Bendamustine Hydrochloride

引言套细胞淋巴瘤（MCL）是一种起源于成熟B细胞的非霍奇金淋巴瘤亚类，占所有非霍奇金淋巴瘤（NHL）的3%~10%，具有不可治愈、易复发和耐药等特点，且复发后患者预后常较差，治疗选择有限1。此外，由于MCL多发于老年患者，而此类患者常伴有多种基础疾病，这使得治疗方案的制定需更审慎权衡安全性与有效性。嵌合抗原受体T（CAR-T）细胞已在MCL中展现了良好的疗效与安全性，为复发/难治性（R/R）MCL患者提供了新的治疗选择，随着该疗法逐步应用于临床实践，其临床应用价值与个体化治疗策略备受关注。基于此，医脉通特邀广东省人民医院李文瑜教授，分享3例经瑞基奥仑赛治疗后获得完全缓解（CR）的病例，并深入探讨此类患者的临床治疗经验与心得体会。病例回顾01病例1男性，50岁现病史患者于2021-1出现无明显诱因咽痛，伴吞咽困难，CT提示舌根恶性肿瘤，伴左颈部淋巴结转移，行颈部淋巴结活检术，术后明确诊断为MCL II期 MIPI 4分。2021-3-23、2021-4-13予R-CHOP与R-DHAP交替治疗2周期，但患者每疗程化疗后均出现咽部肿物及左颈部淋巴结再次增大，2周期后疗效评估为疾病稳定（SD），于2021-5-8、21-5-28开始予二线治疗2周期GDP方案治疗，化疗后扁桃体及颈部肿物较前明显减小，但后期再次增大，完善CT检查，2周期疗效评估为SD，6-18予BTKi口服治疗，服用后病灶仍持续增大；免疫组化示Ki-67（+，热点区约90%），经体格检查、病理学检查及骨髓检查后，诊断为MCL，伴高增殖指数；CAR-T细胞治疗经过患者入组JWCAR029研究，但拟采集单个核细胞当天出现肿瘤破溃出血，遂出组。对侵犯野行36Gy放疗，但右侧颈部新发淋巴结，再次入组；2021-12-7采集单个核细胞；2021-12-9予GDP桥接治疗，肿瘤仍持续增大；2021-12-25至2021-12-27行清淋治疗；2021-12-30回输CAR-T细胞；疗效评估：回输后第30天、第90天，疗效评估均为部分缓解（PR），第180天达到CR，无进展生存（PFS）已达4年余；不良反应：回输后第5天患者出现2级细胞因子释放综合征（CRS）和3级骨髓抑制，未发生免疫效应细胞相关神经毒性综合征（ICANS），予加强补液、托珠单抗、依托考昔及对症支持治疗后好转，回输后第15天顺利出院。02病例2男性，65岁现病史患者于2023-5-5因“发现尿蛋白及隐血2年余，再发尿血半月”入住外院，入院查体发现左侧腹股沟淋巴结肿大，大小约4×4cm，于2023-5-9行左侧腹股沟淋巴结切除活检，病理示MCL，入院查肌酐示771umol/L，遂于5-12开始予甲泼尼龙冲击3天，后给予甲泼尼龙片维持治疗，予行血浆置换2次，并于2023-5-18行利妥昔单抗治疗，于2023-5-20复查肾功能示肌酐245umol/L，后入本院治疗。既往史2020-12因“蛋白尿、血尿、下肢腹胀”于外院就诊，于2020-12-10行左肾穿刺活检，病理示II期膜性肾病。予激素治疗，于2020-12-16、2021-1-4予3次利妥昔单抗治疗。2021-12-29胸部CT示肺隐球菌感染，予停用激素及利妥昔单抗治疗；患者未再发作血尿、下肢浮肿等不适；经体格检查、病理学检查、影像学检查、骨髓检查及生化检查等后，诊断为MCL III期 MIPI 4分治疗经过降肌酐治疗：给予1周甲泼尼龙治疗，同时辅以水化、碱化尿液、利尿等治疗，肌酐水平从245.5umol/L降低至163.91umol/L，肌酐清除率：36.92ml/min；抗肿瘤治疗：2023-6-7至2023-11-16予6周期抗CD20单抗、BTKi靶向治疗，后续予BTKi维持治疗，疗效评估为CR；2023-12-19突发左侧肢体偏瘫，头颅CT提示脑出血，停用BTKi；2024-1-29，予抗CD20单抗联合来那度胺治疗，但患者出现周身皮疹；由于患者拒绝化疗，于是采取CAR-T细胞治疗方案；CAR-T细胞治疗：2024-3-14采集单个核细胞；2024-3-17行抗CD20单抗治疗；2024-4-12起行FC方案化疗；2024-4-16回输CAR-T细胞；疗效评估：回输后第30、90、120、180天疗效评估均为CR，目前回输后1年，持续CR。不良反应：回输后出现3级粒细胞缺乏合并发热、3级贫血、1级CRS、1级ICANS，予地塞米松治疗，回输后第21天好转出院，出院后出现胃肠道不适、周身乏力，予甲泼尼龙口服，1个月后停用。03病例3男性，58岁现病史患者于2015年因肠梗阻就诊于外院，行腹腔镜下小肠部分切除术，术后病理提示MCL，行CHOP方案治疗，后行中药及来那度胺治疗。2021-12出现左眼视物模糊，眼球突出，考虑肿瘤复发，行CHOP方案治疗，2022-1起口服伊布替尼治疗。2024-10考虑复发，予奥布替尼治疗，2024-12疾病进一步进展，拟行CAR-T细胞治疗，遂入院治疗。骨髓检查：送检骨髓可见6个完整的骨髓腔，骨髓增生较低下，髓腔内几乎均为弥漫增生的淋巴样细胞，造血细胞约占骨髓腔面积的20%；增生的淋巴样细胞体积小至中等大，胞浆少量，核圆形或略不规则，核仁不明显，弥漫分布。肿瘤细胞约占髓腔有核细胞的80%。特殊染色结果：Ag（WHO MF分级：1级），Fe（-）。血常规：WBC：16.04×109/L；HGB：85g/L；PLT：118×109/L；中性粒细胞计数：1.54×109/L；经体格检查、影像学检查、骨髓检查及生化检查等后，诊断为MCL IV期 MIPI 6分治疗经过2024-12-17予1疗程R-DHAP以降低肿瘤负荷，治疗后复测血常规：WBC：7.41×109/L；HGB：91g/L；PLT：42×109/L；中性粒细胞计数：3.16×109/L；淋巴细胞计数：2.85×109/L；2025-1-7采集单个核细胞；2025-1-13起予R-BAC方案进行桥接治疗；骨髓检查：镜下所见：送检骨髓可见7个完整的骨髓腔，骨髓增生较活跃，造血细胞约占骨髓腔面积的80%；腔内可见多灶淋巴细胞聚集，细胞体积小至中等大，胞浆少量，核略不规则，核仁不明显；特殊染色结果：Ag（WHO MF分级：0级），Fe（2+）；上述结果提示肿瘤负荷明显降低；2025-2-16行FC清淋化疗；2025-2-21行CD19 CAR-T细胞回输；疗效评估：骨髓检查：送检骨髓增生较活跃，造血细胞约占骨髓腔面积的70%；粒红比例大致正常，均以中晚幼阶段细胞为主；巨核细胞数量和形态未见明显异常。