2024年12月16-17日，第一三共召開2024年的研發日活動，介紹了公司的管理策略、財務預測、未來展望、研發信息以及一些特定的研發項目。從臨床進展來看，第一三共此前主要依靠5款DXd ADC藥物在商業化、臨床以及商業拓展方面取得了巨大的成功，一己之力改變了下一代ADC藥物研發的格局，當前第一三共將依靠五款現有ADC不斷拓展臨床應用，同時投入更多新型療法的分子。乳腺癌方面，以HER2 ADC藥物Enhertu為基石，不斷拓展應用范圍，從HER2陽性到低表達，到三陰乳腺癌，到HR陽性等多中人群，同時也逐步從后期到一線，一線到輔助治療，多范圍覆蓋乳腺癌治療。
肺癌方面，同樣如此，依靠TROP2 ADC和B7-H3 ADC，在非小細胞肺癌和小細胞肺癌多個階段進行療法探索。新分子方面，第一三共此前就介紹了MUC1的ADC藥物DS-3939進展，這也是第六款DXD ADC藥物，MUC1為腫瘤特異性相關靶點，在多種實體瘤中均有所表達。DS-2243為一款NYESO的TCR雙抗，根據UmabsDB數據庫的記錄，今年10月第一三共已經在clinical trials網站上，登記了一項NY-ESO TCR療法藥物DS-2243a，在滑膜肉瘤和非小細胞肺癌等多種實體瘤HLA-A2亞型患者中，啟動一項1期臨床試驗NCT06644755，該臨床于2024年11月啟動，計劃入組人數為150例。
此外第一三共還介紹了最新研發更新、臨床進展、轉化研究和ADC制造與供應相關主題，并進行相關問題的交流，相關問答羅列如下：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.
