A Novel Biotherapeutic Treatment for Pancreatic Cancer

DESCRIPTION (provided by applicant): Carcinoma of the pancreas is the 4th leading cause of cancer deaths. The American Cancer Society has estimated 37,170 new cases and 33,370 deaths in 2007. The cancer generally develops without early symptoms and most pa tients present to treating physicians with advanced-stage of the disease. Surgery, radiation therapy, chemotherapy, immunotherapy and vaccine therapy are treatment options that only marginally prolong survival or relieve symptoms in the cancer patients. As a result, the 5-year survival rate is less than 4%. The development of more effective therapeutic interventions represents a significant unmet medical need. Bexion Pharmaceuticals, LLC is developing a novel first-in-class biotherapeutic compound consistin g of two active components for treating pancreatic cancer. Six lines of preliminary studies suggest the feasibility of the in vitro and in vivo studies proposed in this application. These are: 1) the ability to manufacture sufficient quantities of the anti -neoplastic compound, 2) the compound inhibited growth of over 50 tumor cells, but not normal cell lines, 3) the lack of toxicity in small rodents in initial toxicity studies, 4) the effectiveness of the compound to inhibit tumor growth in a human pancreat ic tumors generated in immunodeficient mice, 5) the compound traffics to and deposits at tumor sites, and 6) the mechanisms of action in non-pancreatic tumors are exerted through induction of programmed cells death. We hypothesize that the anti-neoplastic compound induces programmed cell death of pancreatic tumor cells in vitro as well as tumors in vivo. The goals of this SBIR Phase 1 feasibility study are: 1) to ascertain that the complex formation of the two active ingredients, but not the non-complexed m ixture of the two components, is necessary for growth inhibition of the PANC-1 and MIA PaCa-2 cells in vitro, and to inhibit the growth of the tumors generated by these 2 cell lines in nude mice, and 2) to correlate elevated ceramide levels, increased casp ase activities and induction of DNA fragmentation with the efficacy of the nanovesicles. The successful completion of these goals will be followed by toxicology, absorption/disposition/metabolism/excretion (ADME), pharmacology and chemistry/ manufacturing/ control (CMC) studies, filing an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) and subsequent evaluation in humans. These activities will be proposed in a SBIR Phase 2 application. Pancreatic cancer is the 4 lead ing cause of cancer death. Current treatments are surgery, chemotherapy, radiation therapy and immunotherapy, but they are considerably ineffective. Bexion Pharmaceuticals, Inc. is diligently developing a novel anti-pancreatic biotherapeutic agent that hol ds great promise in improving the prognosis of the disease.