Gocatamig

Back-to-back Presidential Symposium presentations of ENHERTU from DESTINY-Breast11 and DESTINY-Breast05 demonstrate its potential to become a foundational treatment in curative-intent settings of HER2 positive early breast cancer Late-breaking data from TROPION-Breast02 showcase that DATROWAY is the first and only therapy to significantly improve overall survival versus chemotherapy as first-line treatment for patients with first-line metastatic triple negative breast cancer for whom immunotherapy is not an option Data from eight additional trials – DESTINY-Breast09, REJOICE-Ovarian01, IDeate-Lung01, TROPION-PanTumor03, DESTINY-Gastric04, DESTINY-CRC02, DESTINY-PanTumor02 and DS-3939 – further support the strength of the DXd ADC portfolio of Daiichi Sankyo across multiple types of cancer Investor conference call to discuss ESMO TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) will present new clinical research across its DXd antibody drug conjugate (ADC) portfolio with four late-breaking presentations from more than 20 abstracts at the 2025 European Society for Medical Oncology (#ESMO25) Congress. Data at ESMO will spotlight the company’s advances towards creating new standards of care for patients with breast cancer, including back-to-back presentations during Presidential Symposium I featuring data from the DESTINY-Breast11 (291O) and DESTINY-Breast05 (LBA1) phase 3 trials. Results of these two landmark trials will showcase the potential of ENHERTU® (trastuzumab deruxtecan) to become a foundational treatment in curative-intent settings of HER2 positive early breast cancer. Late-breaking DATROWAY® (datopotamab deruxtecan) data from the TROPION-Breast02 phase 3 trial (LBA21), representing the first trial ever to demonstrate a significant improvement in overall survival compared to chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) for whom immunotherapy is not an option, will be featured in a proffered paper session. “Data from these three landmark trials demonstrate how the DXd ADC portfolio of Daiichi Sankyo continues to transform standards of care for patients with breast cancer. The findings from DESTINY-Breast11 and DESTINY-Breast05 highlight the potential of ENHERTU to become a foundational treatment in the curative-intent settings of HER2 positive early breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Additionally, the DATROWAY results from TROPION-Breast02 represent the first time ever that an overall survival benefit has been demonstrated in the first-line setting of patients with metastatic triple negative breast cancer for whom immunotherapy is not an option. Couple these impressive results for DATROWAY with previous results seen with ENHERTU in the HER2 positive, HER2 low and HER2 ultralow disease settings, Daiichi Sankyo will now have two medicines with the potential to treat approximately 90 percent of patients with metastatic breast cancer.” Additional breast cancer data at ESMO includes a mini oral presentation of data from Arm 7 and Arm 8 of the BEGONIA phase 1/2 trial (555MO) evaluating DATROWAY plus durvalumab in patients with first-line metastatic TNBC. The efficacy and safety of this combination strategy is being further investigated in three phase 3 trials – TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05 – across stages and treatment settings of TNBC. Trials Supporting Three Recent Breakthrough Therapy Designations Showcased Data from additional late-stage trials – DESTINY-Breast09, REJOICE-Ovarian01 and IDeate-Lung01 – that supported three recent Breakthrough Therapy Designations (BTD) in the U.S. for ENHERTU, raludotatug deruxtecan (R-DXd) and ifinatamab deruxtecan (I-DXd) will be showcased at ESMO. Two late-breaking proffered paper sessions will highlight the primary analysis from the phase 2 part of the REJOICE-Ovarian01 phase 2/3 trial (LBA42) of raludotatug deruxtecan in patients with previously treated platinum-resistant ovarian cancer, and additional analyses of key subgroups of interest from the DESTINY-Breast09 phase 3 trial (LBA18) evaluating ENHERTU plus pertuzumab versus THP (taxane, trastuzumab, pertuzumab) for the first-line treatment of patients with HER2 positive metastatic breast cancer. Results of DESTINY-Breast09 formed the basis for a supplemental Biologic License Application in the U.S. for ENHERTU, which was recently granted Priority Review under the Real-Time Oncology Review program. Detailed results highlighting the intracranial activity of ifinatamab deruxtecan from the IDeate-Lung01 phase 2 trial (2760MO) in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) and baseline brain metastases will be highlighted during a mini oral session. The primary results of IDeate-Lung01 were presented last month at the 2025 World Conference on Lung Cancer (#WCLC25). Progress Continues in Multiple Cancers Across the DXd ADC Portfolio of Daiichi Sankyo Additional mini oral sessions at ESMO will feature the first presentation of data from two early phase trials from the DXd ADC portfolio of Daiichi Sankyo. These include preliminary results from the first-in-human phase 1/2 trial of DS-3939 (917O), the sixth DXd ADC in clinical development, in patients with previously treated advanced solid tumors refractory to standard treatment, as well as initial results from a sub-study of the TROPION-PanTumor03 phase 2 trial (3072MO) evaluating DATROWAY plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, in patients as first-line or second-line locally advanced or metastatic urothelial carcinoma. Final analyses from two trials – DESTINY-CRC02 and DESTINY-PanTumor02 – that supported the tumor agnostic indication of ENHERTU, which is now approved in more than 10 countries/regions worldwide, will be presented. A mini oral session will feature the final analysis from the DESTINY-CRC02 phase 2 trial (737MO) of ENHERTU in patients with previously treated HER2 positive metastatic colorectal cancer while two poster presentations will highlight the final results (957P) and an exploratory biomarker analysis (145P) from part 1 of the DESTINY-PanTumor02 phase 2 trial in patients with previously treated HER2 expressing solid tumors. Additional regulatory submissions seeking a tumor agnostic approval in patients with HER2 positive metastatic solid tumors currently are under review in the EU and Japan. Further sub-analyses from the DESTINY-Gastric04 phase 3 trial of ENHERTU versus ramucirumab plus paclitaxel in the second-line treatment of patients with HER2 positive metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma will be presented as a poster presentation (2099P) reporting the concordance of central HER2 testing with local HER2 testing along with additional efficacy and safety analyses. Data from DESTINY-Gastric06, a phase 2 trial in patients from China with HER2 expressing advanced gastric or GEJ adenocarcinoma who have received at least two prior regimens including a fluoropyrimidine agent and a platinum agent, will be presented in two poster presentations. The first poster (2105P) will feature an analysis of patients that received prior anti-HER2 treatment other than or in addition to trastuzumab. The second poster (2175P) will report the risk of hepatitis B virus reactivation in patients with past or resolved HBV or inactive chronic HBV infection treated with ENHERTU. Updates of progress in lung cancer include a mini oral session reporting updated results from a phase 1/2 trial of gocatamig (2758MO), a DLL3 targeting T-cell engager being jointly developed by Merck, in patients with small cell lung cancer and other neuroendocrine cancers, as well as a poster presentation that will highlight the initial safety results from a phase 1b trial of valemetostat (2023P), a dual EZH1 and EZH2 inhibitor, in combination with DATROWAY in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC). Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio Several trials-in-progress poster presentations at ESMO further highlight the Daiichi Sankyo R&D strategy of continuing to expand the DXd ADC portfolio to address a broad spectrum of unmet needs for patients with cancer. A trial-in-progress poster will highlight the design of the DESTINY-Endometrial01 phase 3 trial (1223TiP) evaluating ENHERTU in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/ 2+), mismatch repair proficient (pMMR) primary advanced or recurrent endometrial cancer. Three phase 2 trials-in-progress will include the HERTHENA-Breast03 trial (463eTiP) evaluating neoadjuvant patritumab deruxtecan (HER3-DXd) plus pembrolizumab before or after pembrolizumab plus chemotherapy in patients with high-risk early-stage TNBC or HR low positive/HER2 negative breast cancer; the REJOICE-GI01 trial (1001TiP) evaluating the efficacy and safety of raludotatug deruxtecan in patients with gastrointestinal cancers, including pancreatic ductal adenocarcinoma, gastroesophageal adenocarcinoma, biliary tract and colorectal cancer; and, the KEYMAKER-U01 sub-studies 01H/01I (2081eTiP) evaluating ifinatamab deruxtecan, raludotatug deruxtecan or docetaxel in patients with stage IV NSCLC. The design of two additional early phase trials will be shared, including the phase 1/2 trial (2792TiP) evaluating ifinatamab deruxtecan and gocatamig in patients with relapsed/refractory ES-SCLC and a phase 1b trial (977P) of valemetostat in combination with ipilimumab in patients with refractory genitourinary tumors, including prostate cancer, urothelial carcinomas and renal clear cell carcinoma. Investor Briefing During ESMO Daiichi Sankyo will hold a virtual conference call for investors on Tuesday, October 21, 2025 from 8:00 to 9:30 am EDT / 9:00 to 10:30 pm JST. Executives from Daiichi Sankyo will provide an overview of the ESMO data. Daiichi Sankyo Oral Presentations at ESMO Presentation Title Author Abstract Presentation (CEST) Breast Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2-positive (HER2+) primary