Actinium 225-J591

放射性药物疗法研究企业Convergent Therapeutics（以下简称Convergent）再添一员“猛将”。 2024年12月11日，美国生物技术公司Convergent宣布任命Barbara Duncan为其董事会成员。 Barbara Duncan女士是宾西法尼亚大学沃顿商学院工商管理硕士，拥有超过25年的财务管理经验，目前在Atea Pharmaceuticals、皮下药物递送领头羊Halozyme Therapeutics和Ovid Therapeutics三家上市生物制药公司的董事会和各个委员会任职。核药企业Fusion在去年6月被阿斯利康宣布以约24亿美元的价格收购。收购前，Barbara还担任该公司的董事长。 2023年，Convergent完成了奥博资本和RA Capital Management领投，Invus参投的9000万美元A轮融资。去年9月又获得由Novo Holdings（诺和控股）领投的A+轮融资4000万美元。至此，Convergent的A轮融资总额增加到1.3亿美元。 01 25年+开发研究，脱胎于康奈尔大学 Convergent Therapeutics Inc.成立于2020年，总部位于美国马萨诸塞州剑桥。Convergent是一家临床阶段的制药公司，专注于为前列腺癌和其他癌症开发下一代放射性药物疗法。 Philip Kantoff博士是Convergent的首席执行官兼联合创始人，同时担任哈佛Dana-Farber 癌症研究所（DFCI）实体瘤肿瘤学部的主任以及泌尿生殖系统肿瘤学中心的主任。 在创办Convergent之前，Kantoff博士在世界最大的癌症研究中心纪念斯隆—凯特琳癌症中心担任了六年的医学系主任，在治疗癌症患者的同时开发生物标注物和癌症疗法。 如果说Kantoff博士是Convergent的躯干，那放射抗体技术和前列腺特异性膜抗原（PSMA）领域先驱Neil Bander博士就是Convergent的核心。 Neil Bander博士是Convergent联合创始人兼首席科学官，目前就任威尔康奈尔医学院的前泌尿肿瘤学教授。过去25年间，他曾带领团队开发了第一个针对PSMA的单克隆体，并验证了PSMA作为前列腺癌和其他癌症治疗靶点的有效性。 Convergent的核心专有技术—双靶向放射性核素治疗（RNT）便是来自Bander教授的研究，目前已得到康奈尔大学授权。 02 基于α粒子，最大程度减少治疗副作用 放射抗体是一种靶向治疗，其中抗体与放射性有效载荷相关联。这种放射性有效载荷具有通过从内部来破坏细胞来杀死癌细胞的能力。每种放射抗体都是通过精心选择对特定癌症靶标具有高亲和力的抗体而制备的。这使得放射抗体能够归巢并锁定在癌细胞表面。一旦附着，放射性抗体就会被吸入细胞中，将放射性有效载荷输送到细胞核附近，最终杀死癌细胞。 然而，放射治疗是把双刃剑，在杀死癌细胞的同时，也会对周边的健康组织造成无法修复的损伤。经过放射性治疗后，患者可能会出现四肢乏力、恶心呕吐、皮肤变黑等症状。 为此,Convergent基于其专有技术改进了当前放射疗法的局限性。与其他技术相比（包括那些依赖于β发射同位素的技术，如Lu-177），发射α的放射性抗体具有更高的精度和效力，虽然还达不到“0”副作用，但也能在最大程度上减少对其他健康组织的损害，减轻放疗副作用。  α较β粒子的优势  图源:Convergent官网 Convergent公司凭借对α粒子的了解和双靶向放射性核素治疗技术的灵活运用，已经开发了其主要管线产品CONV01-α（Ac-225 rosopatamab tetraxetan）。α粒子具有强大的短程特性，射程相当于几个细胞直径（＜100μm），可最大限度地减少对健康邻近细胞和组织的辐射暴露。当与其专有抗体结合时，便会形成一种有效且精确的放射抗体，能够特异性靶向癌细胞并将放射性有效载荷直接输送到细胞中。 α核素的机制相较于传统β核素更为复杂，存在许多未知领域，其开发极具挑战。首先，这些药物必须具有极高的靶向性，以减少对正常组织的损害。其次，需要克服Actinium-225（释放α粒子的放射性核素之一，通过DNA双链断裂杀死癌细胞）衰变时可能产生的反冲效应，这可能导致药物脱靶。此外，Actinium-225的供应量稀缺也是一个主要问题，因为目前只有少数几个中心能够生产这种核素，且数量有限，无法满足全球医药常规治疗的需求。 拜耳研发的镭-223药物Xofigo是目前唯一获得批准的α发射疗法。根据《靶向阿尔法疗法市场规模、药物批准、专有技术和临床试验洞察（2024）》，目前有超过20种α粒子发射性药物正在进行临床试验。2024年11月，SK Biopharmaceuticals与韩国放射医学科学研究所（KIRAMS）宣布合作，旨在发现和开发使用α粒子放射性同位素Actinium-225的放射性药物候选物。 03 同类最佳，主要候选药物已进入Ⅱ/Ⅲ期临床开发阶段 根据2024年“《柳叶刀》前列腺癌重大报告”（The Lancet Commission on prostate cancer: planning for the surge in cases）的预测，全球前列腺癌病例数将从2020年的每年140万例增加到2040年的每年290万例。 早在去年4月，Convergent的主要候选药物CONV01-α的IND申请就获得了FDA批准。紧接着在9月完成了II期临床首例患者给药，证实其对抵抗性前列腺癌（mCRPC）患者的安全性和有效性。 CONV01-α是一种专有的、同类最佳的Actinium-225标记放射抗体，靶向几乎所有前列腺癌细胞表面表达的蛋白质（抗原）。它结合了抗体的精确性和药代动力学特性，以及α发射型放射性核素的肿瘤杀伤潜力，在精确辐射杀死癌细胞的同时还能保留健康组织。 具体来说，CONV01-α与其他抗体的区别在于能同时使用抗体和α放射性核素。在利用抗体的选择性和α放射性同位素的肿瘤破坏潜力时，Convergent的放射抗体能以有效的局部辐射精确靶向癌细胞。 选择α放射性核素是研发成功的充分条件，而将其与高选择性抗体配对则是创造有效治疗癌症的疗法的必要条件。 单克隆抗体对PSMA等靶标具有更大的亲和力，它能提供更好的肿瘤内化和保留效果，从而使药物的效力更强，所需剂量更少，总体辐射剂量也更低。相比之下，β或α小分子配体则没有这些优势。  抗体作用机理 图源：Convergent官网 此外，通过将Actinium-225与肿瘤靶向抗体连接，在提高肿瘤杀伤辐射传递速度的同时还可以大大降低肿瘤外效应和每个疗程的辐射量，从而提高治疗效果和安全性。 