GAITHERSBURG, Md., July 02, 2024 (GLOBE NEWSWIRE) -- Cartesian Therapeutics, Inc. (NASDAQ: RNAC) (“Cartesian” or the “Company”), a clinical-stage biotechnology company pioneering mRNA cell therapy for autoimmune diseases, today announced positive topline results from its Phase 2b trial of Descartes-08 in patients with generalized myasthenia gravis (MG)..

马里兰州盖瑟斯堡，2024年7月2日（环球通讯社）--Cartesian Therapeutics，Inc.（纳斯达克：RNAC）（“Cartesian”或“公司”），一家临床阶段的生物技术公司，开创了针对自身免疫性疾病的mRNA细胞疗法，今天宣布了其对全身性重症肌无力（MG）患者进行的笛卡尔-08 2b期试验的阳性结果。。

Descartes-08, Cartesian’s lead product candidate, is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) directed against the B cell maturation antigen (BCMA). It is designed to be administered as an outpatient treatment without the need for lymphodepleting chemotherapy required to achieve activity with conventional CAR-T cell therapies.

笛卡尔的主要候选产品Descartes-08是针对B细胞成熟抗原（BCMA）的自体mRNA工程嵌合抗原受体T细胞疗法（mRNA CAR-T）。它被设计为作为门诊治疗，不需要使用常规CAR-T细胞疗法实现活性所需的淋巴消耗化疗。

Descartes-08 was previously granted Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of MG..

Descartes-08之前被美国食品和药物管理局（FDA）授予再生医学高级治疗（RMAT）称号和孤儿药称号，用于治疗MG。。

“We believe the positive data presented today demonstrate clinical proof-of-concept of our novel mRNA platform and highlight the potential of Descartes-08 to provide deep and durable improvements for patients with MG,” said Carsten Brunn, Ph.D., President and Chief Executive Officer of Cartesian. “Our recently granted RMAT designation supports the continued development of Descartes-08 in collaboration with the FDA, with plans to hold an End-of-Phase 2 meeting by the end of the year.

Cartesian总裁兼首席执行官Carsten Brunn博士说：“我们相信今天提供的积极数据证明了我们新型mRNA平台的临床概念验证，并突出了笛卡尔08为MG患者提供深度和持久改善的潜力。”。“我们最近获得的RMAT指定支持与FDA合作继续开发Descartes-08，并计划在年底前举行第二阶段会议。

The results also exemplify what we hope to obtain with other assets in our existing and future pipeline.”.

这些结果也证明了我们希望通过现有和未来管道中的其他资产获得什么。”。

“MG is a devastating, rare autoimmune disorder with high unmet need for short-course treatments. The current standard of care, chronic use of steroids and other immunosuppressants, is often associated with broad immunosuppression and limited efficacy,” said Tahseen Mozaffar, M.D., Professor of Neurology, Pathology and Laboratory Medicine, Director of the Division of Neuromuscular Diseases and Director of the ALS and Neuromuscular Center at the University of California, Irvine.

“MG是一种破坏性的罕见自身免疫性疾病，短期治疗需求很高。目前的护理标准，长期使用类固醇和其他免疫抑制剂，通常与广泛的免疫抑制和有限的疗效有关，”加州大学欧文分校神经病学、病理学和检验医学教授、神经肌肉疾病司司长兼ALS和神经肌肉中心主任Tahseen Mozaffer医学博士说。

“The durable improvements observed across all disease severity scales, the average of which was approximately three times greater than what is considered clinically meaningful, firmly support the potential for Descartes-08 to serve as an important new therapy for patients with MG that can be administered safely in the outpatient setting.

“在所有疾病严重程度量表中观察到的持久改善，其平均值大约是临床意义的三倍，有力地支持了笛卡尔-08作为MG患者的重要新疗法的潜力，可以在门诊安全管理。

I look forward to participating in its continued development.”.

我期待着参与其持续发展。”。

Trial Overview and Topline Results

试验概述和最终结果

In the Phase 2b double-blind, placebo-controlled, crossover trial, a total of 36 heavily pre-treated, highly symptomatic patients with MG were randomized 1:1 to receive either Descartes-08 or placebo administered as six weekly outpatient infusions without preconditioning chemotherapy. At the conclusion of the trial’s Month 3 blinded follow-up assessment, patients receiving placebo were eligible to cross over to Descartes-08 treatment..

