We believe GPR119 represents a promising pharmaceutical target for discovering orally available small molecule agonists for the treatment of type 2 diabetes. GPR119 is expressed in beta cells, which are located in the pancreas and responsible for secreting insulin in response to increases in blood glucose. Stimulation of GPR119 has been shown to promote insulin release by beta cells in response to elevated blood glucose levels. In addition, GPR119 is expressed in cells other than pancreatic beta cells, such as endocrine cells in the gastrointestinal tract. In preclinical studies and clinical trials, GPR119 agonists have stimulated the release of GLP-1, GIP and PYY, incretins that play important roles in insulin regulation and other metabolic pathways.

We own a broad array of internally discovered, orally available GPR119 agonists, including APD597 and next generation compounds that we discovered after the research portion of our collaboration with Ortho-McNeil-Janssen Pharmaceuticals, Inc., ended, and a portfolio of patents and patent applications directed to a range of materials and methods that are related to the discovery and development of GPR119 receptor agonists. The technologies covered by our patents and patent applications include materials and methods that may be used to identify and determine the activity of molecules that modulate the GPR119 receptor, methods that measure the incretin response to GPR119 agonists and pharmaceutical compositions containing both GPR119 agonists and DPP-4 inhibitors.

We are pursuing exclusive collaborations for our GPR119 agonists and non-exclusive licenses for our patent portfolio related to the discovery and development of GPR119 agonists.

According to the Centers for Disease Control and Prevention, diabetes affects approximately 26 million of the people in the United States, and type 2 diabetes accounts for 90-95% of the diabetes prevalence. Type 2 diabetes is characterized by dysregulation of insulin sensitivity, insulin secretion and hepatic glucose production. Therapies for type 2 diabetes act by improving insulin release, enhancing insulin sensitivity, increasing insulin levels, modifying glucose absorption from the gut, or modifying hepatic glucose production. Current oral medications for type 2 diabetes may have side effects that include hypoglycemia, weight gain, edema or possible increases in cardiovascular mortality, prompting continuing efforts to develop therapeutics to improve the treatment of diabetes.

Development

APD597, our internally discovered GPR119 agonist intended for the treatment of type 2 diabetes, was evaluated by Ortho-McNeil-Janssen, under our former collaboration. Ortho-McNeil-Janssen’s Phase 1 program evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of APD597 in single and multiple ascending dose studies in healthy volunteers and patients with type 2 diabetes. APD597 showed dose-proportional pharmacokinetics with a half-life of six to seven hours in solution and approximately 13 hours in suspension in healthy volunteers. The clinical data also provided evidence for increased incretin (GLP-1, GIP and PYY) release and reductions in glucose rise following a test meal or oral glucose load with APD597 treatment in both overweight and obese non-diabetic volunteers and in subjects with type 2 diabetes. In general, reductions in post-meal glucose increases were greater with APD597 in combination with sitagliptin, a DPP-4 inhibitor, compared to sitagliptin alone. We believe APD597 may have utility, possibly in combination with a DPP-4 inhibitor for the treatment of type 2 diabetes.

Our drug candidates have not been approved by the U.S. Food and Drug Administration or any international regulatory agency.