About NASH

The World Health Organization has declared that NASH and NAFLD are now the top causes of liver disease in Western countries and represent a major global health concern. According to the World Gastroenterology Organization Global Guidelines 2014, NASH is an increasingly common chronic liver disease with worldwide distribution that is closely associated with diabetes and obesity, which have both reached epidemic proportions. It is estimated that there are at least 1.46 billion obese adults worldwide. Approximately 6 million individuals in the U.S. are estimated to have progressed to NASH and approximately 600,000 to NASH-related cirrhosis.

COMMITMENT TO RESEARCH AND DEVELOPMENT OF TREATMENTS FOR LIVER DISEASE

Non-Alcoholic Steatohepatitis (NASH)

NASH starts with non-alcoholic fatty liver disease (NAFLD), which is the accumulation of excessive fat in liver cells (steatosis). NAFLD is widely considered to be the liver expression of metabolic disease associated with type 2 diabetes, insulin resistance, obesity and hyperlipidemia.

A subgroup of NAFLD patients has liver cell injury and inflammation (steatohepatitis) in addition to excessive fat. Progression of this condition leads to NASH. Patients with NASH can develop fibrosis and ultimately cirrhosis of the liver, potentially leading to hepatocellular carcinoma or requiring a liver transplant.

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FXR AND EDP-305, AN FXR AGONIST

The Farnesoid X receptor (FXR) is a nuclear hormone receptor that is expressed in the liver, gall bladder, intestine and kidney. Activation of FXR by its natural ligands, namely bile acids, regulates the expression of multiple genes encoding proteins involved in bile acid biosynthesis, transport and metabolism. Beyond the regulation of bile acid homeostasis, FXR agonists exhibit anti-inflammatory and anti-fibrotic activity making it an attractive target for the treatment of NASH.

EDP-305 is a potent FXR agonist and Enanta’s candidate being developed for the treatment of NASH. EDP-305 represents a class of FXR agonists that has been designed to take advantage of increased binding interactions with the receptor. This non-bile acid class contains steroidal and non-steroidal components. It does not contain the carboxylic acid group normally present in other classes of FXR agonists and natural bile acids that can lead to the formation of taurine and glycine conjugates

EDP-297, A FOLLOW-ON FXR AGONIST

EDP-297 is a potent and differentiated follow-on FXR agonist that has demonstrated high target tissue distribution in the liver and intestine as compared to plasma and skin in a preclinical model. Its potency is reported to be greater than that published on any FXR agonist in clinical development today. This is significant because a highly potent and highly targeted FXR agonist may allow for lower doses and reduced drug levels at non-targeted tissues.

For an overview of our research, including our licensed products, please see Our Pipeline.