撰文丨王聪 编辑丨王多鱼 排版丨水成文 CAR-T 细胞疗法 在治疗复发或难治性 多发性骨髓瘤 方面已展现出令人瞩目的疗效。 然而，当前的自体 CAR-T 技术受到制造流程复杂、存储运输要求高、等待时间漫长以及成本高昂等因素 的严重限制。 体内 CAR-T （ in vivo CAR-T） 细胞疗法直接将 CAR 转基因递送至体内的 内源性 T 细胞 ，在体内原位 将其重编程为 CAR-T 细胞，这更像是一种现货型产品，而非定制药物，这省去了 T 细胞分离提取、体外 CAR-T 细胞制造、扩增，以及淋巴细胞清除等步骤。 尽管一些临床前研究已将 慢病毒载体 用于 in vivo CAR-T 细胞工程，但临床证据仍十分匮乏。 2025 年 7 月 2 日，华中科技大学同济医学院附属协和医院 梅恒 教授 团队在国际顶尖医学期刊《 柳叶刀 》 （ The Lancet） 上发表了题为： In-vivo B-cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma 的临床研究论文。 该研究报道了 In-v ...

Legend Biotech CORPORATE PRESENTATION JULY 2025 The safety and efficacy of the agents and/or uses under investigation discussed in this presentation have not been established, except to the extent specifically provided by marketing authorizations previously received from relevant health authorities. Further, for investigational agents and/or uses, the Company cannot guarantee health authority approval or that such agents and/or uses will become commercially available in any country. Certain information cont ...

Oral presentation of CARTITUDE-1 study data showcases long-term outcomes after a single infusion of CARVYKTI® with one-third of patients with relapsed/refractory multiple myeloma progression-free for ≥5 years CARTITUDE-4 subgroup analyses featured in a poster presentation highlight consistent, durable progression-free and overall survival benefit vs. standard therapies across cytogenetic risk groups as early as second-line therapyPromising early results from ongoing Phase 1 dose-escalation studies of LB1908 ...

Core Insights - Johnson & Johnson announced long-term follow-up data from the CARTITUDE-1 study, showing that 33% of patients with relapsed or refractory multiple myeloma treated with CARVYKTI® achieved progression-free survival of five years or more with a single infusion [1][3][4] - The CARTITUDE-4 analysis demonstrated significant overall survival and progression-free survival benefits across various patient subgroups, including those with standard and high-risk cytogenetics [1][5] Group 1: CARTITUDE-1 Study Findings - In the CARTITUDE-1 study, 32 out of 97 patients (33%) achieved progression-free survival for at least five years after receiving CARVYKTI® [1][3] - The median overall survival for patients in the study was reported at 60.7 months, indicating a durable response to the treatment [3] - Among the patients who remained progression-free, the majority had undergone a median of six prior lines of therapy, with 90.6% being triple-class refractory [3][7] Group 2: Safety Profile - The safety profile of CARVYKTI® in the CARTITUDE-1 study remained consistent with previous findings, with no new safety signals identified [4] - Two new cases of second primary malignancies were reported, but no new cases of Parkinsonism or cranial nerve palsies were observed [4] - The incidence of cytokine release syndrome (CRS) was noted in 84% of patients, with 4% experiencing Grade 3 or higher CRS [21] Group 3: CARTITUDE-4 Study Insights - The CARTITUDE-4 study, presented at the ASCO Annual Meeting, showed that CARVYKTI® improved progression-free survival and overall survival compared to standard care in various patient subgroups [5][9] - The study included patients with relapsed and lenalidomide-refractory multiple myeloma who had received one to three prior lines of therapy [9] Group 4: Future Directions - Johnson & Johnson is focusing on shifting treatment strategies from managing progression to aiming for a cure in multiple myeloma [6] - Upcoming presentations at the European Hematology Association (EHA) 2025 Congress will further discuss the findings from the CARTITUDE studies [6]

Investment Rating - The biotechnology industry in North America is rated as Attractive [4]. Core Insights - Initial Phase I/II data for Genmab's Rinatabart sesutecan (Rina-S) in advanced endometrial cancer shows an unconfirmed overall response rate (ORR) of 50% for the 100 mg/m² dosing cohort and approximately 45% for the 120 mg/m² cohort, indicating competitive efficacy [3][6]. - Legend Biotech's Carvykti demonstrates promising outcomes in high-risk multiple myeloma (MM) with a median progression-free survival (mPFS) of 13 months compared to 4 months for standard of care [12]. - The pipeline updates for DLL3 and Claudin 18.2 programs from Legend Biotech show early efficacy signals, warranting further observation [6]. Summary by Relevant Sections Genmab (GMAB) - The report highlights initial data from the GTC1184-01 study, focusing on Rina-S for advanced endometrial cancer, with a median follow-up of approximately 19 weeks [3]. - The safety profile indicates that over 15% of patients required dose reductions, with one Grade 5 event noted [3][7]. - The efficacy signal is considered strong when compared to Merck's TROP2 ADC, which had an ORR of about 34% [3][7]. Legend Biotech (LEGN) - The CART-4 subgroup analysis shows promising outcomes in high-risk MM, with 5-year CART-1 data indicating a functional cure in about one-third of patients [6]. - The ongoing Phase I study of LB2102 in relapsed or refractory small cell lung cancer (SCLC) shows strong tolerability and initial signs of dose-dependent efficacy [10]. - Preliminary results from LB1908 in advanced gastroesophageal adenocarcinoma indicate tumor reductions of 1% to 41% in treated patients [11]. Overall Industry Insights - The report anticipates limited stock impact for both Genmab and Legend Biotech from the ASCO abstracts, with further details expected from full presentations [6]. - The biotechnology sector is viewed positively, with expectations for continued advancements and potential market opportunities [4].

Core Insights - Legend Biotech Corporation is presenting new data on CARVYKTI (ciltacabtagene autoleucel) for multiple myeloma at the 2025 ASCO and EHA meetings, highlighting its status as a market leader in CAR-T therapy for this condition [1][2] - The company is also showcasing preliminary results from ongoing Phase 1 studies targeting solid tumors, specifically lung and gastric cancers, indicating an expansion of its cell therapy pipeline [1][2] CARVYKTI Data - Long-term data from the CARTITUDE-1 study will be presented, showing that heavily pretreated patients with relapsed or refractory multiple myeloma achieved a median progression-free survival of over 5 years after a single CARVYKTI infusion, with a median follow-up of 60.3 months [3][10] - Data from the CARTITUDE-4 study will support a positive benefit-risk ratio for CARVYKTI across various patient subgroups, including those with high-risk cytogenetics [4][10] Solid Tumor Pipeline - Preliminary results from Phase 1 studies of LB2102 and LB1908, targeting small-cell lung cancer and gastroesophageal adenocarcinoma respectively, will be featured in poster presentations at ASCO [6][10] - LB2102 has been licensed to Novartis for further development, with Legend Biotech responsible for the Phase 1 clinical trial in the U.S. [7][8] Clinical Presentations - The company will present data at ASCO and EHA, including an oral presentation on long-term survival outcomes for CARVYKTI and poster presentations on subgroup analyses and preliminary results from solid tumor studies [10][12]