Convergent管线 图源：Convergent官网 目前，Convergent正在进行一项随机、开放标签、多中心的1/2期临床试验研究，旨在评估CONV01-α在mCRPC患者中的安全性和有效性。据其对外披露，结果显示，在威尔康奈尔医学院接受CONV01-α治疗的患者中，67%的患者前列腺特异性抗原（PSA；判断前列腺癌的指标)下降了50%，27%的患者PSA下降了90%。CONVERGE-01的招募工作正在进行中，未来试验的计划仍在继续。 基于对α放射性同位素的开发，Convegent或将利用现有技术开发针对实体瘤的药物。目前处于探索阶段。 Convergent管线 图源：Convergent官网 据动脉网不完全统计，2024年至今，包括阿斯利康、百时美施贵宝在内的多家MNC已投入上百亿美元进军这一领域。近年来，中国在靶向阿尔法粒子放疗领域也取得了显著进展。 2021年7月7日，西南医科大学附属医院完成了我国首例225Ac治疗，标志着我国在该领域的实质性突破。同年9月，我国又开展了国际首例转移性嗜铬细胞瘤225Ac-DOTATATE治疗，并取得了理想疗效。 据磐美迪控股，全球范围内α核素的研究尚处于起步阶段，需要在理论与技术方面取得更多进展。 2024年10月，余飞教授团队在《Theranostics》上发表的“Targeting senescence with radioactive 223Ra/B a SAzymes enables senolytics-unlocked One‐Two punch strategy to boost anti-tumor immunotherapy”研究论文，首次从核辐射驱动的旁观者效应角度探讨了α核素的辐射生物学作用。这是我国在212Pb/212Bi应用基础研究领域的先驱性成果，为α粒子放疗的深入研究和临床应用提供了新的视角和理论支持。 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

First Patient Dosed with CONV01-α in Phase II Clinical Trial in Patients with Metastatic Castration Resistant Prostate Cancer Drug Development Veteran Richard Messmann, MD Appointed as Chief Medical Officer to Lead the Development of CONV01-α Novo Holdings Invests $40 million in Series A Extension to Advance Clinical Development of Radiopharmaceuticals at Convergent Therapeutics CAMBRIDGE, Mass., Sept. 24, 2024 /PRNewswire/ -- Convergent Therapeutics Inc., a clinical stage biotechnology company focused on developing next generation radiopharmaceutical therapies for the treatment of prostate cancer and other cancers, today announced that the first patient has been dosed with CONV01-α in the Phase II CONVERGE-01 trial evaluating CONV01-α, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC). Previously conducted academic studies of CONV01-α have shown encouraging therapeutic results in patients with prostate cancer. According to Neil Bander, MD, Convergent's Co-founder and CSO, "In patients treated at Weill Cornell Medicine, CONV01-α demonstrated a prostate-specific antigen decline of 50% (PSA50) in 67% of patients and a PSA decline of 90% (PSA90) in 27% of patients." These results have prompted initiation of the CONVERGE-01 trial under Convergent's own Investigational New Drug License (IND). "We look forward to evaluating the full potential of CONV01-α and advancing the Phase II trial in the months ahead." The CONVERGE-01 trial is a Phase II, randomized, open-label, multicenter three-part study designed to assess the safety and efficacy of CONV01-α in patients with mCRPC. In Part 1, the first 5 participants will receive In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants will then be enrolled in either Part 2 (dose optimization) or Part 3 (dose escalation) depending on their prior treatment history. Part 2 will enroll Lu-177-PSMA-radioligand therapy-naïve participants and Part 3 will enroll participants who received