New Data Support Robust, Sustained FXR Activation by MET409 in Patients with NASH and Demonstrate Predictability of Liver Fat Reductions as Early as Week 4 of Treatment
/EIN News/ — SAN DIEGO, Oct. 01, 2020 (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 two posters highlighting new data on the company’s lead clinical candidate, MET409, a farnesoid X receptor (FXR) agonist for the treatment of non-alcoholic steatohepatitis (NASH), will be presented at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting Digital Experience™. The virtual meeting is taking place Nov. 13-16, 2020.
“We are pleased to report new pharmacokinetic and pharmacodynamic data from our MET409 Phase 1b proof-of-concept clinical trial in patients with NASH, a prevalent and potentially life-threatening condition for which there are no approved treatments available today,” said Hubert C. Chen, M.D., chief medical officer of Metacrine. “The findings demonstrated robust and sustained FXR activation, which we believe is key to optimizing therapeutic benefits. Combined with a favorable pharmacological and tolerability profile, these results further highlight the therapeutic potential of MET409 for patients with NASH. We look forward to presenting these data, which support the continued advancement of our FXR program, including both MET409 and our second clinical candidate, MET642.”
In addition, new data generated in collaboration with Dr. Mustafa R. Bashir, associate professor of Radiology and associate professor in the Department of Medicine, Gastroenterology, and colleagues at Duke University Medical Center, show that relative liver fat content (LFC) reduction after four weeks of treatment with MET409 was strongly predictive of LFC reduction at week 12 in the proof-of-concept study. “These findings suggest that early measurement of liver fat content may help guide the long-term treatment strategy with FXR agonists in NASH,” said Dr. Bashir.
Title: Dose-dependent changes in pharmacokinetic and pharmacodynamic profiles of MET409, a sustained FXR agonist, after 12 weeks of treatment in patients with NASH
Authors: E.J. Lawitz, K-J Lee, J. Shim-Lopez, J. Lee, H.C. Chen
Publication Number: 1669
Session Title: NAFLD and NASH: Therapeutics – Pharmacologic and Other
Key Findings: In a 12-week, randomized, double-blind, placebo-controlled study, 58 patients diagnosed with NASH were enrolled into three cohorts: 50 mg (n=19), 80 mg (n=20) and placebo (n=19). MET409 treatment resulted in dose-dependent decreases in serum levels of C4, a circulating biomarker of FXR target activity: 71-95% in trough levels at day 84 relative to baseline, and 78-96% in day 84 area-under-the-curve (AUC) relative to placebo (p<0.05 for both comparisons). These results demonstrate robust, sustained FXR activation by MET409 and correlate with previously-reported benefits of LFC reduction and improvement in liver chemistries.
Title: Change in liver fat content at 4 weeks accurately predicts change in liver fat content at 12 weeks in non-alcoholic steatohepatitis patients treated with an FXR Agonist: Analysis from a 12-week, randomized, placebo-controlled study with MET409
Authors: H. Jiang, H.C. Chen, K.J. Lafata, M.R. Bashir
Publication Number: 1489
Session Title: NAFLD and NASH: Diagnostics and Biomarkers
Key Findings: As previously reported, MET409 significantly lowered LFC at week 12, with mean relative reductions of 55% (80 mg) and 38% (50 mg) vs. 6% in placebo (p<0.001). MET409 achieved ≥30% relative LFC reduction in 93% (80 mg) and 75% (50 mg) of patients vs. 11% in placebo (p<0.001). Simple and multiple linear regression analyses demonstrated that week 4 relative LFC reduction (regression coefficient: 1.243, p<0.001) was a significant predictor of week 12 LFC reduction. These findings suggest the potential of early liver fat content assessment as an indicator of long-term treatment response.
About Metacrine
Metacrine, Inc. (Nasdaq: MTCR) is a clinical-stage biopharmaceutical company building a differentiated pipeline of therapies to treat liver and gastrointestinal (GI) diseases. The company’s most advanced programs, MET409 and MET642, target the farnesoid X receptor (FXR), which is central to modulating liver and GI diseases. Both MET409 and MET642 are currently being investigated in clinical trials as potential new treatments for non-alcoholic steatohepatitis (NASH).
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “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 the company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the therapeutic potential of MET409, plans for advancing the clinical development of our FXR program and the potential for our 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. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the company’s filings with the U.S. Securities and Exchange Commission, including “Risk Factors” section of the company’s prospectus dated September 15, 2020 filed pursuant to Rule 424(b)(4) with the Securities and Exchange Commission. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
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