Farnesoid X Receptor (FXR) Program

FXR agonists for the treatment of Non-alcoholic Steatohepatitis (NASH)

Targeting FXR is a very promising strategy for the treatment of liver diseases, i.e. for the indications "Non-alcoholic Fatty Liver Disease" (abbreviated as NAFLD) and "Non-alcoholic Steatohepatitis" (abbreviated as NASH).


FXR functions as a receptor for bile acids. Regulation of FXR leads to a series of transcriptional responses that regulate triglyceride, cholesterol and bile acid metabolism. Selective synthetic FXR agonists have the potential to lower triglycerides and improve the cholesterol profile. Furthermore, in animal models of liver disorders, these compounds are also highly effective in blocking disease progression.

Originating in the fast growing number of people with Metabolic Syndrome (a combined state of obesity, hyperlipidemia, hypertension and insulin resistance) incidences for NAFLD and NASH are dramatically rising worldwide. The combination of an unhealthy sedentary lifestyle and over-nutrition leads to fat accumulation in the liver ("hepatic steatosis" or NAFLD). Hepatic steatosis – if untreated – can progress to a more severe form of fatty liver disease, which is called Non-alcoholic steatohepatitis (NASH). NASH embraces hepatic steatosis together with signs of inflammation and hepatocyte injury with or without fibrosis.

The prevalence of NASH is rather high and is estimated to approach 5-10% of the total population in industrialized countries. NASH markedly increases the risk to develop cirrhosis, liver failure and hepatocellular carcinoma over time. Currently, there is no approved therapy for NAFLD or NASH available. The discovery of fully synthetic FXR agonists offers new hope as pharmacological activation of FXR attacks the underlying causes of NAFLD and NASH and has the potential to stop or even reverse the further progression of the disease.


As of 2015, the FXR program is partnered with Gilead Sciences, Inc., a market leader in the field of liver disease treatments. The collaboration combines Phenex's target-related know-how and its pool of drug candidates on FXR with Gilead's preclinical and clinical development strengths.

The lead compound of this program, GS-9674, is currently in Phase 2.