Tocilizumab

FDA Granted RMAT Designation Based on ALPHA3 Trial Futility Analysis, Highlighting Cema-Cel’s Potential to Transform Disease Treatment in First-Line LBCL Consolidation Cema-Cel Induced Rapid and Substantial MRD Clearance of 58.3%, with a 97.7% Median Decrease in Plasma ctDNA at Day 45, Compared With a 26.6% Median Increase in the Observation Arm Cema-Cel Was Well-Tolerated, With Most Patients Managed in the Outpatient Setting and No Hospitalizations for Treatment-Related Adverse Events FDA Also Granted Fast Track Designation to Cema-Cel for the ALPHA3 Development Program RMAT and Fast Track Status Enable Enhanced FDA Engagement and Support Potential Expedited Development and Review Pathways SOUTH SAN FRANCISCO, Calif., July 29, 2026 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations to cemacabtagene ansegedleucel (cema-cel) for the treatment of adult patients with large B-cell lymphoma (LBCL) who, at the completion of first-line (1L) therapy, are in complete or partial response suitable for observation but test positive for minimal residual disease (MRD). Together, the designations enable more frequent FDA engagement and support an efficient development and review process. Cema-cel is an investigational allogeneic CAR T product being studied in the pivotal ALPHA3 trial as part of 1L treatment for patients with LBCL who are at high risk of relapse. The ALPHA3 trial uses Natera's CLARITY ™ MRD assay, which is powered by its phased variant MRD technology, to identify patients in remission but who are likely to experience disease recurrence following completion of 1L chemoimmunotherapy. Patients who test positive for MRD are enrolled and assigned to receive either a single dose of cema-cel or close observation, the current standard of care, with outcomes compared between the two groups. “The FDA’s decision to grant both RMAT and Fast Track designations provides additional validation for the strategy we defined with the ALPHA3 trial and strengthens our ability to work closely with the agency on an efficient path to advance cema-cel as a first-line consolidation therapy for large B-cell lymphoma,” said Zachary Roberts, M.D., Ph.D., President and Chief Executive Officer of Allogene Therapeutics. “There is a shared goal across the treatment community to reach patients earlier in their disease course and reduce the barriers that limit access to CAR T therapy. The interim ALPHA3 findings, which showed rapid and substantial MRD reduction, with most patients treated in the outpatient setting, support cema-cel’s potential as an off-the-shelf therapy that can be delivered at scale in community settings where approximately 80% of first-line patients receive their care.” The FDA granted RMAT designation for cema-cel as 1L consolidation therapy for patients with high-risk LBCL following full review of the interim futility analysis from the ongoing ALPHA3 trial, underscoring the continued need for new treatment options. At the protocol-defined data cutoff, triggered when the 24 th patient enrolled in the ongoing study arms completed the Day 45 MRD assessment, 58.3% (7/12) of patients in the cema-cel arm achieved MRD negativity compared to 16.7% (2/12) in the observation arm. This represents a 41.6% absolute difference in MRD clearance between the two arms. Published literature and cross-study benchmarks suggest that MRD clearance differences of 25-30% may lead to clinically meaningful improvement at study completion. