IMPT-314

1、CDE连发三个重磅新文件！涉及安全性更新报告、全球同步研发MRCT和嵌合抗原受体T细胞治疗药品说明书等 2月24日，CDE发布《研发期间安全性更新报告的问答文件》、《新药全球同步研发中基于多区域临床试验数据进行获益-风险评估的指导原则（试行）》和《嵌合抗原受体T细胞治疗药品说明书临床相关信息撰写指导原则》，这三个文件均自发布之日起施行！ 2、全球首款可溯源！上海交大团队Nature发文，AI系统破解罕见病诊断世界性难题 2月18日，国际顶级学术期刊《Nature》在线发表了上海交通大学科研团队的重磅研究成果。由谢伟迪、孙锟、余永国、张娅四位学者共同通讯，团队成功研发出全球首个可溯源智能体式罕见病诊断系统DeepRare，凭借首创的Agentic AI（能动型人工智能）架构，一举破解困扰全球医学界多年的罕见病诊断难题，诊断精度刷新世界纪录，相关应用已服务全球600余家顶尖医疗科研机构，为全球3亿多罕见病患者点亮确诊希望。 3、吉利德将以78亿美元收购细胞治疗公司Arcellx，其股价涨78% 2月23日，吉利德科学宣布将以78亿美元总交易额收购细胞治疗公司 Arcellx，核心锁定其主打产品Anito-cel。其股价立即涨78%，该公司48小时即可完成细胞制备。 4、中国CAR-T疗法成功治愈自身免疫性溶血性贫血 2月11日，中国抗癌协会披露，中国医学科学院血液病医院施均、熊海清团队在《新英格兰医学杂志》发表的原创研究证实，靶向CD19的CAR-T细胞疗法可治愈难治复发自身免疫性溶血性贫血(AIHA）。11例对三线治疗无效的患者单次输注后，3个月整体缓解率达100%，中位随访12.2个月，无药物治疗缓解中位时间达到11.5个月。该研究首次系统搭建“CAR-T＋双特异性抗体”的细胞免疫治疗新体系，标志着CAR-T从肿瘤跨界良性血液病的范式确立。 5、吉美瑞生完成3.5亿元C轮融资 近日，再生医疗企业吉美瑞生宣布完成3.5亿人民币C轮融资。本轮融资引入7家新投资方，募集资金将主要用于推进干细胞、前体细胞核心产品的临床应用落地。在政策利好与技术突破双重驱动下，干细胞赛道已成为资本重点布局方向。据统计，2025年全球干细胞市场规模已突破300亿美元，年复合增长率保持在20%以上；中国作为第二大经济体，在该领域的临床转化与产业化潜力正加速释放。 6、自闭症治疗新突破！双靶点干细胞疗法重塑肠道菌群 + 调节神经免疫，为自闭症干预带来新希望 近期，来自广东省科学院生物医学工程研究所、中国科学院广州生物医药与健康研究院等机构的研究团队在国际知名期刊《Stem Cell Research & Therapy》发表重磅研究成果，首次证实人脐带间充质干细胞（hUCMSCs）联合其来源细胞外囊泡（EVs）的双靶点疗法，能在丙戊酸（VPA）诱导的自闭症小鼠模型中，通过协同重塑肠道菌群、调节神经免疫串扰，全面改善自闭症样行为，为自闭症的临床转化治疗提供了全新的可行方案。 7、中科院重大突破：一个干细胞即可生成1400万个杀伤肿瘤的NK细胞 近日，中国科学家取得癌症免疫治疗领域的重大突破，研发出一种实验室大规模制备抗癌免疫细胞的全新方法。团队摒弃传统改造成熟自然杀伤细胞的思路，通过对脐带血来源的早期干细胞进行基因工程改造，打造出一套高效制备体系，能产出海量高活性自然杀伤（NK）细胞，其中包括可精准靶向特定癌症的嵌合抗原受体（CAR）修饰型 NK 细胞。这一技术不仅让抗癌 NK 细胞疗法更廉价、更高效，还实现了规模化生产，单份脐带血即可制备出数千份治疗剂量，为癌症免疫治疗的普及奠定关键基础。 1、三家三甲医院开展脐带间充质干细胞注射液治疗克罗恩病复杂性肛瘘Ⅰ/Ⅱ期临床试验 2月9日，国家药品监督管理局药品审评中心（CDE）公示一项细胞治疗临床试验信息（登记号：CTR20260493）：人脐带间充质干细胞注射液拟用于克罗恩病复杂性肛瘘，开展Ⅰ/Ⅱ期临床试验。项目由中山大学附属第六医院牵头，联合温州医科大学附属第二医院、广州市第一人民医院等三家三甲医院多中心推进，这次CDE公示的Ⅰ/Ⅱ期试验，释放的核心信号是：脐带MSC注射液正在以更规范的临床试验方式，进入克罗恩病复杂性肛瘘这一高需求场景的系统验证阶段。 2、西湖大学登Nature Cancer，全球首款红细胞抗癌药问世，耐药晚期癌症患者迎来生机 2月20日，西湖大学高晓飞教授团队，联合浙江省人民医院杨柳教授、浙江大学梁廷波教授及冯宇雄教授团队（聂小千博士、刘悦华博士和姚星云博士为论文共同第一作者），在国际顶级期刊《Nature》子刊《Nature Cancer》上发表了一项颠覆性研究！针对那些对传统PD-1/PD-L1治疗耐药的晚期实体瘤患者，全球首款红细胞-抗体偶联药物αPD1-Ery的首次人体临床试验，不仅安全性拉满，更实现了部分患者肿瘤完全消失，疾病控制率高达78.6%！ 3、全球首个，93%缓解率的双靶点CAR-T，淋巴瘤治疗再升级 近日，生物医药企业Lyell Immunopharma宣布启动全球首个针对侵袭性大B细胞淋巴瘤的双靶点CAR-T头对头三期临床试验，首款CD19/CD20双靶点CAR-T疗法ronde-cel完成首例患者给药，为复发或难治性淋巴瘤患者带来新希望。这款疗法在早期临床中展现出93%的最佳客观缓解率，且重度不良反应发生率仅4%，刷新了CAR-T疗法的疗效与安全纪录。4、三款国产ADC同步获批临床 近日，国家药监局药审中心(CDE)官网显示，乐普生物、巨石生物、多禧生物自主研发的3款抗体药物偶联物(ADC）相继获得临床试验默示许可，分别在肝癌、乳腺癌、小细胞肺癌领域进入临床阶段，三款ADC同步获批临床，标志着我国在肝癌、小细胞肺癌等难治瘤种ADC管线的靶点差异化布局初显成效，同时展现本土药企在靶点创新、技术平台及全球开发上的综合突破。 1、全球首批！日本获批两款iPS细胞产品，专治心衰与帕金森病 2月19日，日本厚生劳动省专家委员会完成对两款iPS细胞再生医疗产品的上市审核，两款产品分别面向重度心力衰竭与帕金森病患者。若正式获批，将创下全球首批商业化iPS细胞疗法的里程碑。本次审批遵循日本特有的“有条件限时批准”制度，企业需在获批后最长7年时间内，持续完成临床疗效与安全性数据的收集与验证。 2、士泽生物通用细胞治疗帕金森型多系统萎缩获中美药监局正式批准开展注册临床试验 近日，士泽生物宣布，其自主开发的异体通用“现货型”iPSC 衍生亚型神经细胞新药，用于治疗致死性神经退行性罕见病——帕金森型多系统萎缩（Parkinsonian-type Multiple System Atrophy, MSA-P），已一次性无发补获得中国国家药品监督管理局（NMPA）及美国食品药品监督管理局（FDA）的正式批准，开展注册临床 I/II 期试验。这是士泽生物继帕金森病（PD）、渐冻症（ALS）、脊髓损伤(SCI)之后，第四款实现中美双报双批的 iPSC 衍生神经细胞新药。 丽山生物合作单位 火热招募中 咨询热线:0531-5862 9111 编辑：综合运营部 编审：朱文广 宋腾 审核：杨敬 免责声明： 1.本文部分素材来源于网络，相关资料的图文素材其著作权归原作者所有，侵权立删； 2.本公众号文章旨在分享细胞产业知识、行业动态，文章内容仅作参考，不构成相关医疗指导或建议； 3.本公众号对相关转载、分享的内容、陈述的观点保持中立，不对所包含内容的准确性、可靠性或完善性提供任何明示或暗示保证，仅供读者参考，本公众号平台不承担任何责任； 4.以上声明内容的最终解释权在法律许可范围内归本公众号所有，本平台发表的文章将不再一一备注，本声明将适用于公众号所有时间分享与转载的内容

