Gocatamig

Based on results from IDeate-Lung01 phase 2 trial, with support from IDeate-PanTumor01 phase 1/2 trial If approved, ifinatamab deruxtecan would be a first-in-class B7-H3 directed DXd antibody drug conjugate for these patients BASKING RIDGE, N.J.--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and Merck’s, known as MSD outside of the United States and Canada, (NYSE: MRK) Biologics License Application (BLA) for ifinatamab deruxtecan (I-DXd) has been accepted and granted Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck. The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The FDA is also reviewing the BLA under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is October 10, 2026. The BLA is based on results from the IDeate-Lung01 phase 2 trial, with support from the IDeate-PanTumor01 phase 1/2 trial. Results from the primary analysis of IDeate-Lung01 were presented at the 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC25) and published in the Journal of Clinical Oncology . Ifinatamab deruxtecan also was previously granted Breakthrough Therapy Designation by the FDA in August 2025 for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. “The FDA’s granting of Priority Review for ifinatamab deruxtecan marks a significant milestone in our effort to provide new and innovative treatment options for patients with extensive-stage small cell lung cancer,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “We look forward to continuing to work with the FDA to bring this potential first-in-class B7-H3 directed DXd antibody drug conjugate to patients as quickly as possible.” “Small cell lung cancer remains one of the toughest cancers to treat, with few options if the disease progresses after standard of care treatments,” said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. “The FDA’s acceptance of the BLA reinforces the important role that ifinatamab deruxtecan could play in helping to address the needs of patients with extensive-stage small cell lung cancer.” About IDeate-Lung01 IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC who were previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. Patients with asymptomatic brain metastases (untreated or previously treated) were eligible to participate. In the first part of the trial (dose optimization), patients were randomized 1:1 to receive ifinatamab deruxtecan (8 or 12 mg/kg) given intravenously once every three weeks. In the second part of the trial (dose expansion), patients received ifinatamab deruxtecan (12 mg/kg) intravenously at the same dosing interval. The primary endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), time to response (TTR), overall survival (OS), pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis. IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov . About IDeate-PanTumor01 IDeate-PanTumor01 is a global, multicenter, first-in-human, open-label phase 1/2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists. The phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose and recommended dose for expansion (RDE). The phase 2 part of the trial (dose expansion) is evaluating the safety and efficacy of ifinatamab deruxtecan at the RDE of 12 mg/kg in patients with squamous non-small cell lung cancer, metastatic castration-resistant prostate cancer or esophageal squamous cell carcinoma. The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, DCR, PFS, OS and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed. IDeate-PanTumor01 will enroll approximately 250 patients in Asia and North America. For more information about the trial, visit ClinicalTrials.gov . About Small Cell Lung Cancer Approximately 250,000 patients are diagnosed with small cell lung cancer (SCLC) each year globally. 1 There were approximately 27,000 new cases of SCLC in the U.S. in 2025, accounting for about 12% of all lung cancer cases. 2,3 SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate. 4,5 While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches. 6,7,8,9 About B7-H3 B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1. 10,11 B7-H3 is overexpressed in a wide range of cancer types, including SCLC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. 12,13,14,15 There are currently no B7-H3 directed medicines approved for the treatment of cancer. About Ifinatamab Deruxtecan Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Ifinatamab deruxtecan was granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. Ifinatamab deruxtecan has been granted Orphan Drug Designation (ODD) by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of SCLC. Ifinatamab deruxtecan also was granted ODD for the treatment of esophageal cancer by the FDA. About the Ifinatamab Deruxtecan Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan monotherapy and in combination with other cancer medicines across multiple cancers. The program is currently comprised of three phase 3 trials in advanced/metastatic disease, including SCLC ( IDeate-Lung02 ), castration-resistant prostate cancer ( IDeate-Prostate01 ) and esophageal squamous cell carcinoma ( IDeate-Esophageal01 ). About the Daiichi Sankyo and Merck Collaboration Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, entered into a global collaboration in October 2023 to jointly develop and commercialize ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In  August 2024 , the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck & Co., Inc., Rahway, N.J., USA will maintain exclusive rights. Merck & Co., Inc., Rahway, N.J., USA will be solely responsible for manufacturing and supply for gocatamig. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include ENHERTU ® and DATROWAY ® , which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc., Rahway, N.J., USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit . Merck’s Focus on Cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 20 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( ). _____________________________ References: Wang Q, et al. Journal of Thoracic Oncology . 2023 Jan;18(1):31-46. National Cancer Institute. SEER Explorer. Cancer Stat Facts: Lung and Bronchus Cancer . Accessed December 2025. U.S. Centers for Disease Control and Prevention. United States Cancer Statistics. Types of Lung Cancer | U.S. Cancer Statistics | CDC . Accessed December 2025. Rudin CM, et al. Nat Rev Dis Primers . 2021;7(1):3. National Cancer Institute. SEER Explorer. Small cell carcinoma of the Lung and Bronchus: 5-year Relative Survival . Accessed January 2026. American Cancer Society. Treatment Choices for Small Cell Lung Cancer, by Stage . Accessed January 2026. Liu SV, et al. J Clin Oncol . 2021;39(6):619-30. Paz-Ares L, et al. ESMO Open . 2022;7(2):100408. von Pawel J, et al. J Clin Oncol . 2014;32:4012-4019. Zhao B, et al. J Hematol Oncol . 2022;15(1):153. Janakiram M, et al. Immunol Rev . 2017;276(1):26-39. Qiu M-j, et al. Front. Oncol . 2021;11:600238. Picarda E, et al. Clin Cancer Res . 2016;22(14):3425-3431. Bendell JC, et al. J Clin Oncol . 2020;39(15 suppl 1). Abstract TPS3646. Kontos F, et al. Clin Cancer Res . 2021;27(5):1227-1235. Contacts Media Contacts: Daiichi Sankyo Global/US: Jennifer Brennan Daiichi Sankyo jennifer.brennan@daiichisankyo.com +1 (908) 900-3183 (mobile) Japan: Daiichi Sankyo Co., Ltd. DS-PR_jp@daiichisankyo.com Investor Relations Contact: DaiichiSankyoIR_jp@daiichisankyo.com Merck Media: Julie Cunningham julie.cunningham@merck.com Michael McArdle michael.mcardle@merck.com Investors: Peter Dannenbaum (732) 594-1579 Steven Graziano (732) 594-1583

曾几何时，多少制药人意气风发，怀揣着梦想踏上了TCE抗体之路，不承想短短几年，针对CD3、DLL3、CD20、CLDN18.2、BCMA等靶点组合的双抗赛道就已高度拥挤，如今无论是BD合作，还是Biotech融资都已开始转向更高维度的竞争格局。 2026年3月23日，专注于下一代生物制剂发现与开发的生物技术公司Kali Therapeutics宣布，与赛诺菲就一款三特异性T细胞衔接器达成许可协议，用以治疗多种B细胞介导的自身免疫疾病。 2026年3月18日，艾科联生物（Excalipoint Therapeutics）宣布完成总额6870万美元的种子轮及扩展轮融资。并于同日与乐普生物就CTM012、CTM013两款TCE三抗签订NewCo合作协议。 目前来看，TCE领域短期高频的合作，已然清晰勾勒出赛道从双特异性向三特异性跃迁的产业趋势。与拥挤的双抗赛道相比，三特异性TCE也凭借其诸多核心优势，正成为BD与资本竞相追逐的新蓝海。 TCE的临床局限 尽管，当前双抗平台已日趋成熟，多款TCE药物成功实现商业化落地，但随着TCE双抗的快速发展，赛道拥挤与疗效瓶颈两大核心问题的凸显，为其长期临床应用蒙上阴影： 一者，长期治疗易引发T细胞耗竭，导致免疫激活能力持续下降。 