Enanta Announces New Preclinical Data on its FXR Agonist EDP-305 for Non-Alcoholic Steatohepatitis (NASH) and Primary Biliary Cholangitis (PBC) at The International Liver Congress™ 2017
- New preclinical data support investigation of new indication for EDP-305 in primary sclerosing cholangitis (PSC)
Data from three poster presentations being presented at the
NAFLD is the accumulation of excessive fat in the form of triglycerides in patients’ liver cells (steatosis) that is not caused by alcohol. 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 in addition to excessive fat (steatohepatitis). Progression of this condition leads to non-alcoholic steatohepatitis (NASH). Patients with NASH can develop fibrosis and ultimately cirrhosis of the liver, potentially leading to hepatocellular carcinoma or requiring a liver transplant.
The first poster will be presented by
The second poster will be presented by
The third poster will be presented by
“The BALBc.Mdr2-/- mouse model may represent the most relevant model
that we have to evaluate the potential of new agents for the treatment
of primary sclerosing cholangitis (PSC). We are very encouraged by the
results we have observed with EDP-305 showing a very robust response in
this biliary disease model,” stated
“The extensive preclinical profiling of EDP-305 in a variety of in
vitro and in vivo models has given Enanta the confidence to
continue to advance EDP-305 in the clinic and to consider new areas,
such as PSC, for exploration,” stated
EDP-305 is currently in Phase 1 clinical development. Enanta’s ongoing double-blind, placebo-controlled Phase 1a/b study is designed to evaluate the safety, tolerability and pharmacokinetics of single ascending doses (SAD) and multiple ascending doses (MAD) of EDP-305 in healthy adults, and in adults with presumptive non-alcoholic fatty liver disease (NAFLD) (obese, with or without pre-diabetes or type 2 diabetes). The study will enroll approximately 150 subjects and is planned to evaluate at least 5 single and multiple dose cohorts, with EDP-305 administered orally, once daily.
The current study includes subjects with presumptive NAFLD in order to obtain initial safety data and additional data regarding the relationship between EDP-305 plasma concentration levels and certain pharmacological effects in the context of fatty liver disease. This relationship will be explored by using biomarkers that are relevant to the disease and to the activity of EDP-305, such as evaluation of lipids, glucose, insulin resistance and specific markers of FXR activity.
About EDP-305, a Farnesoid X Receptor (FXR) Agonist
EDP-305 is a potent FXR agonist and Enanta’s lead product candidate being developed for the treatment of NASH and PBC. EDP-305 represents a new class of FXR agonists that has been designed to take advantage of increased binding interactions with the receptor. Further, this non-bile acid class contains steroidal and non-steroidal components, and 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-305 has been granted Fast Track Designation by the
About NAFLD, NASH, and FXR
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of excessive fat in the form of triglycerides in patients’ liver cells (steatosis) that is not caused by alcohol. 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 in addition to excessive fat (steatohepatitis). Progression of this condition leads to non-alcoholic steatohepatitis (NASH). Patients with NASH can develop fibrosis and ultimately cirrhosis of the liver, potentially leading to hepatocellular carcinoma or requiring a liver transplant. The Farnesoid X receptor (FXR) is a nuclear receptor and a main regulator of bile acid levels in the liver and small intestine. It responds to bile acids by regulating gene transcription of key enzymes and transporters, many of which play important roles in lipid metabolism, insulin resistance, inflammation, and fibrosis.
Enanta has discovered novel protease inhibitors for use against the
hepatitis C virus (HCV). These protease inhibitors, developed through
Enanta’s collaboration with
Forward Looking Statements Disclaimer
This press release contains forward-looking statements, including statements with respect to the prospects for Enanta’s further development of EDP-305. Statements that are not historical facts are based on management’s current expectations, estimates, forecasts and projections about Enanta’s business and the industry in which it operates and management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors and risks that may affect actual results include: the development risks of early stage discovery efforts in disease areas such as NASH, PBC and PSC; the impact of development, regulatory and marketing efforts of others with respect to competitive treatments for NASH, PBC and/or PSC; regulatory and reimbursement actions affecting any competitive treatment for NASH, PBC and/or PSC; Enanta’s lack of clinical development experience; Enanta’s need to attract and retain senior management and key scientific personnel; the need to obtain and maintain patent protection for EDP-305 and Enanta’s other product candidates and avoid potential infringement of the intellectual property rights of others; and other risk factors described or referred to in “Risk Factors” in Enanta’s most recent Form 10-K for the fiscal year ended