FT-819

正文共： 3400字 12图预计阅读时间： 9分钟今年5月，Century Therapeutics在美国基因与细胞治疗学会（ASGCT）的年会议上报告了其开发的一款无饲养层培育、可扩增的、iPSC衍生的通用型CAR-T细胞疗法的最新研究成果，实验显示其细胞扩增能力与肿瘤控制能力可与原代健康供体T细胞相媲美。▲会议摘要（图片来源：Century官网）iPSC（诱导多能干细胞）经过CD19 CAR和抗排斥编辑的设计，旨在抵御细胞和体液的免疫反应。通过选择一个完全表征的克隆，并使用新工艺进行分化，从而生成CD4+和CD8+T细胞的细胞混合群。对这一分化过程不同阶段的细胞进行scRNA-seq分析证实：这些细胞遵循与正常胸腺细胞相匹配的轨迹。在体外肿瘤刺激下，这些iPSC CAR-T细胞表现出抗原依赖性细胞毒性（ADCC）、可以增殖，并产生细胞因子，包括IL-2。在无需外源性细胞因子或细胞因子工程化改造的情况下，根据NALM6肿瘤模型显示，单次输注iPSC CAR-T细胞具有肿瘤抑制的效果。更为可观的是，在体内模型中，iPSC CAR-T细胞在外周血中持续存在至少21天，并浸润到骨髓中。当肿瘤再次被激发时，会对肿瘤细胞进行攻击并增殖。通过对照，iPSC CAR-T细胞在体内的扩增能力与肿瘤控制能力可与原代健康供体T细胞相媲美。这些数据为通用型iPSC CAR-T细胞领域的发展提供了阶梯，有望促进研究人员开发出可规模化生产、可及性高的iPSC CAR-T细胞药物，缓解当下CAR-T的“天价”困局。iPSC有望斩断CAR-T商业之路上的荆棘如今，细胞疗法已成为击退癌症的新型利器，最为主流的CAR-T正在免疫疗法领域掀起新革命。然而，目前国内已上市的CAR-T细胞疗法价格都在百万人民币附近徘徊，个性化定制的制备方式限制了CAR-T细胞的批量生产，“天价”成为CAR-T商品化之路上的荆棘，也刺痛了患者治疗的希望。而同种异体通用型CAR-T有望让患者以更经济高效的方式获得治疗，但免疫排斥反应仍是悬在通用型CAR-T头顶上的达摩克利斯之剑，更高效、更经济、更安全的设计刻不容缓。iPSCs提供了一个理想的研究方向，有望斩断CAR-T商业之路上的荆棘。由于这些细胞具有无限的增殖能力和向多种成体细胞分化的能力，可以被定向诱导分化为特定的免疫细胞，如T细胞和NK细胞。与传统的免疫细胞疗法相比，iPSC衍生的免疫细胞具有来源广泛、可大规模生产、低免疫排斥风险、无伦理与法律争议等优点。而且，iPSC细胞的扩增和分化潜力不受多次基因编辑的影响，具有应用于开发通用型CAR-T疗法的潜力。科学家们可以通过基因工程技术精确地修改这些细胞的基因，以提高其疗效和安全性。以京都大学的Shin Kaneko教授团队为例，他们已成功利用CRISPR/Cas9基因编辑技术，将iPSC细胞上导致免疫排斥的HLA基因敲除，同时导入CAR基因，得到无排斥的通用型iPSC（U-iPSC），U-iPSC分化得到的CAR-T细胞避免了宿主免疫排斥，而且相比于没有经过基因编辑的细胞能显示出更强的抗癌效果。▲图片来源：Nature官网iPSC CAR-T适应症在逐步扩展近年来，随着iPSC研究技术的不断深化，与CAR-T一样，iPSC CAR-T的应用范围也不再局限于肿瘤治疗领域，并在自免相关疾病的治疗上取得了初步成果。这验证了iPSC在诸多适应症类型中均具有广阔的治疗前景，在降低研发成本的同时，能丰富细胞治疗的赛道，为商业化发展开辟更多的蓝海市场。今年4月，Fate Therapeutics宣布该公司iPSC来源的通用型现货CAR-T细胞疗法FT819获得美国食品药品监督管理局（FDA）授予的再生医学先进疗法（RMAT）资格，用于治疗系统性红斑狼疮（SLE），包括狼疮性肾炎（LN）。值得一提的是，FT819是美国FDA批准临床的首个iPSC来源的通用型CAR-T疗法，当时获批的适应症为CD19+的恶性B细胞肿瘤。而据公司官方透露，旗下另一款治疗B细胞淋巴瘤的通用型CD19 CAR-iNK 疗法FT522也将其适应症扩展到自免领域。▲FT819管线进展（图片来源：Fate官网）FT819除了具有较为广泛的适应症外，其安全性也得到了突破性的升级。FT819通过基因工程改造，确保了T细胞表面的T细胞受体（TCR）被完全去除，从而可大大降低发生GvHD的风险。