Farnesoid X Receptor (FXR) Program

FXR agonist PX-102 for the treatment of Metabolic Syndrome / NAFLD / NASH

The primary indications for Phenex FXR agonist Px-102 are Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH). The incidences for NAFLD and NASH are dramatically rising worldwide and these liver diseases have their origin in the fast growing number of people with Metabolic Syndrome, a combined state of obesity, hyperlipidemia, hypertension and insulin resistance. The hepatic insulin resistance, an outcome of unhealthy sedentary lifestyle together with overnutrition, results in substantial fat accumulation in the liver ("steatosis"). This steatosis − if untreated − can further progress to liver inflammation, liver tissue damage and fibrosis, the next severe stage after NAFLD which is called Non-alcoholic Steatohepatitis (NASH). The prevalence of NASH is estimated to approach 5% of the total population in industrialized countries. NASH markedly increases the likelihood to develop liver cancer or end stage liver cirrhosis. Currently, there is no approved therapy for NAFLD or NASH.

A new hope comes from the discovery of synthetic FXR agonists. Pharmacological activation of the FXR receptor by Phenex´ FXR agonist Px-102 attacks the underlying causes of NAFLD and NASH. It lowers liver lipids and improves hepatic insulin sensitivity, combined with a liver specific anti-fibrotic and anti-inflammatory effect. This was demonstrated for Px-102 and other FXR agonists in various animal models of metabolic syndrome and NASH. A first human clinical trial with Phenex´ proprietary Px-102 has now started. Phenex intends to verify the potent hepatoprotective and metabolic effects of Px-102 in a human Phase II clinical trial in the course of 2012.