Fludarabine Phosphate

点击蓝字 关注我们 编者按 慢性淋巴细胞白血病（CLL）作为最常见的白血病类型，由干扰克隆B细胞增殖和凋亡调节的特定基因组改变引发，通常发生在老年患者中，临床病程变化较大。为更好促进对CLL的疾病认知和临床诊疗，近日Michael Hallek教授在American Journal of Hematology上发表了一篇综述，详细介绍CLL的最新流行病学、发病机制、诊断、预后分层、治疗选择以及未来挑战。本文特整理核心要点，以飨读者。 流行病学 根据最新的SEER数据库更新，CLL的年龄校正发病率约为每10万居民每年4.6例，中位诊断年龄为70岁。男性比女性更容易患病，比例约为1.9:1。CLL占所有新发癌症病例的1%，2024年美国估计有20,700例新病例，约有215,107人患有CLL。尽管发病率在过去二十年中保持稳定，但死亡率持续下降，2024年估计有4,440例死亡，占所有癌症死亡的0.7%。CLL 的5年相对生存率从1975年的65.1%稳步上升到2024年的88.5%。在欧洲，CLL的流行病学数据与美国相似，而在亚洲国家和种族中发病率较低。 发病机制 CLL的特征是成熟B细胞（通常为CD5阳性）在血液、骨髓、淋巴结和脾脏中的克隆增殖和积累。CLL通常由大的染色体物质丢失或增加开始，随后发生额外的突变，使白血病更具侵袭性。约80%的CLL患者至少有四种常见的染色体改变中的一种：del（13q）、del（11q）、del（17p）、12三体。其中del（13q）是最常见的染色体改变，发生在约55%的病例中，通常预示着疾病侵袭性较弱。del（17p）几乎总是包括TP53肿瘤抑制基因，携带del(17p)克隆的CLL患者对DNA损伤化疗表现出明显的耐药性。del(11q)通常包含ATM基因，携带del(11q)克隆的患者通常表现为淋巴结肿大、快速进展和生存期缩短。12三体与中等预后相关。 全外显子测序的应用使我们能够描述CLL的基因组景观。除了上述染色体异常外，还发现了44个复发性突变基因和11个复发性体细胞拷贝数变异。这些包括NOTCH1、MYD88、TP53、ATM、SF3B1、FBXW7、POT1、CHD2、RPS15、IKZF3、ZNF292、ZMYM3、ARID1A和PTPN11等基因。这些分析确定了RNA加工和输出、MYC活性和MAPK信号通路参与CLL发生的中心通路。此外，还涉及DNA损伤信号传导和DNA修复的蛋白质。 CLL的表观基因组已成为另一个疾病定义特征。CLL细胞群体的扩大通过DNA甲基化的随机变化（称为表观突变）实现多样化。通过比较健康供体和CLL患者的B细胞msRRBS（Multiplex Single-cell Reduced Representation Bisulfite Sequencing）技术，为DNA甲基化变化提供了新的见解。这些结果表明，整合单细胞水平的遗传、表观遗传和转录信息可以绘制个体CLL病例的谱系历史及其对治疗的演变。 诊断 CLL的诊断主要基于血细胞计数、血涂片和循环B淋巴细胞的免疫表型分析。世界卫生组织（WHO）第五版将CLL归类为成熟B细胞肿瘤中的“MBL和CLL”类别。CLL被描述为白血病淋巴细胞淋巴瘤，与SLL的区别在于其白血病外观。CLL的诊断需要外周血中B淋巴细胞≥5000个/μL，持续至少3个月。通过流式细胞术确认循环B淋巴细胞的克隆性。CLL细胞在血涂片中通常是小的、成熟的淋巴细胞，具有窄的细胞质边界和密集的核，缺乏可辨识的核仁，部分染色质聚集。这些细胞可能与较大或非典型细胞、裂细胞或幼淋巴细胞混合，占到血液淋巴细胞的55%。幼淋巴细胞超过这个百分比将倾向于诊断为B细胞幼淋巴细胞白血病（B-PLL）。Gumprecht核阴影或细胞碎片是CLL的其他特征性形态学特征。 单克隆B淋巴细胞增多症（MBL）是指在不存在淋巴结病或器官肿大（通过体格检查或CT扫描定义）、血细胞减少或疾病相关症状的情况下，外周血中B淋巴细胞数量少于5000个/μL，持续时间≥3个月。MBL似乎以每年1%～2%的速度进展为典型的CLL。 免疫表型分析在CLL诊断中至关重要。CLL细胞共表达CD5抗原以及B细胞抗原CD19、CD20和CD23。与正常B细胞相比，表面免疫球蛋白、CD20和CD79b的水平通常较低。每个白血病细胞克隆仅表达κ或λ免疫球蛋白轻链。虽然CD5也可以在其他淋巴恶性肿瘤中观察到，如套细胞淋巴瘤，但一系列CD19、CD5、CD20、CD23、κ和λ的检测通常足以建立诊断。在边缘情况下，可以使用CD43、CD79b、CD81、CD200、CD10或ROR1等标记来细化诊断。 预后分层、分期和治疗指征 目前存在两种广泛接受的临床分期系统：Rai分期和Binet分期。 Rai分期将低风险疾病定义为仅有淋巴细胞增多的患者（Rai 0期）。具有任何部位可触及淋巴结和/或脾肿大和/或肝肿大的患者被定义为中风险疾病（Rai I或II期）。高风险疾病包括疾病相关的贫血（血红蛋白<11 g/dL）或血小板减少症（血小板计数<100×10^9/L）的患者（Rai III或IV期）。 Binet分期基于受累区域的数量，包括头颈部（包括Waldeyer环）、腋窝、腹股沟（包括浅表股动脉）、可触及的脾脏和可触及的肝脏。Binet分期将A期定义为Hb≥10 g/dL和血小板≥100×10^9/L，且最多有两个上述受累区域；B期定义为Hb≥10 g/dL和血小板≥100×10^9/L，且有三个或更多区域的器官肿大；C期定义为Hb<10 g/dL和/或血小板计数 <100×10^9/L。 由于CLL治疗的进展，这两种临床分期系统已不足以区分预后亚组。CLL国际预后指数（CLL-IPI）结合了五个独立的预后因素：TP53缺失和/或突变（统称为TP53功能障碍）、IGHV突变状态、血清β2-微球蛋白、临床分期和年龄。CLL-IPI将患者分为四个预后不同的组，5年生存率不同。尽管CLL-IPI在靶向药物时代仍具有预测价值，但其在预测生存方面的影响有所减弱。 表1. 靶向药物时代不同CLL-IPI类别CLL患者的预后 早期CLL国际预后评分（IPS-E）使用三个协变量：未突变的IGHV基因、绝对淋巴细胞计数高于15×10^9/L和可触及的淋巴结，将患者分为低风险、中风险和高风险，5年累积治疗开始风险分别为8.4%、28.4%和61.2%。 iwCLL指南提出了开始治疗的标准，包括：因疾病进展出现的贫血和/或血小板减少症、巨大（≥6厘米）或进行性或症状性脾肿大、巨大淋巴结（最长直径≥10 厘米）或进行性或症状性淋巴结病、淋巴细胞计数在2个月内增加≥50%或淋巴细胞倍增时间（LDT）小于6个月、自身免疫性并发症以及与疾病相关的症状，如体重减轻、疲劳、发热和盗汗。 表2. 根据iwCLL指南，定义“症状性或活动性疾病”的标准 治疗药物 CLL的治疗选择包括多种药物和组合，主要针对有活动性或症状性疾病或处于高Rai或Binet分期的患者。当患者出现疾病进展或症状性疾病时，应开始治疗。对于有活动性疾病或处于高分期的患者，治疗选择包括BCL2抑制剂维奈克拉与奥妥珠单抗的组合，或维奈克拉与伊布替尼的组合，或BTK抑制剂的单药治疗。