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 is a potent, competitive and reversible inhibitor of purified cathepsin B. It has nanomolar inhibitory potency against the cathepsin B enzyme and also has nanomolar inhibitory potency in cellular assays. VBY-376 is selective against other human cathepsins (F, L, V, and S). Using activity-based probe technology, sustained inhibition of cathepsin B in the liver has been shown after VBY-376 dosing in mice.
In a human Phase I study, we demonstrated that the level of exposure of VBY-376 overlapped with that required for antifibrotic efficacy in animal models.