Results for A New First-In-Class Treatment For Diabetes

Metabolex, Inc., a biopharmaceutical company focused on the discovery and development of proprietary new medicines for the treatment of metabolic diseases, announced positive results from a Phase 1a clinical trial of MBX-2982.

MBX-2982 is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion. Preclinical data indicate that MBX-2982 is a potent selective orally active GPR119 agonist that functions through a unique dual mechanism of action. First, it acts directly on the beta cell to increase insulin secretion. In addition, MBX-2982 stimulates release of the incretin GLP-1 from the gut. This dual action is unique and may offer improved glucose homeostasis over existing diabetes therapies, with potential for weight loss and improved islet health.

The Phase 1a study was a randomized, placebo-controlled, double-blind, ascending-dose clinical trial in 60 healthy male and female volunteers examining doses of MBX-2982 in the 10 – 1000 mg range. All doses of the drug were well tolerated and no dose-related adverse events were observed. MBX-2982 was rapidly absorbed, demonstrated excellent exposure and exhibited a half- life consistent with once-daily dosing. As observed in preclinical studies in animals, MBX-2982 showed dose-dependent reductions in glucose and increases in GLP-1 following a mixed meal. These results provide initial clinical validation of the unique mechanism of action of MBX-2982.

“The results of this Phase 1a clinical trial are very encouraging and support the continued development of MBX-2982 as an important new therapy for treating type 2 diabetes,” said Harold Van Wart, Ph.D., Chief Executive Officer of Metabolex. “Based on the excellent safety profile and encouraging effects on glucose levels observed in our Phase 1a trial, we have advanced MBX-2982 into a Phase 1b study in which we are evaluating the multiple-dose pharmacokinetics and pharmacodynamics.”

MBX-2982 is an agonist of GPR119, a GPCR that is expressed in pancreatic islets and the gastrointestinal tract. Pre-clinical studies conducted by Metabolex and others show that GPR119 agonists can stimulate glucose-dependent insulin secretion and release of incretin hormones such as GLP-1, and thus may preserve beta cell health. This novel dual mechanism may provide a unique therapeutic benefit in the treatment of type 2 diabetes. Additionally, the stimulation of GLP-1 release may mimic the benefits of incretin analogues such as exenatide (a GLP-1 analogue marketed as Byetta(R)). Unlike exenatide, however, MBX-2982 can be delivered orally.

 

A summary of the results was presented at the World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy) on November 1, 2008.