ALLO-715

关注并星标CPHI制药在线1. CAR-T疗法开发最新进展       美国最大的癌症治疗和研究组织之一的 City of Hope 日前进行了一项开创性1期研究，针对CAR-T 细胞对胶质母细胞瘤的治疗。这项试验显示出了CAR-T针对无法治愈的脑肿瘤的巨大应用潜力。       这项研究是迄今为止报道过的规模最大的实体瘤 CAR-T 试验，评估CAR-T针对肿瘤相关抗原白细胞介素 13 受体 α 2 (IL13Rα2) 的活性。治疗脑癌的主要挑战之一是药物难以穿过血脑屏障。为了克服这一障碍，这项试验将 CAR T 细胞直接输送到脑肿瘤和脑脊液中，脑脊液是保护和包围大脑和脊髓的液体。       这项1期研究在 65 名复发性高级别胶质瘤患者中评估了靶向 IL-13Rα2的CAR-T 疗法，其中大多数是复发性胶质母细胞瘤 (rGBM)。50% (29/58) 的患者病情稳定或更好，在方案外额外的 CAR-T 周期后出现两次部分缓解、一次完全缓解和第二次完全缓解。对于复发性多形性胶质母细胞瘤，所有患者的中位总生存期为 7.7 个月。该试验最终对一组患者进行了治疗，这个患者组使用了优化的制造工艺，并将 CAR-T 细胞注射到肿瘤部位和脑脊液中。这些患者实现了10.2个月的中位总生存期，显著高于复发性胶质母细胞瘤患者 6 个月的预期生存率。这项研究结果发表在了最新一期的Nature Medicine上。       虽然CAR-T疗法开发方兴未艾，但涉及该疗法的安全性讨论却一直都是行业焦点。2024 年 1 月 23日 ，FDA 要求在目前获批的6 种 CAR-T 治疗产品中添加与继发性癌症风险相关的黑框警告。FDA 于 2024 年 1 月 19 日向各相关公司发出了单独的信函。这些 CAR-T 产品针对抗原 CD19 或 B 细胞成熟抗原 (BCMA)。FDA要求六款CAR-T产品的制造商添加黑框警告，指出“使用 BCMA 和 CD19 导向的转基因自体 T 细胞免疫疗法治疗后可能会导致 T 细胞恶性肿瘤”。       几乎与此同时，FDA 最终确定了CAR-T 治疗产品的指南，涵盖与癌症患者的开发和临床试验设计相关的因素。FDA的另一份最终指南涉及纳入人类基因组编辑的基因治疗产品，为研究性新药应用提供建议，包括产品设计、制造、非临床安全性评估和临床试验设计。       2. CAR-T疗法       嵌合受体雏形是由魏茨曼科学研究所的 Eshhar 小组于 1989 年开发的，到目前CAR-T 细胞已经快速发展了几代（图1B）。       图1. A: CAR-T细胞结构；B: 第一代CAR信号结构域仅具有CD3衍生的信号结构域。第二代 CAR 中加入了共刺激结构域。第三代CAR有两个共刺激域。第四代 CAR-T 细胞激活后可表达 IL-12 等趋化因子。第五代 CAR 具有独特的共刺激结构域，可激活特定的信号通路，例如 JAK/STAT3。（图片来源：Cancer Gene Ther）       CAR 由三个基本结构域组成：细胞外结构域、跨膜结构域和细胞内结构域 （图1A）。胞内结构域在 T 淋巴细胞信号传导中发挥着至关重要的作用，能够不依赖人类白细胞抗原 (HLA) 而杀死恶性细胞。胞外结构域由单链可变片段 (scFv，Single-chain variable fragment) 组成，它是抗体轻链和重链可变区构建的融合蛋白。这个胞外结构域通过间隔区与跨膜结构域连接，并进一步与细胞内信号传导结构域连接，导致癌细胞细胞溶解。胞外 scFv 帮助CAR-T 细胞附着到特定靶向细胞，胞内结构域则有助于 T 细胞激活。在胞内信号传导域上，存在初级刺激域和次级共刺激域（图1）。      CAR-T 疗法根据特定癌症类型和患者需求提供个性化治疗，彻底改变了癌症治疗。CAR-T疗法对患者自身 T 细胞进行基因改造，使其能够识别并结合肿瘤抗原。修饰后的 T 细胞经过增殖后，会被输回患者体内，以靶向并消灭癌细胞（图 2）。       图2. 自体 CAR-T 细胞的生产从患者的白细胞分离开始，然后进行 T 细胞富集和激活。为了促进 CAR 转基因的引入并永 久整合，需要转导活化的 T 细胞（例如使用慢病毒载体）。之后经过基因工程改造的 T 细胞在静态或动态培养物中生长、冷冻保存，然后重新引入患者体内。       3. FDA批准的CAR-T疗法       目前，FDA已批准了六种CAR-T细胞疗法：       Tisagenlecleucel（Kymriah）       图片来源：Clinical Trials Arena       •适应症：急性淋巴细胞白血病、B 细胞淋巴瘤、滤泡性淋巴瘤       •靶标：CD19       •开发商：诺华       •首次获批时间：2017年8月30日       Tisagenlecleucel（商品名Kymriah）用于治疗 B 细胞急性淋巴细胞白血病 (ALL)。       Tisagenlecleucel最初由宾夕法尼亚大学发明，诺华公司完成了开发，并于2017年8月30日首次获得 FDA 批准，成为美国第一个获得 FDA 批准的CAR-T疗法。       Axicabtagene Ciloleucel（Yescarta）       •适应症：B 细胞淋巴瘤、滤泡性淋巴瘤       •靶标：CD19       •开发商：Kite Pharma Inc.       •首次获批时间：2017年10月18日       Brexucabtagene Autoleucel（Tecartus）       •适应症：复发性或难治性 (r/r) B 细胞前体急性淋巴细胞白血病 (B-ALL)、复发/难治性套细胞淋巴瘤（r/r MCL）       •靶标：CD19       •开发商：Kite Pharma, Inc       •首次获批时间：2020年7月24日       Lisocabtagene Maraleucel（Breyanzi）       •适应症：大 B 细胞淋巴瘤 (LBCL)，包括弥漫性大 B 细胞淋巴瘤 (DLBCL)（包括惰性淋巴瘤引起的 DLBCL）、高级别 B 细胞淋巴瘤、原发性纵隔大 B 细胞淋巴瘤和3B 级滤泡性淋巴瘤       •靶标：CD19       •开发商：BMS       •首次获批时间：2021年2月5日       Idecabtagene Vicleucel（Abecma）       图片来源：Abecmahcp.com       •适应症：复发性或难治性多发性骨髓瘤 (经过四种或更多种既往疗法，包括免疫调节剂、蛋白酶体抑制剂和抗 CD38 单克隆抗体)。   •靶标：BCMA       •开发商：Celgene Corporation（隶属于BMS）       •首次获批时间：2021年3月26日       Ciltacabtagene autoleucel（Carvykti）       •适应症：多发性骨髓瘤       •靶标：BCMA       •开发商：Janssen Biotech, Inc       •获批时间：2022年2月28日       4. 