在复发时，如果治疗间隔超过3年，可以重复初始治疗。如果疾病在较短时间内复发，应改用替代方案。 01 化疗药物 烷化剂：苯丁酸氮芥曾是CLL的一线治疗，具有毒性低、成本低和口服方便等优点。然而，由于其低至不存在的完全缓解（CR）率和长期使用后的副作用（如持续性细胞减少、骨髓增生异常和继发性急性白血病），其使用受到限制。 嘌呤类似物：氟达拉滨、喷司他丁（pentostatin）和克拉屈滨（cladribine，2-CdA）是研究的三种嘌呤类似物。氟达拉滨在CLL中的研究最多，其疗效优于其他化疗药物，但并未改善总生存期（OS）。克拉屈滨单药治疗的CR率高于苯丁酸氮芥联合泼尼松，但未改善生存率。 苯达莫司汀：与苯丁酸氮芥相比，苯达莫司汀提高了反应率，但未显示出生存益处。 02 抗CD20抗体 利妥昔单抗：自1998年引入后改善了大多数CD20阳性非霍奇金淋巴瘤的治疗，包括CLL。尽管利妥昔单抗单独治疗CLL的疗效不如在滤泡性淋巴瘤中显著，但其与化疗的组合被证明非常有效。 ofatumumab：ofatumumab是一种针对CD20分子独特表位的全人源化抗体。尽管其具有有趣的生物学和临床特性，但已不再用于治疗B细胞恶性肿瘤。 奥妥珠单抗（GA101）：奥妥珠单抗是一种人源化和糖基工程改造的单克隆抗体，与利妥昔单抗相比，体外诱导B细胞凋亡的能力更高。在复发/难治性CLL患者中，奥妥珠单抗单药治疗的ORR为62%，中位PFS为10.7个月。 03 靶向B细胞受体（BCR）信号通路的药物 BCR信号在CLL细胞的存活中起重要作用。BCR信号通过不同的酪氨酸激酶，如BTK、Syk、ZAP70、Src家族激酶（特别是Lyn）以及PI3K进行传递。BTK抑制剂或PI3Kδ抑制剂的出现彻底改变了B细胞恶性肿瘤的治疗。 3.1 PI3K抑制剂 idelalisib：idelalisib是一种口服PI3Kδ亚型选择性抑制剂，在复发/难治性CLL患者中显示出良好的疗效，但毒性限制了其应用。 duvelisib：duvelisib是一种口服抑制PI3Kδ和γ亚型的药物，在复发/难治性CLL患者中显示出疗效，但毒性与idelalisib相似。 umbralisib：umbralisib是一种PI3Kδ和CK1ε双重抑制剂，在复发/难治性CLL患者中显示出疗效，但与其他PI3K抑制剂相比，其优势不明显。 3.2 BTK抑制剂 伊布替尼：伊布替尼是一种口服BTK抑制剂，在复发/难治性CLL患者中诱导了高反应率和持久的缓解。 阿可替尼：阿可替尼是一种高选择性的、不可逆的BTK抑制剂，与伊布替尼相比，具有更好的安全性和有效性。 泽布替尼：与阿可替尼一样，泽布替尼是一种第二代、共价结合的BTK抑制剂，具有更高的特异性和更少的脱靶抑制。 匹妥布替尼：匹妥布替尼是一种高选择性的、可逆的（非共价）BTK抑制剂，对BTK C481S突变患者有效。 04 BCL-2 抑制剂 BCL-2家族蛋白是凋亡过程的关键调节因子。维奈克拉是一种BH3模拟药物，旨在阻断BCL-2蛋白的功能。维奈克拉在复发/难治性CLL患者中显示出高反应率，包括TP53突变或del(17p)的患者。维奈克拉与利妥昔单抗或奥妥珠单抗的组合在CLL患者中显示出持久的缓解。 02 免疫检查点抑制剂 帕博利珠单抗：在一项针对复发和转化CLL患者的2期试验中，帕博利珠单抗在9名Richter转化患者中观察到44%的客观反应，但在16名复发性CLL患者中未观察到反应。 06 CAR-T细胞疗法 CAR-T细胞疗法：CAR-T细胞疗法在CLL患者中显示出令人印象深刻的疗效，特别是在复发或难治性患者中。然而，CAR-T细胞疗法在CLL中的疗效低于其他淋巴瘤类型，可能与T细胞功能障碍和肿瘤微环境有关。 治疗选择 01 一线治疗 对于需要治疗的患者，无论其体能状态如何，推荐使用固定期限的维奈克拉联合奥妥珠单抗、第二代BTK抑制剂（如阿可替尼、泽布替尼）单药治疗，或维奈克拉与BTK抑制剂的组合。对于携带del(17p)或TP53突变的患者，建议单独使用BTK抑制剂或与维奈克拉联合治疗。对于体能良好且不可获得靶向药物的患者，仍可考虑使用FCR免疫化疗方案，以实现长期缓解或治愈。 图1. CLL一线治疗（2024年10月更新） 02 二线治疗 对于复发患者，如果首次缓解持续时间超过3-4年，可以重复一线治疗方案。对于早期复发（3-4年内）或携带del(17p)的患者，应选择不同的有效二线方案，如维奈克拉联合利妥昔单抗或奥妥珠单抗，或更换为非共价BTK抑制剂（如匹妥布替尼）。 图2. CLL二线治疗 03 三线治疗 对于双耐药（2R）CLL患者，治疗选择有限，包括PI3K抑制剂（如idelalisib和rituximab）、细胞疗法如CAR-T细胞疗法或异基因造血干细胞移植，以及免疫化疗或alemtuzumab。这些患者预后不良的风险很高，因此是纳入试验性方案和测试新药的良好候选者。 总 结 CLL的治疗在过去几十年中取得了显著进展，多种新的靶向药物和治疗方案显著改善了患者的预后。然而，尽管取得了这些进展，CLL的管理仍面临挑战，特别是对于耐药患者和双耐药患者。未来的研究需要进一步探索新的治疗策略和组合，以提高CLL患者的长期生存率和生活质量。 参考文献： [1]Hallek M. Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy. Am J Hematol. 2025 Mar;100(3):450-480. doi: 10.1002/ajh.27546. Epub 2025 Jan 28. PMID: 39871707; PMCID: PMC11803567. （来源：《肿瘤瞭望–血液时讯》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Phase 1 Dose Expansion Initiated for FT819 Off-the-Shelf CAR T-cell Product Candidate with Fludarabine-free Conditioning in Moderate-to-Severe SLE Completed Type D Meeting with FDA to Enable FT819 Off-the-Shelf CAR T-cell Dose Expansion in Additional B Cell-mediated Autoimmune Diseases First FT819 Off-the-Shelf CAR T-cell Patient Treated without Conditioning Chemotherapy as Add-on to Maintenance Therapy in SLE $307 Million in Cash, Cash Equivalents and Investments with Projected Operating Runway through YE26 SAN DIEGO , March 05, 2025 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a