A Phase 2, Open-label, Multi-centre Study of FPI-2265 (225Ac-PSMA-I&T) and Olaparib in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)

This study is an open-label, multicenter study designed to investigate the efficacy, safety and tolerability of FPI-2265 (225Ac-PSMA-I&T) in combination with Olaparib in participants with mCRPC. The dose optimization Phase 2 part will be investigating the safety, tolerability, and anti-tumor activity of novel dosing regimens of FPI-2265 and Olaparib in participants with metastatic castration-resistant prostate cancer.

开始日期2025-02-26

申办/合作机构

Fusion Pharmaceuticals, Inc.

NCT06402331

/ Recruiting临床2/3期

A Phase 2/3, Randomized, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of FPI-2265 (225Ac-PSMA-I&T) in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC), Previously Treated With 177Lu-PSMA Radioligand Therapy (RLT)

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I&T). Patient population is adult participants with PSMA positive mCRPC who have had previous treatment with with 177Lu-PSMA-617 or another 177Lu-PSMA radioconjugate (RC). The purpose of the study is to determine the safety and tolerability, and recommended dose and regiment of FPI-2265.

开始日期2024-03-05

申办/合作机构

Fusion Pharmaceuticals, Inc.

CTIS2024-513729-22-01

/ Recruiting临床1期

Phase I study of 225Ac-PSMA I&T in prostate cancer

开始日期2022-03-22

申办/合作机构

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

100 项与 FPI-2265 相关的临床结果

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100 项与 FPI-2265 相关的转化医学

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100 项与 FPI-2265 相关的专利（医药）

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项与 FPI-2265 相关的文献（医药）

2021-04-01·European Journal of Nuclear Medicine and Molecular Imaging

Image-based dosimetry for 225Ac-PSMA-I&T therapy using quantitative SPECT

Article

作者: Böning, G ; Gildehaus, F J ; Kaiser, L ; Ilhan, H ; Gosewisch, A ; Schleske, M ; Brosch, J ; Bartenstein, P ; Berg, I ; Todica, A

Kratochwil C, et al. Targeted alpha therapy of mCRPC with 225actinium-PSMA-617: dosimetry estimate and empirical dose finding. J Nucl Med. 2017;8(10):1624–31 p. jnumed. 117.191395. Article Google Scholar Robertson A, et al. Multi-isotope SPECT imaging of the 225Ac decay chain: feasibility studies. Phys Med Biol. 2017;62(11):4406. CAS Article Google Scholar Usmani S, et al. 225Ac prostate-specific membrane antigen posttherapy α imaging: comparing 2 and 3 photopeaks. Clin Nucl Med. 2019;44(5):401–3. Article Google Scholar Vatsa R, et al. 225Ac-PSMA-617 radioligand posttherapy imaging in metastatic castrate-resistant prostate cancer patient using 3 Photopeaks. Clin Nucl Med. 2020;45(6):437–8. Article Google Scholar Chun SY, Fessler JA, Dewaraja YK. Correction for collimator-detector response in SPECT using point spread function template. IEEE Trans Med Imaging. 2012;32(2):295–305. Article Google Scholar Delker A, et al. Dosimetry for 177 Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43(1):42–51. CAS Article Google Scholar Gosewisch A, et al. Patient-specific image-based bone marrow dosimetry in Lu-177-[DOTA 0, Tyr 3]-Octreotate and Lu-177-DKFZ-PSMA-617 therapy: investigation of a new hybrid image approach. EJNMMI Res. 2018;8(1):76. Article Google Scholar Download references Open Access funding enabled and organized by Projekt DEAL. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany A. Gosewisch, M. Schleske, F. J. Gildehaus, I. Berg, L. Kaiser, J. Brosch, P. Bartenstein, A. Todica, H. Ilhan & G. Boning You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to H. Ilhan. All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The retrospective evaluation was approved by the local ethic committee (20-178). Written informed consent was obtained prior to the exam. The authors declare that they have no conflict of interest. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is part of the Topical Collection on Image of the month. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Reprints and Permissions Gosewisch, A., Schleske, M., Gildehaus, F.J. et al. Image-based dosimetry for 225Ac-PSMA-I&T therapy using quantitative SPECT. Eur J Nucl Med Mol Imaging (2020). https://doi.org/10.1007/s00259-020-05024-1 Download citation Received: 13 June 2020 Accepted: 31 August 2020 Published: 21 September 2020 DOI: https://doi.org/10.1007/s00259-020-05024-1

