THOUSAND OAKS, Calif.--(BUSINESS WIRE)--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 preclinical data on ATA3431, a next-generation allogeneic CD20/CD19-dual targeted chimeric antigen receptor (CAR) EBV T-cell therapy candidate.

加利福尼亚州千橡树市（商业新闻短讯）--T细胞免疫疗法的领导者Atara Biotherapeutics，Inc.（纳斯达克：ATRA），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，今天宣布了ATA3431的临床前数据，下一代同种异体CD20/CD19双靶向嵌合抗原受体（CAR）EBV T细胞治疗候选物。

Findings support ATA3431 advancement into clinical testing, initially focused on the treatment of B-cell malignancies. The data will be presented in a poster presentation at the 65th American Society of Hematology (ASH) Annual Meeting taking place December 9-12, 2023, in San Diego..

研究结果支持ATA3431进入临床测试，最初专注于B细胞恶性肿瘤的治疗。这些数据将在2023年12月9日至12日于圣地亚哥举行的第65届美国血液学会（ASH）年会上以海报形式呈现。。

“We’re very excited that ATA3431 is progressing towards an IND submission in 2025 with such a compelling and competitive profile,” said Cokey Nguyen, Ph.D., Executive Vice President, Chief Scientific & Technical Officer at Atara. “Our EBV T-cell technology is well validated with over 500 patients treated across our portfolio, and allogeneic EBV T-cell based CD19 targeting is further supported by long-term academic outcomes data with an earlier-generation allogeneic EBV CD19 T-cell construct.1 Building on this robust experience, these preclinical findings provide strong proof-of-concept reinforcing the potential of ATA3431 as a best-in-class approach which we look forward to further evaluating in the clinic.”.

Atara执行副总裁兼首席科学技术官Cokey Nguyen博士说：“我们非常高兴ATA3431正在2025年提交IND，具有如此引人注目和竞争优势。”。“我们的EBV T细胞技术在我们的投资组合中得到了500多名患者的充分验证，基于同种异体EBV T细胞的CD19靶向进一步得到了早期同种异体EBV CD19 T细胞构建的长期学术成果数据的支持。1基于这一强大的经验，这些临床前发现提供了强有力的概念证明，增强了ATA34的潜力31作为一种一流的方法，我们期待在临床上进一步评估。”。

ATA3431 is an allogeneic, bispecific CAR directed against CD20 and CD19, built on Atara’s EBV T-cell platform that does not require T-cell receptor (TCR) or human leukocyte antigen (HLA) gene editing. The design consists of a tandem CD20-CD19 design, with binders oriented to optimize potency. ATA3431 also incorporates the clinically validated 1XX costimulatory domain that enhances stemness and modulates exhaustion to extend functional persistence..

ATA3431是一种针对CD20和CD19的同种异体双特异性CAR，建立在Atara的EBV T细胞平台上，不需要T细胞受体（TCR）或人类白细胞抗原（HLA）基因编辑。该设计由串联CD20-CD19设计组成，粘合剂旨在优化效力。ATA3431还结合了临床验证的1XX共刺激结构域，该结构域可增强干性并调节衰竭以延长功能持久性。。

Compared to an autologous CD20/CD19 CAR-T benchmark, the ATA3431 preclinical data demonstrate potent antitumor activity, long-term persistence, and superior tumor growth inhibition. Data highlights include:

与自体CD20/CD19 CAR-T基准相比，ATA3431临床前数据显示出有效的抗肿瘤活性，长期持久性和优异的肿瘤生长抑制作用。数据亮点包括：

In functional evaluation, ATA3431 showed stable CAR expression with a predominantly CD8+ T-cell distribution. The 1XX signaling domain and optimized manufacturing process that enriches for a less differentiated phenotype yielded a high central memory population compared with autologous CD20/CD19 bispecific CAR-T cells, achieving consistent killing of CD20+ and/or CD19+ tumor cells following repeated in vitro challenges..

在功能评估中，ATA3431显示出稳定的CAR表达，主要是CD8+T细胞分布。与自体CD20/CD19双特异性CAR-T细胞相比，1XX信号传导结构域和优化的制造过程丰富了分化程度较低的表型，产生了较高的中枢记忆群体，在反复体外挑战后实现了CD20+和/或CD19+肿瘤细胞的一致杀伤。。

ATA3431 demonstrated minimal alloreactivity against HLA mismatched targets due to the inherent ability of EBV T cells to recognize defined viral antigens. The cells also showed HLA-independent activity against CD20+/CD19+ targets in vitro.

由于EBV T细胞识别确定的病毒抗原的固有能力，ATA3431显示出对HLA错配靶标的最小同种异体反应性。细胞在体外还显示出针对CD20+/CD19+靶标的HLA非依赖性活性。

ATA3431 mediated highly potent tumor growth inhibition in a lymphoma animal model that correlates with long-term persistence without additional exogenous cytokine support.

ATA3431在淋巴瘤动物模型中介导了高度有效的肿瘤生长抑制，该模型与长期持续性相关，而无需额外的外源性细胞因子支持。

ATA3431 showed superior in vivo anti-tumor efficacy, survival, and functional persistence, in both CD19 high- and low-expressing lymphoma models, compared to autologous benchmark CAR-T cells with no observed treatment-related toxicities. This demonstrates ATA3431’s potential to overcome antigen escape, which is hypothesized to be a major cause of treatment resistance or disease relapse with current CD19-targeted CAR-T treatment..