prior Lu-177-PSMA-radioligand therapy. All patients will receive Ac-225 rosopatamab tetraxetan in a single fractionated two-week cycle. Further details of the trial can be found at under NCT identifier: NCT06549465. Chief Medical Officer Appointment Convergent announced that Richard Messmann, MD, MHS, MSc, has joined the company as Chief Medical Officer. Dr. Messmann is a medical oncologist and biochemist with over 25 years of experience in oncology drug development, including responsibility for the global clinical development and successful regulatory submission of Pluvicto® and Locametz® for the treatment of men with PSMA-expressing, mCRPC. Dr. Messmann has held leadership positions at Endocyte, Advanced Accelerator Applications (a subsidiary of Novartis), Fusion Pharmaceuticals, Amgen, Eli Lilly & Co., and others. Immediately prior to joining Convergent Therapeutics, Dr. Messmann was the Senior Vice President and clinical lead for Fusion's development of the actinium radiotherapeutic FPI-2265. While at Amgen, he was the executive medical director and global program lead for the development of xaluritamig (AMG 509) in prostate cancer. "We are excited to welcome Dr. Messmann to the Convergent team as we expand our clinical program for CONV01-α," said Convergent's Co-founder and CEO, Philip Kantoff, MD. "His deep knowledge and experience in oncology drug development, specifically leading the late-stage development of radiopharmaceuticals, is an important addition to our team as we look forward to progressing this asset forward." Series A Extension Funding Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent's radiopharmaceutical pipeline, including CONV01-α. Jim Trenkle, PhD, Partner in the Venture Investments group at Novo Holdings, joins the Convergent Board of Directors. About CONV01-α CONV01-α, Convergent's alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeting prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called 225Ac, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers. About Convergent Therapeutics, Inc. Convergent Therapeutics Inc. is a clinical-stage biotechnology company focused on developing tumor-selective alpha radioantibodies to target cancer. The company was founded by world-renowned experts in clinical care and research, drug development and cancer biology and its proprietary platform is licensed from Cornell University. In harnessing the selectivity of antibodies and tumor-destructive potential of alpha radioisotopes, Convergent's radioantibodies precisely target cancer cells with potent, localized radiation. For more information, please visit and follow us on Twitter and LinkedIn. Media Relations: Bryan Blatstein Spectrum Science 917-714-2609 [email protected] SOURCE Convergent Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED