Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today announced the U.S.

T细胞免疫疗法的领导者阿塔拉生物治疗公司（Nasdaq:ATRA）今天宣布，利用其新型同种异体爱泼斯坦-巴尔病毒（EBV）T细胞平台为癌症和自身免疫性疾病患者开发转化疗法。

Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for ATA3219, an allogeneic, anti-CD19 chimeric antigen receptor (CAR) T-cell monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]).

美国食品和药物管理局（FDA）已批准ATA3219的研究性新药（IND）申请，ATA3219是一种同种异体抗CD19嵌合抗原受体（CAR）T细胞单一疗法，用于治疗系统性红斑狼疮（SLE）肾脏受累（狼疮性肾炎[LN]）。

“Expanding upon an extensive clinical experience encompassing the treatment of over 600 patients using our allogeneic T-cell platform in both oncology and autoimmune diseases, we are excited to clinically evaluate the potential of our differentiated allogeneic CAR T-cell approach. We are eager to address the significant unmet need in lupus nephritis as we initiate our Phase 1 trial,” said Pascal Touchon, President and Chief Executive Officer of Atara.

“我们拥有丰富的临床经验，包括在肿瘤学和自身免疫性疾病中使用我们的同种异体T细胞平台治疗600多名患者，我们很高兴能够临床评估我们分化的同种异体CAR T细胞方法的潜力。在我们启动1期试验时，我们渴望解决狼疮性肾炎尚未满足的重大需求。”Atara总裁兼首席执行官PascalTouchon表示。

“We look forward to bringing the promise and accessibility of a potentially curative off-the-shelf cell therapy option to patients with severe autoimmune diseases, potentially eliminating the burdens of autologous CAR T therapies like costly infrastructure and treatment delays.”

“我们期待着为患有严重自身免疫性疾病的患者带来潜在治愈性现成细胞治疗选择的希望和可获得性，从而有可能消除自体CAR T治疗的负担，如昂贵的基础设施和治疗延迟。”

The multi-center, Phase 1, open-label, single-arm, dose-escalation study will evaluate the safety and preliminary efficacy of ATA3219 in subjects with LN. Subjects will receive lymphodepletion treatment followed by ATA3219 at a dose of 40, 80, or 160 x 106 CAR+ T cells. ATA3219 is designed to be given as a one-time infusion and followed for safety and efficacy.

多中心，第一阶段，开放标签，单臂，剂量递增研究将评估ATA3219在LN受试者中的安全性和初步疗效。受试者将接受淋巴清除治疗，然后接受剂量为40、80或160 x 106 CAR+T细胞的ATA3219。ATA3219旨在一次性输注，并遵循安全性和有效性。

Each dose level is designed to enroll 3-6 patients, with the first subject expected to be enrolled in the second half of 2024.

每个剂量水平旨在招募3-6名患者，第一名受试者预计将于2024年下半年入选。

“Existing therapeutic agents for lupus nephritis yield suboptimal responses and have limitations due to their requirement for ongoing administration, susceptibility to treatment failures, and limited accessibility to inflamed tissues resulting in incomplete depletion of B cells,” said Rajani Dinavahi, Chief Medical Officer at Atara.

Atara首席医疗官拉贾尼·迪纳瓦希（RajaniDinavahi）说：“现有的狼疮性肾炎治疗药物反应不佳，并且由于需要持续给药，易受治疗失败的影响，以及对发炎组织的可及性有限，导致B细胞不完全消耗，因此存在局限性。”

“CAR T cells can naturally infiltrate deep into target tissues to mediate B-cell depletion and produce durable responses. Building on the encouraging academic data in lupus nephritis with autologous CD19 CAR T, ATA3219 is an off-the-shelf therapy that could significantly reduce constraints for patients and physicians like leukapheresis and long waiting times, therefore potentially improving access to a large population of patients.”

“CAR T细胞可以自然深入靶组织，介导B细胞耗竭并产生持久的反应。基于自体CD19 CAR T在狼疮性肾炎中令人鼓舞的学术数据，ATA3219是一种现成的疗法，可以显着减少患者和医生的限制，如白细胞分离术和长时间等待，因此有可能改善access给大量患者。”

Proof of concept for a CD19 CAR T approach in autoimmune disease was first demonstrated in early academic results from an investigator-sponsored study showing 100% (8/8) of LN patients rapidly attaining drug-free, durable remission with an autologous CD19-targeted CAR T therapy. The therapy eliminated the pathogenic, autoreactive B cells and allowed healthy B cells to return after treatment, enabling the patients’ immune system to function normally again with associated improvement of clinical symptoms.1 These early proof of concept clinical data with CD19 targeted CAR T support further development of CAR T for LN with differentiated and off-the-shelf allogeneic approaches.

CD19 CAR T方法在自身免疫性疾病中的概念验证首先在研究者赞助的一项研究的早期学术结果中得到证实，该研究显示100%（8/8）的LN患者通过自体CD19靶向CAR T治疗迅速获得无药物，持久缓解。该疗法消除了致病性，自身反应性B细胞，并使健康的B细胞在治疗后恢复，使患者的免疫系统再次正常工作，并伴有临床症状的改善。这些以CD19为靶点的CAR T的早期概念验证临床数据支持通过分化和现成的同种异体方法进一步开发用于LN的CAR T。

The ATA3219 IND submission included in vitro data reflecting the CD19 antigen-specific functional activity of ATA3219 and CAR-mediated activity against B cells from SLE patients. ATA3219 led to robust CD19-specific B-cell depletion compared to controls.