breast cancer with residual invasive disease after neoadjuvant therapy: interim analysis of DESTINY-Breast05 C. Geyer LBA1 Presidential Symposium I Saturday, October 18 4:30 – 6:15 pm DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer N. Harbeck 291O Presidential Symposium I Saturday, October 18 4:30 – 6:15 pm Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for patients with HER2+ advanced/metastatic breast cancer: additional analyses of DESTINY-Breast09 in key subgroups of interest S. Loibl LBA18 Proffered Paper Session Sunday, October 19 8:30 – 10:00 am First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple negative breast cancer for whom immunotherapy was not an option: primary results from the randomized, phase 3 TROPION-Breast02 trial R. Dent LBA21 Proffered Paper Session Sunday, October 19 8:30 – 10:00 am Datopotamab deruxtecan (Dato-DXd) + durvalumab as first-line treatment for unresectable locally advanced/ metastatic triple negative breast cancer: final results from the phase 1b/2 BEGONIA study P. Schmid 555MO Mini Oral Session Monday, October 20 10:15 – 11:45 am Lung Intracranial activity of ifinatamab deruxtecan (I-DXd) in patients with extensive-stage small cell lung cancer and baseline brain metastases: primary analysis of IDeate-Lung01 P. Rocha 2760MO Mini Oral Session Saturday, October 18 4:30 – 6:00 pm Updated results from a phase 1/2 study of gocatamig for small cell lung cancer and other neuroendocrine cancers H. Beltran 2758MO Mini Oral Session Saturday, October 18 4:30 – 6:00 pm Ovarian Raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer: primary analysis of the phase 2 dose- optimization part of the REJOICE-Ovarian01 study I. Ray-Coquard LBA42 Proffered Paper Session Sunday, October 19 2:45 – 4:15 pm Bladder Datopotamab deruxtecan (Dato-DXd) + rilvegostomig in patients with locally advanced or metastatic urothelial cancer: results from the phase 2 TROPION-PanTumor03 study S. Rha 3072MO Mini Oral Session Friday, October 17 4:00 – 5:30 pm CRC Trastuzumab deruxtecan (T‑DXd) in patients with HER2 positive (HER2+) metastatic colorectal cancer: final analysis of DESTINY-CRC02, a randomized, phase 2 trial K. Raghav 737MO Mini Oral Session Sunday, October 19 2:45 – 4:15 pm PanTumor DS-3939, a tumor-associated mucin 1 (TA-MUC1)-directed antibody drug conjugate (ADC), in patients with advanced/metastatic solid tumors: initial results from a first-in-human study M. Patel 917O Proffered Paper Session Sunday, October 19 2:45 – 4:20 pm Daiichi Sankyo Poster Presentations at ESMO Presentation Title Author Abstract Presentation (CDT) Breast Final real-world safety and effectiveness results of REALITY-01 study: trastuzumab deruxtecan (T-DXd) in patients received ≥2 prior treatment lines for HER2+ metastatic or unresectable breast cancer J. Pierga 539P Poster Session The effectiveness of post-trastuzumab deruxtecan (T-DXd) treatment regimens and the incidence of recurrent interstitial lung disease (ILD) in patients with HER2+ metastatic breast cancer who discontinued T-DXd due to ILD J. Tsurutani 540P Poster Session HERTHENA-Breast03: a phase 2, randomized, open-label study evaluating neoadjuvant patritumab deruxtecan + pembrolizumab before or after pembrolizumab + chemotherapy for early-stage TNBC or HR low+/HER2− breast cancer M. Danso 