PURPOSE OF THIS MODIFICATION IS TO EXERCISE THE I-CORP OPTION

NomoCan制药公司正在开发一种一流的人源化单抗NMC-521，以对抗一种新的 MDM2蛋白的质膜结合变体作为一种副作用较少的癌症靶向治疗方法， 最初专注于胰腺癌(PC)。PC是所有癌症类型中五年存活率最低的癌症之一， 在过去的40年里保持在10%以下，这表明需要有效的PC疗法。研究表明， NMC-521选择性地与几种PC细胞系结合，具有显著的抗肿瘤效果，已证明具有治疗作用 作为单一疗法或联合疗法受益。在这些有希望的结果之后，NomoCan开发了一种 人源化NMC-521单抗(HU-NMC-521)用于进一步研究。通过这项NCI概念提案，NomoCan计划 证明了HU-NMC-521在体外的有效性和选择性，随后在多个PC小鼠模型上进行了测试 在将主要候选药物推向配方和毒理学/药理学之前确认疗效概况 在未来工作中的研究。NomoCan旨在证实胰腺癌细胞中HU-NMC-521与PM-MDM2的结合 细胞系和原发胰腺患者肿瘤样本，以及缺乏与正常胰腺细胞的结合，以及 正常未转化细胞及HU-NMC-521的体内免疫原性筛选及其在胰腺的抗肿瘤作用 癌症小鼠模型。

NomoCan Pharmaceuticals is developing a first-in-class humanized monoclonal antibody, NMC-521, against a novel plasma membrane-bound variant of the protein MDM2 as a targeted treatment for cancer with fewer side effects, initially focusing on pancreatic cancer (PC). PC has one of the lowest 5-year survival rates among all cancer types, remaining below 10% for the past 40 years, indicating a need for effective PC therapies. Studies have shown that NMC-521 binds selectively to several PC cell lines with marked anti-tumor efficacy, having demonstrated therapeutic benefit as a monotherapy or combination therapy. Following these promising results, NomoCan developed a humanized NMC-521 mAb (hu-NMC-521) for further studies. Through this NCI Concept proposal, NomoCan plans to demonstrate the efficacy and selectivity of hu-NMC-521 in vitro, followed by testing in multiple mouse models of PC to confirm the efficacy profile before advancing the lead drug candidate to formulation and toxicology/pharmacology studies in future works. NomoCan aims to confirm the binding of hu-NMC-521 to PM-MDM2 in pancreatic cancer cell lines and primary pancreatic patient tumor samples, as well as the lack of binding to normal pancreatic cells, and normal untransformed cells and screen in vivo immunogenicity of hu-NMC-521 and anti-tumor efficacy in pancreatic cancer mouse models.