2024年待批CAR-T疗法       Carvykti (ciltacabtagene autoleucel, cilta-cel)       •BLA属性：新适应症       •适应症：癌症-治疗已接受过至少一种既往疗法 (包括蛋白酶体抑制剂和免疫调节剂) 的复发性和lenalidomide难治性多发性骨髓瘤成人患者       •靶标：BCMA       •开发商：Janssen 和 Legend Biotech       •BLA类型：标准审评       •PDUFA时间：2024年4月5日       Breyanzi (lisocabtagene maraleucel)       •BLA属性：新适应症       •适应症：癌症 -治疗成人复发性或难治性滤泡性淋巴瘤 (FL)       •靶标：CD19       •开发商：BMS       •BLA类型：优先审评       •PDUFA时间：2024年5月23日       Breyanzi (lisocabtagene maraleucel)       •BLA属性：新适应症       •适应症：癌症 -治疗布鲁顿酪氨酸激酶抑制剂后复发或难治性套细胞淋巴瘤 (MCL) 成人患者       •靶标：CD19       •开发商：BMS       •BLA类型：优先审评       •PDUFA时间：2024年5月31日       Obecabtagene autoleucel (obe-cel)       •BLA属性：新疗法       •适应症：治疗复发性或难治性成人 B 细胞急性淋巴细胞白血病 (ALL)       •靶标：CD19       •开发商：Autolus Therapeutics       •BLA类型：标准审评       •PDUFA时间：2024年11月16日       5. 引领CAR-T开发的生物科技公司       随着CAR-T疗法不断被大型制药公司看重，专注于这种细胞疗法的生物科技公司也成为了行业的关注焦点。       Allogene Therapeutics       •总部：美国加州旧金山       •创立时间：2017年       •主要CAR-T资产：ALLO-501A（cema-cel，复发性或难治性非霍奇金淋巴瘤 ，2期）       图3. Allogene的CAR-T项目ALLO-501A作用机理示意图。（图片来源：Allogene）       Allogene的技术平通通过开发同种异体 CAR-T 细胞治疗产品来解决自体 CAR-T 疗法的局限性。同种异体疗法使用来自健康捐赠者的 T 细胞。其最 先进的项目是 cema-cel（ALLO-501A，图3），是一种抗CD19 CAR-T 疗法，目前处在复发性或难治性非霍奇金淋巴瘤的2期研究，也在一项1期研究中针对复发/难治性慢性淋巴细胞白血病。除此之外，Allogene还在两项 1 期试验中以 B 细胞成熟抗原 (BCMA) 为靶标，研究其治疗多发性骨髓瘤的 CAR-T 候选药物 ALLO-715 和 ALLO-6053。       Anixa Biosciences       •总部：美国加州圣荷西       •创立时间：1982年       •主要CAR-T资产：1项1期资产（卵巢瘤）       Anixa Biosciences 专注于癌症治疗，是一家从事 CAR-T 细胞治疗和癌症疫苗领域的公司。Anixa Biosciences的一项1期资产针对卵巢瘤开发。这项研究是Anixa Biosciences与Moffitt癌症中心合作进行的，靶标是卵巢上存在的卵泡刺激素受体（FSHR）。       Autolus Therapeutics       •总部：英国伦敦       •创立时间：2014年       •主要CAR-T资产：Obe-cel（obecabtagene autoleucel，AUTO1，复发/难治性 B-细胞急性淋巴细胞白血病，已提交BLA申请）       Autolus Therapeutics是CAR-T 疗法的领跑者，他们最 先进的CAR-T资产obe-cel已经递交了BLA申请。Obe-cel以 CD19 为靶点，针对当前 CD19 CAR-T 细胞疗法在临床活性和安全性方面的局限性。Obe-cel 具有快速与靶标结合并解离速率，最大 程度地减少工程化T细胞的过度激活，降低毒性和T 细胞耗竭，从而增强持久性，提高工程化T 细胞连续杀死目标癌细胞的能力。       Obe-cel 在成人急性淋巴细胞白血病的达到了终点并向CBER递交了BLA，它的PDUFA 日期定为 2024 年 11 月 16 日。       BioNTech       •总部：德国美因茨       •创立时间：2008年       •主要CAR-T资产：BNT211（实体瘤，1期），BNT221（难治性转移性黑色素瘤，1期）       德国生物技术公司 BioNTech 的主要开发重点是mRNA 癌症疫苗，但其管线中也拥有三款 CAR-T 资产。       BioNTech 的BNT211针对实体瘤，其晚期实体瘤的 1/2 期研究表现出了优良的抗肿瘤活性，总体缓解率为 59%，疾病控制率为 95%。BioNTech的另一款候选CAR-T资产BNT221 正在难治性转移性黑色素瘤患者中进行1期研究。       2024年2月， BioNTech向 Autolus Therapeutics 支付了 2.5 亿美元，使用后者在英国的生产和临床基地来进一步开发 BNT211。       Cartesian Therapeutics       •总部：美国麻省沃特敦       •创立时间：2007年       •主要CAR-T资产：Descartes-08（重症肌无力，2期；系统性红斑狼疮和其它自免疫疾病，1期）       Cartesian Therapeutics的特别之处在于他们的CAR-T资产针对的不是肿瘤学，而是自免疫疾病。他们开发了首 个针对自身免疫性疾病的 mRNA CAR-T 细胞疗法。       mRNA 细胞疗法是一种集传统mRNA 疗法与传统 DNA 工程细胞疗法之优势而创造出的新疗法。与传统的基于纳米颗粒的 RNA 疗法相比，mRNA 细胞疗法在重复给药时可能具有最小的免疫原性。它还可以用组织特异性归巢蛋白进行工程改造。       与传统昂贵的DNA细胞疗法相比，mRNA细胞疗法的设计不需要预处理化疗，具有可预测和可控的药代动力学，并避免基因组整合的风险。与 DNA 类似物相比，mRNA 细胞疗法可能更安全、更有效且更便宜，并且有可能在门诊环境中进行。此外，mRNA 细胞疗法旨在实现真正的联合治疗，无需受限于载体载荷。       Descartes-08正在针对重症肌无力进行II期研究。