CAIX

▎Armstrong2025年美国癌症研究协会年会（AACR）即将于4月25-30日在美国芝加哥举行，最近会议摘要已经公开，中国创新密集亮相。以ADC领域为例，绝大部分的报告来自中国药企，创新ADC接近100款，覆盖各种技术路线和靶点上的创新，真正开始引领ADC的创新前沿。双靶点ADC为ADC领域当前最热门的方向之一，百力司康、百奥赛图、博锐生物、橙帆医药、多禧生物、恒瑞医药、基石药业、金赛药业、康宁杰瑞、康源博创、联进生物、启德医药、石药集团、拓济生物、先声药业、信达生物、映恩生物、亲和力生物等多家企业布局。双毒素ADC也开始走到台前，康弘药业、亲和力生物系统布局双毒素ADC，康弘药业的KH815为全球首款进入临床阶段的双毒素ADC新药。两种payload分别为TOP1i和RAN POL2i，同时抑制RNA合成并诱导DNA双链断裂。康宁杰瑞进一步开发了双靶点双毒素ADC，即EGFR/HER3双毒素ADC新药JSKN021。传统ADC的理念是毒素经抗体结合受体介导内吞后释放，DXd-ADC则证明了旁观者效应的重要作用，宜联生物则进一步开发了非内吞ADC，靶向游离靶标VEGF，通过肿瘤微环境特异性酶来释放毒素，进一步打开了ADC药物的应用空间。维立志博开发了首款TCE的ADC，即DLL3/CD3 ADC新药LBL-058，由DLL3/CD3双抗偶联TOP1i而成，T细胞杀伤与payload细胞毒杀伤效应协同。虽然TCE在少数靶点已经开始突破实体瘤，但TCE-ADC的设计无疑为突破实体瘤提供了一种全新强化设计的思路。总结从此次AACR会议来看，中国ADC无论在数量上，还是在差异化设计上，毫无疑问都在真正引领ADC的创新前沿，新靶点ADC、新靶点组合双靶点ADC、双毒素ADC、PDC、TCE-ADC、非内吞ADC等等，以及AACR会议不涉及的自免ADC（映恩生物已经进入临床阶段）等。未来几年，国产ADC的临床突破和出海交易仍然是值得期待的行业焦点所在。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