pipeline of induced pluripotent stem cell (iPSC)-derived off-the-shelf cellular immunotherapies to patients, today reported business highlights and financial results for the fourth quarter and full year ended December 31, 2024 . “We begin 2025 with resolve and focus to advance our lead clinical programs in autoimmunity and oncology,” said Bob Valamehr, Ph.D. MBA, President and Chief Executive Officer of Fate Therapeutics . “The team continues to make great progress in our pursuit of achieving therapeutic differentiation for patients with B cell-mediated autoimmune diseases, and we look forward to providing clinical and regulatory updates as we advance our FT819 off-the-shelf CAR T-cell product candidate in SLE. We remain focused on driving patient enrollment and engaging with the FDA to further discuss novel development pathways for CAR T-cell therapy in autoimmune disease, including the use of fludarabine-free conditioning as well as add-on to maintenance therapy without conditioning. We also plan to explore FT819 clinical trial expansion in additional autoimmune diseases. In addition, our FT825 off-the-shelf CAR T-cell program for advanced solid tumors is advancing into higher-dose cohorts as monotherapy and in combination with monoclonal antibody therapy under our collaboration with Ono Pharmaceutical. We look forward to sharing clinical data from these two high-priority programs throughout the year.” FT819 iPSC-derived 1XX CAR T-cell Program Phase 1 Dose Expansion Initiated for SLE using Flu-free Conditioning Regimen. Based on clinical data from the first three patients treated with FT819 in its ongoing multi-center, Phase 1 clinical trial for moderate-to-severe systemic lupus erythematosus (SLE) (NCT06308978), the Company has initiated dose expansion in up to 10 patients at 360 million cells. The dose expansion stage is designed to evaluate the safety and efficacy of a fludarabine (flu)-free conditioning regimen, consisting of either bendamustine alone or cyclophosphamide alone, followed by a single dose of FT819. The Company is also assessing the safety, pharmacokinetics, and anti-B cell activity of FT819 at 900 million cells in dose escalation. FT819 is the Company’s off-the-shelf CD8αβ+ T-cell product candidate that incorporates a CD19-targeted chimeric antigen receptor (CAR) with a novel 1XX costimulatory domain into the T-cell receptor alpha constant (TRAC) locus. Clinical Data from First Three SLE Patients Presented at ASH. In December 2024 , the Company highlighted clinical and translational data from the first three patients treated with FT819 for SLE at the American Society of Hematology (ASH) Annual Meeting. Each patient presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies and received flu-free conditioning followed by a single dose of FT819 at 360 million cells. As of a data cutoff date of December 4, 2024 , there were no dose-limiting toxicities (DLTs), and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). All three patients showed rapid, deep, and sustained