其IIa研究表明，这款候选药物是安全且耐受性良好的，并且能够引起持久的反应。2b 期研究已开始招募患者。Descartes-08还有一项I期研究针对系统性红斑狼疮和其它自免疫疾病。       2023年11 月，Cartesian Therapeutics与美国 Selecta Biosciences 合并，合并后的公司拥有超过 1.1 亿美元的资金支持 Descartes-08 进入临床第 3 阶段。       CARGO Therapeutics       •总部：美国加州圣马特奥       •创立时间：2019年       •主要CAR-T资产：CRG-22（接受CD19 CAR-T细胞疗法后患有复发/难治性大B细胞淋巴瘤的患者，2期；尚未接受 CAR-T 细胞治疗的大B细胞淋巴瘤，1期；儿童 B-细胞急性淋巴细胞白血病，1期）       CARGO Therapeutics 在首次公开募股中筹集了超过 2.8 亿美元资金，已开始对资产 CAR-T 细胞疗法候选药物 CRG-022 进行 2 期试验。该候选药物靶向 CD22，是一种 B 细胞特异性抗原，在超过 8% 的弥漫性 LBCL 病例中有表达（图4）。由于对 CD19 CAR-T 细胞疗法产生耐药性的患者在 CD19 抗原表达丧失（antigen escape）后，CD22 表达通常会保留，因此CRG-022被设计为在患者接受 CD19 靶向 CAR-T 疗法后使用。       图4. CARGO Therapeutics针对的抗原逃逸（Antigen Escape）问题。（图片来源：CARGO Therapeutics）       除此之外，Cargo 正在努力解决共刺激配体（T 细胞表达的分子，如 CD58）的丢失问题。它通过开发 CAR-T 细胞来实现这一目标，无论肿瘤细胞上潜在的 CD58 下调或缺失，CAR-T 细胞都能通过肿瘤抗原诱导 CD2 共刺激信号传导，通过这种方式解决免疫疗法的耐药性问题。Kite Pharma       •总部：美国洛杉矶       •创立时间：2009年（2017年被吉利德收购）       •主要CAR-T管线资产：Axicabtagene ciloleucel（2L+ 高危滤泡性淋巴瘤，3期；1L高危大B细胞淋巴瘤，3期）       从前文介绍的获批CAR-T疗法中就不难看出Kite Pharma在这个领域的地位。六款上市CAR-T疗法中他们开发了两款。其旗帜性产品是治疗 LBCL 的自体 CAR-T 药物 Yescarta ，早在2017 年就获得 FDA 批准，目前正在进行针对其它形式淋巴癌的临床测试。       2023年年底，Kite Pharma宣布将扩大与美国生物技术公司Arcellx的合作关系，推进后者针对BCMA的多发性骨髓瘤候选药物。       Ref.       Brown, C. E. et al. Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med (2024). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41591-024-02875-1       KYMRIAH Patient Site. https://www.us.kymriah.com/       Cartesian Therapeutics website. https://www.cartesiantherapeutics.com/rna-cell-therapy/       Stansfield, N. FDA Finalizes Sets of Guidelines for Both CAR-T Products and Genome Editing Products. CGTLive. 12. 03. 2024.       FDA Activity Recap: January 2024 Features Major Approval, New Black Box Warnings, and Updated Guidance Documents. CGTLive. 05. 02. 2024.       Peter, R. M. Eight CAR-T cell therapy companies you should know about. Labiotech. 21. 03. 2024.【智药研习社近期课程预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

Presented Long-Term Data for an Allogeneic CD19 CAR T Product Candidate in Relapsed/Refractory Large B Cell Lymphoma (LBCL) at the American Society of Clinical Oncology (ASCO) Annual Meeting and International Conference on Malignant Lymphoma (ICML) Lugano ALLO-501/501A Demonstrated Rates of Durable Complete Responses Similar to Approved Autologous CAR T Therapies Enrollment Ongoing in the ALLO-501A ALPHA2 and EXPAND Phase 2 Trials in LBCL ALPHA2 Trial Expected to Complete Enrollment in 1H 2024 with the First Data Readout Planned by Year-End 2024 Ended Q2 2023 with $545 Million in Cash, Cash Equivalents and Investments Includes Approximately $88 Million in Net Proceeds from At-the-Market (“ATM”) Equity Financing Facility During the Second Quarter; Cash Runway Now Projected to Extend into 2H 2025 Conference Call and Webcast Scheduled for Today at 2:00 PM PT/5:00 PM ET SOUTH SAN FRANCISCO, Calif., Aug. 02, 2023 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer, today provided a corporate update and