Advinus Therapeutics recently announced that it has successfully completed a 14-day Proof of Concept (POC) study in 60 type II diabetic patients on its lead molecule, GKM-001, a glucokinase activator.  The results of the trial show effective glucose lowering across all doses tested without any incidence of hypoglycemia or any other clinically relevant adverse events.  Advinus is at present actively exploring partnership options to expedite further development and global marketing of GKM-001.

The clinical trials on GKM-001 validate the company’s pre-clinical hypothesis that a liver selective Glucokinase activator would not cause hypoglycemia (very low blood sugar), while showing robust efficacy.

“GKM-001 is differentiated from most other GK molecules that are in development, or have been discontinued, due to its novel liver selective mechanism of action. GKM-001 has a prolonged pharmacological effect and a half-life that should support a once a day dosing as both mono and combination therapy,” informed Dr Rashmi Barbhaiya, managing director  and CEO, Advinus Therapeutics.

GKM-001 belongs to a novel class of molecules for treatment of type II diabetes. It is an activator of Glucokinase (GK), a glucose-sensing enzyme found mainly in the liver and pancreas. Being liver selective, GKM-001 mostly activates GK in the liver and not in pancreas, which is its key differentiation from most competitor molecules that activate GK in pancreas as well. The resulting increase in insulin secretion creates a potential for hypoglycemia—a risk GKM-001 is designed to avoid.

Advinus has the composition of matter patent on GKM-001 for all major markets globally. Both the Single Ascending Dose data, in healthy and type II diabetics, and the Multiple Ascending Dose Study in Type II diabetics has shown that the molecule shows effective glucose lowering in a dose dependent manner and has excellent safety and tolerability profile over a 40-fold dose range.

The pharmacokinetic properties of the molecule support once a day dosing. GKM-001 has the potential to be first-in-class drug to address this large, growing and yet poorly addressed market. Advinus also has identified a clinical candidate as a back-up to GKM-001, which is structurally different. In its portfolio, the company has a growing pipeline for COPD, sickle cell disease, inflammatory bowel disease, type 2 diabetes, acute and chronic pain and rheumatoid arthritis in various stages of late discovery and pre-clinical development.