NASH and Type 2 Diabetes


NASH (non-alcoholic steatohepatitis) is causally related to obesity, type 2 diabetes and viral infection and is impacted by genetic predisposition. NASH is associated with a two-fold increase in cardiovascular mortality and a 10-fold increase in hepatic failure and death. Moreover, NASH can further progress to cirrhosis and liver cancer, which may require liver transplantation.  The prevalence is staggering as is the cost to society.  It is estimated that world-wide one billion people have hepatic steatosis or fatty liver disease. In the U.S., ~30% of adults and ~10% of children (81 million) are afflicted by fatty liver and some 16 million progress to NASH. It is estimated that in the next 10 years the healthcare burden will reach $35 billion in the US. NASH was first described 35 years ago, to date no FDA approved drug for NASH is available, although the development pipeline of new drug candidates has significantly expanded. A most critical hurdle is meeting the current surrogate endpoint established by the FDA as demonstrating the reversal of steatohepatitis with no progression of fibrosis. A number of companies have failed at the critical fibrosis stage of the disease. Therein, the probability of success of most of the current drug candidates remain low and this provides opportunity for new mechanisms for the treatment of NASH.

An important aspect of fatty liver disease is the relationship to diabetes as >80% of diabetics are affected, of which some 20-50% progress to NASH. In fact, mortality due to liver disease is 2 to 3 times higher in diabetics compared to the general population.  Mito Biopharma has capitalized on the recent breakthrough revealing that ectopic accumulation of lipid inside liver cells is one of the most important causal factors of insulin resistance and progression of type 2 diabetes.  Reducing or depleting hepatic lipid load would thus greatly improve diabetic symptoms or even provide a cure in some patients. Similarly, effective depletion of lipid cellular content would decrease fat accumulation in the liver and minimize inflammation and fibrosis. Therein, the key and unifying underlying mechanism of both diseases can be effectively targeted.

Mito BioPharma’s proprietary technology and lead compounds have been shown to dissipate hepatic lipid accumulation by modulating mitochondrial function via uncoupled mitochondrial respiration. Proof-of-concept efficacy studies of lead compounds on reducing NASH and reducing insulin resistance in animal models have been successfully conducted. Lead compounds are selected with the goal of initiating IND enabling studies in 2019 and initial clinical trials in 2020.