elimination of CD19+ B cells in the periphery during the first month of treatment. The first and only patient eligible for disease assessment at six-month follow-up as of the data cutoff date achieved DORIS (Definition Of Remission In SLE) clinical remission and was free of all immunosuppressive therapy. First Patient Treated with FT819 as Add-on to Maintenance Therapy. The Company amended the clinical protocol of its FT819 Phase 1 study to include a new treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient in the new arm was on a stable dose of oral mycophenolate mofetil (MMF) and was treated with a single dose of FT819 at 360 million cells without administration of any conditioning chemotherapy. There were no DLTs and no events of CRS, ICANS, or GvHD. The patient remains on-study. Completed Type D Meeting with FDA for Inclusion of Additional Diseases in FT819 Phase 1 Study. In December 2024 , the Company reached an agreement with the U.S. Food and Drug Administration (FDA) to allow for the clinical investigation of additional B cell-mediated autoimmune diseases under our current Phase 1 clinical trial of FT819. As a follow-up to the meeting, the Company has submitted an amended clinical protocol to the FDA that enables the conduct of independent dose-expansion cohorts for SLE as well as anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). The Company plans to initiate dose-expansion cohorts in one or more of AAV, IIM, and SSc in 2025. Additionally, the FDA agreed to allow for investigation of a multi-dose treatment cycle as well as for re-treatment upon disease progression, making the treatment dosing paradigm more aligned with traditional biological therapies. The FDA also permitted the expansion of study eligibility criteria, including the inclusion of patients between the ages of 12 and 17. FT825 / ONO-8250 iPSC-derived CAR T-cell Program First Patient Treated with FT825 / ONO-8250 in Combination with Monoclonal Antibody Therapy. 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). Enrollment is currently ongoing at the third dose level of 900 million cells as monotherapy and at the second dose level of 300 million cells in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy. Initial Phase 1 Clinical Data Presented at 2024 SITC. At the 2024 Society of Immunotherapy of Cancer (SITC) in November, the Company presented initial clinical data from three heavily pre-treated patients, all of whom were previously treated with at least five prior lines of therapy including HER2-targeted therapy. Each patient was administered conditioning chemotherapy and a single dose of FT825 / ONO-8250 as monotherapy at the first dose level of 100 million cells. As of a data cutoff date of October 25, 2024 , FT825 / ONO-8250 demonstrated a favorable safety profile with no DLTs and no events of any grade of CRS, ICANS, or GvHD. In addition, at Day 8 following treatment, peak CAR T-cell expansion was observed and phenotyping of FT825 / ONO-8250 sourced from the patients’ peripheral blood was indicative of an