit VEGF-A signalling, and in patients who continue to lose vision despite treatment, the consequences can be profound. Vision loss affects daily living and can lead to increased cost of care and susceptibility to falls and injuries. This review will explore the VEGF family of ligands and receptors and their role in nAMD, as well as novel therapeutics in development that target mediators beyond VEGF-A with the potential to provide improved vision benefits to patients. In particular, sozinibercept, an investigational trap biologic inhibitor of VEGF-C and VEGF-D ligands, has shown promising efficacy with superior vision gains when used in combination with ranibizumab dosed monthly (standard-of-care therapy) vs. standard-of-care alone (i.e. monthly ranibizumab). This adds to the increasing evidence that multifaceted approaches that target the VEGF family beyond VEGF-A have the potential to provide better vision outcomes for patients with nAMD.

01 Jul 2025·Ophthalmology science

Sozinibercept (Anti-VEGF-C/-D) Combined with Ranibizumab for Polypoidal Choroidal Vasculopathy: Phase IIb Predefined Subgroup Analysis

Article

Author: Wykoff, Charles C ; Slakter, Jason ; Khanani, Arshad M ; Cheung, Chui Ming Gemmy ; Jackson, Timothy L ; Baldwin, Megan E ; Leitch, Ian M

Purpose:

The aim of this study was to assess the efficacy of sozinibercept, a novel "trap" inhibitor of VEGF-C and VEGF-D, when combined with ranibizumab for the treatment of polypoidal choroidal vasculopathy (PCV).

Design:

Prespecified subgroup analysis of a randomized, double-masked, sham-controlled phase IIb trial.

Participants:

Adults with treatment-naïve neovascular age-related macular degeneration.

Methods:

Participants were randomized 1:1:1 to receive a total of 6 intravitreal injections of ranibizumab 0.5 mg given 4-weekly, in combination with either 0.5 mg sozinibercept, 2 mg sozinibercept, or sham injection (control). Active PCV was determined at baseline by masked readers at an independent imaging center based on multimodal imaging, including OCT (notched, sharply peaked, or multilobular pigment epithelial detachments with or without a ring of hyperreflectivity along the inner border), fundus photography (subretinal orange nodules), and fluorescein angiography (typical primarily occult multifocal lesions).

Main Outcome Measures:

The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) through week 24. Secondary end points included categorical changes in BCVA from baseline, anatomical changes in lesion morphology, and safety.

Results:

Of 366 participants, PCV was identified in 66 (18%) using predefined criteria. Sozinibercept combination therapy produced a dose response, with a mean BCVA change from baseline to week 24 of +13.54 (2 mg, n = 22) and +10.87 (0.5 mg, n = 24) letters compared with +6.9 letters for ranibizumab (n = 20), respectively. The 2 mg sozinibercept combination group had a superior BCVA gain versus ranibizumab (+6.7 letter difference in least squares mean; P = 0.0253) with more participants gaining ≥10 letters (77.3 vs. 47.4%) and ≥15 letters (40.9 vs. 31.6%) and fewer losing ≥5 letters (4.5 vs. 15.8%). Anatomic responses were consistent with functional outcomes and at week 24, fewer participants in the 2 mg sozinibercept combination group had subretinal fluid (19%) or intraretinal cysts (9.1%) than with ranibizumab monotherapy (42.1% and 25%, respectively). The safety profile of sozinibercept combination therapy was similar to ranibizumab.

Conclusions:

In this predefined phase IIb subgroup of patients with PCV, sozinibercept combination therapy through inhibition of VEGF-C/-D achieved improved visual and anatomic outcomes compared with ranibizumab monotherapy consistent with the overall population.

Financial Disclosures:

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

01 May 2025·Ophthalmic Surgery Lasers & Imaging Retina

Sozinibercept Combination Therapy for Neovascular Age-related Macular Degeneration: Phase 2b Study Subgroup Analysis by Lesion Type

Article

Author: Slakter, Jason ; Wykoff, Charles C. ; Jackson, Timothy L. ; Price, Clare F. ; Leitch, Ian M. ; Baldwin, Megan E.

Background and Objective:

The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept.

Patients and Methods:

Prespecified and post hoc subgroup analyses of a phase 2b, randomized, double-masked, sham-controlled trial of 240 participants with treatment-naïve neovascular age-related macular degeneration, comparing monthly intravitreal sozinibercept 0.5 mg or 2 mg, plus ranibizumab 0.5 mg, versus monthly ranibizumab monotherapy.

