Discovery compounds

INT-767: an orally administered second generation agent with potent dual activity against farnesoid X receptor (FXR) and TGR5, a G-protein coupled bile acid receptor

  • INT-767 is Intercept's second bile acid analog to enter phase 1 clinical development
  • INT-767 is a more potent FXR agonist than obeticholic acid (OCA), Intercept's lead product candidate, and has the potential to demonstrate greater efficacy in liver disease
  • INT-767 also activates TGR5, a second bile acid receptor. TGR5 has been shown to affect energy metabolism, glucose homeostasis, bile composition/secretion, and inflammation
  • In animal models, INT-767 has shown the potential to both prevent and reverse organ damage due to fibrosis

INT-777: an orally administered selective TGR5 agonist

In animal models of diabetes, treatment with INT-777 induced glucagon-like peptide-1 (GLP-1) secretion.

  • In vitro studies demonstrate that INT-777 selectively targets TGR5 with no effects on a broad range of other receptors
  • Activation of TGR5 is directly linked to release of GLP-1 in the intestine, and INT-777 has the potential to improve
    • Liver steatosis, fibrosis, and blood lipid levels
    • Insulin sensitivity
    • Glycemic control