Cathepsin B is involved in the development of liver fibrosis, in the injury and death of hepatocytes as well as the development of hepatic stellate cells. Inhibition of its activity results in a reduction in liver fibrosis in pharmacology disease models.
VBY-376 for the Treatment of Liver Fibrosis in Patients with Nonalcoholic Steatohepatitis
Our product candidate, VBY-376, is a potent cathepsin B inhibitor. We are developing VBY-376 as an orally-delivered drug for the treatment of nonalcoholic steatohepatitis, or NASH. In our preclinical testing using standard disease models, VBY-376 reduced and reversed liver fibrosis. We have completed a Phase 1 clinical trial of VBY-376 in 46 healthy volunteers, using an initial formulation of the drug. We plan to enter into Phase 1 clinical trials with an enhanced formulation of VBY-376 in the second half of 2015 and, if successful, into clinical trials in NASH patients in 2016. We believe a small molecule inhibitor of cathepsin B, such as VBY-376, may reduce and potentially reverse fibrosis in patients with fibrotic liver diseases.
NASH is a serious liver disease in which fat accumulation in the liver induces chronic inflammation, leading in later stages to progressive fibrosis that may result in cirrhosis and liver failure. Approximately eight million people in the United States suffer from NASH, for which there is no currently approved disease-modifying therapeutic. In the United States, at least 900,000 NASH patients have advanced liver fibrosis or cirrhosis due to the disease. NASH is the third leading cause of liver transplant in the United States and accounts for 10% of liver transplants.
We have conducted preclinical testing of VBY-376 in a widely-accepted disease model of liver fibrosis evaluating the prevention and treatment of liver fibrosis. The results of these studies in mice demonstrated that VBY-376 was successful in reducing and reversing liver fibrosis, shown as a decrease in the hepatic fibrosis score. In these animal studies, mice were treated with a liver toxin for a period of 28 days in order to induce liver fibrosis. In the prevention model represented below, treatment with VBY-376 started while liver injury was occurring. In the reversal model, VBY-376 administration started after injury.
VBY-376 efficacy in preclinical fibrosis models