reported financial results for the quarter ended June 30, 2023. “The last few months have been exciting for cell therapy as the transformative potential of an allogeneic CAR T product becomes more evident. Within this framework, we are thrilled that our off-the-shelf CD19 AlloCAR T data continues to demonstrate what I believe to be both first-in-class and best-in class promise in hematological cancers,” said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. “We remain focused on advancing the industry’s first potentially pivotal allogeneic CAR T trials in order to enable more patients to receive cell therapy.” Pipeline Updates ALLO-501A: Anti-CD19 AlloCAR T Program The Company is enrolling patients in the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A across sites in the United States and Canada. The European Medicines Agency (EMA) recently approved the ALPHA2 Clinical Trial Application (CTA) and patient enrollment in Europe is expected to begin in Q3 2023 and in Australia by year-end. The single-arm ALPHA2 trial in relapsed/refractory (R/R) large B cell lymphoma (LBCL) utilizes a single dose of ALLO-501A (120 million CAR+ cells) following lymphodepletion with FCA90 (fludarabine, 30 mg/m2; cyclophosphamide 300 mg/m2; and ALLO-647 30 mg, daily for 3 days). This trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint is overall response rate (ORR), and the key secondary endpoint is duration of response (DoR). Patients may receive treatment as an outpatient at the investigator’s discretion. The Company expects to complete enrollment in 1H 2024 with the first data readout by the end of 2024. Long-term follow up data from the Phase 1 ALPHA/ALPHA2 trials in LBCL was presented at both the American Society of Clinical Oncology (ASCO) Annual Meeting with an encore presentation at the European Hematology Association Congress, and the International Conference on Malignant Lymphoma (ICML) Lugano in June 2023. The Phase 1 trials enrolled heavily pre-treated patients with a median of three prior lines of therapy. Data from 33 CAR T-naïve LBCL patients receiving Alloy™ cell product including 12 patients treated with the Phase 2 regimen, are the first to demonstrate the potential for an allogeneic CAR T product to induce complete responses at rates and durability similar to approved autologous therapies. Treatment with ALLO-501/501A was generally well tolerated with no incidence of Grade 3 or greater cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome or graft versus host disease. Cytopenia and infections were manageable and comparable to the experience with autologous CAR T cell therapies in patients with r/r LBCL. The EXPAND trial is also underway to support licensure of ALLO-647, the Company’s anti-CD52 monoclonal antibody used in conjunction with standard low-dose FC (fludarabine, 30 mg/m2 and cyclophosphamide 300 mg/m2, daily for 3 days) lymphodepletion regimens to control premature rejection of AlloCAR T cells by the patient’s immune system. At