2025 年 08 月 23 日 科济药业-B(02171.HK) 自体 CAR-T 进入兑现阶段，通用型 CAR- T 快速推进中 事件：公司发布 2025 年中期业绩，报告期内公司实现营业收入 0.51 亿元，实现归母净利润-0.75 亿元。 自体 CAR-T：Claudin18.2 CAR-T 舒瑞基奥仑赛 NDA 获受理， BCMA CAR-T 泽沃基奥仑赛持续放量。2025 年上半年，公司两款自 体 CAR-T 药物均取得较大进展，其中舒瑞基奥仑赛注射液新药上 市申请（NDA）获 CDE 受理，用于治疗 Claudin18.2 表达阳性、至 少二线治疗失败的晚期胃/食管胃结合部腺癌（G/GEJA）；泽沃基 奥仑赛完成认证及备案的医疗机构覆盖全国 20 多个省市，科济 药业共计从商业化合作伙伴华东医药获得 111 份有效订单。 通用型 CAR-T：多个产品正在快速开发中。其中，靶向 BCMA 通 用型 CAR-T 细胞产品 CT0596 正在中国开展研究者发起的临床试 验。初步临床数据已于 2025 年 5 月在公司官网发布，根据初步安 全性及疗效数据，CT0596 用于 R/R MM 患者总体耐受性 ...

Core Viewpoint - The study highlights the urgent need for advancements in treatment for late-stage pancreatic ductal adenocarcinoma (PDAC), where the median survival is less than one year [3]. Group 1: Clinical Trial Findings - A phase 1 clinical trial evaluated the safety and efficacy of anti-MSLN CAR-T cell therapy in patients with advanced PDAC, showing good tolerance but limited effectiveness [4][12]. - The trial involved three groups of patients receiving CAR-T cells via different administration routes: intravenous, intraperitoneal, and hepatic artery, with overall good tolerance and no severe treatment-related adverse events [8]. - The median overall survival for patients was 6.7 weeks, and the median progression-free survival was 3.9 weeks [8]. Group 2: Mechanisms of Resistance - Single-cell genomics revealed that infused CAR-T cells expressed exhaustion markers, including transcription factors ID3 and SOX4, indicating functional impairment [9]. - In mouse models, knocking out ID3 or SOX4 individually enhanced efficacy, but dual knockout of both genes led to longer progression-free survival, suggesting a potential pathway for designing more effective CAR-T cells for PDAC [9][12]. Group 3: Implications for Future Research - The findings suggest that while anti-MSLN CAR-T cell therapy is well-tolerated, further research is needed to overcome the limitations in efficacy observed in PDAC patients [12]. - The study provides insights into the mechanisms of resistance and potential strategies for improving CAR-T cell therapy in treating PDAC [9][12].

Core Viewpoint - The article discusses the evolution and potential of CAR-T cell therapy, particularly focusing on the emerging in vivo CAR-T approach, which aims to simplify the treatment process and reduce costs while maintaining efficacy [2][3][6]. Group 1: Current State of CAR-T Therapy - CAR-T cell therapy has become a leading treatment for various blood cancers, with a projected market size of $11 billion in 2023, expected to grow to $190 billion by 2034 [2]. - The traditional CAR-T therapy process is complex and time-consuming, requiring several weeks for preparation and costing upwards of $500,000, limiting accessibility for many patients [3][4]. Group 2: In Vivo CAR-T Development - In vivo CAR-T therapy aims to generate CAR-T cells directly within the body, significantly simplifying the production process and potentially reducing costs by an order of magnitude [6][7]. - Companies like Capstan Therapeutics and Azalea Therapeutics are at the forefront of developing in vivo CAR-T therapies, with significant investments from major pharmaceutical companies [7]. Group 3: Advantages of In Vivo CAR-T - In vivo CAR-T therapy eliminates the need for pre-treatment chemotherapy, reducing associated side effects and expanding the patient population that can benefit from the treatment [12]. - The risk of severe side effects, such as cytokine release syndrome (CRS), may be lower with in vivo CAR-T compared to traditional ex vivo methods [12]. Group 4: Challenges and Innovations - The delivery of CAR genes to the correct cells in vivo presents challenges, with companies exploring various methods, including targeted lipid nanoparticles and modified viral vectors [10][11]. - Capstan Therapeutics and others are shifting towards using lipid nanoparticles to deliver RNA, which may offer a safer alternative to viral vectors [15]. Group 5: Clinical Trials and Future Outlook - Several in vivo CAR-T therapies are currently in clinical trials, with expectations for increased activity in the field by 2025 and 2026 [19]. - The article highlights the growing interest and competition in the CAR-T space, with many companies striving to make CAR-T therapy more accessible and effective [19].