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Cema-cel was well-tolerated as of the data cutoff with no treatment-related serious adverse events. There were no cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), graft-versus-host disease (GvHD) or high-grade infections. No tocilizumab or steroids were administered for toxicity prophylaxis or treatment, and no patients were hospitalized for treatment-related adverse events. This pro favorably with the broader CAR T experience, where hospitalization for toxicity management remains common. Regenerative Medicine Advanced Therapy (RMAT) designation is intended to expedite the development and review of regenerative medicine therapies intended to treat, modify, or cure a serious or life-threatening disease or conditions when preliminary clinical evidence indicates the therapy has the potential to address an unmet medical need for that disease or condition. Fast Track designation further supports expedited development and review, including potential eligibility for rolling review and priority review, if relevant criteria are met. About Allogene Therapeutics Allogene 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 and autoimmune disease. Led by cell therapy veterans applying proven CAR T experience, Allogene is developing a pipeline of off-the-shelf CAR T cell 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 , and follow Allogene Therapeutics on X and LinkedIn. Cautionary Note on Forward-Looking Statements for Allogene This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as “anticipate,” “expect,” “believe,” “aim,” “plan,” “goal,” “intend,” “seek,” “estimate,” “target,” “potential,” “may,” “could,” “will,” “would,” “should,” “designed to,” “suggest,” “support,” “enable,” “possible” and similar expressions to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the potential benefits and regulatory implications of the RMAT and Fast Track designations for cema-cel, including enhanced FDA engagement, an efficient or expedited development and review process, and potential eligibility for rolling review or priority review; the ongoing pivotal Phase 2 ALPHA3 trial and the potential for the trial or its results to support the advancement or regulatory approval of cema-cel; the potential clinical benefits, safety, tolerability, durability and efficacy of cema-cel, including its potential to transform treatment and enable earlier intervention for patients with LBCL who are at high risk of relapse; the interpretation and predictive value of the interim futility analysis and the reported MRD clearance and plasma ctDNA results, including whether the observed differences or literature-based benchmarks will translate into clinically meaningful improvement or improved clinical outcomes at study completion; the ability of Natera’s CLARITY™ MRD assay to identify patients who are likely to experience disease recurrence following first-line treatment; cema-cel’s potential as an off-the-shelf therapy that can be delivered at scale in outpatient and community settings and broaden patient access to CAR T therapy; comparisons of cema-cel’s safety, tolerability and outpatient administration pro the broader CAR T experience; and Allogene’s ability to develop and deliver readily available allogeneic CAR T products on-demand, more reliably and at greater scale to more patients. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, but not limited to: risks and uncertainties inherent in clinical development, including that interim or early data from a small number of patients may not be predictive of later or final results and may change as additional patients are enrolled and followed; uncertainties related to MRD and ctDNA testing and their clinical significance, reliability and ability to predict clinical outcomes, including whether MRD clearance will translate into improvements in event-free survival or other clinical endpoints; limitations of comparisons to published literature, cross-study