未见明显异常的淋巴细胞聚集灶。特殊染色结果：Ag（WHO MF分级：1级），Fe（4+）；疗效评估为CR；不良反应：回输后出现4级粒细胞缺乏合并发热、4级贫血、2级CRS、1级ICANS，予支持治疗，骨髓抑制于回输后1.5个月恢复；回输后2个月出现带状疱疹，予丙种球蛋白提高免疫力及抗病毒治疗。*R-CHOP：利妥昔单抗、多柔比星、环磷酰胺、长春新碱、泼尼松；R-DHAP：利妥昔单抗、地塞米松、多柔比星、阿糖胞苷、顺铂；FC：氟达拉滨、环磷酰胺；R-BAC：利妥昔单抗、苯达莫司汀、阿糖胞苷；GDP：吉西他滨、地塞米松、顺铂；专家访谈医脉通：病例1患者伴高增殖指数，经化疗及BTKi治疗后仍疾病进展。在这样的治疗困境下，您和您的团队最终选择CAR-T细胞治疗作为挽救方案，是基于何种考量？李文瑜教授MCL是一类相对少见的淋巴瘤类型，在NHL中约占5%。然而，该疾病极为凶险，严重威胁患者生命。BTKi的应用，改善了R/R MCL患者的生存，但其目前仍无法实现对患者的根治。当患者对BTKi产生耐药后，其中位总生存期（OS）仅为6-8个月2。在此情况下，无论是常规的化疗、靶向治疗，还是其他各类治疗手段，患者的生存期均有限，因此亟需新的治疗方法。随着淋巴瘤治疗的不断进步，《中国临床肿瘤学会（CSCO）淋巴瘤诊疗指南2025》指出3，对于接受过共价BTKi治疗后出现疾病进展的患者，CAR-T细胞治疗是一种可行的选择。其中瑞基奥仑赛凭借临床研究的良好结果，经国家药品监督管理局的批准，用于MCL的治疗。瑞基奥仑赛的II期临床研究数据表明，瑞基奥仑赛在MCL患者中展现出了良好的疗效。R/R MCL患者接受治疗后，最佳总缓解率（ORR）和CR率分别为81.36%和67.8%；同时，瑞基奥仑赛的安全性良好，≥3级细胞因子释放综合征（CRS）和神经毒性发生率低，均为6.8%4。从临床指南以及相关临床数据综合来看，瑞基奥仑赛为R/R MCL患者提供了一种有效的治疗方案。此外，本中心也参与了瑞基奥仑赛的临床研究，观察到了患者的长期生存情况，这也进一步增强了中心对于瑞基奥仑赛治疗R/R MCL的经验和信心。医脉通：老年患者常患有多种基础疾病，如病例2患者合并肾功能不全，能否请您分享一下在合并基础疾病时，CAR-T细胞治疗对此类患者的疗效及安全性如何？李文瑜教授对于老年且合并肾功能不全的MCL患者，许多靶向药物和化疗方案的应用往往受到限制。这类患者常需合并使用治疗肾病的药物，进一步增加了治疗的复杂性和用药风险。值得关注的是，CAR-T细胞治疗在先前存在肾损伤的患者中不影响疗效并兼顾安全性。研究表明，对一组包括有肾脏功能障碍的NHL患者进行的分析表明，基线时的慢性肾脏病（CKD）或急性肾损伤（AKI）对治疗后的OS和PFS没有影响；另有研究提示在合并CKD的CAR-T细胞治疗患者中，尽管CRS与ICANS的发生率较未合并患者略高，但二者间差异无统计学意义5。因此，对于第二例BTKi治疗失败且存在肾功能不全的患者，CAR-T细胞治疗从安全性和治疗效果层面综合考量，均为当前更佳的治疗选择。医脉通：针对经历多线治疗且肿瘤负荷高的MCL患者例如病例3，CAR-T细胞治疗需从多维度优化策略以提升疗效并降低风险。对于此类患者，您有何治疗经验？李文瑜教授第三例是一位MCL且生存期已达10年以上的患者。该患者此前已接受过化疗、靶向治疗等后疾病仍进展。目前，该患者存在腹腔、肠道大肿块，且淋巴瘤侵犯骨髓，外周血中存在大量淋巴瘤细胞。对于此类情况的患者，若直接进行CAR-T细胞治疗，不仅会影响疗效，而且不良事件（AEs）的发生风险增高。这是因为MCL患者的细胞表面CD19的表达较高，因此使用靶向CD19的CAR-T细胞治疗时，CRS和ICANS的发生概率可能高于弥漫大B细胞淋巴瘤（DLBCL）患者。针对这一情况，为提高疗效并降低AEs，需从多维度进行考量。鉴于该患者外周血中大量的淋巴瘤细胞会对CAR-T细胞质量产生影响，所以在第一个疗程中采取了该患者曾用过的阿糖胞苷方案以降低肿瘤负荷。经过此方案治疗后，外周血中的淋巴瘤细胞数量大幅降低，腹腔大肿块以及腹膜后的肿块也明显缩小。在肿瘤负荷显著下降、外周血淋巴瘤细胞减少的情况下进行单个核细胞采集，能够获得质量更好的细胞。并且，由于肿瘤负荷下降，CRS和ICANS的发生风险也明显降低。而后再实施CAR-T细胞治疗，在治疗后一个月的疗效评价中，患者达到了CR，同时未出现严重的CRS和ICANS。医脉通：结合这三例MCL患者通过CAR-T细胞治疗实现深度缓解的成功经验，您认为CAR-T细胞治疗未来在MCL治疗中应如何优化和拓展？李文瑜教授上述三例患者均为R/R MCL，在BTKi治疗失败后，CAR-T细胞治疗是当前更佳的治疗选择。临床实践及研究提示，对于此类患者，尽早启动CAR-T细胞治疗可显著改善疗效，并降低AEs发生率，体现了早期干预的重要性。值得关注的是，现有数据显示，R/R MCL患者接受BTKi治疗的中位PFS不足2年6。基于此，临床提出新的治疗策略探讨：是否可将CAR-T细胞治疗前移至BTKi使用前？国外研究数据表明，未经BTKi治疗的患者接受CAR-T细胞治疗后，疗效优于BTKi治疗失败后的患者7-8。这一结果引发了关于CAR-T细胞治疗线序前移的思考，即是否可将其应用于二线治疗，使患者更早获益。此外，参照DLBCL的治疗模式，对于极高危的MCL患者，或可考虑在一线治疗后采用CAR-T细胞治疗作为巩固维持方案。若CAR-T细胞治疗得以早期应用，或可实现MCL治愈的可能性。然而，上述治疗策略的优化及治疗线序的调整，仍需通过更多高质量的临床试验进行验证，以明确CAR-T治疗在MCL全程管理中的最佳应用时机与模式，实现患者更佳生存获益。漫漫长路，终见曙光——一位经历多线复发的MCL患者的自述患者于2020年6月确诊MCL，先后辗转当地医院及广东省人民医院治疗。经多次化疗、靶向治疗后，病情仍复发，并于2024年病情加重。