在2b期双盲，安慰剂对照，交叉试验中，共有36名重度预处理，高度症状的MG患者被随机分配1:1，接受笛卡尔-08或安慰剂治疗，每六周门诊输注一次，无需预处理化疗。在试验的第3个月盲法随访评估结束时，接受安慰剂的患者有资格接受笛卡尔-08治疗。。

The primary efficacy endpoint assessed the proportion of patients with a reduction of five points or more in the MG Composite (MGC) score, a 10-item, 60-point weighted instrument composed of selected components of other validated scales to measure MG severity and impact. Whereas a reduction of three points or more is generally regarded as clinically meaningful, the more stringent endpoint of five points was selected based on clinical responses observed in an earlier study with Descartes-08 in MG.

。尽管减少三分或更多通常被认为具有临床意义，但根据早期使用Descartes-08在MG中观察到的临床反应，选择了更严格的五分终点。

Secondary endpoints assessed safety and tolerability and other validated MG severity scales, including Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and MG Quality of Life Revised Scale (MG-QoL-15R)..

次要终点评估了安全性和耐受性以及其他经过验证的MG严重程度量表，包括日常生活活动（MG-ADL），定量MG（QMG）和MG生活质量修订量表（MG-QoL-15R）。。

The pre-specified primary efficacy dataset (n=26) consisted of a modified intent-to-treat (mITT) population of all subjects enrolled at academic medical centers who received at least one dose of Descartes-08 (n=14) or placebo (n=12) and completed at least one post-baseline MGC score follow-up assessment.

预先指定的主要疗效数据集（n=26）由在学术医学中心登记的所有受试者的改良意向治疗（mITT）人群组成，这些受试者接受了至少一剂笛卡尔-08（n=14）或安慰剂（n=12），并完成了至少一次基线后MGC评分随访评估。

The safety dataset comprised all subjects who received at least one dose of Descartes-08 (n=19) or placebo (n=17)..

安全数据集包括接受至少一剂笛卡尔-08（n=19）或安慰剂（n=17）的所有受试者。。

Primary Endpoint

主要终点

The trial achieved its primary endpoint with statistical significance in the pre-specified mITT efficacy population, with 71% (10/14) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 25% (3/12) of patients treated with placebo (p=0.018)..

该试验在预先指定的mITT疗效人群中达到了具有统计学意义的主要终点，71%（10/14）接受笛卡尔-08治疗的患者在第3个月时观察到MGC评分改善5分或更高，而安慰剂治疗的患者中有25%（3/12）（p=0.018）。。

In addition, the trial also achieved its primary endpoint with statistical significance in the per-protocol population, with 69% (11/16) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 33% (5/15) of patients treated with placebo (p=0.048)..

。。

Secondary Endpoints

次要端点

Consistent with previously reported results from the Phase 2a open-label portion of the trial, Descartes-08 responders experienced deep improvements across the MG severity scales at Month 3 (average MG-ADL = -5.6; MGC= -8.3; QMG = -5.0; QoL-15r = -7.9). The improvements seen at Month 3 persisted or further improved in patients evaluated at their Month 4 (n=5) and Month 6 (n=3) follow-up visits, as of the June 19, 2024 data cutoff date..

与之前报道的试验2a期开放标签部分的结果一致，笛卡尔-08应答者在第3个月时在MG严重程度量表上经历了深度改善（平均MG-ADL=-5.6；MGC=-8.3；QMG=-5.0；QoL-15r=-7.9）。截至2024年6月19日的数据截止日期，在第4个月（n=5）和第6个月（n=3）的随访中评估的患者在第3个月看到的改善持续或进一步改善。。

Safety Results

安全结果

Descartes-08 continues to demonstrate a favorable safety profile supporting outpatient administration without the need for lymphodepleting chemotherapy. Consistent with findings from the Phase 2a open-label portion of the trial, Descartes-08 was observed to be well tolerated, and adverse events were transient and mostly mild.