2021-04-01·European Journal of Nuclear Medicine and Molecular Imaging

Response to 225Ac-PSMA-I&T after failure of long-term 177Lu-PSMA RLT in mCRPC

Article

作者: Bartenstein, Peter ; Ilhan, Harun ; Zacherl, Mathias ; Völter, Friederike ; Gosewisch, Astrid ; Todica, Andrei ; Gildehaus, Franz Josef ; Böning, Guido ; Unterrainer, Marcus

Czerwinska M, Bilewicz A, Kruszewski M, Wegierek-Ciuk A, Lankoff A. Targeted radionuclide therapy of prostate cancer-from basic research to clinical perspectives. Molecules. 2020;25. https://doi.org/10.3390/molecules25071743. Khreish F, Ebert N, Ries M, Maus S, Rosar F, Bohnenberger H, et al. (225)Ac-PSMA-617/(177)Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. Eur J Nucl Med Mol Imaging. 2020;47:721–8. https://doi.org/10.1007/s00259-019-04612-0. CAS Article Google Scholar Sathekge M, Bruchertseifer F, Vorster M, Lawal IO, Knoesen O, Mahapane J, et al. Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving (225)Ac-PSMA-617 radioligand therapy. J Nucl Med. 2020;61:62–9. https://doi.org/10.2967/jnumed.119.229229. CAS Article Google Scholar Sathekge M, Bruchertseifer F, Knoesen O, Reyneke F, Lawal I, Lengana T, et al. (225)Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study. Eur J Nucl Med Mol Imaging. 2019;46:129–38. https://doi.org/10.1007/s00259-018-4167-0. CAS Article PubMed Google Scholar Download references Open Access funding enabled and organized by Projekt DEAL. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany Harun Ilhan, Astrid Gosewisch, Guido Boning, Friederike Volter, Mathias Zacherl, Peter Bartenstein, Andrei Todica & Franz Josef Gildehaus Department of Radiology, University Hospital, LMU Munich, Munich, Germany Marcus Unterrainer You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Harun Ilhan. All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This retrospective evaluation was approved by the local ethic committee (20-178). Written informed consent was obtained prior to the exam. The authors declare that they have no conflict of interest. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is part of the Topical Collection on Image of the month. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Reprints and Permissions Ilhan, H., Gosewisch, A., Boning, G. et al. Response to 225Ac-PSMA-I&T after failure of long-term 177Lu-PSMA RLT in mCRPC. Eur J Nucl Med Mol Imaging (2020). https://doi.org/10.1007/s00259-020-05023-2 Download citation Received: 13 June 2020 Accepted: 31 August 2020 Published: 22 September 2020 DOI: https://doi.org/10.1007/s00259-020-05023-2

Biomedicines

Total Tumor Volume on 18F-PSMA-1007 PET as Additional Imaging Biomarker in mCRPC Patients Undergoing PSMA-Targeted Alpha Therapy with 225Ac-PSMA-I&T

Article

作者: Cyran, Clemens C. ; Unterrainer, Marcus ; Unterrainer, Lena M. ; Bartenstein, Peter ; Todica, Andrei ; Schmidt-Hegemann, Nina-Sophie ; Casuscelli, Jozefina ; Albert, Nathalie L. ; Wenter, Vera ; Brendel, Matthias ; Herlemann, Annika ; Beyer, Leonie ; Stief, Christian G. ; Ilhan, Harun ; Zacherl, Mathias J. ; Sheikh, Gabriel T. ; Kunte, Sophie C. ; Ricke, Jens ; Holzgreve, Adrien ; Gildehaus, Franz J. ; Kunz, Wolfgang G.

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions.

