MET409, a non-bile acid sustained FXR agonist, showed no change in LDL cholesterol, no pruritis and favorable trends in liver fat reduction
SAN DIEGO, May 29, 2019 – Metacrine, Inc., a clinical-stage biotechnology company focused on building an innovative pipeline of best-in-class drugs to treat liver and gastrointestinal (GI) diseases, today announced interim results from its Phase 1b clinical study of MET409 in ten patients with nonalcoholic steatohepatitis (NASH). MET409 dosed orally once-daily at 50 mg resulted in a 20% mean relative reduction in liver fat measured by MRI-PDFF and improved liver function tests after only four weeks of treatment. MET409 was safe and well-tolerated, with no serious adverse events, no changes in LDL cholesterol and no incidence of pruritis. Further details will be presented at an upcoming scientific meeting.
“These initial clinical results with Metacrine’s sustained FXR agonist are highly encouraging,” said Stephen Harrison, MD, Medical Director of Pinnacle Clinical Research, founder of Summit Clinical Research and the principal coordinating investigator of the study. “The lack of LDL cholesterol increase seems to be a differentiating feature from other FXR agonists in development and the early signs of efficacy as judged by rapid liver fat improvement at four weeks is noteworthy.”
These interim results are from an open-label cohort and represent the first of a two-part study evaluating MET409 in NASH patients. The second cohort will evaluate MET409 at higher doses in a double-blind, placebo-controlled, multicenter study design. The study with the second cohort is scheduled to start in June 2019 and will be conducted in partnership with Summit Clinical Research. Initial interim results from this second cohort are expected before the end of 2019.
“Our R&D efforts on FXR have been purposeful to incorporate specific design features to build a best-in-class portfolio,” said Hubert Chen, MD, Chief Medical Officer of Metacrine. “In addition to an improved tolerability profile, the magnitude of liver fat reduction after 4 weeks of treatment with MET409 appears to match or exceed those observed with longer-term dosing of other FXR agonists.”
NASH is a liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation and ballooning, resulting in progressive fibrosis that can lead to cirrhosis and eventual liver failure requiring liver transplant. There are currently no medications approved for the treatment of NASH. The proportion of liver transplants attributable to NASH has increased significantly in past years and is projected to be the leading cause of liver transplant by the end of 2020.
Metacrine has developed an extensive portfolio of oral FXR agonists that are taken once a day and have sustained activation of the target over 24 hours. MET409 is a representative non-bile acid sustained FXR agonist. The company is developing a “best of breed” FXR agonist from its library of over 2,500 compounds and plans to initiate human clinical studies in early 2020.
Metacrine is a clinical-stage biopharmaceutical company focused on building an innovative pipeline of best-in-class drugs to treat liver and gastrointestinal (GI) diseases. The most advanced program is focused on the farnesoid X receptor (FXR) an important drug target in multiple liver and GI diseases. Metacrine has purposefully designed a series of compounds to be optimized, next-generation FXR agonists. Beyond the FXR program, a pipeline of novel drug candidates against other drug targets is being explored by taking advantage of internal drug discovery and development capabilities. Privately held Metacrine is headquartered in San Diego, California. For additional information, please visit www.metacrine.com.
Chief Financial Officer