NOMOCAN PHASE I - DEVELOPMENT OF THERAPEUTIC OR PREVENTATIVE TECHNOLOGIES FOR TREATMENT OR PREVENTION OF PEDIATRIC CANCERS AND/OR RARE CANCERS SBIR CONTRACTPHASE I - DEVELOPMENT OF THERAPEUTIC OR PRE

Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second leading cause of cancer-relateddeaths by 2030 with a 5-year overall survival rate is only about 13%. For the majority of PDAC patients withmetastatic PC, the current standard of care is systemic chemotherapy, which only extends survival by a fewmonths. There is a critical need for less toxic, more potent targeted therapeutics for PDAC. NomoCan hasdeveloped a monoclonal antibody (Hu-NMC-521) that specifically targets a novel, membrane-bound splicevariant of MDM2 (PM-MDM2) overexpressed in PDAC cells, while sparing normal pancreatic acinar cells. ForPhase I of this Fast-Track application, we proposed development and optimization of an antibody-drugconjugate (ADC), Hu-NMC-521-MMAE, using in vitro and in vivo PDAC models. In Phase II of this project, wepropose to 1) determine immunogenicity and pharmacokinetics of Hu-NMC-521-MMAE ADC and 2) establisha Master Cell Bank (MCB) for Hu-NMC-521 expression. Upon completion of these key IND-enabling studies,we would have determined how to enhance efficacy while minimizing toxicity of our Hu-NMC-521 ADC anddeveloped a GLP-compliant stable cell line for successful generation of Hu-NMC-521 antibodies against thenovel target, PM-MDM2.