经医生对于各类药物方案的介绍，患者了解并选择了CAR-T细胞治疗。回输后无明显不适。目前患者已实现缓解近7个月，身体恢复佳，生活状态良好。患者认为CAR-T细胞治疗效果显著，并对医院医护团队，尤其李主任等的悉心照料表示衷心感谢。李文瑜 教授广东省人民医院医学博士，主任医师，硕士生导师广东省人民医院肿瘤医院淋巴瘤科行政主任广东省女医师协会淋巴瘤专业委员会主任委员广东省基层医药学会淋巴瘤专业委员会主任委员广东省女医师协会血液学专业委员会副主任委员广东省医学会肿瘤内科分会副主任委员 广州市血液肿瘤专业委员会副主任委员 广州市抗癌协会淋巴瘤专业委员会常务委员参考文献：1.王晓晖,等. 肿瘤药学,2024,14(01):1-8+143.2.Eyre TA, et al. Blood. 2022;139(5):666-677.3.中国临床肿瘤学会(CSCO)淋巴瘤诊疗指南 2025.4.瑞基奥仑赛注射液说明书.5.Sadowski K, et al. Transplant Cell Ther. Published online March 17, 2025.6.Wang ML, et al. N Engl J Med 2013;369(6):507–16.7.M.L. Wang, et al. The 47th Annual Meeting of the EBMT. Abstract OS19-4.2.8.M.L. Wang, et al. The 47th Annual Meeting of the EBMT. Abstract OS3-3.免责声明本文转载自医脉通血液科，版权归原作者或原平台所有，转载此文旨在传递行业资讯与学术分享。文章内容仅供读者参考，不可替代专业医疗建议，具体诊疗请遵循医疗机构或医师指导。关于瑞基奥仑赛注射液（商品名：倍诺达®）- 滑动查看更多介绍 -瑞基奥仑赛注射液（简称relma-cel，其血液肿瘤适应症的商品名：倍诺达®）是药明巨诺在巨诺医疗（百时美施贵宝旗下的公司）的CAR-T细胞工艺平台的基础上，自主开发的一款靶向CD19的自体CAR-T细胞免疫治疗产品。作为药明巨诺的首款产品，瑞基奥仑赛注射液已被中国国家药品监督管理局批准三项适应症，包括治疗经过二线或以上系统性治疗后成人患者的复发或难治性大B细胞淋巴瘤（r/r LBCL）、治疗经过二线或以上系统性治疗的成人难治性或24个月内复发的滤泡性淋巴瘤（r/r FL），以及治疗经过包括布鲁顿酪氨酸激酶抑制剂(BTKi)治疗在内的二线以及系统性治疗的成人复发或难治性套细胞淋巴瘤(r/r MCL)，成为中国首个获批为1类生物制品的CAR-T产品。倍诺达®是一款获得“重大新药创制”专项、新药上市申请优先审评资格及突破性治疗药物认定三项殊荣的CAR-T细胞免疫治疗产品。关于药明巨诺- 滑动查看更多介绍 -药明巨诺（股份代码：2126）是一家独立的、创新型的生物科技公司，专注于研发、生产及商业化细胞免疫治疗产品，并致力于以创新为先导，成为细胞免疫治疗引领者。创建于2016年，药明巨诺已成功打造了国际领先的细胞免疫治疗的综合性产品开发平台，以及涵盖血液肿瘤、实体肿瘤和自身免疫性疾病的细胞免疫治疗产品管线。药明巨诺致力于以突破性、高质量的细胞免疫治疗产品给中国乃至全球患者带来治愈的希望，引领中国细胞免疫治疗产业的健康规范发展。欲了解更多详情，请访问：www.jwtherapeutics.com前瞻性声明- 滑动查看更多介绍 -本发布所包含的前瞻性声明是基于管理层现有的期望和信心，会存在一定的不确定性或风险从而导致实际结果在实质上与所描述的有所区别。显著的风险和不确定性，可能包括了以下涉及的内容，以及在公司提交给香港交易所（HKEx）的报告中予以更为全面的描述。除非另有注明，公司提供截至发布日期当日的信息，并且明确无义务更新相关事项及其所含内容或提供任何解释。具体内容，详见公司官网：www.jwtherapeutics.com/cn/forward-looking-statements/

Additional Phase 1 Data for FT819 Off-the-Shelf CAR T-cell Product Candidate in Moderate-to-Severe Systemic Lupus Erythematosus to be Featured in Oral Presentation at EULAR 2025 Congress in June Regenerative Medicine Advanced Therapy Designation Granted by the FDA for FT819 in Moderate-to-Severe Systemic Lupus Erythematosus Expanding FT819 Phase 1 Study to Include Treatment of Multiple Additional B Cell-mediated Autoimmune Diseases and Ex-US Territories $273 Million in Cash, Cash Equivalents, and Investments with Projected Operating Runway through 1H27 SAN DIEGO, May 13, 2025 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived off-the-shelf cellular immunotherapies to patients, today reported business highlights and financial results for the first quarter ended March 31, 2025. “We continue to be pleased with the initial clinical profile of our FT819 off-the-shelf CAR T-cell program in patients with moderate-to-severe SLE, and