MV2C2 antibody as a new therapeutic for Myasthenia Gravis

项目总结 重症肌无力(MG)是一种以肌肉无力为特征的自身免疫性疾病，由 自身抗体，主要针对肌乙酰胆碱受体(AChR)和肌特异性激酶 (穆斯克)在神经肌肉接头(NMJ)。这些抗体是由特定的淋巴细胞亚群产生的。 但还没有完全表现出来。出于这个原因，任何MG治疗都不能专门针对产生 自身抗体和目前的治疗方法效果很差，而且都有不良影响，这对 影响生活质量。尽管MG是一种罕见的疾病，但它的成本很高，住院费用只有 每年十亿美元。为了克服这一临床、科学和社会经济挑战，MimiVax提出了 开发一种新的特异性治疗方法，MV2C2抗体，它将针对特定的细胞亚群证明 他们是在自身抗体的产生中起关键作用的人。具体根除这一现象 细胞亚群将消除自身抗体的存在，并显著改善体征和症状 极大地减少了目前治疗方法的不良影响。收集数据来证明 这项创新的技术可行性和临床潜力MimiVax将进行关键的体内研究 实验性MG动物模型完成新治疗剂的表征，证实其 在了解系统的作用机制和引起的病理生理变化时的特异性 靠它。此外，还将对MG患者的淋巴细胞进行体外研究，以研究细胞和 MV2C2抗体作用的分子机制最后，MimiVax将继续推进 MV2C2抗体这些活动旨在降低风险并加快第二阶段活动的进程，这些活动包括 关键的IND前安全性/毒理学、药效学和药代动力学研究将为 向试点试验、IND批准和临床验证迈进。

PROJECT SUMMARY Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness, and caused by autoantibodies, mainly targeting the muscle acetylcholine receptor (AChR) and the muscle specific kinase (MuSK) in the neuromuscular junction (NMJ). These antibodies are produced by a specific subset of lymphocytes yet not fully characterized. For this reason, no MG treatment is able to specifically target the cells producing autoantibodies and current treatments are poorlyeffective and uniformly have adverse effects, which negatively impact quality of life. Despite being a rare disease, MG is a costly one with a hospitalization expense of half a billion dollars per year. To overcome this clinical, scientific and socio-economic challenge MimiVax proposes the development of a new specific therapy, the MV2C2 antibody, that will target the specific subset of cells proving that they are the ones playing a critical role in the production of autoantibodies. The specific eradication of this subset of cells will eliminate the presence of autoantibodies and significantly improve the signs and symptoms of the disease reducing dramatically the adverse effects of the current therapies. To collect data proving the technical feasibility and the clinical potential of this innovation MimiVax will perform pivotal in vivo studies on experimental MG animal model to complete the characterization of the new therapeutic agent confirming its specificity whilst understanding the system in mechanism of action and the pathophysiological changes induced by it. Furthermore, in vitro studies on MG patients’ lymphocytes will be performed to investigate the cellular and molecular mechanism of action of the MV2C2 Ab. Finally, MimiVax will proceed with the humanization of the MV2C2 Ab. These activities aim to de-risk and accelerate the path towards the Phase II activities that include critical pre-IND safety/toxicology, pharmacodynamics, and pharmacokinetics studies that will pave the way towards pilot trials, IND approval and clinical validation.