the ASCO and Lugano data presentations, the Company’s proprietary lymphodepletion strategy was shown to promote robust AlloCAR T cell expansion and best-in-class longest persistence without incurring significant changes in infectious or immunosuppressive complications as compared to autologous CAR T therapies. The EXPAND trial, which is designed to demonstrate the contribution of ALLO-647 to the standard low dose FC lymphodepletion, will enroll approximately 70 patients with r/r LBCL who will be randomized to lymphodepletion with FCA90 (which includes 90 mg of ALLO-647) versus FC alone before receiving a single 120 million cell dose of ALLO-501A. The primary endpoint of the study is progression free survival (PFS). ALLO-316: Anti-CD70 AlloCAR T ProgramThe ongoing Phase 1 dose escalation TRAVERSE study is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy. Initial data from TRAVERSE were presented at the American Association of Cancer Research (AACR) conference in April and demonstrated the potential of an allogeneic CAR T product to treat CD70 expressing RCC. In this trial, ALLO-316 showed early anti-tumor activity with deepening responses over time and a trend toward greater tumor shrinkage in patients with higher levels of CD70 expression. The Dagger™ effect, which is a feature of ALLO-316, enables ALLO-316 CAR T cells to target and eliminate alloreactive host immune cells, thereby mitigating potential premature rejection of AlloCAR T cells by the patient’s immune system. Translational results shared at AACR suggest this unique immunomodulatory effect of ALLO-316 contributed to robust AlloCAR T cell expansion and persistence, and clinical remissions. The TRAVERSE trial is now deploying an investigational in vitro companion diagnostic (IVD) assay designed to prospectively assess CD70 expression levels in patients. Dose escalation in the TRAVERSE trial is expected to be completed in 2023. Based on preclinical results demonstrating the ability to combine anti-CD19 and other AlloCARs™ with the Dagger technology, the Company intends to explore this approach to potentially enhance the activity of next generation AlloCAR T products candidates, including those that target other hematological and solid tumors. ALLO-715: Anti-BCMA AlloCAR T Program The Company previously presented ALLO-715 Phase 1 data from the UNIVERSAL trial which was the first study to demonstrate that an allogeneic anti-BCMA CAR T could produce response rates in multiple myeloma similar to an approved autologous CAR T therapy. As treatments in multiple myeloma advance, the Company is evaluating manufacturing process improvement across its BCMA candidates to achieve an improved competitive profile. Second Quarter Financial Results The Company had $544.5 million in cash, cash equivalents, and investments as of June 30, 2023, which includes net proceeds of approximately $87.9 million raised in the second quarter from an at-the market (ATM) equity financing facility. Based on current