we look forward to sharing new clinical data from our ongoing FT819 Phase 1 study at the EULAR Conference in June,” said Bob Valamehr, Ph.D. MBA, President and Chief Executive Officer of Fate Therapeutics. “Our primary focus remains on driving patient enrollment and achieving therapeutic differentiation in SLE, including administration of FT819 with fludarabine-free conditioning and as an add-on to maintenance therapy without conditioning. We plan to work closely with the FDA under our FT819 RMAT designation to align on a registrational pathway for FT819 in SLE, and we have now initiated regulatory submissions in Europe to expand the geographic reach of the program for lupus patients. The expansion of patient population and reach is well supported by the ability to produce FT819 in large quantities from a master cell bank, ensuring consistent on-demand product supply for a large number of patients.” FT819 iPSC-derived 1XX CAR T-cell Program Phase 1 Study Ongoing using Flu-free Conditioning Regimen for SLE. The Company’s ongoing multi-center, Phase 1 clinical trial of FT819 for moderate-to-severe systemic lupus erythematosus (SLE) (NCT06308978) is designed to evaluate the safety, pharmacokinetics, and efficacy of a single dose of FT819 following a fludarabine (flu)-free conditioning regimen, consisting of either bendamustine alone or cyclophosphamide alone. The Company is currently enrolling patients at two dose levels – a single dose of 360 million cells and a single dose of 900 million cells – with the intent of identifying a recommended dose for later-stage development. In addition, the Company is assessing the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 at 360 million cells as an add-on to maintenance therapy without conditioning chemotherapy. The Company plans to present new clinical data from its FT819 Phase 1 study during an oral session at the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress in Barcelona, Spain on June 11. RMAT Designation Received from the FDA for SLE. In April 2025, the Company was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. Food and Drug Administration (FDA) for FT819 to treat moderate-to-severe SLE. The RMAT designation was established under the 21st Century Cures Act to expedite the development and review of regenerative medicine therapies for serious or life-threatening diseases or conditions. The Company’s RMAT application included initial clinical safety and activity data from patients treated with FT819 in its ongoing multi-center, Phase 1 clinical trial. The Company plans to pursue differentiated treatment approaches, including