与没有观察到治疗相关毒性的自体基准CAR-T细胞相比，ATA3431在CD19高表达和低表达淋巴瘤模型中均显示出优异的体内抗肿瘤功效，存活率和功能持久性。这证明了ATA3431克服抗原逃逸的潜力，这被认为是目前针对CD19的CAR-T治疗产生治疗耐药性或疾病复发的主要原因。。

Separately, an academic study presented long-term follow-up data on heavily pre-treated patients infused with an earlier generation off-the-shelf CD19 targeted EBV CAR T-cell construct in B-cell lymphoma and acute lymphoblastic leukemia. Encouraging overall survival of up to three years was observed in 12 patients with relapsed/refractory B-cell malignancies after hematopoietic cell transplant (HCT) treated with 3rd party donor derived allogeneic EBV CD19 CAR T.1.

另外，一项学术研究提供了关于在B细胞淋巴瘤和急性淋巴细胞白血病中注入早期现成CD19靶向EBV CAR T细胞构建体的重度预处理患者的长期随访数据。在用第三方供体来源的同种异体EBV CD19 CAR T.1治疗的造血细胞移植（HCT）后，12例复发/难治性B细胞恶性肿瘤患者的总生存期长达三年。

ATA3431 Poster Presentation Details:

ATA3431海报展示详情：

Title: ATA3431: Allogeneic CD19/CD20 Bispecific CAR EBV T-cells for the Treatment of B-Cell Malignancies

标题：ATA3431：用于治疗B细胞恶性肿瘤的同种异体CD19/CD20双特异性CAR EBV T细胞

Presenting Author: Seung Sarah Cha, PhD, Atara Biotherapeutics, Thousand Oaks, CA

演示作者：Seung Sarah Cha，博士，Atara Biotherapeutics，千橡树，加利福尼亚州

Date & Time: Monday, December 11, 2023, 6-8 p.m. PST

日期和时间：2023年12月11日星期一，太平洋标准时间下午6-8点

Abstract Number: 4800

摘要编号：4800

Poster Session: 703. Cellular Immunotherapies: Basic and Translational: Poster III

海报环节：703。细胞免疫疗法：基础和翻译：海报III

Location: San Diego Convention Center, Halls G-H

地点：圣地亚哥会议中心G-H厅

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 500 patients treated, 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500多名接受治疗的患者的经验，以及新型嵌合抗原受体（CAR）技术，通过推进肿瘤学和自身免疫性疾病领域潜在的同类最佳CAR-T管道，迎头赶上自体和同种异体CAR疗法的当前局限性。

Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, EBV T cells maintain expression of native TCRs 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，EBV T细胞维持天然TCR的表达，其促进体内功能持久性，同时还表现出固有的低同种异体反应性，因为它们识别确定的病毒抗原和部分人类白细胞抗原（HLA）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, including multiple sclerosis, that can be rapidly delivered to patients within days. 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，包括多发性硬化症，这些疾病可以在几天内迅速传递给患者。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 Epstein-Barr virus (EBV) 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 non-EBV-associated liquid and solid tumors.

我们先进而通用的爱泼斯坦-巴尔病毒（EBV）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，此外还有下一代AlloCAR Ts，专为广泛的非EBV相关液体和实体肿瘤提供一流的机会。

Atara is headquartered in Southern California. For more information, visit atarabio.com and follow @Atarabio on X (formerly known as Twitter) and LinkedIn..

阿塔拉总部位于南加州。有关更多信息，请访问atarabio.com并关注X（以前称为Twitter）和LinkedIn上的@atarabio。。

Forward-Looking Statements

前瞻性声明

This press release contains or may imply 'forward-looking statements' within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding the development, timing and progress of Atara’s AlloCAR-T programs, including preclinical data for ATA3431, the potential characteristics and benefits of ATA3431, and a potential IND submission for ATA3431.

本新闻稿包含或可能暗示1933年《证券法》第27A节和1934年《证券交易法》第21E节所指的“前瞻性声明”。例如，前瞻性声明包括有关Atara AlloCAR-T计划的开发，时间和进展的声明，包括ATA3431的临床前数据，ATA3431的潜在特征和益处，以及ATA3431的潜在IND提交。

Because such statements deal with future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release.

由于此类声明涉及未来事件，并基于Atara当前的预期，因此会面临各种风险和不确定性，Atara的实际结果、业绩或成就可能与本新闻稿中所述或暗示的结果、业绩或成就存在重大差异。

These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic and the wars in Ukraine and the Middle East, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in Southern California and Denver and at our clinical trial sites, as well as the business or operations of our third-party manufacturer, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital, and (iii) the value of our common stock; the sufficiency of Atara’s cash resources and need for additional capital; and other risks and uncertainties affecting Atara’s and its development programs, including those discussed in Atara’s filings with the Securities and Exchange Commission , including in the “Risk Factor.

这些前瞻性陈述具有风险和不确定性，包括但不限于与昂贵且耗时的药品开发过程相关的风险和不确定性以及临床成功的不确定性；新型冠状病毒（COVID-19）大流行以及乌克兰和中东的战争可能会对（i）我们的业务、研究、临床开发计划和运营产生重大影响，包括我们在南加州和丹佛以及我们的临床试验地点的运营，以及我们第三方制造商的业务或运营，与我们开展业务的合同研究机构或其他第三方，（ii）我们获取资本的能力，以及（iii）我们普通股的价值；Atara现金资源充足且需要额外资本；以及影响Atara及其发展计划的其他风险和不确定性，包括Atara向证券交易委员会提交的文件中讨论的风险和不确定性，包括“风险因素”。

1Shahid, S, et al. Long Term Follow-up after Treatment with Allogeneic Off-the-Shelf CAR T Cell Therapy for Relapsed or Refractory B-Cell Malignancies. Poster presented at American Society of Hematology; December, 11 2023; San Diego, CA.

1Shahid，S等人。用同种异体现成CAR T细胞治疗复发或难治性B细胞恶性肿瘤后的长期随访。海报在美国血液学会展出；2023年12月11日；加利福尼亚州圣地亚哥。