FAP inhibitor(Boehringer-Ingelheim/Capital Medical Univ/Harvard Medical School)

MELBOURNE, Australia, Nov. 19, 2024 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX; Nasdaq: TLX, Telix, the Company) today announces it will expand its theranostic pipeline with new assets targeting Fibroblast Activation Protein (FAP), one of the most promising pan-cancer targets in nuclear medicine. Telix's development program will initially focus on the treatment of bladder cancer, rounding out its urology franchise, which includes late-stage therapeutic programs for kidney and prostate cancers. FAP is a pan-cancer marker expressed in the tumour microenvironment of epithelial cancers and on the surface of some specific cancer types, including sarcomas and mesotheliomas. Telix has entered into asset purchase and exclusive worldwide in-licence agreements for a suite of clinically validated FAP-targeting therapeutic and precision medicine (diagnostic) radiopharmaceutical candidates developed by Professor Frank Roesch and his collaborators at the Institute of Nuclear Chemistry at the Johannes Gutenberg-Universität Mainz, Germany. The next-generation therapeutic assets are differentiated by a novel structure that drives extended tumour retention while minimising off-target uptake, potentially overcoming the limitations seen with first-generation compounds. The diagnostic and therapeutic compounds have been clinically validated in over 500 patients across a variety of solid tumours and are the subject of multiple peer-review publications[1]. Richard Valeix, Chief Executive Officer, Telix Therapeutics, said, "We are delighted to partner with Professor Roesch and his team on this exciting frontier of radiopharmaceuticals. Telix will gain access to assets that are already significantly de-risked, with clinically demonstrated safety profile and efficacy. We will develop these assets in bladder cancer as a primary indication, in line with our focus on urological cancers, and explore the potential of FAP as a pan-cancer target, adding significant value to our pipeline." Frank Roesch, professor emeritus, said, "Over the past two years, our FAP inhibitor-based theranostic candidates have seen extensive preclinical and clinical evaluation. Collaboration has been very important, and I am grateful to many colleagues around the world who have contributed to advancing the molecules to this point. We are excited to be working with Telix as a leader in radiopharmaceutical innovation, development and commercialisation, to further develop and bring these drug candidates to regulatory approval. The ultimate goal is to improve the diagnostic precision and therapeutic outcomes of cancer patients in need." Visit the Telix corporate website to view an interactive explainer on FAP: Attack on Stroma Deal terms and conditions Under an exclusive worldwide licence agreement with a German company controlled by Professor Roesch, SCV GmbH, and a concurrently-signed asset purchase agreement with German company Medianezia GmbH, which collectively hold the intellectual property rights to the FAP assets, Telix will pay €7 million in cash as of closing (inclusive of €700,000 paid at or prior to the signing of the agreements) and a further €3 million in 12 months' time subject to any potential indemnity setoff. Telix will pay up to a further €132 million contingent upon achievement of certain clinical development and regulatory milestones related to both the diagnostic and therapeutic products under both agreements. An additional €20 million will be payable under the licence agreement on achievement of certain commercial milestones related to the diagnostic product; as well as royalties on net sales in the low to mid-single digits on the diagnostic product and an earlier formulation of the