笛卡尔-08继续显示出良好的安全性，支持门诊管理，而不需要淋巴清除化疗。与试验2a期开放标签部分的结果一致，观察到笛卡尔-08耐受性良好，不良事件是短暂的，大部分是轻微的。

Notably, there were no cases of cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome..

值得注意的是，没有细胞因子释放综合征的病例，也没有免疫效应细胞相关神经毒性综合征的病例。。

Updated Phase 2a Open-Label Trial Results

更新了2a期开放标签试验结果

Cartesian today also announced positive updated results from two patients enrolled in the Phase 2a open-label portion of the trial. Both retreated patients experienced rapid improvement in clinical scores and maintained minimal symptom expression for up to one year after receiving a second treatment cycle.

Cartesian今天还宣布了两名参加试验2a期开放标签部分的患者的积极更新结果。两名接受治疗的患者在接受第二个治疗周期后，临床评分迅速改善，并在长达一年的时间内保持最小的症状表达。

The time course and magnitude of treatment response upon retreatment were similar to those seen when the patients were first treated. Four of the seven patients from the Phase 2a portion of the trial maintained clinically meaningful responses for at least one year following initial dosing..

再治疗后治疗反应的时间过程和程度与患者首次接受治疗时相似。试验2a期部分的7名患者中有4名在初次给药后至少一年内保持了临床上有意义的反应。。

The Company previously announced positive long-term follow up data from the Phase 2a trial in which Descartes-08 was administered in an outpatient setting without preconditioning chemotherapy. Durable depletion of autoantibodies and clinically meaningful improvements in MG severity scores were observed at the one-year follow-up period.

该公司之前宣布了2a期试验的长期随访数据，其中笛卡尔-08在门诊进行，无需预处理化疗。在一年的随访期间，观察到自身抗体的持续消耗和MG严重程度评分的临床意义改善。

The data were subsequently featured during an oral session at the American Society of Gene and Cell Therapy 27th Annual Meeting in May 2024..

这些数据随后在2024年5月举行的美国基因与细胞治疗学会第27届年会上的一次口头会议上发表。。

Conference Call and Webcast

电话会议和网络广播

Cartesian will host a conference call and webcast to discuss the topline results today, Tuesday, July 2, 2024 at 8:00 am ET. To access the conference call, please dial 1-877-317-6789 (toll-free) or 1-412-317-6789 (international) at least 10 minutes prior to the start time and ask to be joined into the Cartesian Therapeutics call.

Cartesian将于今天（美国东部时间2024年7月2日星期二上午8:00）主持电话会议和网络广播，讨论topline结果。要访问电话会议，请在开始时间前至少10分钟拨打1-877-317-6789（免费）或1-412-317-6789（国际），并要求加入Cartesian Therapeutics call。

The live audio webcast, along with accompanying slides, can be accessed on the Events & Presentations section of Cartesian’s website at https://ir.cartesiantherapeutics.com/news-and-events/events-presentations. A replay of the webcast will be available for a limited time following the event on Cartesian’s website..

现场音频网络广播以及随附的幻灯片可以在Cartesian网站的活动和演示部分访问，网址为https://ir.cartesiantherapeutics.com/news-and-events/events-presentations.活动结束后，Cartesian网站将在有限的时间内重播网络广播。。

Descartes-08 for Systematic Lupus Erythematosus (SLE)

笛卡尔-08治疗系统性红斑狼疮（SLE）

Today, Cartesian also announced that the first patient has been dosed in a clinical trial evaluating Descartes-08 in patients with SLE. The Phase 2 open-label trial, which is expected to enroll up to 30 adult patients, is designed to evaluate the safety and tolerability of outpatient administration of Descartes-08 without preconditioning chemotherapy for the treatment of patients with moderate or severe SLE refractory to immunosuppressant therapy..

