IGF::OT::IGF - IND ENABLING DEVELOPMENT OF NANOGMP: TARGETED

吉西他滨是一种被批准用于几种癌症的化疗药物，包括非小细胞肺癌、胰腺癌、乳腺癌和卵巢癌。然而，由于其半衰期短、易产生耐药性和显著的全身毒性，其使用受到了限制。这项SBIR第二阶段合同提案使NanoGMP这一以前由第一阶段SBIR合同资助的产品向探索性研究新药(IND)迈进。纳米GMP利用新型靶向脂质-钙-磷酸(LCP)纳米颗粒平台将吉西他滨(GMP)输送到癌细胞。与吉西他滨相比，纳米GMP显著提高了肺癌和胰腺癌小鼠模型的疗效和耐受性。根据这项提议，NanoGMP将被大批量生产，并用于非临床IND使能研究。这些研究将包括三个动物物种的探索性非GLP毒理学研究，PK/生物分布，以及在标准异种移植和患者来源的肿瘤模型中确定最佳剂量和方案。此外，纳米GMP批次将在NCI的纳米技术表征实验室进行广泛的表征。这些非临床研究的结果将补充其他IND支持研究，以完成IND申报。开发NanoGMP将提高一种已知化疗的有效性和安全性，创造一种“定向化疗”，增强胰腺癌、肺癌和其他癌症患者的临床受益潜力。

Gemcitabine is a chemotherapy approved for several cancers, including non-small cell lung cancer, pancreatic, breast and ovarian cancer. However, its use has been limited due to its short half-life, susceptibility to resistance development and significant systemic toxicity. This SBIR Phase II contract proposal progresses NanoGMP, a product previously funded by Phase I SBIR contract, toward exploratory Investigational New Drug (IND) studies. NanoGMP utilizes novel targeted Lipid-Calcium-Phosphate (LCP) nanoparticle platform for the delivery of gemcitabine monophosphate (GMP) to cancer cells. NanoGMP has significantly improved efficacy and tolerability compared to gemcitabine in lung and pancreatic cancer mouse models. Under this proposal, NanoGMP will be manufactured in larger batches and utilized for non-clinical IND enabling studies. The studies will include exploratory non-GLP toxicology studies in three animal species, PK/biodistribution, and determination of optimal dose and schedule in standard xenograft and patient-derived tumor models. Furthermore, NanoGMP batches will be extensively characterized at NCI's Nanotechnology Characterization Laboratory. Results from these non-clinical studies will augment other IND enabling studies for completion of IND filing. Development of NanoGMP will improve the effectiveness and safety of a known chemotherapy, creating a "targeted chemotherapy" that enhances the potential for clinical benefit to patients with pancreatic, lung and other cancers.