Development of novel therapeutics for obesity and type 2 diabetes

PROJECT SUMMARY / ABSTRACT Obesity and type 2 diabetes affect millions of patients worldwide and have enormous clinical impact but are not fully addressed by existing pharmacotherapies. Two of the most important unmet medical needs are for pharmacologic agents that promote weight loss without muscle loss, and for pharmacologic agents that protect against dysfunction of pancreatic beta cells. A major goal of our company, Emmyon, Inc., is to discover and develop new pharmacologic agents for obesity and type 2 diabetes. Emmyon is led by physicians and scientists with clinical and scientific expertise in obesity and type 2 diabetes, and by an exceptional medicinal chemist who has been lead inventor of 8 FDA-approved drugs to date. In Phase I-equivalent studies, Emmyon discovered and patented a confidential and proprietary small molecule (EMMY1-25) that promotes weight loss without muscle loss and that protects against dysfunction of pancreatic beta cells in well-established in vivo mouse models of obesity and type 2 diabetes. EMMY1-25 is orally administered and possesses excellent oral bioavailability, pharmacokinetics, and tolerability in rodent models, strong efficacy towards obesity and type 2 diabetes, and pharmacologic effects (promotion of weight loss without muscle loss, and protection against dysfunction of pancreatic beta cells) that could fill important unmet needs in clinical management of obesity and type 2 diabetes. In this Phase II SBIR proposal, we seek to continue this exciting work by advancing the development of EMMY1-25 and related molecules as pharmaceuticals for obesity and type 2 diabetes. Specifically, we will further investigate EMMY1-25's safety, efficacy, dose response, and mechanisms of action in four distinct and complementary mouse models of obesity and type 2 diabetes, and in cultured pancreatic islets from humans with type 2 diabetes. In parallel to our detailed studies of EMMY1-25, we will also design, synthesize, and characterize novel compounds that are structurally related to EMMY1-25, seeking to discover additional compounds with pharmacologic properties that are similar to or perhaps even better than those of EMMY1-25 in preclinical models of obesity and type 2 diabetes. Collectively, these studies will rigorously advance the scientific understanding and commercial development of a highly innovative and promising new class of pharmaceutical agents. In SBIR Phase III, the most promising compound from this project will be carried forward into an IND application and clinical studies geared towards FDA approval for the treatment of obesity and type 2 diabetes. Through this work, we hope to ultimately discover and develop a pharmacologic agent that could significantly improve clinical outcomes for millions of patients who suffer from obesity and type 2 diabetes.