ATA3219 IND提交的体外数据反映了ATA3219的CD19抗原特异性功能活性和CAR介导的针对SLE患者B细胞的活性。与对照组相比，ATA3219导致强大的CD19特异性B细胞耗竭。

LN is a serious and most common complication of SLE, a chronic multisystem autoimmune disease. The prevalence of SLE in the U.S. is 73 per 100,000 people, afflicting more than 200,000 U.S. patients alone, and occurs in women much more commonly than men. Up to 60% of adult patients with SLE develop renal disease during the course of their illness, and up to 70% of patients with LN are refractory to standard immunosuppressive therapies.

LN是SLE（一种慢性多系统自身免疫性疾病）的严重且最常见的并发症。在美国，SLE的患病率为每10万人中有73人，仅在美国就有20多万患者患病，女性比男性更常见。高达60%的成年SLE患者在患病过程中会发生肾脏疾病，而高达70%的LN患者对标准免疫抑制疗法无效。

Despite recent advances in treatment strategies, the response rate using existing therapies remains low, with significant risk of long-term morbidity and mortality associated with refractory LN.

尽管治疗策略取得了最新进展，但使用现有疗法的缓解率仍然很低，与难治性LN相关的长期发病率和死亡率风险很大。

About ATA3219

关于ATA3219

ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]).

ATA3219将未经编辑的T细胞的自然生物学与同种异体疗法的益处相结合。它由同种异体爱泼斯坦-巴尔病毒（EBV）致敏的T细胞组成，表达CD19 CAR构建体，用于治疗CD19+复发或难治性B细胞恶性肿瘤，包括B细胞非霍奇金淋巴瘤和B细胞介导的自身免疫性疾病，包括系统性红斑狼疮（SLE）伴肾脏受累（狼疮性肾炎[LN]）。

ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence.

ATA3219经过优化，提供了一个潜在的同类最佳配置文件，具有现成的可用性。它结合了多种经过临床验证的技术，包括改良的CD3ζ信号传导结构域（1XX），该结构域可优化扩增并减轻衰竭，在制造过程中富集，以获得分化程度较低的表型，从而实现强大的扩增和持久性，并保留内源性T细胞受体，而无需基因编辑作为T细胞持久性的关键生存信号。

Next-Generation Allogeneic CAR T Approach

下一代同种异体CAR T方法

Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease.

Atara专注于应用爱泼斯坦-巴尔病毒（EBV）T细胞生物学，拥有600多名接受同种异体EBV T细胞治疗的患者的经验，以及新型嵌合抗原受体（CAR）技术，以满足目前自体和同种异体CAR治疗的局限性。通过推进肿瘤学和自身免疫性疾病领域潜在的一流CAR T管道，迎头赶上。

Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promote in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching.

与旨在灭活T细胞受体（TCR）功能以降低移植物抗宿主病风险的基因编辑方法不同，Atara的同种异体平台维持了天然EBV TCR的表达，从而促进了体内功能的持久性，同时由于识别了确定的病毒抗原和部分人类白细胞抗原（HLA），也表现出固有的低同种异体反应性匹配。

A molecular toolkit of clinically-validated technologies—including the 1XX costimulatory domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T.

临床验证技术的分子工具包，包括1XX共刺激结构域，旨在改善细胞适应性和减少疲劳，同时保持干性，为解决下一代CAR T的重大未满足需求提供了一种不同的方法。

About Atara Biotherapeutics, Inc.

关于Atara Biotherapeutics，Inc。

Atara is harnessing the natural power of the immune system to develop off-the-shelf cell therapies for difficult-to-treat cancers and autoimmune conditions that can be rapidly delivered to patients from inventory. With cutting-edge science and differentiated approach, Atara is the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy.

Atara正在利用免疫系统的天然力量开发现成的细胞疗法，用于治疗难以治疗的癌症和自身免疫性疾病，这些疾病可以从库存中快速传递给患者。凭借尖端科学和差异化方法，Atara是世界上第一家获得同种异体T细胞免疫疗法监管批准的公司。

Our advanced and versatile T-cell platform does not require T-cell receptor or HLA gene editing and forms the basis of a diverse portfolio of investigational therapies that target EBV, the root cause of certain diseases, in addition to next-generation AlloCAR-Ts designed for best-in-class opportunities across a broad range of hematological malignancies and B-cell driven autoimmune diseases.

我们先进且多功能的T细胞平台不需要T细胞受体或HLA基因编辑，并且形成了针对EBV（某些疾病的根本原因）的多种研究疗法组合的基础，此外还设计了下一代AlloCAR Ts，用于在广泛的血液恶性肿瘤和B细胞驱动的自身免疫性疾病中获得最佳机会。

Atara is headquartered in Southern California.

阿塔拉总部位于南加州。