SHANGHAI and NANJING, China and SAN JOSE, Calif., Feb. 29, 2024 /PRNewswire/ -- On February 26, 2024, the impactful international academic journal, EMBO Molecular Medicine, published the clinical data of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, CT103A) for the treatment of two refractory myasthenia gravis (MG) subjects.

中国上海、南京和加利福尼亚州圣何塞，2024年2月29日/PRNewswire/--2024年2月26日，有影响力的国际学术期刊EMBO Molecular Medicine发布了全人BCMA靶向自体CAR-T细胞注射（Equecabtagene Autoleucel，Equecel，CT103A）治疗两名难治性重症肌无力（MG）受试者的临床数据。

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis, initially demonstrated the good tolerability and safety of Eque-cel in the treatment of MG, as well as the durable clinical efficacy. .

B细胞谱系重建是难治性重症肌无力患者CAR-T细胞治疗效果的基础，最初证明了Equi-cel在MG治疗中的良好耐受性和安全性，以及持久的临床疗效。。

MG is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorders mediated by antibodies. Antibodies to the Acetylcholine Receptor (AChR) are the most common pathogenic antibodies; in addition, antibodies such as Muscle-Specific receptor tyrosine Kinase (MuSK), low-density Lipoprotein Receptor-related Protein 4 (LRP4), and Ryanodine Receptor (RyR), have also been found to be involved in the pathogenesis of MG.

MG是一种自身免疫性疾病，具有由抗体介导的获得性神经肌肉接头（NMJ）传播障碍。乙酰胆碱受体（AChR）的抗体是最常见的致病性抗体；此外，还发现肌肉特异性受体酪氨酸激酶（MuSK），低密度脂蛋白受体相关蛋白4（LRP4）和Ryanodine受体（RyR）等抗体与MG的发病机制有关。

Currently, the treatment of MG is still based on cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The main causes of death in MG patients include respiratory failure and pulmonary infections. .

目前，MG的治疗仍基于胆碱酯酶抑制剂，糖皮质激素，免疫抑制剂，静脉注射免疫球蛋白，血浆置换和胸腺切除术。MG患者死亡的主要原因包括呼吸衰竭和肺部感染。。

This is an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557).  It was conducted by Prof. Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. .

这是一项由研究者发起的开放标签研究，旨在评估Eque cel治疗复发/难治性抗体介导的神经系统特发性炎症性疾病的安全性和有效性（NCT04561557）。这项研究由华中科技大学同济医学院同济医院王伟教授的团队进行。。

Two subjects with refractory MG were enrolled in this study. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody.

本研究纳入了两名难治性MG患者。一名33岁女性，AChR IgG和Titin IgG阳性，在入组前21个月接受了胸腺切除术治疗，在用胆碱酯酶抑制剂，糖皮质激素，免疫抑制剂和抗CD20单克隆抗体治疗后未达到临床缓解。

The other subject was a 60-year-old female, MuSK- IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg， respectively. .

另一名受试者是一名60岁的女性，MuSK-IgG4阳性，有20年的疾病史，之前用激素，免疫抑制剂和抗CD20单克隆抗体治疗失败。两名受试者分别以1.01×106 CAR-T/Kg和0.96×106 CAR-T/Kg的剂量单次输注Eque-cel。。

Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. .

安全性：在2名受试者中，只有1名受试者出现1级细胞因子释放综合征（CRS），并且没有免疫效应细胞相关神经毒性综合征（ICANS）。输注后4周内，所有≥3级血细胞减少症均恢复。没有发现新的安全风险，安全性优于多发性骨髓瘤适应症。。

Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS).

有效性：两名受试者的临床症状在18个月内持续改善。输注后3个月，患者肢体力量和肺活量显着改善，重症肌无力日常生活活动评分（MG-ADL），定量重症肌无力评分（QMG），重症肌无力生活质量评分（MG-QOL）和改良Rankin评分（mRS）持续改善。

No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. .

在随访期间，除低剂量吡啶斯的明（分别为90 mg/天和60 mg/天）外，未使用其他免疫调节疗法。。

PK/PD: Eque-cel expanded well after infusion and persisted for a shorter period than that in multiple myeloma patients. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually.

PK/PD：输注后Eque细胞扩张良好，持续时间短于多发性骨髓瘤患者。输注后，两名受试者的抗AChR抗体，抗Titin抗体和抗MuSK抗体迅速下降，并保持在非常低的水平。输注后2个月内，两名受试者的B细胞和浆细胞均降至检测不到的水平，然后逐渐恢复。

At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. .

输注后18个月，两名受试者的B细胞均恢复正常水平，其中约80%为幼稚B细胞，而浆细胞仍处于低水平。该结果表明，CAR-T细胞疗法的长期疗效可能与以幼稚表型为主的B细胞的重建和浆细胞的持续清除有关。。

The principal investigator of this study, Prof. Wei Wang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, said 'Myasthenia Gravis has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of Myasthenia Gravis to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality.

这项研究的首席研究员、华中科技大学同济医学院同济医院的王伟教授说，“重症肌无力病程长，难以治愈，并且容易复发。目前使用传统药物治疗虽然能够在一定程度上改善重症肌无力的症状，但在疾病控制和长期安全性方面存在不足，迫切需要患者获得更好的临床结果和治疗方式。

In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients.' .

在我们的研究中，令人欣慰的是，BCMA CAR-T细胞疗法可以预防MG疾病的进展，并显示出疾病逆转的迹象，这有望改变MG治疗的前景，并为患者带来治愈的希望。”。

In addition to the results of this published study, IASO Bio and a team of investigators continue to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other antibody-mediated autoimmune diseases, including optic neuromyelitis optica spectrum disorders (NMOSD), Immune-Mediated Necrotizing Myelopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with an aim to change the landscape of treatment for autoimmune diseases. .

除了这项已发表的研究结果外，IASO Bio和一组研究人员继续探索Equecabtagene Autoleucel在治疗其他抗体介导的自身免疫性疾病中的安全性和有效性，包括视神经脊髓炎-视神经谱系障碍（NMOSD），免疫介导的坏死性脊髓病（IMNM）和慢性炎症性脱髓鞘性多发性神经病（CIDP），旨在改变自身免疫性疾病的治疗格局。。

About IASO Bio

关于IASO Bio

IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production..

IASO Bio是一家生物制药公司，致力于发现和开发用于肿瘤学和自身免疫性疾病的新型细胞疗法和生物制剂。IASO Bio拥有跨越整个药物开发过程的综合能力，从早期发现到临床开发，监管批准和商业生产。。

The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S.

该公司的产品线包括10多种新产品的多元化组合，包括Equecabtagene Autoleucel（一种全人类BCMA CAR-T注射剂）。Equecabtagene Autoleucel获得了中国国家医药产品管理局（NMPA）和美国的新药申请（NDA）批准。

FDA IND approval for the treatment of RRMM..

FDA IND批准用于治疗RRMM。。

Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit http://www.iasobio.com or www.linkedin.com/company/iasobiotherapeutics..

IASO凭借其强大的管理团队、创新的产品线、GMP生产以及集成的制造和临床能力，旨在为中国以及世界各地的患者提供变革性、可治愈和负担得起的治疗方法，以满足未满足的医疗需求。有关更多信息，请访问http://www.iasobio.com或www.linkedin.com/company/iasobiotherapeutics。。

SOURCE IASO Bio

来源IASO生物