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