129

项与 FPI-2265 相关的新闻（医药）

2025-06-23

·同写意

核药浪潮汹涌而至，BMS、诺华重金押注

同写意年度巨献！！大会特设“核药全产业链开发”分会，7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！近日，BMS子公司RayzeBio豪掷13.5亿美元引进前列腺癌核药OncoACP3，诺华同步在华启动SSTR2靶向药Lutathera治疗晚期胃肠胰神经内分泌瘤的III期临床。两大巨头重金加码与关键进展齐发，标志着全球核药行业进入加速发展的新阶段，全球核药浪潮来袭。TONACEA01核药的全球浪潮全球医疗产业正迎来治疗性核药的爆发性增长，这一领域凭借其精准靶向和诊疗一体化的独特优势，重塑肿瘤等重大疾病的治疗范式。据Precedence Research数据，2024年全球放射性药物市场规模达67.4亿美元，并以8.2%的复合年增长率加速扩张，预计2034年将突破144.4亿美元。这一增长主要源于放射性核素偶联药物（RDC）的技术突破与商业化落地。RDC的结构与抗体偶联药物（ADC）类似，但作用机理截然不同，其通过靶向配体引导放射性核素（如镥-177、锕-225）精准定位病灶，实“体内精准放疗”，而非ADC的细胞毒性杀伤。2024年-2034年放射性药物市场规模/图片来源：Precedence Research其中，诺华的两款RDC药物Pluvicto和Lutathera成为行业标杆。2024年，靶向PSMA的前列腺癌疗法Pluvicto销售额达13.92亿美元，同比增长42%，成为核药领域首个“重磅炸弹”。为了巩固Pluvicto地位，诺华正在进行Pluvicto的适应证拓展。2025年3月，Pluvicto获批用于更早期的前列腺癌治疗的新适应证，根据诺华在2025 JPM大会上预测，其销售峰值预计超50亿美元；而另一款靶向SSTR的神经内分泌肿瘤药物Lutathera在2024年收入7.24亿美元，同比增长20%。两者合计贡献21.16亿美元，验证了治疗性核药的商业潜力。另外，诊断性核药增长势头同样喜人，2024年两款PSMA-PET显影剂Plarify和Illuccix销售额合计16亿美元，同比增长33%，美国医保支付改革将进一步推动诊断核药的市场扩容，据Lantheus预测，2025年PSMA PET诊断规模有望超25亿美元，预计到2030年其市场规模有望超过35亿美元。2025年-2030年美国PSMA PET诊断市场预测/图片来源：LantheusTONACEA02MNC争相入局随着诺华旗下Pluvicto和Lutathera的商业化成功，核药赛道已成为MNC战略布局的新焦点。2024年至2025年初，礼来、BMS、阿斯利康等巨头通过高溢价收购和战略合作加速布局。礼来成为最活跃的投资者，2023年10月以14亿美元收购Point Biopharma，获得其PSMA靶向疗法PNT2002；2024年先后与Aktis Oncology、Radionetics Oncology达成合作；2025年2月又与AdvanCell扩大合作，整合后者领先的Pb212生产技术，共同开发靶向α核素疗法。BMS以41亿美元收购RayzeBio，创下核药领域最高交易纪录，核心资产为225Ac靶向药物RYZ101，意图挑战诺华的Lutathera。2025年6月10日，BMS全资子公司RayzeBio又以13.5亿美元的潜在总金额引进一款临床在研前列腺癌治疗和诊断药物OncoACP3，其野心可见一斑。主要MNC布局核药情况汇总/图片来源：平安证券研报阿斯利康从试水转向全面投入，2020年与Fusion Pharmaceuticals合作后，2024年3月以24亿美元直接收购该公司，获得其FastClear linker技术平台及4款在研核药，包括靶向PSMA的225Ac疗法FPI2265，同年还投资CDMO企业Nucleus RadioPharma完善产业链。诺华在巩固先发优势的同时，2024年5月以17.5亿美元收购礼来曾投资的Mariana Oncology，加码放射性配体疗法（RLT）管线，并加速推进225AcPSMA617等新一代药物。近些年，拜耳也持续布局核药领域。2021年，拜耳收购Noria Therapeutics和PSMA Therapeutics，扩展了基于Ac-225的核药产品研发管线。2023年5月，拜耳与Bicycle Therapeutics达成战略合作，开发RDC。截至2024年末，其研发管线中已拥有7款处于临床前研究阶段、2个进入早期临床开发的RDC项目。TONACEA03国内商业化征程已然开启近年来，国内核药产业同样迎来实质性突破，从研发阶段迈入商业化价值兑现期。2020年2025年初，国内共获批5种新型核药，其中远大医药的钇[90Y]微球注射液表现最为亮眼，2024年实现收入近5亿港元，同比增长140%。后续伴随着2025年商保推出及落地，钇[90Y]微球注射液有望放量。此外，2025年成为国内核药商业化进程的关键节点。其中，安迪科的氟[18F]化钠已于5月底获NMPA批准上市。同时，诺华围绕PSMA靶点的前列腺癌治疗药镓[68Ga]戈泽肽及配套诊断药镥[177Lu]特昔维匹肽于2024年11月获CDE优先审评，2025年有望双双获批。值得一提的是，2025年6月10日，诺华还在中国启动了SSTR2靶向核药Lutathera在1级和2级晚期胃肠胰神经内分泌瘤（GEP-NET）患者III期临床研究。与此同时，国内企业的研发与管线布局同样进入收获期。远大医药核药抗肿瘤诊疗板块目前已储备12款创新产品，3款RDC产品处于III期临床阶段，其中前列腺癌诊断药物TLX591-CDx计划2025年递交上市申请。远大医药还提出“自研核药出海”战略，目标是自2025年起每年向FDA递交一个产品申请，2028年-2029年首个产品完成临床试验并向FDA递交上市申请。远大医药介入治疗和RDC管线/图片来源：远大医药2024年财报东诚药业则聚焦诊断核药商业化，旗下产品氟[18F]化钠已于2025年5月底获批上市，锝[99mTc]-GSA等产品有望年内提交新药申请；治疗性核药中，其FAP靶点药物177Lu-LNC1004获FDA快速通道资格，全球进度领先。结语：随着国内外企业加速布局与商业化破局，核药必将引爆下一个百亿美元级的蓝海市场。精准“核爆”，未来已来！