463eTiP ePoster Lung Phase 1b study of valemetostat in combination with datopotamab deruxtecan (Dato-DXd) in advanced non-squamous non-small cell lung cancer: initial safety results A. Spira 2023P Poster Session A phase 1b/2 study of gocatamig (MK-6070; HPN328) and ifinatamab deruxtecan for relapsed/refractory extensive-stage small cell lung cancer J. Sun 2792TiP Poster Session KEYMAKER-U01 phase 2 substudies 01H/01I: ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) or docetaxel in stage IV non-small cell lung cancer E. Nadal 2081eTiP ePoster Gastrointestinal Trastuzumab deruxtecan (T-DXd) vs ramucirumab plus paclitaxel in second-line treatment of patients with HER2+ unresectable/metastatic gastric cancer/gastroesophageal junction adenocarcinoma: additional data from DESTINY-Gastric04 F. Pietrantonio 2099P Poster Session Trastuzumab deruxtecan (T-DXd) in patients with HER2+ gastric cancer or gastroesophageal junction adenocarcinoma who received prior anti-HER2 treatment other than/in addition to trastuzumab in DESTINY-Gastric06 Z. Peng 2105P Poster Session Risk of hepatitis B virus reactivation in patients with past or resolved HBV or inactive chronic HBV infection treated with trastuzumab deruxtecan (T-DXd) in the DESTINY-Gastric06 L. Shen 2175P Poster Session Raludotatug deruxtecan in participants with gastrointestinal cancers: phase 2 REJOICE-GI01 trial M. Ueno 1001TiP Poster Session Endometrial A randomized phase 3 study of first-line trastuzumab deruxtecan (T-DXd) with rilvegostomig or pembrolizumab in patients with HER2 expressing, mismatch repair-proficient, primary advanced or recurrent endometrial cancer: DESTINY-Endometrial01/GOG-3098/ENGOT-EN24 B. Slomovitz 1223TiP Poster Session PanTumor Trastuzumab deruxtecan (T-DXd) for pretreated patients with HER2 expressing solid tumors: DESTINY-PanTumor02 part 1 final analysis V. Makker 957P Poster Session Trastuzumab deruxtecan (T-DXd) in pretreated patients with HER2 expressing solid tumors: exploratory biomarker analysis of DESTINY-PanTumor02 part 1 D. Oh 145P Poster Session DS3201 (valemetostat), an EZH1/2 inhibitor, with ipilimumab in patients with refractory genitourinary tumors S. Goswami 977P Poster Session About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 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 www.daiichisankyo.com.

9月下旬，泽璟制药的注射用ZG006（一款靶向CD3/DLL3/DLL3的三特异性抗体）登记启动III期临床研究，用于治疗复发性小细胞肺癌——由此ZG006成为全球首个进入III期的肿瘤三抗。 前后脚，一场震动行业的收购案落定：丹麦Genmab以约80亿美元将荷兰公司Merus收入囊中，交易金额刷新了欧洲生物科技领域的高额收购纪录。 被收购的Merus，除了颇受关注的双抗在研管线，赋予其想象空间的还有公司专有的三抗平台Triclonics®。一年半前，正是这一平台帮助Merus斩获与吉利德总额超15亿美金的合作。 几家公司以截然不同的方式，将“三特异性抗体”这一前沿技术再度推向了行业聚光灯下。 凭借多一个靶点结合位点的结构优势，三抗旨在实现更强的靶向特异性、更优的临床疗效与更低的脱靶毒性，从而被视为下一代免疫疗法的重点方向。 不仅国内外企业都在积极参与研发，全球在研项目突破百个，艾伯维、默沙东等跨国巨头更在近年来以数十亿美元的密集交易为其潜力“投票”，一场关于未来治疗格局的新角逐正在进行。 一个核心问题随之浮现：在双抗成功开辟的道路上，能够同时靶向三个靶点的三抗，是简单的技术叠加，还是足以复制甚至超越前者的范式革命？ 当康方生物凭借AK104和AK112两款双抗药物的贡献，从市值不足100亿港元的“小透明”成长为突破1000亿港元的“小巨头”，未来，三抗企业又能否复制康方生物的“神话”？ TONACEA 01 三抗站上新风口 单抗药物因其特异性强、靶向性高和毒副作用小等特点，已在肿瘤、自身性免疫疾病等领域广泛应用。 但是，由于疾病的复杂性，例如在肿瘤治疗领域，由于免疫抑制性微环境及肿瘤免疫逃逸机制的复杂性，这种针对单一靶点的药物往往难以达到理想的治疗效果，临床上表现为响应率不高，获益群体比较有限。 双抗药物应运而生，为治疗提供了新途径。目前全球已有多款双抗药物获批上市，适应症主要集中在肿瘤领域。 然而，作为“敌人”的癌细胞不会坐以待毙，其在治疗过程中往往会展现出狡猾本性，改变表面抗原的表达模式，避开双抗的识别，并主动构建各种“防御工事”来抵抗免疫系统的攻击。 因此，科学家开始深入思考：能否设计出更加智能和坚固的"桥梁"，让它不仅能够同时识别敌人的多种伪装，还能够招募不同类型的友军，形成更加全面和持久的包围攻势？ 