Sozinibercept

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

正文共：3063字 15图预计阅读时间：8分钟    眼科是一个庞大的市场，其中黄斑水肿市场超过200亿美金。黄斑水肿主要是由于血视网膜屏障功能破坏，使视网膜缺血，促使大量VEGF释放，促进血管新生进入黄斑区，导致液体渗漏在黄斑区积累，而导致黄斑水肿和视力受损。现在上市的药物主要是抑制血管新生，有Aflibercept、Ranibizumab、Faricimab。Aflibercept在2024年的年销售额已达到95.46亿美金。因此，多家公司均有布局眼科管线。    现有药物主要通过抑制VEGF-A通路抑制血管新生。据统计，大于45%的患者在接受VEGF-A阻断药物后未实现显著视力增加，25%的患者在一年后视力仍会继续恶化，仍存在未满足的临床需求。    除了VEGF-A外，VEGF-C/D也可以激活VEGF通路（图1），促进血管新生。并且在wAMD患者接受VEGF阻断药物后，眼内VEGF-C会上升（图2）。提示机体可能通过增加VEGF-C代偿阻断VEGF-A的作用，从而降低VEGF-A阻断药物的药效。    Opthea这家公司引进了一款anti-VEGF-C/D药物OPT-302。在小鼠激光照射眼睛诱导脉络膜血管新生模型中发现，OPT-302能够抑制血管新生，且能增强Aflibercept的药效（图3）。    该公司对这款药充满了信心，专注对OPT-302进行临床开发。我们来看看这家公司是怎样推进临床试验的。    黄斑水肿按诱因分为多种亚型，其中最大的市场是nAMD (Neovascular Age-related Macular Degeneration，新生血管型年龄相关性黄斑水肿)，其次是DME (Diabetic macular edem，糖尿病性黄斑水肿)。Opthea将OPT-302定位于现有VEGF阻断药物的后续治疗，并且需要与现有VEGF阻断药物联用。图4展示了公司的临床试验计划和进展。    在开展3期前，在DME中选择的VEGF阻断药物经治病人，未见对Aflibercept的增效；在nAMD中选择的未使用过VEGF阻断药物的病人，其1期结果未见披露，仅披露了2期结果。在nAMD中的2期试验是非常大的2期试验，招募了962人，入组了366人；虽然在第24周2mg OPT-302与Ranibizumab联用后，较Ranibizumab有显著药效（图5），但可见药效差异并不到。Opthea对nAMD亚型进行了细分，发现在Occult lesion type和PCV lesion type亚型中有更显著地提升。    基于此，其开展了2个3期试验，一个选择了2期试验所用的对标药物Ranibizumab，另一个选择了Aflibercept；并且在这2个3期试验中均同时测试OPT-302两个给药频率。招募规模与2期相似，均是九百多人，并且在招募中提高了上述有更显著药效的nAMD亚型病人。    可惜公司2025年3月披露，两项3期试验在整个人群，以及在任何亚群中，均未看到显著药效。    OPT-302的失败并非偶然，三点促成了其失败：    1. 忽略了OPT-302的2大自身短板，未积极开发和推进二代药物短板1：机制上只能与VEGF-A阻断药物联用。因为VEGF-A在血管新生中占主导作用，单独阻断VEGF-C/D药效肯定弱于现在上市的靶向VEGF-A的药物。短板2：成药性差。针对的适应症需要在眼睛玻璃体内注射，注射体积有限，一般给药体积是50-70ul。注射体积太大会引起眼内压升高风险，因此，药物比拼的是最小体积能达到多少mg。同时可以达到的浓度越大，越有可能提高给药周期。因为病人不愿意进行频繁的眼内注射，所以现在上市药物不断在探索增加单次给药量来降低给药频率。Aflibercept已经能做到8 mg/70ul，由原来的Q4W，可以实现Q16W。OPT-302只能做到2 mg/50ul。因此，联用用药就是50ul + 50ul，很容易引起眼内压升高，且延长给药周期的潜力较小。未积极布局二代药物。公司未披露与αVEGF-A组合双抗的开发情况，但官网显示有布局OPT-302与VEGF-A药物co-formulation制剂，只是还在评估可行性。反观信达生物，其开发了VEGF-A Trap x VEGF-C双抗，机制上能保证药效。    2.  临床试验太过激进定位过高。最开始直接定位于prior-treated的患者。在临床2期测试时，才专注treatment naïve患者，且直接在nAMD中测试。一般策略是先在treatment naïve DME（这群病人对VEGF阻断药物响应更好）中确定临床药效后，再逐步放大。临床试验太多。由于是测试OPT-302与Aflibercept或Ranibizumab联用后的增效能力，对比组和对照组均需要Aflibercept或Ranibizumab，试验成本很高。公司却仍然选择在wAMD和DME两个适应症中测试，并开展2项3期试验，2项试验中均测试了OPT-302的两个给药周期（Q4W和Q8W）。    3.  对临床数据盲目自信    2期试验中，DME适应症选择的prior-treated DME患者，在整个人群（n = ~108）中，没看到OPT-302对Aflibercept的增效；nAMD适应症选择的treatment naïve nAMD患者，实际招募了962人，入组了366人，每个测试组大概120人。在这么大型的nAMD 2期临床试验中，在低剂量组（0.5mg）没有看到药效；在最高剂量组（2mg）看到了显著差异（p=0.01 at week 24, 图5），但这个差异并不大。并且这个2期试验是在10个国家、109个中心开展的。对这样混杂的大型的临床数据的解读是不是应该更保守点？    3期试验是在33个国家、~400个中心开展的。从2021年3月开始招募，2023年公司披露该试验已完成~75%的入组，但公司迟迟未公布topline data，直到今年3月才披露开展的2项3期失败的结果。    公司应该默默承担着不少压力，因为其临床试验过于激进，导致其虽然在2020年已经纳斯达克上市，但仍需获得额外融资。由于对临床数据的盲目自信，在2022年其选择进行非股权稀释性融资。如今临床失败，可能面临巨额还款。    靠一款药撑起一家公司已有很多成功案例，但是能否赌对一款药，还是要综合分析现有治疗药物的最大短板、突破性药物的作用机制和目标市场。在这个万物皆可联的时代，比拼的还是对疾病发病机制、靶点和药物作用机制的理解，当然还有从成药性角度优化分子的能力。参考资料：1. 公司官网2. 药时代BD需求 | 寻找眼科创新药项目，考虑小分子、单抗/多抗、核酸药物、分子胶、基因疗法......3. 其它公开资料图片来源：公司官网、豆包AI药时代BD需求 | 寻找眼科创新药项目，考虑小分子、单抗/多抗、核酸药物、分子胶、基因疗法......2025-07-21重磅合作！BMS & 贝恩资本成立自免NewCo2025-07-292025-07-286000万美元！ADC新锐获得Pre-A+轮融资2025-07-285亿美元首付款！恒瑞达成120亿美元出海交易2025-07-28具有Best-in-Class潜力的CDH17 ADC寻找合作伙伴 | 药时代BD项目版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩内容！