expectations, the Company expects its cash runway to fund operations into 2H 2025.Research and development expenses were $62.0 million for the second quarter of 2023, which includes $6.9 million of non-cash stock-based compensation expense.General and administrative expenses were $18.5 million for the second quarter of 2023, which includes $9.7 million of non-cash stock-based compensation expense.Net loss for the second quarter of 2023 was $78.0 million, or $0.53 per share, including non-cash stock-based compensation expense of $16.6 million. 2023 Financial Guidance As previously reported, the Company expects a decrease in cash, cash equivalents, and investments of approximately $230 million in 2023. GAAP Operating Expenses are expected to be approximately $340 million, including estimated non-cash stock-based compensation expense of approximately $80 million. These estimates exclude any impact from potential business development activities. Conference Call and Webcast DetailsAllogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company's website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company's website for approximately 30 days. About Allogene TherapeuticsAllogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com and follow @AllogeneTx on Twitter and LinkedIn. Cautionary Note on Forward-Looking StatementsThis press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," “projects,” "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: ALPHA2 being a potentially pivotal trial; expected enrollment and related timelines; the expected timing to complete dose escalation; the potential of an allogeneic CAR T product to treat CD70 express RCC based on emerging data; study design; the timing and ability to progress the ALPHA2 and TRAVERSE trials; clinical outcomes, which may materially change as more patient data become available; the ability to achieve optimal clinical performance through manufacturing processes improvements; the design and potential benefits of our Dagger technology, including its ability to resist rejection of AlloCAR T cells by the host immune cells and the expected benefits therefrom, and our plans to deploy Dagger technology; the potential for our product candidates to be approved; the potential benefits of AlloCAR T products and 2023 financial guidance, including expected cash runway. Various factors may cause material differences between Allogene’s expectations and actual results, including, risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; Servier’s discontinuation of its involvement in the development of all CD19 products pursuant to our Exclusive License and Collaboration Agreement and our disputes with Servier may have adverse consequences; the limited nature of our Phase 1 data from our clinical trials and the extent to which such data may or may not be validated in any future clinical trial; our ability to maintain intellectual property rights necessary for the continued development of our product