benchmarks or other CAR T therapies; the occurrence of adverse safety events; patient enrollment and trial execution risks; regulatory risks and uncertainties, including that RMAT or Fast Track designation does not ensure expedited development or review or regulatory approval and that the FDA may disagree with Allogene’s clinical or regulatory plans, interpretation of results or proposed development pathway or may require additional data or trials; risks related to the development, regulatory approval and performance of the CLARITY™ MRD assay; manufacturing and CMC risks; reliance on third parties and licensors; competitive developments; intellectual property and contractual risks; and financial risks, including the need for additional capital. These and other risks and uncertainties are described more fully in Allogene’s filings with the SEC, including under the heading “Risk Factors” in its Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 12, 2026, and its Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the SEC on May 13, 2026, and other filings that Allogene may make from time to time with the SEC. All forward-looking statements in this press release speak only as of the date of this press release, and Allogene undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Allogene’s investigational AlloCAR T oncology products utilize Cellectis technologies. Cemacabtagene ansegedleucel (cema-cel) was developed based on an exclusive license granted by Cellectis to Servier. Servier has granted Allogene exclusive rights to cema-cel in the U.S., all EU Member States and the United Kingdom. Allogene Media/Investor Contact: Christine Cassiano EVP, Chief Corporate Affairs & Brand Strategy Officer Christine.Cassiano@allogene.com

一、类风湿关节炎不止伤关节，肺病才是隐形致命威胁 类风湿关节炎（RA）大家熟知的表现是关节肿痛、变形，但很多患者不知道：类风湿关节炎相关间质性肺病（RA-ILD） 是该病最严重的关节外并发症，也是类风湿患者主要死亡原因之一。 简单来说，自身免疫紊乱不仅攻击关节，还持续损伤肺部肺泡之间的间质组织，造成肺部慢性炎症、纤维化。早期仅有干咳、活动后气短，极易当成支气管炎；等到出现持续缺氧、呼吸困难时，肺部已经发生不可逆硬化，失去气体交换功能，治疗难度大幅上升。 目前临床针对 RA - 缺乏统一最优治疗方案，两种主流生物制剂托珠单抗（IL-6 受体抑制剂）、利妥昔单抗（抗 CD20 单抗） 都被广泛用于控制自身免疫肺部损伤，但二者疗效、安全性一直缺少头对头对比。2026 年《Chest》杂志发表一项模拟目标临床试验研究，直接对比两种药物治疗 RA-ILD 的真实效果，给临床和患者提供清晰选择依据。二、研究背景：两种药作用机制完全不同1. 利妥昔单抗 靶向清除体内产生自身抗体的 B 淋巴细胞，从源头减少攻击肺、关节的自身抗体，长期用于难治类风湿、各类自身免疫性肺病，是传统一线免疫抑制药物。2. 托珠单抗 阻断 IL-6 炎症通路，IL-6 是驱动关节炎症、肺部间质纤维化的核心细胞因子，既能快速缓解关节肿痛，也可抑制肺部慢性炎症，近年在间质性肺病中应用越来越多。 过往小样本临床观察各有优劣，缺少大样本真实世界数据直接对比，这项发表于国际呼吸顶刊《Chest》的研究填补了空白。三、研究核心设计 这项模拟目标试验，严格模拟随机对照试验逻辑，筛选真实临床大样本类风湿合并间质性肺病患者，匹配基线年龄、病程、肺部损伤程度、关节活动度、既往用药、吸烟史等混杂因素，消除个体差异干扰，客观对比托珠单抗与利妥昔单抗两类人群的长期肺部预后、关节控制、不良反应。四、核心研究结论（通俗解读）肺部病情稳定、延缓纤维化进展方面 两种药物均能有效抑制肺部间质炎症，减缓肺功能（DLCO、肺活量）下降速度，无显著整体优劣差异。对于轻中度 RA-ILD，两种药物都能稳定肺部 CT 磨玻璃、网格病变，阻止肺部持续纤维化。关节炎症控制差异 托珠单抗抑制 IL-6 通路，针对类风湿关节肿胀、疼痛、晨僵起效更快，短期关节改善优于利妥昔单抗；利妥昔单抗清除 B 细胞，长期免疫抑制作用更持久，适合反复发作、多重抗体阳性的难治类风湿。安全性区分 利妥昔单抗：B 细胞清除后体液免疫下降，感染风险（尤其是肺部、呼吸道感染）相对更高，用药后需定期复查免疫球蛋白； 托珠单抗：感染风险更低，但更容易出现血脂升高、肝功能轻度异常，用药期间需定期监测肝功、血脂指标。适用人群分层 优先选托珠单抗：以关节肿痛为主要困扰、轻中度肺损伤、反复呼吸道感染病史、基础免疫力偏弱患者； 优先选利妥昔单抗：多重自身抗体强阳性、重度难治类风湿、托珠单抗治疗效果不佳、快速进展型肺纤维化患者。五、类风湿间质性肺病患者用药选择指南1 初诊轻中度 RA-ILD 无反复感染、关节疼痛明显：优先托珠单抗，快速控制关节同时稳定肺部，定期监测肝功能、血脂。 反复肺炎、低免疫球蛋白：优先利妥昔单抗，长期稳定自身免疫，每半年复查 IgG 免疫球蛋白水平。2 快速进展重度 RA-ILD（CT 纤维化持续加重、肺功能快速下降） 优先利妥昔单抗，更强的长期免疫抑制，延缓肺部硬化进程；若使用后关节仍持续活动，可联合 IL-6 通路抑制剂协同治疗。3 合并基础疾病人群 慢阻肺、反复呼吸道感染：避开利妥昔单抗，选择托珠单抗降低感染风险； 脂肪肝、高血脂人群：优先利妥昔单抗，减少托珠单抗带来的血脂、肝损伤副作用； 老年体弱患者：首选托珠单抗，整体耐受度更好。六、重要提醒：药物选择不能自行决定 RA-ILD 属于风湿 + 呼吸跨学科疾病，用药前必须完善高分辨胸部 CT、全套肺功能（含弥散 DLCO）、类风湿抗体、免疫球蛋白、肝肾功能全套评估； 两种生物制剂均存在输液 / 皮下注射相关不良反应，首次用药需在医院监护下完成； 用药期间定期复查：肺部 CT（6~12 个月一次）、肺功能、炎症指标、免疫、生化； 无论使用哪种药物，出现干咳加重、活动喘憋、发热、咳痰，需立即就医排查肺部感染或肺病进展。七、总结 这项发表于权威呼吸期刊《Chest》的对比研究明确：托珠单抗和利妥昔单抗均可有效治疗类风湿关节炎相关间质性肺病，肺部保护效果总体相当，二者选择核心取决于关节症状轻重、个人感染风险、基础脏器功能。 关节症状突出、易感冒肺炎的患者更适合托珠单抗；重度难治类风湿、快速进展肺纤维化人群更推荐利妥昔单抗。患者切勿自行换药、停药，需由风湿科联合呼吸科医生综合肺部、关节、全身情况个体化制定治疗方案，在保护关节的同时守住肺部健康。