并购抗体药物偶联物临床3期放射疗法

2025-06-11

·BioSpace

BMS Expands Radiopharma Presence With $1.35B Biobucks Deal for Philochem

iStock, hapabapa Instead of homing in on PSMA—currently the most validated target in prostate cancer—BMS and Philochem will instead collaborate on an early-stage molecule that binds to a novel marker called ACP3. Bristol Myers Squibb is trying to unlock an alternative pathway to treating prostate cancer. The company’s radiopharma-focused subsidiary RayzeBio has fronted $350 million to partner with Italian-Swiss biotech Philochem to advance an early-stage small-molecule radiotherapeutic targeting a novel biomarker. BMS is also promising up to $1.35 billion in development, regulatory and commercial milestones, plus mid-single to low-double-digit royalties on global net sales. BMS and Philochem expect to close the transaction in the third quarter, pending customary clearances and approvals. Philogen, Philochem’s parent company, surged 20% on Wednesday morning. The star of Wednesday’s agreement is OncoACP3, a small-molecule radiotracer that targets a biomarker called ACP3. According to Philochem, ACP3 is highly expressed in prostate cancer—but not in healthy tissue—and at levels that match or exceed that of PSMA, which is currently the prevailing target of choice for prostate cancer therapies. “A side-by-side comparison between ACP3 and PSMA . . . has shown that ACP3 is more abundantly expressed in prostate cancer than PSMA,” the biotech wrote on its website. OncoACP3 is a small-molecule ligand that has high affinity for the ACP3 protein. Notably, it can carry both Lutetium-177 and Actinium-225—both currently the most common payloads for radiopharmaceuticals. In a statement on Wednesday, RayzeBio president Ben Hickey said that by potentially opening an alternative pathway to PSMA, the Philochem partnership “provides a differentiated entry” for BMS “into the prostate cancer arena.” The decision to zero in on a novel prostate cancer target could also help BMS distinguish itself in a radiopharma field that is becoming increasingly crowded . Currently leading the pack is Novartis, which owns two FDA-approved therapies: Lutathera, indicated for gastroenteropancreatic neuroendocrine tumors, and Pluvicto, which targets PSMA and is approved for prostate cancer. Another pharma trying to catch Novartis is AstraZeneca, which entered the ring in March 2024 with the $2.4 billion acquisition of Fusion Pharmaceuticals, which gave the pharma its lead radiopharma asset FPI-2265, an actinium-based radioconjugate that is being developed for prostate cancer—and targets PSMA. Also in the running is Eli Lilly, which spent $1.4 billion to buy Point Biopharma in October 2023 and $1.1 billion for Aktis Oncology in May 2024. Anchoring its radiopharma pipeline is PNT2002, another PSMA-targeting candidate for prostate cancer.