candidates, including pursuant to our license agreements; our product candidates may cause undesirable side effects or have other properties that could halt their clinical development, prevent their regulatory approval or limit their commercial potential; the extent to which COVID-19 adversely impacts our business, including our preclinical studies and clinical trials; the extent to which the Food and Drug Administration disagrees with our clinical or regulatory plans or the import of our clinical results, which could cause future delays to our clinical trials or require additional clinical trials; we may encounter difficulties enrolling patients in our clinical trials; we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which could prevent or delay regulatory approval and commercialization; challenges with manufacturing or optimizing manufacturing of our product candidates; and our ability to obtain additional financing to develop our products and implement our operating plans. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factors” heading in its Annual Report on Form 10-K for the year ended December 31, 2022, and in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, being filed with the SEC today. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. Caution should be exercised regarding statements comparing autologous CAR T data. There are differences in the clinical trial design, patient populations, published data, follow-up times and the product candidates themselves, and the results from the clinical trials of autologous products may have no interpretative value on our existing or future results. AlloCAR T™, AlloCAR™ and Dagger™ are trademarks of Allogene Therapeutics, Inc. Allogene’s AlloCAR T™ programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. The anti-BCMA and anti-CD70 AlloCAR T programs are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these AlloCAR T programs. ALLOGENE THERAPEUTICS, INC. SELECTED FINANCIAL DATA (unaudited; in thousands, except share and per share data) STATEMENTS OF OPERATIONS Three Months Ended June 30, 2023 2022Collaboration revenue - related party$44 $86Operating expenses: Research and development$62,038 $57,171General and administrative 18,524 19,509Total operating expenses 80,562 76,680Loss from operations (80,518) (76,594)Other income (expense), net: Interest and other income, net 3,778 315Other income (expenses) (1,249) 1,492Total other income, net 2,529 1,807Net loss (77,989) (74,787)Net loss per share, basic and diluted$(0.53) $(0.52)Weighted-average number of shares used in computing net loss per share, basic and diluted 146,795,826 143,385,045 SELECTED BALANCE SHEET DATA As of June 30, 2023 As of December 31, 2022Cash, cash equivalents and investments$544,548 $576,471Total assets 770,971 817,079Total liabilities 148,065 151,209Total stockholders’ equity 622,906 665,870 Allogene Media/Investor Contact:Christine CassianoChief Communications OfficerChristine.Cassiano@allogene.com