Welcome back to Endpoints Weekly! A programming note: We won’t be sending our usual newsletters on Monday, Feb. 16. Our team will be off for Presidents’ Day. Our reporters closely followed several big updates this week, including Moderna’s response after it received a refusal-to-file letter over its flu vaccine application and Paul Hudson’s exit from Sanofi. Senior editor Max Gelman also dug into what makes clinical trials so costly. And our team reported on readouts for AstraZeneca’s obesity pill and the launch of a head-to-head CAR-T trial. Enjoy the weekend — we’ll be back on Tuesday! — Nicole DeFeudis The FDA refused to review Moderna’s flu vaccine application, in a decision that the company is describing as a shifting of standards for its pivotal trial. The Phase 3 trial tested Moderna’s mRNA-based flu shot against a standard flu dose in adults 50 and older. But in a refusal-to-file letter, the agency criticized Moderna for not using the “best-available standard of care” in the comparison group. Typically, patients 65 and older are advised to get a higher or enhanced dose. Moderna took the debate public on Tuesday, publishing the refusal-to-file letter signed by vaccines and biologics chief Vinay Prasad. In the letter, Prasad wrote that the decision was “consistent with FDA’s advice given to you prior to your study.” In a news release, Moderna said the agency recommended in 2024 that Moderna use a higher-dose flu vaccine in adults 65 and older, but also agreed at the time that “it would be acceptable to use a licensed standard-dose influenza vaccine as the comparator in your Phase 3 study.” “We thought it was pretty clear that it was acceptable, and even agreed it was an acceptable approach in writing,” Moderna president Stephen Hoge said in a Tuesday interview. The debate was further complicated by reports from Endpoints News and others that Prasad overruled the review team and head of the vaccine group as part of the regulator’s refusal to review the application. On Wednesday, a senior agency official told reporters it was “entirely feasible” that Moderna could resubmit the application for adults aged 50 to 64. If approved, the vaccine could be used off-label for the oldest adults, the official said. They also said, “There was a healthy scientific debate on the refuse-to-file.” Moderna has requested a Type A meeting with the FDA to further discuss the application. On its fourth-quarter earnings call Friday, Moderna’s CFO Jamey Mock said it’s “too early to tell” whether the company’s goal of reaching break-even cash flow will be pushed back after the FDA declined to review its flu shot for adults 50 and older. For more discussion, watch our Post-Hoc Live session with the Endpoints reporters who tracked this story. Sanofi’s board elected not to renew Paul Hudson’s director mandate, the company announced this week, ending Hudson’s tenure as CEO . He will be replaced by Merck KGaA’s Belén Garijo, who will start on April 29. Hudson’s last day is Feb. 17, and head of general medicines Olivier Charmeil will take over as interim CEO during the transition. The ouster comes after years of pipeline setbacks for Sanofi. Hudson, who started in his role in September 2019, had attempted to reposition the company as an immunology powerhouse. By acquiring companies like Principia and Kymab, Hudson bet that not only could Sanofi be at the forefront of immunology’s next frontier, but it could also minimize risk from the Dupixent patent cliff in the early 2030s. That strategy ended up being rocky, and Sanofi’s board appeared to have lost patience as the company faced a number of pipeline setbacks. One of the Principia programs was scrapped three years after the acquisition, and another was rejected by the FDA late last year. The centerpiece of the Kymab deal, an anti-OX40L program