A Novel Peptide Therapeutic for Obesity

Project Summary The goal of this project is to develop a novel peptide therapeuticVTC Gfor the treatment of obesityTodayone third of adults in the United StatesUSare obesewith an estimated annual healthcare burden of approximately $billionByit is projected that overof adults in the US will be obese with a yearly healthcare burden expected to exceed $billionwhich will account for approximatelyof the total US health care costsGLPis a glucoincretin hormone that augments glucose dependent insulin secretionThe Habener group at Massachusetts General Hospital originally discovered that the administration of GLPamidethe major form of GLPpresent in the circulationis cleaved by the endopeptidase neprilysinleading to the formation of a pentapeptidereferred to as VTC Gin mouse plasma withinminutessuggesting that it might play a unique role in the regulation of metabolismIndeedour more recent studies demonstrate that VTC Gis able to reduce blood glucose following shortterm administration in dogsIn additionlonger term administration of VTC Gincreases basal energy expenditureburns fatand normalizes blood glucose and triglyceride levels in diet induced obeseDIOmiceThe pre clinical data generated in mice and dogs suggests that VTC Ghas the potential to provide immediate glucose normalizationwhile increasing basal energy expenditure and burning fatto provide longterm weight loss and normalization of blood glucoseOur goal is to develop VTC Gas an oral therapeutic that functions physiologically as a weight reducer for the treatment of obesityTo our knowledgeno approved drug on the market or in clinical development is able to induce energy expenditure and burn fat and is the product of a natural proteinin this case GLPThis PhaseSBIR application is designed to develop additional IND enabling efficacy and safety data on VTCGThe key aims of this proposal are tosynthesize sufficient VTC Gpeptide and standardize analytical product release assaysdetermine the biodistribution and pharmacokineticsPKprofiles of VTC Gin micedetermine the pharmacodynamicsPDprofile of VTC Gusing blood biomarkers in micemeasure the bioavailability and optimal dose of VTC Gfollowing oral administrationanddevelop the INDenabling preclinical plan for advancing VTC Ginto the clinic for obesity