treatment of patients in community centers without hospitalization, and novel registrational strategies with the FDA under its RMAT designation. Expanded Phase 1 Study to Include Multiple Additional B Cell-mediated Autoimmune Diseases. In December 2024, the Company reached agreement with the FDA to allow for clinical investigation of multiple B cell-mediated autoimmune diseases under its current Phase 1 clinical trial of FT819. The Company has submitted an amended clinical protocol to the FDA that enables the conduct of independent dose-expansion cohorts for anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). The Company plans to initiate dose-expansion cohorts in each of AAV, IIM, and SSc in 2025. FT825 / ONO-8250 iPSC-derived CAR T-cell Program Phase 1 Study Ongoing for Advanced Solid Tumors. Under its collaboration with Ono Pharmaceutical Co., Ltd. (Ono), the Company is conducting a multi-center, Phase 1 study to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250, a multiplexed-engineered CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2), in patients with advanced solid tumors (NCT06241456). Dose escalation is currently ongoing, with each patient administered conditioning chemotherapy and a single dose of FT825 / ONO-8250 either as monotherapy or in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy. FT825 / ONO-8250 has demonstrated a favorable safety profile with no dose-limiting toxicities (DLTs) to date. Next-generation iPSC-derived CAR T-cell Programs FT836 MICA/B-targeted CAR T-cell Program. FT836 is the Company’s multiplexed-engineered CAR T-cell product candidate uniquely targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB). The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation and is detectable across many types of cancer cells with limited expression on healthy tissue. At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting being held in New Orleans on May 13-17, the Company plans to present preclinical data showing that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. FT836 is the Company’s first product candidate to incorporate its novel Sword & Shield technology that couples its novel Alloimmune Defense Receptor (ADR) technology with the complete knock-out of CD58 (CD58KO), which is uniquely designed to both target and evade host alloreactive immune cells and to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In January 2025, the Company secured a $4 million award from the California Institute of Regenerative Medicine (CIRM) to support IND-enabling activities for FT836. FT839 Dual CAR T-cell Program. FT839 is the Company’s