COTI‐219 is an oral small molecule inhibitor of mutant KRAS protein. COTI‐219 is designed to selectively bind to the mutant forms of KRAS protein, but not to the wild type KRAS, and block its function ‐ thereby inhibiting the downstream cell growth and proliferation signaling cascade. In validated cell culture and in vivo preclinical rodent models of colorectal and lung cancers at one of the leading cancer research centers in the world, our collaborators demonstrated that COTI‐219 treatment as a single agent resulted in significant and robust efficacy. Moreover, in a lung cancer rodent model, COTI‐219 performed significantly better in reducing tumor volume compared to certain approved standard‐of‐care lung cancer therapies.
Acute Myelogenous Leukemia
Approximately 18,500 new cases of AML are diagnosed worldwide each year and the trend in overall incidence of AML is expected to grow by 7% by 2015 and beyond. Five-year survival rates remain poor. COTI has undertaken a drug discovery project targeting multiple kinases (enzymes) that are abnormal in AML. COTI has identified multiple scaffolds and optimized several drug candidates on each scaffold. Early preclinical results are promising.
HIV Integrase Inhibitors
COTI believes that future optimal therapy for HIV infection will continue to include a combination of a Reverse Transcriptase Inhibitor, a Protease Inhibitor and an Integrase Inhibitor. However, there is a need for second-generation integrase inhibitors that are active against emergent resistant strains of the virus. COTI has focused on the discovery and development of novel HIV integrase inhibitors. Early preclinical results are promising.