Results:

Visual acuity benefits at week 24 were greatest in participants with occult lesions receiving 2 mg sozinibercept combination therapy (+15.65 [ n = 53] letters versus +9.62 [ n = 51] with ranibizumab monotherapy; least squares mean difference +6.03; P = 0.0009). A composite analysis of occult and minimally classic lesions excluding retinal angiomatous proliferation ( n = 175/240) also favored sozinibercept over control (+16.08 versus +10.34 letters; +5.74; P = 0.0002). Structural outcomes mirrored sozinibercept visual acuity benefits, with less leakage and smaller lesions on multimodal imaging.

Conclusion:

Angiographic lesion characteristics were found to predict the response to sozinibercept combination therapy. [ Ophthalmic Surg Lasers Imaging Retina 2025;56:287–296.]

News (Medical) associated with Sozinibercept

18 Aug 2025

·ir.opthea.com

Opthea Provides Corporate Update

Successful DFA settlement reached Company with cash and cash equivalents of approximately USD20M Dr Fred Guerard , CEO, Tom Reilly , CFO, and Sujal Shah , Director, to step down Dr Jeremy Levin to continue as Chairman and to assume additional responsibilities as of September 1st MELBOURNE, Australia and PRINCETON, N.J. , Aug. 18, 2025 (GLOBE NEWSWIRE) -- Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), today provided a corporate update following the successful settlement of the Development Funding Agreement ("DFA") with the two investors under the DFA. DFA Settlement In March of 2025, after the primary endpoints were not met in both COAST and ShORe phase 3 clinical trials, Opthea , and Ocelot SPV LP and Sanba II Investment Company (together the " DFA Investors ") agreed to discontinue the development of sozinibercept in wet AMD. As previously disclosed, certain termination events under the DFA could have triggered payments by the Company of up to USD680 million . In light of these matters, there was material uncertainty as to Opthea's ability to continue as a going concern and trading of Opthea’s stock on ASX and NASDAQ was suspended. After extensive negotiations, Opthea has reached a binding agreement with the DFA Investors to terminate the DFA. As part of the settlement arrangements, all parties have entered into an agreement of settlement and release ("Settlement Agreement") and an equity subscription deed ("Subscription Deed"). Pursuant to the Subscription Deed: The DFA Investors will be collectively issued equity equivalent to 9.99% of the total issued share capital of the Company on a fully diluted basis, being 136,661,003 fully paid ordinary shares ("Subscription Shares") with no subscription payment required from the DFA Investors . The Subscription Shares will be issued in consideration for the DFA Investors' entry into the Settlement Agreement, the key terms of which are summarized below. The Subscription Shares will be issued under the Company's existing placement capacity under ASX listing Rule 7.1, and rank equally with existing fully paid ordinary shares in the Company. The issuance of the Subscription Shares will take place contemporaneously with payment by the Company of the Cash Amount under the Settlement Agreement (as described below). The DFA Investors have agreed to a voluntary 12-month escrow period, subject to certain carveouts, including disposals where required by law, under any equal access share buyback, capital return or capital reduction, to an affiliate or related body corporate, or circumstances where disclosure to investors would not be required under s 708 of the Corporations Act 2001 (Cth). If a court determines the issuance of more than 68,262,103 Subscription Shares to be avoidable or unenforceable, and such issuance is rescinded or the shares must otherwise be returned to the Company ("Equity Avoidance"), then, to the extent of such Equity Avoidance, the Company must take all actions reasonably required by the DFA Investors to reissue or otherwise replace those Subscription Shares with such number of shares as will restore the DFA Investors' holdings to the position immediately after the issuance of the Subscription Shares. The parties have agreed various standard form representations and warranties. Pursuant to the Settlement Agreement: The DFA Investors will collectively receive from the Company a one-time payment of USD20 million ("Cash Amount"). Upon payment by the Company of the Cash Amount and issuance of the Subscription Shares (the "Effective Date"), the DFA Investors will release all liens on the collateral, the DFA will be terminated, and all parties will mutually release all suits, actions, damages and other claims in relation to the DFA. If any portion of the Cash Amount in excess of USD1,000,000 is determined by a court to be unenforceable ("Avoidance Amount") and such Avoidance Amount is rescinded or must otherwise be returned by a DFA Investor, the Company must repay the Avoidance Amount to that DFA Investor. From the date on which a DFA Investor returns the Avoidance Amount until the date the Company repays that amount to that DFA Investor, all of that DFA Investor's security interests and lien over the Company's assets shall be reinstated ("Springing Lien"), and will be released immediately upon the Company's repayment of the Avoidance Amount to that DFA Investor. For two years after the Effective Date, the Company is restricted from granting any security interest, lien, or charge (a “Prohibited Lien”) over its