并购上市批准引进/卖出

2025-06-07

·同写意

巨头药企，砸了上千亿

同写意年度巨献！！7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！随着生物医药并购、BD持续高涨，跨国巨头作为“收割者”的形象似乎越发牢固。虽然Biotech贡献了更多原始创新已成为定论，但这不意味着MNC就在新药开发方面乏善可陈。Evaluate Pharma最新报告显示，2024年全球制药行业的研发支出增长1.5%，其中，来自MNC的资金占据大半。考虑到2023年整体研发预算飙升了11.5%，以行业自身的标准来看，2024年的1.5%属于一个相对温和的增幅。尽管如此，去年用于新药开发的资金规模仍然令人震惊：全球药企在研发方面投入了近2880亿美元。众所周知，从Lipitor、Humira再到今天的“药王”Keytruda，无论多么成功的“重磅炸弹”，都有其专利时限。如果药企不持续投入研发资金，产品组合得不到更新，那么“专利悬崖”带来的压力就将是实打实的“刀刀见血”——营收减少、股价下滑乃至需要裁员重组。直接买资产固然是条快捷通道，然而归根结底，这仍需要有人来完成“从0到1”的工作。因此，Evaluate Pharma预计，到2030年，该行业的研发开支将继续增加，达到3400亿美元左右。不确定之处在于，制药行业的研发支出模式可能面临越来越不稳定的外部环境。例如，美国特朗普政府正在推动的“最惠国定价”政策会导致药企在美国市场的收入骤减，进而影响可用的研发资金。分析师认为，制药公司可能更加注重对管线的排序，优先考虑盈利能力更强、竞争优势更大的研发项目。换言之，把握这些“金主”的动向，某种程度就是在捕捉未来的创新机会。下文将就2024年制药行业研发支出排名前五的MNC进行梳理。TONACEA01默沙东 2024年研发支出：179亿美元同比变化：-41%对于默沙东而言，2023年是一个耗资不菲的交易大年。这家巨头先是与Proxygen达成一项最高25.5亿美元的分子胶开发合作协议，随后宣布斥资108亿美元收购免疫药物开发商Prometheus Biosciences、以30亿美元收购新锐眼科公司EyeBio，下半年又以40亿美元的预付款、总计220亿美元的对价获得第一三共旗下三种ADC的授权许可。由于2023年的研发资金特别庞大，2024年默沙东的研发支出同比减少41%，更像是对预算的合理调整。事实上，它仍以179.4亿美元的巨额投资领先于其MNC，相当于其总收入的28%。不惜成本的砸钱，很直接的因素是“现金牛”Keytruda即将迎来专利到期，默沙东不得不大开发力度，以弥补这款“药王”留下的约300亿美元营收缺口。根据默沙东披露的信息，一些值得密切的研发管线，包括约20种潜在的“重磅炸弹”，未来有望给其带来超过500亿美元的回报。其中，包括ifinatamab deruxtecan，这款ADC靶向一种在多种癌症中过表达的跨膜蛋白B7-H3。默沙东正在进行一项III期临床（IDeate-Esophageal01研究），测试该药在晚期或转移性食管鳞状细胞癌中的疗效。Ifinatamab deruxtecan也有望用于治疗已接受过大量治疗的晚期小细胞肺癌，目前该适应症正处于后期开发阶段。默沙东还在探索从Prometheus获得的tulisokibart（MK-7240）在多种炎症性疾病中的疗效。II期临床试验数据显示，与安慰剂相比，使用这款TL1A抗体治疗的溃疡性结肠炎患者中，获得临床缓解的比例更高。目前，tulisokibart正处于治疗溃疡性结肠炎和克罗恩病的III期临床。2月，默沙东首席执行官Robert Davis透露，由于EyeBio的加入，公司眼科业务将迎来巨大机遇。此次收购的核心资产是一款三特异性抗体restoret，现阶段正在评估治疗糖尿病性黄斑水肿（DME）和新生血管性年龄相关性黄斑变性（AMD）的效果。2024年9月，默沙东启动了restoret治疗DME的IIb/III期临床试验，这项名为BRUNELLO的研究最快将在2027年底完成。TONACEA02强生 2024年研发支出：172亿美元同比变化：14.2%早在2023年财报电话会上，强生首席执行官Joaquin Duato就告诉投资者，2024年开始，强生将重新关注其三大优先治疗领域——肿瘤学、免疫学和神经科学，而该公司去年的研发支出在很大程度上反映了这一点。