二者，部分肿瘤细胞可通过抗原丢失（如下调肿瘤表面靶抗原表达）规避药物攻击，进而产生耐药性。 三者，肿瘤微环境中残留的抑制性信号，会进一步削弱TCE双抗的作用效能，导致多数实体瘤患者难以从治疗中获益。 这些问题的存在，意味着仅依靠传统双抗机制，已无法满足临床对复发/耐药性肿瘤的治疗需求。 因此，为进一步提升治疗窗口、拓展适应症边界，TCE双抗新一代平台设计持续迭代涌现。其中，三特异性TCE作为下一代研发的核心方向之一，目前业内已有多款在研产品凭借差异化分子设计领跑赛道。 TCE三抗技术原理与设计逻辑 所谓TCE三抗，即三抗的主流分支，其核心功能是招募并激活T细胞杀伤肿瘤，与其并列的还有“NKCE三抗”与“免疫检查点三抗”。 数据来源：公开数据整理 早在2022年，赛诺菲的SAR443216就作为全球首款进入临床阶段的管线出现，可由于早期分子设计上存在诸多缺陷，其在靶点的选择、亲和力的优化以及半衰期设计均有诸多考虑不周的地方，最终于2023年终止研究，不过其设计逻辑却为全球制药同仁提供了重要思路。 其实，TCE三抗设计的底层逻辑并不复杂，即在TCE双抗的基础上新增一个额外功能结构域，用以解决TCE双抗的安全性和疗效局限的问题。而针对不同的临床需求，功能结构域的选择也主要分为两类： ① 新增“共刺激信号” 首先，对于TCE疗法而言，由于其功能主要依靠T细胞实现，而治疗中的目标T细胞可大致分为外周T细胞与肿瘤浸润性T细胞（TIL）两者，前者是早期TCE疗法与CAR-T的主要发力方向，场景主要为血液肿瘤；而后者则是TCE疗法市场下一目标（实体瘤）的重要T细胞来源。 但在实体瘤中，复杂的肿瘤微环境抑制了效应T细胞的功能，因此早期TCE疗法在实体瘤里尤其是冷肿瘤或者PD-1耐药的患者，实际能调动的正常的T细胞非常少，甚至很多都是耗竭性T细胞。 而为了应对上述情况，在CD3的一级刺激信号之外，额外引入二级刺激信号，一定程度上就有望让懒惰的T细胞重新焕发生机，T细胞活性增强、缓解T细胞耗竭。比如，复宏汉霖的HLX-3901，其在CD3/DLL3结构基础上引入了CD28共刺激信号，增强了T细胞的持续激活能力并减少其耗竭，有望产生更持久的抗肿瘤反应。 ② 新增肿瘤/致病细胞靶向位点（TAA） 如果说新增共刺激信号是为了提升疗法有效性，那么在TCE基础上额外引入肿瘤/致病细胞靶点的目的则多是为了应对TCE疗法脱靶毒性、耐药等需求。 比如，当TCE三抗拥有两个不同的肿瘤靶点之后，理论上只有同时满足两大靶点结合位点的情况下才能被正确识别，即“双重识别”，可大幅降低对正常细胞的脱靶结合风险，减少治疗相关毒副作用。 同时，双TAA的设计还可有效应对肿瘤细胞的抗原丢失问题，即便某一靶抗原表达下调，另一靶抗原仍能确保药物与肿瘤细胞结合。以Tarlatamab（CD3/DLL3）与ZG006（CD3/DLL3/DLL3）为例，后者在前者的基础上新增另一表位，产生双表位协同效应，使其能更早与肿瘤细胞结合，并表现出更持久的T细胞激活效果。 目前来看，无论是双TAA组合还是双刺激信号，TCE三抗独特的设计，从作用层面解决了TCE在面对复发、耐药、脱靶毒性、实体瘤有效性不足等方面劣势；而在产业角度，其差异化布局，既能与TCE形成差异化竞争，却又不具备“新靶点发现”那么高的创新难度，拉高了整体市场空间。 因此，无论是应对当前肿瘤治疗的临床痛点，还是推动抗体药物的技术升级，三抗都已成为不可或缺的重要方向，研发与应用需求持续升温。 TCE三抗的市场格局 就当下TCE整体疗法的竞争格局而言，趋势显而易见，即谁掌握更成熟、更具差异化的TCE平台，谁就能在靶点同质化的竞争中占据主动，掌握赛道话语权。 而目前，全球已有超过10款TCE疗法获批上市，覆盖血液瘤与实体瘤两大战场，其市场规模正在高速增长。其中，安进的CD19×CD3双抗Blincyto（贝林妥欧单抗）2024年销售额已达12.16亿美元，成为全球首个突破“十亿美元”的代表性重磅炸弹级TCE药物，充分印证了疗法的商业价值。 那么，对于TCE药企而言，一方面TCE疗法本身局限性愈发凸显，另一方面管线在获批产品的压力之下后来居上压力倍增，TCE三抗作为迭代产品顺势成为探究热点目标。 据药智数据显示，当下全球范围内尚无任何一款TCE三抗获批上市，但已有超30条TCE三抗管线处于临床阶段（下图）。 部分临床进展靠前的“TCE三抗” 数据来源：药智数据（如有错误请指正，点击查看大图） 临床阶段方面，截止2026年4月，全球共有32款TCE三抗进入临床，其中临床Ⅲ期管线仅有强生的JNJ-79635322与Gensun/艾伯维的ZG-006两款；处于临床Ⅱ期的管线共计3款，分别是默沙东的Gocatamig、武田的TAK-186与Harpoon Therapeutics的HPN-823；而临床I期-临床Ⅱ期阶段的管线共9款；临床I期管线则数量最多，超过20款。 原研企业方面，中国已成为全球TCE三抗研发的第二大阵营，32款进入临床的TCE三抗中，国产TCE三抗共14款，占比达41%。不过，国产TCE三抗整体进度稍落后于海外，最高进度仅处于临床I期-临床Ⅱ期。 数据来源：药智数据 靶点组合方面，目前TCE三抗领域中最为主流的组合为CD3/GPRC5D/TNFRSF17，共有5款新药进入临床；其次是CD3/CD19/CD20与CD3/CD20/CD79B，领域内均有3款新药进入临床；之后则是CD3/ALB/DLL3与CD3/CD19/CD28，各自均有2款新药进入临床；其余在研管线则基本上均为临床阶段的独有靶点组合。 数据来源：药智数据 其中，CD3/GPRC5D/TNFRSF17作为TCE三抗集中度最高的靶点组合，属双TAA类型，适应症多集中于容易被攻克的血液瘤方向，旨在通过双重靶向骨髓瘤细胞抗原，旨在克服肿瘤异质性，同时抑制耐药性的产生。 而在该靶点组合领域中，强生的JNJ-79635322不仅是无可争辩的First-in-Class，同时也是整合TCE三抗中唯二进入临床Ⅲ期的疗法，而在其之后则是4款国产新药紧随其后，分别是IBI-3003、MBS-314、QLS4131与SIM-0500。 数据来源：药智数据（如有错误请指正，点击查看大图） 该药采用“1+1+1”的设计，抗体可以通过两种不同的机制对MM肿瘤进行杀伤： 靶向BCMA和GPRC5D的Fab同时结合到同一个肿瘤上，并招募T细胞对肿瘤进行杀伤。 靶向BCMA和GPRC5D的Fab结合不同的肿瘤细胞，并利用同一个T细胞对不同的肿瘤细胞进行杀伤。 