dual CAR T-cell product candidate that incorporates its novel Sword & Shield technology and is designed to express two unique CARs: a first CAR targeting CD19+ B cells, and a second CAR targeting additional disease-causing cells. At the ASGCT Annual Meeting in May, the Company plans to present preclinical data demonstrating iPSC-derived CAR T cells targeting CD19 and the cell-surface glycoprotein CD38 specifically eliminated a variety of malignant cell types, including CD19+ lymphoma and CD38+ multiple myeloma cell lines. In addition, using unmatched peripheral blood mononuclear cells sourced from a patient with SLE, dual CAR T cells showed robust eradication of aberrant CD19+ B cells, CD38+ plasma cells, and CD38+ activated T cells. FT522 iPSC-derived CAR NK Cell Program New Phase 1 Translational Data to be Presented at ASGCT. FT522 is the Company’s off-the-shelf CAR NK cell product candidate and its first to incorporate Alloimmune Defense Receptor (ADR) technology. The FDA has allowed the Company’s Investigational New Drug (IND) application to assess the safety, pharmacokinetics, and activity of FT522 across a basket of B cell-mediated autoimmune diseases. The Company is currently evaluating opportunities and timelines for the clinical development of FT522 in autoimmunity without administration of conditioning chemotherapy. At the ASGCT Annual Meeting in May, the Company plans to present new clinical and translational data from its multi-center, Phase 1 clinical trial of FT522 in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334), where initial translational data demonstrated the potential of FT522 to persist and function in the presence of an unmatched, fully-intact immune system. First Quarter 2025 Financial Results Cash & Investment Position: Cash, cash equivalents, and investments as of March 31, 2025 were $272.7 million. Total Revenue: Revenue was $1.6 million for the first quarter of 2025, which was derived from the conduct of preclinical development activities for a second collaboration candidate targeting an undisclosed solid tumor antigen under the Company’s collaboration with Ono Pharmaceutical. Total Operating Expenses: Total operating expenses were $42.9 million for the first quarter of 2025, including research and development expenses of $29.1 million and general and administrative expenses of $13.8 million. Such amount included $7.4 million of non-cash stock-based compensation expense. Shares Outstanding: As of March 31, 2025, common shares outstanding were 114.6 million, pre-funded warrants outstanding were 3.9 million, and preferred shares outstanding were 2.8 million. Each preferred share is convertible into five common shares. About Fate Therapeutics’ iPSC Product Platform Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be administered in combination with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with patient- and donor-sourced cell therapies. