C-CAR088

▎药明康德内容团队报道北京时间1月11日，西比曼生物董事长兼首席执行官刘必佐先生在第42届摩根大通医疗健康年会（JPM）发表了演讲。在报告中，刘必佐先生介绍了西比曼生物的新药开发策略、在研管线、近期的两项合作进展，以及2024年潜在的里程碑进展。根据西比曼生物报告，该公司致力于为癌症和自身免疫性疾病患者开发创新的细胞疗法，其目前已经搭建了包含5个临床阶段项目和多个IIT/临床前阶段项目的研发管线。（扫描文末二维码，可获得包括西比曼生物在内60余家生物医药公司的2024年JPM大会演讲PPT）。图片来源：西比曼生物演讲报告截图西比曼生物是一家处于临床阶段的全球性生物医药公司。根据西比曼生物报告，该公司正在中、美两国利用不同的策略推动新药的全球开发。在美国，西比曼生物将利用其内部研发和制造能力，与全球医药公司建立动态合作伙伴关系，推动新药的全球开发。在中国，西比曼生物将利用KOL和医院网络进行研究者发起的临床试验（IIT）试验，实现创新项目早期验证，推动这些项目在中国的开发。目前，西比曼生物在研产品有十余款，覆盖血液肿瘤、自身免疫性疾病和实体瘤领域。其中3款针对血液瘤的CAR-T疗法C-CAR039（靶向CD19/CD20双靶点新型双特异性CAR-T）、C-CAR066（新型CD20靶向CAR-T）、C-CAR088（靶向BCMA的新型自体CAR-T细胞产品）和1款针对实体瘤的TIL疗法C-TIL051进展较快。图片来源：西比曼生物演讲报告截图在报告中，刘必佐先生也介绍了西比曼生物在2023年先后与两家全球性药企达成的合作。在血液肿瘤领域，西比曼生物于2023年5月宣布与强生旗下强生创新制药（Johnson & Johnson Innovative Medicine）达成一项全球独家合作，后者获得了C-CAR039和C-CAR066两款CAR-T细胞治疗产品在中国以外地区独家开发权，以及在中国地区开发的优先选择权。2023年12月，强生创新制药又获得了这两款产品的中国区商业化权利。西比曼生物也在第65届美国血液学会（ASH）年会上公布了这两款CAR-T细胞治疗产品的最新临床数据：C-CAR039用于治疗复发或难治性（r/r）B细胞非霍奇金淋巴瘤（B-NHL）的研究显示，在可评价的r/r NHL患者中，中位随访时间30.0个月，总缓解率为91.5%，完全缓解率为85.1%；C-CAR066用于治疗既往CD19 CAR-T治疗失败的r/r大B细胞淋巴瘤（LBCL）的研究显示，在既往CD19 CAR-T治疗失败的LBCL患者中，中位随访时间27.7个月，总缓解率为92.9%，完全缓解率为57.1%。在实体瘤领域，西比曼生物于2023年12月宣布与阿斯利康（AstraZeneca）就C-CAR031签署联合开发协议。C-CAR031是一种针对肝细胞癌（HCC）的自体抗GPC3 CAR-T疗法。该产品基于阿斯利康新型的GPC3靶向CAR-T（AZD5851），由阿斯利康的创新平台设计，并由西比曼生物在中国生产。西比曼生物在美国癌症研究协会（AACR）2023年年会上公布了一项在中国开展的IIT试验结果。数据显示，C-CAR031在晚期HCC患者中具有良好的抗肿瘤活性和稳健的PK/PD特征。根据西比曼生物报告，该公司还与阿斯利康就Claudin 18.2 CAR-T产品C-CAR036（AZD6422）达成了合作。阿斯利康正在中国以外地区开发该产品，西比曼生物有资格获得该产品在中国以外地区开发的里程碑付款和特许权使用费。图片来源：西比曼生物演讲报告截图展望2024年，西比曼生物在报告中展示了血液瘤、自身免疫性疾病、实体瘤领域代表性管线将取得的里程碑进展，包括： 在血液肿瘤领域管线中，C-CAR039、C-CAR066将分别于2024年上半年在美国进行针对LBCL的1b期临床招募，并于下半年获得临床结果，C-CAR039还将于2024年在中国开展2期临床研究；在自身免疫性疾病领域管线中，C-CAR168将于2024年一季度在中国开展研究者发起的临床研究（IIT）。该产品将于2024年二季度在美国申报临床，并于下半年启动1期临床研究；在实体瘤领域管线中，C-TIL051将于2024年上半年在美国启动1期临床；C-CAR031将于2024年上半年在中国申报临床，于下半年进行1期临床招募，并有望于2024年上半年在美国进行1b期临床招募。扫描下方二维码，您可以获得60余家生物医药公司的2024年JPM大会演讲PPT。参考资料：[1]西比曼生物2024年JPM大会演讲报告本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

With the FDA's approval for Elrexfio, Pfizer will challenge Johnson & Johnson, which boasts a star-studded portfolio in multiple myeloma. Another off-the-shelf, BCMA-directed drug has arrived for the treatment of multiple myeloma. Monday, the FDA approved Pfizer’s Elrexfio, or elranatamab, for patients with multiple myeloma who've tried at least four prior lines of therapy. Elrexfio will go toe to toe with Johnson & Johnson’s Tecvayli. Both drugs are bispecific antibodies that engage T cells to target BCMA-expressing cancer cells, and both are delivered under the skin. So far, the two therapies’ efficacy data are largely similar, while Elrexfio appears to boast a convenience edge—for now. Pfizer will make Elrexfio available in the following weeks, a Pfizer spokesperson told Fierce Pharma. The drug bears an average monthly list price of $41,500, and a treatment course could cost around $330,000 based on the duration of treatment observed in a clinical trial, the spokesperson said. By comparison, J&J priced Tecvayli initially at $39,500 per