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

NomoCan Pharmaceuticals正在开发一种一流的人源化单克隆抗体，NMC-521， MDM 2蛋白质的质膜结合变体作为癌症的靶向治疗，具有较少的副作用， 最初专注于胰腺癌（PC）。PC是所有癌症类型中5年生存率最低的癌症之一， 在过去的40年里，这一比例一直低于10%，表明需要有效的PC治疗。研究表明 NMC-521选择性地结合几种具有显著抗肿瘤功效的PC细胞系，已经证明了治疗作用。 作为单药治疗或联合治疗获益。根据这些有希望的结果，NomoCan开发了一种 人源化NMC-521 mAb（hu-NMC-521）用于进一步研究。通过NCI概念提案，NomoCan计划 证明hu-NMC-521在体外的功效和选择性，然后在PC的多种小鼠模型中测试， 在将先导候选药物推进到制剂和毒理学/药理学之前确认疗效特征 在未来的工作中学习。NomoCan旨在确认胰腺癌细胞中hu-NMC-521与PM-MDM 2的结合 细胞系和原发性胰腺患者肿瘤样品，以及缺乏与正常胰腺细胞的结合，和 正常未转化的细胞，并筛选hu-NMC-521的体内免疫原性和胰腺癌中的抗肿瘤功效。 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.