例如，2024年1月，强生斥资20亿美元收购ADC明星公司Ambrx，从而扩大自己在这种癌症治疗热门资产上的布局。对于免疫业务，强生去年还推进了两项巨额投资：以8.5亿美元收购Proteologix及其抗炎皮肤病学资产，并向Numab Therapeutics支付12.5亿美元来收购其用于治疗特应性皮炎的双抗。2024年，强生的研发支出总计超过172亿美元，占其总收入的19%以上。业内人士分析，这些交易不仅帮助强生扩充其早期和中期研发管线，去年该公司也积极推进其后期研发资产的开发。在免疫领域，强生2024年8月递交了申请nipocalimab单抗用于治疗重症肌无力的上市许可申请，并今年4月获得批准，商品名为Imaavy。值得注意的是，神经科学是强生2024年研发计划的薄弱环节。2024年10月，强生削减了其早期、中期神经研究管线，将正在研究的人类食欲素-2受体阻滞剂seltorexant搁置一旁。此前，这家MNC一直在探索seltorexant用于治疗AD患者的躁动和攻击行为。此外，强生还取消了一款用于治疗双相抑郁症的II期离子通道阻滞剂，以及一款用于治疗帕金森病的I期药物。但这种处境似乎正在逆转。1月，强生以146亿美元收购Intra-Cellular Therapies，获得斩获多个适应症的商业化产品Caplyta。强生预计，该药峰值年销售额将达到50亿美元。除了Intra-Cellular的产品组合，当前强生在CNS领域还布局了其他管线，包括esketamine新适应症的拓展，以及开发重度抑郁症药物aticaprant（已处于III期临床），未来销售额峰值预计最高达50亿美元。TONACEA03罗氏研发支出：130亿瑞士法郎（158亿美元）同比变化：1%2024年财报中，罗氏领导层承认，公司面临销售额停滞不前的挑战，主要原因是其COVID产品需求暴跌以及当时的经济困难。该公司将交易列为重振增长的战略之一。不过，与默沙东、强生大幅调整预算不同，罗氏2024年的研发支出同比基本持平。这家瑞士巨头去年在研发和业务发展方面投入了略高于130亿瑞士法郎（约合158亿美元）的资金，较2023年增长1%。在癌症领域研发工作上，2024年也给罗氏带来巨大挑战。例如，2024年7月，TIGIT抗体tiragolumab在用于治疗非小细胞肺癌的II/III期临床试验SKYSCRAPER-06中，未能显著改善患者的无进展生存期，迫使罗氏终止了该试验。同年11月，tiragolumab针对非小细胞肺癌的SKYSCRAPER-01研究数据披露，疗效再次令人失望。或许因为肿瘤药物的开发风险，2024年4月，罗氏就砍掉了三条早期管线，包括曾达成超13亿美元合作、一度被认为是新一代合成致死疗法的camonsertinib。2024年8月，罗氏关闭了其子公司基因泰克的癌症免疫学部门，当时一位发言人称，此次重组的原因是“免疫肿瘤学科学的转变”。与肿瘤治疗赛道不同，过去一年罗氏在肥胖症产品组合布局上可谓收获颇丰，而这得益于其2023年12月以27亿美元现金、4亿美元里程碑付款收购Carmot Therapeutics所获得的资产。2024年5月，罗氏宣布，Carmot开发的GLP-1/GIP受体双重激动剂CT-388在24周内能够使体重降低18.8%。同年7月，罗氏又发布另一项源自Carmot的候选药物数据。根据I期临床结果，口服GLP-1受体激动剂CT-996在使用四周后可使体重减轻6.1%。罗氏去年最引人瞩目的交易，是2024年11月以10亿美元预付款收购Poseida Therapeutics。二者长期保持合作——2022年8月，罗氏就与Poseida达成一项60亿美元的战略合作——罗氏表示，收购加强了双方在CAR-T疗法领域的协同。Poseida手握一系列通用型CAR-T，主要针对多发性骨髓瘤、B细胞淋巴瘤以及其他血液肿瘤。2025年还剩下一半多的时间，罗氏的研发预算将如何变化尚不明朗。不过，这家MNC不太可能在短期内大举花钱。2月份发布的最新年报中，罗氏首席执行官Thomas Schinecker称，公司今年将在交易方面保持“谨慎”，只专注于对公司财务状况有利的资产。TONACEA04阿斯利康 2024年研发支出：136亿美元同比变化：25%阿斯利康首席执行官Pascal Soriot在2024年2月的电话会上表示，公司从2024年开始“投资新技术和新产品”。