therapeutic product, if used. Closing of the licence agreement and asset purchase agreement is expected to occur simultaneously and is subject to customary closing conditions including, with respect to the acquisition of assets, assignment of patents rights and foreign direct investment (FDI) approval of Germany's Ministry for Economic Affairs and Climate Action. Telix cannot guarantee these transactions will close in any specific timeframe or upon the terms summarised herein, if at all. About Telix Pharmaceuticals Limited Telix is a biopharmaceutical company focused on the development and commercialisation of therapeutic and diagnostic radiopharmaceuticals and associated medical technologies. Telix is headquartered in Melbourne, Australia, with international operations in the United States, Europe (Belgium and Switzerland), and Japan. Telix is developing a portfolio of clinical and commercial stage products that aims to address significant unmet medical needs in oncology and rare diseases. Telix is listed on the Australian Securities Exchange (ASX: TLX) and the Nasdaq Global Select Market (Nasdaq: TLX). Telix's lead imaging product, gallium-68 (68Ga) gozetotide injection (also known as 68Ga PSMA-11 and marketed under the brand name Illuccix®), has been approved by the U.S. Food and Drug Administration (FDA)[2], by the Australian Therapeutic Goods Administration (TGA) [3], and by Health Canada[4]. No other Telix product has received a marketing authorisation in any jurisdiction. Visit for further information about Telix, including details of the latest share price, announcements made to the ASX, investor and analyst presentations, news releases, event details and other publications that may be of interest. You can also follow Telix on X and LinkedIn. Telix Investor Relations Ms. Kyahn Williamson Telix Pharmaceuticals Limited SVP Investor Relations and Corporate Communications Email: [email protected] This announcement has been authorised for release by the Telix Pharmaceuticals Limited Disclosure Committee on behalf of the Board. Legal Notices You should read this announcement together with our risk factors, as disclosed in our most recently filed reports with the Australian Securities Exchange (ASX), U.S. Securities and Exchange Commission (SEC), including our registration statement on Form 20-F filed with the SEC, or on our website. The information contained in this announcement is not intended to be an offer for subscription, invitation or recommendation with respect to securities of Telix Pharmaceuticals Limited (Telix) in any jurisdiction, including the United States. The information and opinions contained in this announcement are subject to change without notification. To the maximum extent permitted by law, Telix disclaims any obligation or undertaking to update or revise any information or opinions contained in this announcement, including any forward-looking statements (as referred to below), whether as a result of new information, future developments, a change in expectations or assumptions, or otherwise. No representation or warranty, express or implied, is made in relation to the accuracy or completeness of the information contained or opinions expressed in the course of this announcement. This announcement may contain forward-looking statements, including within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, that relate to anticipated future events, financial performance, plans, strategies or business developments. Forward-looking statements can generally be identified by the use of words such as "may", "expect", "intend", "plan", "estimate", "anticipate", "believe", "outlook", "forecast" and "guidance", or the negative of these words or other similar terms or expressions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Forward-looking