Islet Sciences, Inc. Highlights Remogliflozin Etabonate as Novel Treatment for Non-alcoholic Steatohepatitis (NASH)

RALEIGH, N.C., June 23, 2014

Remogliflozin etabonate is uniquely positioned as an effective therapy for NAFLD/NASH due to its proven insulin-sensitizing activity as a selective SGLT2 inhibitor, combined with its intrinsic anti-oxidant activity, which is independent of its ability to inhibit SGLT2 and may be differentiated from other drugs in this class.

Arun Sanyal, M.D., Professor of Medicine at Virginia Commonwealth University Medical Center and former President of the American Association for the Study of Liver Diseases (AASLD) commented, "The combination of two distinct mechanisms of action – improved insulin sensitivity via selective SGLT2 inhibition and inherent antioxidant activity – into a single, small molecule, oral drug may be significant for the future treatment of NAFLD/NASH, which is becoming an even greater public health issue as the global incidence of obesity and diabetes continue to rise."

In its peer-reviewed poster titled, "Remogliflozin Etabonate Improves Non-Alcoholic Steatohepatitis," Islet Sciences described positive preclinical efficacy results for remogliflozin etabonate in a diet-induced model of fatty liver disease.  In this study, diet-induced obese (DIO) mice treated orally with remogliflozin etabonate displayed reduced liver transaminases (AST and ALT; 35% and 80%, respectively), which are well-recognized biomarkers for NAFLD/NASH, compared to paired-fed controls over the four-week treatment period.  Islet also observed a reduction in liver transaminases in its 12-week Phase 2b study of remogliflozin etabonate in diabetic patients.  Treatment of DIO mice with remogliflozin etabonate also resulted in significantly reduced liver weight (50%) as well as total liver TAG content (40%), compared to paired-fed controls.  In another study performed with genetically obese (KKA^y) mice, an approximately 50% decrease in liver triglycerides was observed after 8 weeks of oral remogliflozin etabonate treatment.  Remogliflozin etabonate also demonstrated robust in vivo anti-oxidant activity, reducing the level of oxidative stress markers, both in plasma and in the liver (30%), compared to controls.  This appears to be a unique property of active remogliflozin, which also demonstrated greater than ten times the antioxidant activity of canagliflozin and dapagliflozin when measured by oxygen radical antioxidant capacity in vitro.

William Wilkison, Ph.D., Islet Sciences' Chief Operating Officer, stated, "The preclinical results presented at ENDO, combined with what we have observed in the clinic, establishes a strong rationale for pursuing fatty liver disease as a potential indication for remogliflozin etabonate.  Its ability to reduce glucose levels and increase insulin sensitivity in diabetic patients, which we've demonstrated in our previous clinical studies, combined with the significant reductions in liver steatosis and enzyme levels we've described in this preclinical study are highly encouraging.  Importantly, we are pleased to see remogliflozin's positive effect on reducing the oxidative stress that occurs with fatty liver disease, which may be mediated by remogliflozin's innate anti-oxidant activity.  This is a unique and potentially meaningful differentiator for our best-in-class SGLT2 inhibitor."

NAFLD affects up to 25% of the U.S. population, and may reach as high as 50% by 2030¹. Early stage NAFLD is marked by increased fat in the liver stored as triacylglycerol (TAG), which is often caused by obesity and/or insulin resistance.  It is hypothesized that fatty liver (hepatic steatosis), combined with changes in lipid metabolism, create a highly lipotoxic environment characterized by an increase in oxidative cellular stress and resultant decrease in liver function.  If not treated, NAFLD can progress to more severe NASH, which can cause significant scarring of the liver and development of cirrhosis and other serious complications.  There are no therapies approved specifically for treating NAFLD/NASH, although anti-diabetic medications and anti-oxidants are being examined based on these important hallmarks of the disease. 

BHV Pharma owns exclusive rights to remogliflozin etabonate in the global territory outside of Japan, Korea and Taiwan, through a license from Kissei Pharmaceuticals.