同年3月，阿斯利康兑现承诺，签署了两项高价收购协议，以扩充其后期研发管线。第一笔交易是与Amolyt Pharma达成的，阿斯利康以8亿美元的预付款收购后者。几天后，阿斯利康又斥资20亿美元收购Fusion Pharmaceuticals。Amolyt核心产品之一是甲状旁腺功能减退症候选药物eneboparatide，该药最近在III期临床中取得了成功，另外，阿斯利康还获得其他正在开发的罕见疾药物。而作为核药明星公司，Fusion为阿斯利康提供了一系列放射性药物研发管线，包括基于锕-225开发的FPI-2265，拟用于治疗转移性去势抵抗性前列腺癌。2024年，阿斯利康也向其早研端投入重金，扩大了其产品组合。例如去年5月，阿斯利康与和铂医药子公司诺纳生物达成总计超6亿美元的协议，引进临床前阶段肿瘤靶向治疗单抗项目。同月，阿斯利康开始进军肥胖领域，斥资8000万美元参与初创公司SixPeaks的A轮融资，后者计划开发可以减肥增肌的ActRIIA/B抗体药物。当然，作为一家肿瘤药物巨头，阿斯利康备受关注的资产除了开创HER2乳腺癌治疗新范式的Enhertu，还有跟第一三共合作开发的TROP2 ADC Dato-DXd。今年1月，该药以Datroway商品名获得FDA批准用于治疗乳腺癌，不过，2024年的开发并未一帆风顺，先后在针对乳腺癌、非小细胞肺癌的III期临床试验中折戟。阿斯利康旗下其他抗癌药物研发线中，AKT阻断剂Truqap在2024年11月取得III期临床胜利，显著改善某些类型前列腺癌的放射学无进展生存期。然而，今年4月，Truqap在一项III期前列腺癌研究中遭遇挫折，迫使阿斯利康终止CAPItell-280的III期临床。在2025年，阿斯利康似乎保持其加大研发支出的步伐。例如，仅在3月，这家MNC就斥资10亿美元收购EsoBiotec及其细胞疗法产品线，并与韩国的Alteogen签署两项协议，合作研发皮下癌症疗法——总计而言，阿斯利康支付给Alteogen金额有望达到13.5亿美元。TONACEA05艾伯维 2024年研发支出：128亿美元同比变化：60%不仅是前五MNC，纵观20家上榜公司，艾伯维的研发支出增幅都是最大的：2024年同比增长60%，达到近128亿美元。或许最大的推动因素，是艾伯维2023年12月斥资87亿美元收购Cerevel Therapeutics。此次收购重点是下一代抗精神病药物emraclidine，但该药最终在两项II期临床试验中失败，令艾伯维的神经疾病治疗战略被质疑。然而，收购Cerevel对艾伯维来说并非满盘皆输。2024年9月，这笔交易完成仅一个月后，同样来自Cerevel的候选药物tavapadon，在帕金森病治疗领域取得III期临床胜利。Tavapadon是首个且唯一一个作为帕金森病每日一次疗法的在研D1/D5受体部分激动剂，艾伯维预计2025年向FDA提交新药上市申请。除了收购Cerevel，艾伯维在2024年继续推进其神经疾病领域业务。同年5月，艾伯维与Gilgamesh Pharmaceuticals达成总计超过20亿美元的合作，重点开发用于精神疾病的神经塑性药物。在免疫学方面，2024年艾伯维也持续加码，以2.5亿美元收购专注开发炎症性疾病的Celsius Therapeutics，包括一款潜在first-in-class的TREM1抗体CEL383。去年，艾伯维在抗肿瘤领域也取得不小进展：2024年ESMO年会上，公布了卵巢癌、非小细胞肺癌和其他实体瘤的一系列积极结果；同年ASH年会上，更新了支持TCE双抗CD3/CD20 epcoritamab单药或联合治疗弥漫大B细胞淋巴瘤患者的数据。尽管研发支出位列前排，艾伯维似乎并未满足。2025年至今，该公司已达成数笔巨额交易。例如1月，艾伯维宣布与Neomorph共同开发分子胶降解剂，合作金额最高可达16.4亿美元。分子胶降解剂也引起了其他MNC的注意，例如渤健、诺华、武田和诺和诺德在2024年都达成类似协议，可能在该领域投入超过60亿美元。渤健、诺和诺德都与Neomorph进行交易。参考资料：Undeterred by Political, Economic Headwinds, Pharma Ups R&D Investment in 2024 and Beyond