根据其在ASCO会议上展示I期临床数据显示，其针对大部分未经同靶点TCE双抗治疗的患者，总体ORR达73%［相似患者群体的Teclistamab（TCE：CD3/TNFRSF17）临床Ⅱ期数据为63%］，且更关键的是，JNJ-5322在针对既往未接受过抗BCMA/-GPRC5D治疗的患者中（n=27），RP2D剂量（100mg）的ORR直接达到了100%，这无疑从正面说明三抗的疗效是要好于双抗的——至少在三线治疗后但未接受BCMA/GPRC5D疗法治疗的患者来说。 而CD3+CD19+CD20作为管线数量仅次于前者的存在，其与上述靶点组合类似，也属于常规的双TAA组合类型，适应症最初应用于血液瘤，但近来开始有企业尝试应用于其他领域，比如2024年10月GSK以3亿美元的首付款从恩沐生物收购 CMG1A46，计划将其开发用于B细胞驱动的自免疾病，如系统性红斑狼疮（SLE）和狼疮性肾炎（LN）。而目前该靶点范围内共有3款新药进入临床，分别是CMG-1A46（国产）、GSK-5926371与BR-110（国产）。 数据来源：药智数据（如有错误请指正，点击查看大图） 目前TCE三抗领域中双TAA组合类型的管线集中度与临床进展较双刺激信号组合类型更高，是领域发展的基础方向，但同时也是竞争更集中的板块，而双刺激信号组合、功能性模块融合等差异化设计，以及适应症向实体瘤、自免疾病的延伸，正成为打破同质化竞争、抢占下一赛道高地的关键突破口，行业竞争逻辑已从单纯的靶点组合比拼，逐步转向平台技术、分子设计与适应症拓展的综合较量。 TCE三抗的未来：四抗、自免适应症 在肿瘤免疫治疗的技术迭代浪潮中，自TCE向TCE三抗的逐步升级已成为破解肿瘤治疗瓶颈的核心方向之一。 而随着全球TCE研发管线的持续扩容，以及技术平台的不断成熟，三抗的发展边界正不断拓宽，不仅朝着更高特异性、更低毒性的四抗方向迭代，更突破了传统肿瘤治疗的局限，向自身免疫疾病等非肿瘤领域延伸，开启了TCE技术多元化发展的全新阶段。 首先是适应症扩展方向，TCE的适应症边界正在向自身免疫疾病延伸，2025年，以CC312（CD19/CD28/CD3）为代表的三特异性TCE已进入系统性红斑狼疮（SLE）等适应症的早期临床探索，同时CM336（CLDN18.2/CD3）在实体瘤之外，也开始尝试自身免疫性溶血性贫血（AIHA）等非肿瘤场景，TCE通过“深度清除致病B细胞”的机制，开始展现出区别于传统免疫抑制剂的潜力，自免领域正成为其新的增长方向。 其次是四抗迭代方向，尽管目前尚未有三抗TCE成功上市，但以复宏汉霖、百利天恒为代表的药企已率先切入四抗赛道，提前布局下一代产品的竞争优势。 虽然，当前进入临床阶段的四抗较少，但设计思路已十分清晰，即两个靶点针对肿瘤抗原以强化肿瘤识别的特异性与结合力，两个靶点对应T细胞活化以构建完整的T细胞激活信号通路。 其中百利天恒早在2020年就将四抗新药GNC-038推进至临床阶段，是全球首个成功获批临床的四抗，而复宏汉霖则基于自主研发的创新型TCE平台开发了DLL3/DLL3/CD3/CD28四抗HLX3901，该药物已获得NMPA批准IND，拟用于晚期或转移性实体瘤的治疗。 总体而言，TCE四抗作为三抗之上的迭代产品，其通过精巧的分子设计，兼具持久的特异性T细胞激活、攻克低T细胞浸润肿瘤及显著降低细胞因子释放综合征（CRS）等多重优势，旨在克服TCE在实体瘤治疗中的主要障碍。同时，双TAA+双刺激信号的设计不仅能显著提升肿瘤识别精度，还可以形成更完整的T细胞激活信号，毫无疑问，多抗设计也成为了药企打造差异化竞争优势的重要方向。 小结 总体而言，由于上述TCE疗法逐渐暴露的诸多局限性所影响，当下TCE三抗迎来前所未有的发展机遇，现如今已处于技术逻辑完全验证、临床价值初步确立、即将迎来首个商业化产品的关键转折点，已从早期的概念探索阶段稳步迈入工程化快速迭代与临床规模化验证的成熟期。 从技术发展的轨迹来看，TCE三抗的演进路径分外清晰且扎实，自2022年赛诺菲的SAR443216作为全球首款进入临床的TCE三抗，虽因设计缺陷于2023年终止研究，但其但其“新增额外功能结构域”的核心设计逻辑却为整个行业奠定了基石。以至于短短四年，就已形成了当下“双TAA降毒抗耐药”和“共刺激信号增强T细胞活性”两大主流技术路线。如今的TCE三抗的技术壁垒俨然已从“能否做出三抗”转向“能否做出差异化三抗”。 从关键管线疗效数据来看，TCE三抗的核心目标必定是证明其相较TCE疗法的优势，而强生的JNJ-79635322作为全球进展最快的TCE三抗，在相似患者群体基础上，整体患者OOR高于Teclistamab（73% VS 63%），且针对未接受过抗BCMA/-GPRC5D治疗的患者ORR可达100%。充分说明，至少在三线治疗后但未接受BCMA/GPRC5D疗法治疗的患者来说，TCE三抗具有提升疗效、克服耐药性和改善安全性方面的独特价值。 从临床进展来看，TCE三抗已形成完整的研发梯队。截至2026年4月，全球共有32款TCE三抗进入临床阶段，并已有两款新药成功进入临床III期，预计未来三年内或可迎来首款获批上市的TCE三抗。而另一方面，中国作为全球TCE三抗研发的第二大阵营，虽管线数量占比上已接近半数（41%），但在临床进度上却整体落后海外1-2个阶段，后续要想在整体市场上有所建树，或还需要从其他方面下一番功夫。 展望未来，TCE三抗的崛起，标志着抗体药物正式进入多抗时代。随着首批产品的即将上市和更多临床数据的读出，TCE三抗将逐步从“下一代技术”转变为“主流治疗手段”，行业竞争也将从靶点组合的简单比拼，转向平台技术、分子设计、适应症拓展和商业化能力的综合较量。 博腾股份成立于2005年，主要为全球药企、生物科技公司、科研机构等提供从临床前研究到药品上市全生命周期所需的小分子药物、多肽与寡核苷酸药物、蛋白与偶联药物以及细胞与基因治疗药物等一站式服务解决方案，研发、生产、运营场地覆盖中国（重庆、上海、四川、江苏、江西、湖北）、美国、斯洛文尼亚、比利时、瑞士和丹麦等地。我们始终坚持以客户为中心，致力于为客户提供创新、可靠的全球化、端到端CDMO服务，让好药更早惠及大众。 免责声明：本文仅作者个人观点的表达，文中观点不代表博腾及其所属子公司立场，亦不对本文所提供信息做任何形式的保证。同时，本文不做治疗方案推荐，也不承担因使用或依赖本文信息所产生的任何直接或间接的后果。如需获得治疗方案指导，请前往正规医院就诊。