此外，它富含具有记忆表型特征的CD8αβ⁺T 细胞，且此类细胞呈现高 CXCR4分子表达特性，有助于促进T细胞在组织内的有效迁移。收获橄榄枝，iPSC衍生免疫细胞疗法成新宠作为干细胞领域的前沿技术，iPSC因其无限增殖的分化潜能与突破性的重编程技术，展现出更高的技术壁垒和更广阔的市场潜力。随着技术的不断突破和临床应用的逐步推进，不少药企嗅到iPSC技术在免疫细胞疗法领域的商业价值后纷纷抛出橄榄枝。2024年10月，Century宣布完成了对Clade Therapeutics的收购，用于增强其基于iPSC的细胞疗法管线和平台。同时，Century还完成了6000万美元的私募融资以支持其在自身免疫性疾病领域的进一步研发。而早在2022年，Century就与BMS达成30亿美元合作协议，共同开发和商业化四个iPSC衍生的工程化自然杀伤细胞（iNK）和/或T细胞（iT）项目，适应症包括血液瘤和实体瘤。这不难看出，当前Century面对Fate在iPSC CAR-T赛道上的强烈势头，也在积极扩大适应症的布局，在自免蓝海分一杯羹。2024年11月，Takeda(武田)宣布与Alloy Therapeutics达成战略合作和许可协议，Alloy 将开发武田专有的iPSC衍生的CAR-T细胞平台(iCAR-T)和iPSC衍生的CAR-NK 平台 (iCAR-NK)，以期加速开发关键疗法，治疗实体和血液系统恶性肿瘤。iCAR-T技术具有开发通用型现货细胞疗法的潜力，可提供一流的性能和增强的效力。与自体细胞疗法相比，制造成本显著降低。回看国内市场，11月，中盛溯源宣布完成了1.5亿元B轮融资首关，资金将用于加速推进中盛溯源在iPSC细胞治疗领域多款临床管线的临床开发，以及后续产品商业化。在此之前，中盛溯源研发的iPSC衍生的NK细胞（iNK）疗法NCR-300成为国内首个获得临床批准的iPSC-NK细胞疗法。该技术的进展给资本市场带去了振奋的信心，强有力的资金支持也将大力推进国内细胞治疗领域的发展。敢为人先，iPSC国内市场充满机遇在iPSC衍生免疫细胞疗法的赛道上，我国的企业丝毫不弱于全球其他国家的发展技术，并有其独特之处，敢为人先。中盛溯源、启函生物等iPSC头部企业更偏爱iPSC-CAR-NK、iPSC-NK，这或许是因为与生成T细胞相比，NK细胞分化方案更成熟，具有更高安全性。而赛元生物则另辟蹊径，基于iPSC分化获得的表达CAR的巨噬细胞，打造出了国内首个iCAR-M候选药物SY001，正在开展针对实体瘤的探索性临床试验。创新的研究总能与机遇撞个满怀，广阔的蓝海市场正向中国企业伸出双臂。▲全球范围内，进入临床阶段的iPSC免疫细胞疗法信息来源：根据公开资料整理写在最后当然，相较于走上商业化进程的细胞疗法而言，iPSC衍生免疫细胞疗法的开发还处于筚路蓝缕的摸索阶段，如何确保iPSC在体外的大量扩增、定向分化诱导的稳定性，如何保证生成的T细胞能够与天然T细胞具有相媲美的抗肿瘤潜力，如何减少未分化的iPSC导致恶性转化的致癌风险等等还需进一步研究。iCAR-T、iCAR-NK、iCAR-M谁能逐出胜负犹未可知。充满挑战也将意味着充满机遇，相信iPSC衍生免疫细胞疗法一鸣惊人的未来不会太久，“天价”药物将有更多机会飞入寻常百姓家，更高效、更经济、更安全的治疗时代正在来临。参考来源：1. https://investors.centurytx.com/news-releases/news-release-details/century-therapeutics-announces-two-upcoming-presentations-asgct2. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-025-08974-43. 各企业官网图片来源：正文美国蒙大拿州立法：无需FDA，一期临床后药物即可上市2025-05-19【全程直播】今天上午9点！欢迎线上观看「金赛药业2025研发日」活动！2025-05-17用时6个月！全球首款个体化CRISPR疗法问世2025-05-16版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩内容!

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.