并购抗体药物偶联物专利到期

100 项与 FPI-2265 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性去势抵抗性前列腺癌	临床3期	美国	Fusion Pharmaceuticals, Inc.	2024-03-05
PSMA阳性去势抵抗性前列腺癌	临床3期	美国	Fusion Pharmaceuticals, Inc.	2024-03-05
去势抵抗性前列腺癌	临床1期	美国	RadioMedix, Inc.	2021-08-02

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05219500 (TATCIST, PRNewswire) 人工标引	临床2期	转移性去势抵抗性前列腺癌	25	FPI-2265	憲鬱糧鏇蓋範壓窪觸繭(築襯遞憲壓鬱廠壓範夢) = 壓築糧鏇願醖夢遞構鑰構網鑰製鑰餘夢襯餘顧 (艱選簾餘鹽夢糧壓糧鹽 ) 更多	积极	2024-04-09
NCT05219500 (TATCIST, AACR2024) 人工标引	临床2期	转移性去势抵抗性前列腺癌 Prostate specific antigen	30	FPI-2265	蓋膚觸簾齋糧遞選衊鏇(鹹淵夢鑰獵淵醖襯積範) = dry mouth (18/21 [86%]), fatigue (10/21 [48%]) dry eye (6/21 [28%]), and anemia (6/21 [28%]). All were Grade 1-2 in severity, expect anemia Grade 3 which was observed in (5/21 [24%]). Other Grade 3 TRAEs included decreased platelet count (3/21 [14%]). No Grade 4 or 5 TRAEs were reported. Dry mouth was primarily Grade 1 (13/21 [62%]) with only 5 patients (24%) experiencing Grade 2 dry mouth; 壓鬱鏇遞築鏇鑰窪顧網 (艱壓製襯艱醖襯選襯遞 )	积极	2024-04-05