Sustained pharmacodynamic effects with once-daily oral dosing, without increases in LDL cholesterol or pruritus at any dose level in healthy volunteers
SAN DIEGO, March 11, 2021 (GLOBE NEWSWIRE) -- Metacrine, Inc. (Nasdaq: MTCR), a clinical-stage biopharmaceutical company focused on discovering and developing differentiated therapies for patients with liver and gastrointestinal diseases, today announced that final results from the company’s Phase 1 trial of MET642, a farnesoid X receptor (FXR) agonist in development for the treatment of non-alcoholic steatohepatitis (NASH), will be presented as a distinguished abstract at the 2021 NASH-TAG Conference. The conference is taking place March 11-13, 2021 in Park City, Utah and virtually on-line.
Expanding on initial findings reported in December 2020, MET642 demonstrated both an encouraging safety and tolerability profile in healthy volunteers, and sustained FXR target engagement after 14 days of daily oral dosing. There were no serious adverse events, and all treatment-emergent adverse events were mild to moderate in severity. MET642 exhibited significant FXR target engagement up to 24 hours after once-daily oral dosing, as evidenced by robust suppression of 7α-hydroxy-4-cholesten-3-one (C4), a key pharmacodynamic marker of FXR activation, at all dose levels. Of equal importance, MET642 was not associated with increased levels of low-density lipoprotein (LDL) cholesterol or reports of pruritus, known side effects reported with other FXR development candidates.
“We believe that a unique chemical scaffold and continuous target engagement are key to optimizing the therapeutic benefits of FXR agonism for the treatment of NASH,” said Hubert C. Chen, M.D., chief medical officer of Metacrine. “We are encouraged by the overall clinical profile of MET642 to date. We are very pleased to have recently initiated our Phase 2a trial in patients with NASH to further elucidate the therapeutic potential of MET642 and look forward to sharing interim data from that study later this year.”
About the Trial
The MET642 Phase 1 trial was a first-in-human, randomized, placebo-controlled, double-blind, single-ascending dose (SAD) and multiple-ascending dose (MAD) trial, in which healthy volunteers received a single oral dose of MET642 ranging from 10 mg to 300 mg in the SAD cohorts and daily oral doses ranging from 2.5 mg to 10 mg for 14 days in the MAD cohorts.
About the Abstract
“MET642, FXR agonist with a unique chemotype, demonstrates a safe, sustained profile in a 14-day randomized study in healthy subjects”, is to be presented by Richard Pencek, Ph.D., executive director of clinical science at Metacrine. Co-authors include Kyoung-Jin Lee, Ph.D. and Jonathan Lee.
About Non-alcoholic Steatohepatitis (NASH)
Non-alcoholic steatohepatitis, or NASH, is a liver disease characterized by excess liver fat, inflammation and fibrosis. In 2015, there were an estimated 17 million people in the United States with NASH, which is expected to increase to an estimated 27 million people by 2030. Left untreated, patients’ disease may progress to liver failure, which is life-threatening without a successful liver transplant. NASH is expected to become the leading cause for liver transplants in the United States. Additionally, patients with NASH often present with metabolic disease and other co-morbidities, which is likely to require combination therapy. Currently, there are no approved therapies for NASH.
Metacrine, Inc. (Nasdaq: MTCR) is a clinical-stage biopharmaceutical company building a differentiated pipeline of therapies to treat liver and gastrointestinal (GI) diseases. Metacrine has developed a proprietary farnesoid X receptor (FXR) platform utilizing a unique chemical scaffold, which has demonstrated a differentiated and improved therapeutic profile in clinical trials. The company’s two product candidates, MET409 and MET642, are currently being investigated in clinical trials as potential new treatments for non-alcoholic steatohepatitis (NASH). MET409 has completed a 12-week monotherapy trial in patients with NASH and is being evaluated in a 12-week combination trial with empagliflozin in patients with both NASH and type 2 diabetes. MET642 has completed a 14-day Phase 1 trial in healthy volunteers and is being evaluated in a 16-week monotherapy trial in patients with NASH.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Statements in this press release that are not purely historical are forward-looking statements. Forward-looking statements contained in this press release include statements regarding the therapeutic potential of MET642; the differentiated nature of Metacrine’s FXR program; plans underlying Metacrine’s clinical trials; plans for advancing the clinical development of Metacrine’s FXR program; and the potential for its FXR product candidates to be long-term therapies for NASH. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies and uncertainties related to the regulatory approval path for the NASH indication. Words such as “may,” “could,” “will,” “encourage,” “expect,” “plan,” “aim,” “anticipate,” “estimate,” “intend,” “potential,” “prepare” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Metacrine’s expectations and assumptions that may never materialize or prove to be incorrect. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks and uncertainties regarding regulatory approvals for MET409 or MET642; potential delays in initiating, enrolling or completing any clinical trials; potential adverse side effects or other safety risks associated with Metacrine’s product candidates; competition from third parties that are developing products for similar uses; and Metacrine’s ability to obtain, maintain and protect its intellectual property. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in Metacrine’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 12, 2020, and in Metacrine’s other filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except as required by law, Metacrine assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.