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

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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.