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications. About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived T-cell and natural killer (NK) cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Company’s results of operations, financial condition, anticipated operating expenses and cash runway, and sufficiency of its cash and cash equivalents to fund its operations, as well as statements regarding the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, including the Company’s plans to complete IND-enabling studies and to submit IND applications and other regulatory submissions, including regulatory submissions in Europe, for its product candidates, the initiation and continuation of enrollment in the Company’s clinical trials, the initiation of additional clinical trials, including in new indications, and additional dose cohorts in ongoing clinical trials of the Company’s product candidates, the availability of data from the Company’s clinical trials and the Company’s plans to provide updates on its clinical trials, the therapeutic and market potential of the Company’s research and development programs and product candidates, the Company’s clinical and product development strategy, the Company’s plans to work with the FDA on a registrational pathway for FT819 in SLE, the Company’s ability to benefit from RMAT designation for FT819, and the Company’s expectations regarding progress and timelines, and the objectives, plans and goals of its collaboration with Ono. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company’s research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company’s product candidates or in the initiation and conduct of, or enrollment and continued participation of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects, the risk that the Company may not comply with its obligations under and otherwise maintain its collaboration agreement with Ono, the risk that research funding and milestone payments received by the Company under its collaboration may be less than expected, and the risk that the Company may incur operating expenses in amounts greater than anticipated. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise. Contact: Christina Tartaglia Precision AQ 212.362.1200 christina.tartaglia@precisionaq.com Source: Fate Therapeutics, Inc.