DEVELOPMENT OF A WNT PATHWAY INHIBITOR FOR METASTATIC COLORECTAL CANCER

ABSTRACT Colorectal cancerCRCrepresents the fourth most commonly diagnosed cancer withnew cases each yearUnfortunatelyCRC results in a disproportionate number of deathsprojected indue to advanced stage at diagnosisthe aggressive phenotype of the disease and lack of effective therapeuticsGreater thanof CRC patients possess activating mutations in the WNT signaling pathwayWNT pathway activation is a critical step in the initiation of CRC tumorigenesisCurrentlythere are no FDA approved drugs or drugs in late stage clinical trials that target the WNT pathwayAs a resulthere is an urgent need for the development of inhibitors of the WNT pathway to treat not only CRCbut other WNT driven cancersStemSynergy Therapeutics IncSSTIis a biopharmaceutical company focused on the discoverydevelopment and commercialization of novel therapeutic approaches to target critical cancer stem cellsincluding WNTHedgehog and NotchSSTI has identified a class of small molecules that regulate WNT signaling via activation of Casein KinaseIn this applicationwe describe detailed characterization of mechanism of actiondemonstrate SSTfunctions downstream of activating mutations found in CRC to produce excellent in vitro potency in a range of CRC cell lines and provide significant in vivo efficacy data using various genetic and xenograft models in miceSignificantlySSTdoes NOT affect normal GI architecturewhich is in contrast to two other major classes of WNT inhibitors currently being developed where GI toxicity is dose limitingThis Phase IIb application outlines the next logical steps in the development of SSTcompletion of rodent and non rodent safety studiesIND preparation and initiation of a Phase I clinical trial for advanced or metastatic cancerSuccessful completion of this Phase IIb project will provide all of the necessary studies for progression to proof of concept Phase II efficacy study in humans and accomplish the mission of the SBIR program of supporting small businesses in bringing forward innovative solutions to major public health concernsThe WNT pathway plays a role in many different cancer subtypes and because there are no drugs on the market that target the WNT pathwayby continuing to move SSTthrough the oncology development pipelineSSTI has the potential to improve and prolong the lives of millions of cancer patients worldwideThe multi disciplinary Randamp D team at SSTI has strong credentials and experience in all relevant areasenabling us to complete the key science and business aspects of the developmentAs part of our commercialization planSSTI is collaborating with GeneyusLLCfunded by Three Seasons Capitalto provide matching funds for this applicationas well as significant follow on commercialization funding contingent on SSTI meeting the milestones outlined hereinIn summarywe provide strong preclinical data supporting the molecular targetingtherapeutic efficacy and preliminary safety studies for SSTjustifying transition to the next stages of developmentnon human primate safety studies and a phase I clinical trialSupport of this Phase IIb application will ensure that SSTdoes not succumb to delays in development due to funding and will support SSTI bringing to market a first generation of WNT inhibitors to capture a significant share of the global market for cancer drugs PROJECT NARRATIVE Colorectal cancer is usually an aggressive and deadly disease with limited treatment optionsThe Wnt pathway is a major growth pathway that plays a critical role in andgtof all cases and there are currently no inhibitors in the clinicWe intend to develop our lead compound Wnt pathway inhibitors through pre clinical and clinical trials for a treatment of colorectal cancer