assets to any creditor existing as of the Effective Date with respect to any claim(s) existing as of the Effective Date, unless such Prohibited Lien is made expressly junior to any lien that may arise by operation of the Springing Lien. As a result of the above settlement arrangements, the directors of the Company have determined that, on and from the Effective Date, they no longer need to avail themselves of the "safe harbour" protections under section 588GA of the Corporations Act 2001 (Cth). These settlement terms will result in Opthea remaining solvent and with estimated unaudited cash and cash equivalents of approximately USD20 million as at the Effective Date, after payment of the Cash Amount. “I am very grateful to the DFA Investors for their understanding and collaboration which resulted in settlement of the DFA and Opthea remaining solvent,” said Dr Fred Guerard , outgoing Chief Executive Officer. Corporate Update Now that the clinical trials activities have been concluded and a settlement on the DFA reached, Dr Fred Guerard , CEO, will depart the Company on September 1 st, 2025. Tom Reilly , CFO, and Sujal Shah , Director, will depart on September 15 th, 2025. Opthea's overall strategy to streamline its operations has resulted in the Company reducing its work force by over 80%, reducing the Board of Directors by over 50% and renegotiating all contracts related to the clinical trials. The Board of Directors will continue to focus on maximizing shareholder value and will assess the following: Full strategic review over the next six months Targeted internal development Strategic partnerships or potential BD/Licensing, where appropriate Return of capital to shareholders, where appropriate “The Board of Directors and I are very grateful for Fred and Tom’s dedication and professionalism in navigating these complex negotiations,” said Dr Jeremy Levin , Chairman. “I would also like to express my gratitude to Sujal Shah for his commitment to the Board of Directors.” Dr Jeremy Levin will continue as Chairman. In addition, the Board has determined to engage Dr Levin to fulfil the roles and responsibilities of the outgoing chief executive officer, with effect from September 1st, 2025 . “I am honoured to continue to act as Chairman and to assume these additional responsibilities for the Company as we enter a new phase and evaluate all options for the future," said Dr Jeremy Levin , Chairman. A summary of the material terms of Dr Levin's arrangements are set out in Annexure A. Trading in Opthea's listed securities remains suspended by ASX under ASX Listing Rule 17.3. Opthea is currently engaging with the ASX regarding these matters. The Company will host a webcast on Tuesday 19 August at 7pm ET /Wednesday 20 August at 9am AEDT. Links to register or access the webcast will be available on the Investor Section of the Company’s website under “Events and Presentations”. 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 changes in management and the Board of Directors of the Company and the timing of such changes 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 the Company's ability to identify future product candidates, 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, continued compliance with listing requirements 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. Investors InquiriesEmail: info@opthea.com Web: www.opthea.com Source: Opthea Limited Annexure A – Summary of Dr Jeremy Levin's arrangements The material terms of Dr. Jeremy Levin's engagement are as follows: Dr Levin's agreement is effective from 1 September 2025 . Dr. Levin will continue to act as Chairman and will be engaged by the Company as a consultant to fulfil the roles and responsibilities of the outgoing chief executive officer. Cash remuneration of: as Chairman, AUD $150,000 per annum; as a Board Committee member, AUD $6,500 per annum per Board Committee; to fulfil the roles and responsibilities of the CEO, AUD $210,000 per annum, excluding statutory entitlements (if applicable), being AUD $379,500 per annum (assuming three Board Committees), plus a 30% retention bonus. Dr Levin already holds securities under the Company's incentive scheme in his role as Chairman. In respect of Dr Levin's engagement to fulfil the roles and responsibilities of CEO, no short-term or long-term incentives have been agreed between the parties, though Dr Levin remains entitled to participate in the incentive scheme. Either party may terminate the engagement for any reason on giving three months’ notice, unless a shorter notice period is mutually agreed by the parties. Opthea may elect to make a payment in lieu of the notice period. Dr Levin's engagement is otherwise on customary terms for an agreement of this nature. as Chairman, AUD $150,000 per annum; as a Board Committee member, AUD $6,500 per annum per Board Committee; to fulfil the roles and responsibilities of the CEO, AUD $210,000 per annum, excluding statutory entitlements (if applicable), being AUD $379,500 per annum (assuming three Board Committees), plus a 30% retention bonus. Source: Opthea Limited

Executive ChangePhase 3

31 Mar 2025

·ir.opthea.com

Opthea Announces Decision to Discontinue Wet AMD Trials

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

Phase 3Clinical Result

25 Mar 2025

·www.biospace.com

Opthea, UNITY Fail to Unseat Regeneron’s Eylea in Vision Disorders

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.