called amlitelimab, was positioned as a “pipeline-in-a-product,” but reported disappointing data in January despite achieving its primary goal. A new safety concern also cropped up, casting a growing shadow on the mechanism. Despite the change in leadership, reception for Garijo was frosty. Investors are concerned that Garijo doesn’t have a track record of delivering R&D productivity at Merck KGaA, according to analysts who spoke to Endpoints, partly due to pipeline misfires. But some of that criticism may be misplaced. Read more about the challenges Garijo will face here . And be sure to read more about Hudson’s departure, as well as all the other pharma job changes this week, in our weekly Peer Review column here . US clinical trials, particularly in oncology, have become increasingly redundant, inefficient and expensive. In a story this week, senior editor Max Gelman examined why this is the case . A closet full of identical EKG machines, as recounted by Eli Lilly’s head of oncology Jacob Van Naarden, illustrated the issue. Ironically, one of the most commonly cited problems of developing new drugs was the cost of older drugs. Precision oncology has exploded since Herceptin’s approval in 1998, and successful checkpoint inhibitors like Yervoy and Keytruda mean that even before a patient gets a dose of an experimental medicine, trials can cost hundreds of thousands of dollars a year. Other factors only compound the problem. Companies must staff trial sites and manufacture new therapies while contending with American patients’ unwillingness to take experimental medicines and payers’ reluctance to foot the bill. As costs have risen, many big companies — and some smaller biotechs — have turned to China, but it’s not a simple solution. Unfortunately, there’s no silver bullet to fixing this problem. The solution depends on who you ask. Read more from Max here . The Bay Area biotech announced this week that it treated the first patient in a Phase 3 trial that pits its experimental cell therapy ronde-cel against two currently available CAR-T treatments for certain patients with aggressive large B cell lymphoma. Lyell CEO Lynn Seely told Endpoints’ Lei Lei Wu that the company “wanted a randomized, controlled trial so we could have a very fair evaluation” of whether ronde-cel can beat the existing therapies. Lyell, Gilead and Johnson & Johnson are all studying next-generation CAR-T therapies for lymphoma that target two proteins — CD19 and CD20 — typically found at abnormally high levels in cancers, as opposed to CD19 alone. Gilead has outlined plans for a head-to-head Phase 3 trial in which it will go up against its existing therapy, Yescarta. Click here for more details. AstraZeneca added to the obesity pill mania this week when it reported that its oral GLP-1 elecoglipron succeeded in two Phase 2b studies — one for obesity and one for diabetes. Specific data were not announced, but the drugmaker said they would come in June. According to the trial protocol, senior biopharma journalist Elizabeth Cairns says it can be inferred that the drug produced greater weight loss than placebo at the 26-week mark and also allowed more subjects to lose at least 5% of their weight at the same point. AstraZeneca will start Phase 3 trials this year. The UK pharma licensed elecoglipron from the Hong Kong company Eccogene in November 2023. AstraZeneca paid $185 million upfront for the asset. Eccogene is aiming to go public, probably this year. Read more from Elizabeth here . DON’T MISS