activated state (as evidenced by high levels of Granzyme B expression and maintenance of CAR expression) with no evidence of exhaustion (as evidenced by low levels of PD-1 and TIM3 expression). FT522 iPSC-derived CAR NK Cell Program Initial Translational Data of FT522 without Conditioning Chemotherapy Presented at ACR Convergence. FT522 is the Company’s off-the-shelf, CD19-targeted CAR NK cell product candidate and first product candidate to incorporate Alloimmune Defense Receptor (ADR) technology, which is designed to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In November 2024 , the Company presented initial translational data from its ongoing multi-center, Phase 1 clinical trial of FT522 in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334). The presentation illustrated that live FT522 cells with anti-B cell activity were detected in the patients’ peripheral blood through Day 15, demonstrating the potential of FT522 to persist and function in the presence of an unmatched, fully-intact immune system. The Company intends to assess any further clinical development of FT522 in relapsed / refractory BCL upon completion of dose escalation at the second dose level of 900 million cells. Unique Clinical Development Opportunities for FT522 in Autoimmunity under Evaluation. 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 Phase 1 clinical protocol allows for treatment of patients with up to four weekly doses of FT522, without administration of conditioning chemotherapy, as an add-on to rituximab induction therapy (Regimen A) and as an add-on to maintenance therapy in combination with rituximab (Regimen B). The Company is currently evaluating opportunities and timelines for the clinical development of FT522 in autoimmunity. Fourth Quarter 2024 Financial Results Cash & Investment Position: Cash, cash equivalents, and investments as of December 31, 2024 were $306.7 million . Total Revenue: Revenue was $1.9 million for the fourth quarter of 2024, 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 $63.6 million for the fourth quarter of 2024, including research and development expenses of $33.6 million and general and administrative expenses of $15.3 million . Such amount included $9.1 million of non-cash stock-based compensation expense and a one-time non-cash asset impairment charge of $14.7 million related to equipment and right-of-use assets. Shares Outstanding: As of December 31, 2024 , common shares outstanding were 113.9 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 PlatformHuman 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 first-in-class 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 StatementsThis 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 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, 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 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 or from CIRM 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 AQ212.362.1200christina.tartaglia@precisionaq.com Source: Fate Therapeutics, Inc.