HealthCare Royalty and Heidelberg Pharma amend royalty financing agreement to provide for USD 20 million payment Heidelberg Pharma extends cash runway into 2027 Ladenburg, Germany, 13 March 2025 – Heidelberg Pharma AG (FSE: HPHA), a clinical stage biotech Company developing innovative Antibody Drug Conjugates (ADCs), and HealthCare Royalty (HCRx) today announced that they have signed an amendment to the royalty financing agreement entered into in March 2024. The March 2024 royalty financing agreement and current amendment cover the partial monetization of Heidelberg Pharma’s future royalties on the worldwide sales of TLX250-CDx, a radiopharmaceutical Positron Emission Tomography (PET) imaging agent for the diagnosis and characterization of clear cell renal cancer. An upfront payment of USD 25 million was already made to Heidelberg Pharma in March 2024. Key terms of the amended agreement between Heidelberg Pharma and HCRx are as follows: Heidelberg Pharma will receive a payment of USD 20 million upon signature. The USD 15 million sales-based milestone for year 2025 is eliminated. The originally agreed USD 75 million payment upon FDA approval of TLX250-CDx will be reduced to USD 70 million, with further reductions if FDA approval occurs after the end of 2025. The second tier of the two-tier escalating cap on cumulative royalties sold to HCRx has increased. When the escalating cap has been reached, royalty payments will return to Heidelberg Pharma and HCRx will receive a low single digit royalty tail percentage thereof. Prof. Dr. Andreas Pahl, Chief Executive Officer at Heidelberg Pharma, commented: “The amendment with HCRx provides us with non-dilutive financing and will significantly increase our cash reach. Due to the delay in FDA approval of TLX250-CDx, the agreed sales-based milestone payment would have been difficult to achieve and has now instead been converted into another payment. We are very pleased that our development and commercialization partner Telix has received positive feedback from the FDA on its Biologics License Application and has been granted priority review. We expect an approval decision and the next significant milestone payment by the end of August.” Based on the agreement with HCRx and expected incremental payments of USD 90 million to Heidelberg Pharma, the company anticipates an extended cash runway into 2027. About TLX250-CDx TLX250-CDx is a radiolabeled form of the antibody girentuximab which binds to the tumor-specific antigen CAIX on clear cell renal cell carcinomas. TLX250-CDx also has potential as a PET diagnostic imaging agent for other tumor types. Heidelberg Pharma developed the antibody up to a first completed Phase III clinical trial prior to licensing it to Telix Pharmaceuticals Limited (Telix), an Australian company based in Melbourne, Australia, in 2017. About Heidelberg Pharma Heidelberg Pharma is a biopharmaceutical company working on a new treatment approach in oncology and developing novel drugs based on its ADC technologies for the targeted and highly effective treatment of cancer. ADCs are antibody-drug conjugates that combine the specificity of antibodies with the efficacy of toxins to fight cancer. Selected antibodies are loaded with cytotoxic compounds, the so-called payloads, that are transported into diseased cells. Inside the cells, the toxins then unleash their effect and kill the diseased cells. Heidelberg Pharma uses several compounds and has built up an ADC toolbox that overcomes tumor resistance via numerous pathways and addresses different types of cancer using various antibodies. The goal is to develop targeted and highly effective ADCs for the treatment of a variety of malignant hematologic and solid tumors. Heidelberg Pharma is the first company to use the compound Amanitin from the green death cap mushroom in cancer therapy. The biological mechanism of action of the toxin represents a new therapeutic modality and is used as a compound in the Amanitin-based ADC technology, the so-called ATAC technology. The company is based in Ladenburg, Germany, and is listed on the Frankfurt Stock Exchange: ISIN DE000A11QVV0 / WKN A11QVV / Symbol HPHA. More information is available at www.heidelberg-pharma.com. ATAC® is a registered trademark of Heidelberg Pharma Research GmbH. ITAC™, ETAC™ are pending trademark applications of Heidelberg Pharma Research GmbH. About Healthcare Royalty HealthCare Royalty (HCRx) is a leading royalty acquisition company focused on commercial or near-commercial biopharmaceutical products. With offices in Stamford, Conn., San Francisco, Boston, London and Miami, HCRx has invested $5+ billion in over 90 biopharmaceutical products since inception. For more information, visit https://www.hcrx.com. HEALTHCARE ROYALTY® and HCRx® are registered trademarks of HealthCare Royalty Management, LLC.

HealthCare Royalty and Heidelberg Pharma amend royalty financing agreement to provide for USD 20 million payment Heidelberg Pharma extends cash runway into 2027 Ladenburg, Germany, 12 March 2025 – Heidelberg Pharma AG (FSE: HPHA), a clinical stage biotech Company developing innovative Antibody Drug Conjugates (ADCs), and HealthCare Royalty (HCRx) today announced that they have signed an amendment to the royalty financing agreement entered into in March 2024. The March 2024 royalty financing agreement and current amendment cover the partial monetization of Heidelberg Pharma’s future royalties on the worldwide sales of TLX250-CDx, a radiopharmaceutical Positron Emission Tomography (PET) imaging agent for the diagnosis and characterization of clear cell renal cancer. Key terms of the amended agreement between Heidelberg Pharma and HCRx are as follows: Heidelberg Pharma will receive a payment of USD 20 million upon signature. The USD 15 million sales-based milestone for year 2025 is eliminated due to the delay of the potential market launch of TLX250-CDx; FDA approval could be granted by 27 August 2025. The originally agreed USD 75 million payment upon FDA approval of TLX250-CDx will be reduced to USD 70 million, with further reductions if FDA approval occurs after the end of 2025. The second tier of the two-tier escalating cap on cumulative royalties sold to HCRx has increased. When the escalating cap has been reached, royalty payments will return to Heidelberg Pharma and HCRx will receive a low single digit royalty tail percentage thereof. Based on the agreement with HCRx and expected incremental payments of USD 90 million to Heidelberg Pharma, the company anticipates an extended cash runway into 2027. +++ End of the ad hoc announcement +++ About TLX250-CDx TLX250-CDx is a radiolabeled form of the antibody girentuximab which binds to the tumor-specific antigen CAIX on clear cell renal cell carcinomas. TLX250-CDx also has potential as a PET diagnostic imaging agent for other tumor types. Heidelberg Pharma developed the antibody up to a first completed Phase III clinical trial prior to licensing it to Telix Pharmaceuticals Limited (Telix), an Australian company based in Melbourne, in 2017.