2024年12月16-17日，第一三共召开2024年的研发日活动，介绍了公司的管理策略、财务预测、未来展望、研发信息以及一些特定的研发项目。从临床进展来看，第一三共此前主要依靠5款DXd ADC药物在商业化、临床以及商业拓展方面取得了巨大的成功，一己之力改变了下一代ADC药物研发的格局，当前第一三共将依靠五款现有ADC不断拓展临床应用，同时投入更多新型疗法的分子。乳腺癌方面，以HER2 ADC药物Enhertu为基石，不断拓展应用范围，从HER2阳性到低表达，到三阴乳腺癌，到HR阳性等多中人群，同时也逐步从后期到一线，一线到辅助治疗，多范围覆盖乳腺癌治疗。
肺癌方面，同样如此，依靠TROP2 ADC和B7-H3 ADC，在非小细胞肺癌和小细胞肺癌多个阶段进行疗法探索。新分子方面，第一三共此前就介绍了MUC1的ADC药物DS-3939进展，这也是第六款DXD ADC药物，MUC1为肿瘤特异性相关靶点，在多种实体瘤中均有所表达。DS-2243为一款NYESO的TCR双抗，根据UmabsDB数据库的记录，今年10月第一三共已经在clinical trials网站上，登记了一项NY-ESO TCR疗法药物DS-2243a，在滑膜肉瘤和非小细胞肺癌等多种实体瘤HLA-A2亚型患者中，启动一项1期临床试验NCT06644755，该临床于2024年11月启动，计划入组人数为150例。
此外第一三共还介绍了最新研发更新、临床进展、转化研究和ADC制造与供应相关主题，并进行相关问题的交流，相关问答罗列如下：Q1. How will Dato-DXd and HER3-DXd be positioned in EGFR-mutatednon-small cell lung cancer (NSCLC)? Can they be used sequentially?A: Both agents offer efficacy with distinct safety profiles, allowingphysicians to tailor treatment. Studies are ongoing to understand DXdresistance mechanisms (target-vs. payload-related) to inform potentiasequential use strategies and maximize patient benefit.Q2. What are the advantages of the PBD payload, and why was Claudin6 chosen as the first target?A: The PBD payload provides an alternative to overcome DXd resistanceand allows sequencingflexibility,enhancing treatment options. Claudin6 was selected due to its relevance as a tumor antigen in cancers withhigh unmet needs,including gastric, ovarian, lung, and germ cell tumors03.When will the OCS analysis results from the AVANZAR study beavailable,and what are the plans for the second-line pivotal trial?A: A pivotal second-line study will evaluate Dato-DXd against docetaxelinTROP2 QCS-positive patients with non-squamous NsCLC. This trial isexpected to begin soon. For the AVANZAR study, a pre-specified QCsanalysis will assess the efficacy of Dato-DXd, and the results areanticipated in the second half of 2025.Q4.ls QCS-NMR specific to non-squamous NsCLc? Can it be applied toother tumor types?A: The QCS-NMR biomarker was specifically optimized for use in non-squamous NSCLC.While its application to squamous NSCLC and othertumor types is being explored, no definitive data is currently available forthese populations.Q5.Beyond conventional lHC and QCS, are there additional biomarkerscritical for ADC development?A: While lHC works for some ADCs like T-DXd, it proved insufficient fo!Dato-DXd.To improve precision, digital and computational pathologyquantify target expression and its intracellular distribution. Otherbiomarkers are under investigation but remain in the early stagesQ6. Are there plans to consolidate ADC manufacturing into a singlelocation for efficiency?A: While consolidating production into one location might appear moreefficient, we prioritize risk mitigation.Diversifying manufacturingprocesses across in-house facilities and CDMOs ensures greaterresilience,minimizing disruptions from potential risks.