month. Elrexfio’s label shows that the Pfizer drug shrank tumors in 58% of patients who had received at least four lines of therapy prior to enrollment in cohort A of the phase 2 MagnetisMM-3 study. Updated data in June linked the drug to a 61% objective response rate, including 35% of patients who experienced a compete response or better. None of the patients had tried a BCMA-directed therapy before the study. In J&J’s MajesTEC-1 trial, meanwhile, Tecvayli delivered an overall response rate of 63%, with 45% of patients experiencing complete responses or better, according to longer-term follow-up data shared in June. But the Tecvayli results came from a group that also included patients who had tried three prior lines of therapy. In the BCMA bispecific rivalry, Pfizer is banking on Elrexfio’s ability to be dosed every other week following 24 weeks of weekly treatment. For now, J&J’s Tecvayli is given weekly during the maintenance phase. But J&J has submitted new data in hopes of turning Tecvayli into a biweekly treatment as well. Among responders who switched to biweekly Tecvayli treatment in the MajesTEC-1 study—most of whom initially had a complete response—68.7% remained in response for at least two years from the time of first response, according to data released in June. Drug profiles aside, between the two companies, J&J has more clout in multiple myeloma. J&J’s Darzalex is the leading CD38 antibody that’s approved as a front-line myeloma treatment. J&J’s Legend-partnered BCMA CAR-T drug Carvykti has yielded impressive efficacy data, recently showing it can reduce the risk of tumor progression or death by 74% over standard of care in the second- to fourth-line setting. And J&J has just won FDA approval for Talvey, its first-in-class bispecific antibody that targets GPRC5D. The drug has shown strong tumor shrinkage ability in patients irrespective of prior exposure to BCMA-targeted agents, and it can be dosed biweekly. By comparison, Elrexfio is Pfizer’s lone myeloma product. Seagen, which Pfizer is acquiring in a $43 billion deal, also has a BCMA-directed antibody dubbed SEA-BCMA. But the candidate recently disappeared from Seagen’s clinical development pipeline. With Monday’s accelerated approval, Pfizer is still on the hook to prove Elrexfio’s benefits. The phase 3 MagnetisMM-5 trial will gather confirmatory evidence for Elrexfio in patients who had tried two classes of medicines, including Bristol Myers Squibb’s immune modulator Revlimid and a proteasome inhibitor such as Takeda’s Velcade. Pfizer is also running the MagnetisMM-7 study with Elrexfio as maintenance treatment in newly diagnosed patients after transplant. Like Tecvayli, Elrexfio is available through an FDA-mandated safety program because of the risk of cytokine release syndrome (CRS) and neurotoxicity. In Tecvayli’s clinical trial, CRS occurred in 72% of patients—including 0.6% at grade 3—who received the drug at the recommended dose. In Elrexfio’s trial, the rate of grade 3 CRS was 2.3%, according to an update in June.