在此驱动下，可以同时靶向三种不同的靶抗原或标志物的三抗，成为下一代免疫疗法研发的核心焦点。 与双抗相比，三抗还能够与肿瘤细胞或免疫细胞表面的另一个靶点相结合，或桥接免疫细胞并阻断双信号通路等作用，更有利于将药物或免疫细胞重定向至肿瘤部位，增强结合特异性，提高靶向性，降低脱靶毒性，从而提升抗肿瘤能力。 以泽璟制药开发的ZG006为例，结合两个不同表位的DLL3，通过靶向DLL3和CD3将肿瘤细胞和T细胞结合，用于T细胞介导的肿瘤细胞杀伤，对于DLL3不同表达量的肿瘤细胞均有较好的杀伤效果。 近十年来，三抗从概念验证快速步入临床研究，已有多家生物医药企业布局。不完全数据统计，在研三抗产品已突破100个，大多数项目处于临床早期阶段，适应症主要集中在肿瘤和眼科疾病，尤其是肿瘤领域。 来源：药智数据 作用靶点上，在研三抗作用靶点比较多样，主要集中在CD3、PD-L1、BCMA、VEGF等，其中CD3靶点最热门。从靶点组合来看，GPRC5D/BCMA/CD3、PD-L1/VEGF/TGF-β相对热门，且在研药物进展较快。 TONACEA 02 BD交易潜力初现 虽然目前未有三抗获批上市，但其潜力已引发国内外药企关注，并促使达成多项交易，不乏MNC的身影。 2025年，艾伯维先后就有两笔出手：先是1月，以10.55亿美元引进先声药业GPRC5D/BCMA/CD3三抗SIM0500；紧接着半年后的7月，豪掷将近20亿美金，拿下IGI主要资产CD3/CD38/BCMA三抗TCE ISB 2001，在北美、欧洲、日本和大中华区开发、制造和商业化的独家权利。 连续引进两款TCE三抗产品，可见艾伯维对多特异性抗体药物的态度改变以及行业技术迭代加速的信号。其首席执行官Rob Michael也曾在6月高盛的一次活动上表示，将多特异性抗体作为公司肿瘤领域交易的重点。 相比艾伯维通过BD引进潜力重磅品种，补足其在血液瘤领域的优势，默沙东的收购要来得更早且更加猛烈。 2024年5月，默沙东将以13亿美元的前期付款和高达17亿美元的未来里程碑付款收购EyeBio公司。 EyeBio的先导候选药物Restoret（EYE103）是一种在研的、潜在的“first-in-class”的四价、三特异性Wnt抗体，旨在解决视网膜疾病患者未满足的医疗需求。Restoret通过玻璃体内注射给药，旨在通过激动Wnt途径消除视网膜血管疾病中的渗漏，恢复和维持血-视网膜屏障（BRB）。 在这之前，2024年1月，默沙东还以约6.8亿美元收购了Harpoon Therapeutics，后者的核心管线HPN328（MK-6070）为一款DLL3/CD3/Albumin三特异性抗体。7个月后，第一三共和默沙东宣布将共同开发及商业化MK-6070，默沙东仅保留了日本权益。 当然，近两年，出手三抗的MNC除了艾伯维、默沙东，还有吉利德、GSK、辉瑞。 吉利德于2024年3月与Merus达成一项研究合作许可协议，共同开发靶向新型双重肿瘤相关抗原（TAA）的三抗；GSK在同年10月和恩沐生物达成合作，以3亿美元的首付款从恩沐生物收购CMG1A46；辉瑞则紧随其后，在11月与天广实达成GPRC5D/BCMA/CD3三抗MBS314共同开发合作。 还值得注意的是，去年11月，维立志博与风险投资公司Aditum Bio达成了NewCo交易，基于维立志博全球首创CD19xBCMAxCD3三抗TCE抗体LBL-051成立新药研发公司Oblenio Bio，并达成了独家选择权及许可协议。 Aditum为Oblenio提供资金，双方合作推进LBL-051进入临床，Oblenio拥有全球范围内开发、生产和商业化LBL-051的独家选择权和许可，维立志博则获得3500万美元的首付款和近期付款，在达成开发、监管注册、销售里程碑事件后，维立志博还将有权获得最高达5.79亿美元的总交易额款项，以及未来产品的销售分成。此外，维立志博还将有权获得Oblenio的股权。 可以看到，在海外巨头这一轮轰轰烈烈的”扫货“中，恩沐生物、先声药业、天广实、维立志博的三抗产品，凭借其差异化的优势受到青睐，成功出海。 TONACEA 03 下一个BD爆点？ 除了以上交易涉及的产品，随着PD-1/VEGF的靶点组合已在临床上得到验证，且拥有超越PD-1的潜力，针对PD-1/VEGF靶点组合延伸出来的三抗靶点，有望成为引爆市场的下一个风口。 根据开源证券的统计，截至2025年8月8日，全球共有32款处于临床及临床前PD-(L)1三抗（项目状态积极），其中16款为PD-(L)1/VEGF三抗药物。 从迭代逻辑来看，现有的PD-(L)1/VEGF双抗PFS获益显著，但总生存期获益仍需进一步明确。而三抗的升级，正是希望在这一方面做更多努力。 目前全球药企的核心思路，是叠加一些已经被验证，或者机制相对清晰的靶点，因而在多种PD-(L)1/VEGF三抗中，PD-(L)1/VEGF/TGFβ三抗及PD-(L)1/VEGF/CTLA-4三抗是最早进入临床阶段的两类多抗。 例如华东医药DR30206，临床前数据显示，在肺癌小鼠模型中，高剂量（25mg/kg）DR30206 比低剂量肿瘤抑制效果更佳，且DR30206 所有剂量组均比Atezolizumab(5mg/kg)联合或不联合Bevacizumab（5mg/kg）组治疗效果更显著。 R30206已在中国开展两项临床，分别为DR30206单药（1mg/kg~30mg/kg Q2W/Q3W）治疗多种实体瘤及DR30206（15/20mg/kg Q2W、30mg/kg Q3W）联合化疗一/二线治疗胃癌、食管腺癌和结直肠癌。 还有基石药业CS2009，已于2024年12月开展中国/澳大利亚首个I/II临床试验，预计年底前入组超100例患者。截至基石药业公告日，CS2009 在所有已评估的剂量水平上展现出良好的耐受性，并且已在低剂量组的“冷肿瘤”及PD-(L)1 经治患者中观察到抗肿瘤活性。 除了上述产品，PD-(L)1/VEGF 双抗和 PD-(L)1/IL-2 双抗的显著进展验证了 PD-(L)1 与 VEGF和 IL-2 的疗效协同性，作为将这两个具有明确协同效应的靶点同时整合的三抗药物，PD-(L)1/VEGF/IL-2 也颇受关注，目前仅有一款（上海谊众）处于临床前阶段。 上海谊众YXC-001有望于2025年内完成国内与国际的IND同步申报。YXC-001临床前初步药效试验显示，该多功能抗体能够多靶点协同发挥作用，对比帕博利珠单抗等单抗及双抗类药物，具有抑制肿瘤优势。 几款重点产品，谁能率先在临床端带来新突破，并刷新国产创新药出海记录？拭目以待。 — 结语—   整体来看，三抗的发展仍处于相对早期，研发并不容易，靶点叠加并不直接等同于效果提高，也绝不是简单的排列组合，复杂性远超预期。 有人如是比喻：如果把传统单抗比作制造一把简单而可靠的工具，那么三抗就像是要制造一台能够同时执行三种不同任务的精密设备——这种复杂性的提升带来了前所未有的技术挑战。 三抗的征途，也绝非简单复制双抗的路径。 它以其内在的复杂性与灵活性，呈现出三大趋势：纵向的技术迭代，向着四特异性抗体等更复杂形式演进；横向的适应症扩展，从肿瘤迈向自免、感染等更广阔疾病领域；以及深度的联合疗法探索（如三抗+ADC），旨在构建协同作战的“组合拳”。 当科学的探索从“能否实现”迈向“如何整合”，三抗的故事，才真正进入了最激动人心的章节。 参考资料： 1.SinoTalk津津乐道，《起风了 三抗江湖》 2.博药，《从“双”到“三”：多特异抗体的进化与未来》 3.药事纵横，《全球首个三抗药物进入三期，盘点国产三抗进度》 4.药智网，《巨头加码，三抗成为“新风口”》 5.SAIMed赛麦德咨询，《三抗：药物研发新风口，企业合作频发》 6.氨基观察，《PD-(L)1/VEGF三抗越来越热闹了》 7.开源证券，《二代 IO 升级迭代，PD-1/VEGF 三抗加速推进》