今天，Cartesian还宣布，第一名患者已在一项评估Descartes-08治疗SLE患者的临床试验中服用药物。第二阶段开放标签试验预计将招募多达30名成年患者，旨在评估门诊使用笛卡尔-08治疗免疫抑制剂治疗难治性中度或重度SLE患者的安全性和耐受性。。

Appointment of Kemal Malik to Board of Directors

任命凯末尔·马利克为董事会成员

Today, Cartesian also announced the appointment of Kemal Malik, MBBS, to its Board of Directors. Dr. Malik brings to Cartesian over 30 years of global development, regulatory, and commercial expertise at leading pharmaceutical organizations.

今天，Cartesian还宣布任命MBBS Kemal Malik为董事会成员。Malik博士为Cartesian带来了领先制药组织30多年的全球发展、监管和商业专业知识。

About Myasthenia Gravis

关于重症肌无力

Myasthenia gravis (MG) is a chronic autoimmune disorder that causes disabling muscle weakness and fatigue. For most people with MG, the disease is characterized by the presence of antibodies against the acetylcholine receptor, a protein found on the surface of nerve cells that plays a key role in muscle contraction.

重症肌无力（MG）是一种慢性自身免疫性疾病，可导致肌肉无力和疲劳。对于大多数MG患者来说，这种疾病的特征是存在针对乙酰胆碱受体的抗体，乙酰胆碱受体是神经细胞表面发现的一种蛋白质，在肌肉收缩中起着关键作用。

There is currently no cure for MG, and treatment typically requires chronic immunosuppressive medicines, with their attendant risks and side effects..

目前尚无治愈MG的方法，治疗通常需要慢性免疫抑制药物，并伴有风险和副作用。。

About Descartes-08

关于笛卡尔-08

Descartes-08, Cartesian’s lead mRNA cell therapy candidate and a potential first-in-class mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T), is an autologous mRNA CAR-T product targeting B-cell maturation antigen (BCMA) in clinical development for generalized myasthenia gravis (MG) and systemic lupus erythematosus.

笛卡尔的主要mRNA细胞治疗候选物笛卡尔-08是一种潜在的一流mRNA工程嵌合抗原受体T细胞疗法（mRNA CAR-T），是一种靶向B细胞成熟抗原（BCMA）的自体mRNA CAR-T产品，用于全身性重症肌无力（MG）和系统性红斑狼疮的临床开发。

In contrast to conventional DNA-based CAR T-cell therapies, mRNA CAR-T administration does not require preconditioning chemotherapy, can be administered in the outpatient setting, and does not carry the risk of genomic integration associated with cancerous transformation. Descartes-08 has been granted Orphan Drug Designation and Regenerative Medicine Advanced Therapy Designation by the U.S.

与传统的基于DNA的CAR T细胞疗法相反，mRNA CAR-T给药不需要预处理化疗，可以在门诊环境中给药，并且不具有与癌症转化相关的基因组整合风险。Descartes-08已被美国授予孤儿药称号和再生医学高级治疗称号。

Food and Drug Administration for the treatment of MG..

美国食品和药物管理局治疗MG。。

About Cartesian Therapeutics

关于笛卡尔疗法

Cartesian Therapeutics is a clinical-stage company pioneering mRNA cell therapies for the treatment of autoimmune diseases. The Company’s lead asset, Descartes-08, is a potential first-in-class mRNA CAR-T in Phase 2b clinical development for patients with generalized myasthenia gravis and Phase 2 development for systematic lupus erythematosus, with a Phase 2 basket trial planned in additional autoimmune indications.

Cartesian Therapeutics是一家临床阶段公司，开创了用于治疗自身免疫性疾病的mRNA细胞疗法。该公司的主要资产Descartes-08是针对全身性重症肌无力患者的2b期临床开发和系统性红斑狼疮的2期开发中潜在的一流mRNA CAR-T，计划在其他自身免疫适应症中进行2期篮式试验。

The Company’s clinical-stage pipeline also includes Descartes-15, a next-generation, autologous anti-BCMA mRNA CAR-T. For more information, please visit www.cartesiantherapeutics.com or follow the Company on LinkedIn or X, formerly known as Twitter..

该公司的临床阶段管道还包括下一代自体抗BCMA mRNA CAR-T Descartes-15。有关更多信息，请访问www.cartesiantherapeutics.com或在LinkedIn或X（以前称为Twitter）上关注该公司。。