statements are based on Telix's good-faith assumptions as to the financial, market, regulatory and other risks and considerations that exist and affect Telix's business and operations in the future and there can be no assurance that any of the assumptions will prove to be correct. In the context of Telix's business, forward-looking statements may include, but are not limited to, statements about: the initiation, timing, progress and results of Telix's preclinical and clinical trials, and Telix's research and development programs; Telix's ability to advance product candidates into, enrol and successfully complete, clinical studies, including multi-national clinical trials; the timing or likelihood of regulatory filings and approvals for Telix's product candidates, manufacturing activities and product marketing activities; Telix's sales, marketing and distribution and manufacturing capabilities and strategies; the commercialisation of Telix's product candidates, if or when they have been approved; Telix's ability to obtain an adequate supply of raw materials at reasonable costs for its products and product candidates; estimates of Telix's expenses, future revenues and capital requirements; Telix's financial performance; developments relating to Telix's competitors and industry; and the pricing and reimbursement of Telix's product candidates, if and after they have been approved. Telix's actual results, performance or achievements may be materially different from those which may be expressed or implied by such statements, and the differences may be adverse. Accordingly, you should not place undue reliance on these forward-looking statements. ©2024 Telix Pharmaceuticals Limited. The Telix Pharmaceuticals® and Illuccix® names and logos are trademarks of Telix Pharmaceuticals Limited and its affiliates – all rights reserved. Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

过去两年，Lutathera、Pluvicto等靶向放射性核素疗法（Targeted Radionuclide Therapy, TRT）的成功推动核药赛道迎来了新一轮发展浪潮，这类疗法也带来了转移性癌症治疗范式的转变。传统的放射性配体（radioligand）通常是一种双功能偶联物，将放射性核素标记模块与肿瘤靶向配体连接起来。由于大多数配体与受体的相互作用是可逆的，因此，传统放射性配体的肿瘤滞留时间往往不足，这会损害最终的疗效。基于此，科学家们设想，如果能够开发一种平台技术，能够以肿瘤选择性的方式不可逆地将放射性配体固定在癌症靶点上，这或将大大提升靶向放射性核素疗法的疗效。5月22日，最新发表在Nature杂志上的一项研究中，北京大学刘志博教授团队及其合作者开发了一种共价靶向放射性配体（covalent targeted radioligand，CTR，图1b），这是一种三功能偶联物，在传统放射性配体分子的合适位置连接了一个基于硫（Ⅵ）-氟交换反应（SuFEx）的共价“弹头”。当CTR到达肿瘤时，先非共价地与靶点结合，随后通过邻近效应进行不可逆的共价结合（实现了binding-to-ligation的转变），以防止被快速清除。未结合靶点的游离CTR将被快速排出，从而限制了全身毒性的风险[1]。图1 通过SuFEx工程开发CTR，并在荷瘤小鼠中成功进行概念验证作为概念验证，研究人员选择了成纤维细胞激活蛋白(FAP)作为开发CTR的靶点。优选这个靶点，一方面是因为，FAP是一款泛癌靶点且具有较高的肿瘤特异性表达，另一方面是因为，DOTA偶联FAP抑制剂（FAP inhibitor, FAPI）FAPI-04已被成功用于诊断超过28种癌症。不过，由于肿瘤摄取低，清除快，迄今为止还没有FAPI获得令人满意的临床治疗结果。该研究首先证实，通过与酪氨酸残基的共价连接，CTR-FAPI可与FAP不可逆结合，导致在癌细胞中更高的摄取和更长的滞留时间。接着研究证实，基于SuFEx的共价“弹头”，尤其是mFS（aryl-sulfone fluoride），可能不会在健康组织中引起脱靶共价结合。然后，研究在荷瘤小鼠中测了偶联FS的FAPI能否实现更好的肿瘤摄取。结果显示，[68Ga]Ga-FAPI-mFS（放射性核素-肿瘤靶向配体-共价弹头）的肿瘤摄取明显高于[68Ga]Ga-FAPI-04，SUVmax（maximum standard uptake value）增加了257%。在这些有希望的临床前数据的鼓舞下，研究者们在癌症患者中开展一项IIT研究，以测试[68Ga]Ga-FAPI-mFS。结果显示，在两例代表性纵隔淋巴结转移的甲状腺髓样癌（MTC）患者中，[68Ga]Ga-FAPI-mFS比[68Ga]Ga-FAPI-04 发现了更多的可疑病变。图2 CTR-FAPIs改善了荷瘤小鼠的肿瘤摄取，并精确检测癌症患者的病变对FAPI-mFS的长期药代动力学研究显示，与[86Y]Y-FAPI-04相比，[86Y]Y-FAPI-mFS在肿瘤中积累更快，摄取更好，72小时内几乎没有清除。[86Y]Y-FAPI-mFS的肿瘤滞留时间增加了13倍。图3 CTR-FAPIs改善了放射性核素在肿瘤中的滞留，并导致肿瘤几乎完全消退。研究还探索了FAPI-mFS应用于225Ac（α-放射性核素）的有效性。考虑到225Ac的半衰期长，杀伤细胞效率高，按照以往报道，研究采用1/1000放射性剂量的单轮治疗方案。结果显示，单剂[225Ac]Ac-FAPI-mFS (22.2 kBq) 导致更快的肿瘤抑制，更高剂量(33.3 kBq)的[225Ac]Ac-FAPI-mFS在所有小鼠中实现了完全的肿瘤抑制。此外，研究显示，靶向前列腺特异性膜抗原(PSMA)的CTR疗法也显示出增强的治疗效果。研究团队认为，这项创新策略有望用于多种其他癌症靶点。据称，这是Nature杂志近50年来发布的首篇放射性核素治疗领域论文[2]。相关研究团队正在肺癌、乳腺癌、前列腺癌、头颈部癌症等大癌种中进行效果验证。备注：文中所有图片均来自Nature。参考资料：[1]https://www.nature.com/articles/s41586-024-07461-6[2]https://mp.weixin.qq.com/s/0NJMZyXZxBWUZpjak4KPHgCopyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。