Clinical ResultPhase 3Phase 2

100 Deals associated with Sozinibercept

External Link

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D12635	-	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Wet age-related macular degeneration	Phase 3	United States	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Argentina	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Australia	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Austria	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Brazil	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Bulgaria	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Canada	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Colombia	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Croatia	Ceryvyn Therapeutics Ltd.	12 Mar 2021
Wet age-related macular degeneration	Phase 3	Czechia	Ceryvyn Therapeutics Ltd.	12 Mar 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04757636 (COAST, CTgov)	Phase 3	Wet age-related macular degeneration	998	2.0 mg OPT-302+2.0 aflibercept (2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302)	gkzdzxvtgz(ltjegivakp) = ecyjvkakry murbkfhdyt (xqtntdxkrz, 0.729) View more	-	05 Aug 2025
				2.0 mg OPT-302+2.0 aflibercept (2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302)	gkzdzxvtgz(ltjegivakp) = lzoadqytit murbkfhdyt (xqtntdxkrz, 0.728) View more
NCT04757610 (ShORe, CTgov)	Phase 3	Wet age-related macular degeneration	986	2.0 mg OPT-302+0.5 mg ranibizumab (0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302)	zwekjkdrys(mrkxmihsdl) = orjfozlezy ntimfoakvg (ajckgzqazo, 0.728) View more	-	22 Jul 2025
				2.0 mg OPT-302+0.5 mg ranibizumab (0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302)	zwekjkdrys(mrkxmihsdl) = bhfrygoprv ntimfoakvg (ajckgzqazo, 0.731) View more
NCT04757636 (COAST, Company_Website) Manual	Phase 3	Wet age-related macular degeneration	-	Sozinibercept 2 mg every four weeks + aflibercept	akfhfpycga(kmprdjnxyk) = cckilzudmy hanikcxotl (canrisxtvj ) Not Met	Negative	24 Mar 2025
				Sozinibercept 2 mg every eight weeks + aflibercept	akfhfpycga(kmprdjnxyk) = xowsxmlslg hanikcxotl (canrisxtvj ) Not Met
NCT03345082 (Literature) Manual	Phase 2	Wet age-related macular degeneration First line	240	sozinibercept 2 mg,+ranibizumab 0.5 mg	urnkbyequt(yzhvgwybtc) = ttdfsmsspm wfewvstffl (aqpqrtvuky )	Positive	01 Feb 2025
				ranibizumab 0.5 mg	urnkbyequt(yzhvgwybtc) = ndexedndul wfewvstffl (aqpqrtvuky )
NCT03345082 (EURETINA2024) Manual	Phase 2	Polypoidal choroidal vasculopathy	66	Ranibizumab 0.5 mg	nzawcqyfgw(atrhjzsjbm) = tzpvunsuok pboiqehhwi (lkwyvjkkfh ) View more	Positive	19 Sep 2024
				Sozinibercept 0.5 mgRanibizumab	nzawcqyfgw(atrhjzsjbm) = zpwckptvpq pboiqehhwi (lkwyvjkkfh )
NCT03397264 (CTgov)	Phase 1/2	Diabetic macular oedema	153	OPT-302+Aflibercept (Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302)	usmxkgjzwq = rbzbulhrrs iqkldcsbhv (avdqoduedl, mlwwyzlarz - kilkxcdjzq) View more	-	22 Jun 2022
				OPT-302+Aflibercept (Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302)	usmxkgjzwq = lwbxinpdry iqkldcsbhv (avdqoduedl, uvgfmrncmm - hfauywmbau) View more
NCT03397264 (GlobeNewswire) Manual	Phase 2	Diabetic macular oedema	115	Aflibercept+OPT-302	vgqircnylv(mwqbdhchem) = zfvqgxgchp rowpkpiepk (cmrjdhsgew ) View more	Positive	09 Jun 2020
				Aflibercept+Sham Procedure	vgqircnylv(mwqbdhchem) = zbxcdetfge rowpkpiepk (cmrjdhsgew ) View more
NCT02543229 (Pubmed) Manual	Phase 1	Wet age-related macular degeneration	51	OPT-302	knryqfkkwx(vzftjldonj) = timdyzyiiu nrqyizqyqc (nmzfnilrnq )	Positive	01 Mar 2020
				ranibizumab+OPT-302	knryqfkkwx(pvgzpwjjkb) = zngklzfvtl bgbqfrzhus (cgdlmrvhjx, 3 - 7) View more

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