MTCR Metacrine Inc.

8.5
+0.06  (+1%)
Previous Close 8.44
Open 8.4
52 Week Low 7.64
52 Week High 16.19
Market Cap $220,628,550
Shares 25,956,300
Float 17,812,835
Enterprise Value $125,215,180
Volume 25,255
Av. Daily Volume 71,070
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Upcoming Catalysts

Drug Stage Catalyst Date
MET409 with Empagliflozin
Type 2 Diabetes and Nonalcoholic steatohepatitis (NASH)
Phase 2a
Phase 2a
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Drug Pipeline

Drug Stage Notes
MET642
Non-alcoholic steatohepatitis (NASH
Phase 2a
Phase 2a
Phase 2a trial in NASH to commence 1H 2021.

Latest News

  1. SAN DIEGO, Feb. 19, 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 Preston Klassen, M.D., MHS, president and chief executive officer of Metacrine, will present at the SVB Leerink 10th Annual Global Healthcare Conference on Friday, February 26, 2021 at 4:20 p.m. ET.

    The live webcast will be available in the investor section of the company's website at www.metacrine.com. The webcast will be archived for 60 days following the presentation.

    About Metacrine
    Metacrine, Inc. (NASDAQ:MTCR) is a clinical-stage biopharmaceutical company building a differentiated…

    SAN DIEGO, Feb. 19, 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 Preston Klassen, M.D., MHS, president and chief executive officer of Metacrine, will present at the SVB Leerink 10th Annual Global Healthcare Conference on Friday, February 26, 2021 at 4:20 p.m. ET.

    The live webcast will be available in the investor section of the company's website at www.metacrine.com. The webcast will be archived for 60 days following the presentation.

    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. 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 advanced into a 16-week monotherapy trial in patients with NASH.

    Contact:

    Chelcie Lister

    THRUST Strategic Communications

    910.777.3049



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  2. SAN DIEGO, Feb. 16, 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 the Journal of Hepatology has published the results from the company's 12-week, randomized, placebo-controlled Phase 1b study of MET409, the company's lead farnesoid X receptor (FXR) agonist, in patients with non-alcoholic steatohepatitis (NASH).

    "The publication of our Phase 1b study data in this highly regarded, peer-reviewed journal further underscores the promise of an optimized FXR to treat patients with NASH, a potentially life-threatening liver disease with no approved treatments…

    SAN DIEGO, Feb. 16, 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 the Journal of Hepatology has published the results from the company's 12-week, randomized, placebo-controlled Phase 1b study of MET409, the company's lead farnesoid X receptor (FXR) agonist, in patients with non-alcoholic steatohepatitis (NASH).

    "The publication of our Phase 1b study data in this highly regarded, peer-reviewed journal further underscores the promise of an optimized FXR to treat patients with NASH, a potentially life-threatening liver disease with no approved treatments," said Hubert C. Chen, M.D., chief medical officer of Metacrine. "MET409 has demonstrated improvements in the efficacy and tolerability profile for the FXR class. These findings highlight its potential as both a front-line monotherapy and backbone of combination therapies, including with anti-diabetic medications in patients with both NASH and type 2 diabetes, who represent a patient segment with significant unmet needs. We are excited about the broad potential for MET409."

    Metacrine has developed a proprietary FXR platform utilizing a unique chemical scaffold, which has demonstrated a differentiated and improved therapeutic profile in the clinic. MET409 is a once-daily, orally administered FXR agonist that is being evaluated as both a monotherapy and a combination therapy for the treatment of NASH. In the 12-week Phase 1b trial in patients with NASH, MET409 (50 mg) achieved approximately 38% mean relative liver fat reduction and was associated with a 16% overall pruritus rate, with no discontinuations due to pruritus, and a 7% LDL-cholesterol increase, findings that are favorable and perceived as class-leading for FXR agonists.

    About the Publication

    The Journal of Hepatology article, entitled "A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis", was published online on February 11, 2021. Authors include Stephen A. Harrison, M.D., University of Oxford and Pinnacle Clinical Research; Mustafa R. Bashir, M.D., Duke University Medical Center; and Eric J. Lawitz, M.D., University of Texas Health San Antonio and Texas Liver Institute.

    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.

    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. 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 advanced into a 16-week monotherapy trial in patients with NASH.

    Forward-Looking Statements

    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 MET409; statements regarding Metacrine's timelines; 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; the potential for its FXR product candidates to be long-term therapies for NASH; the potential for its FXR product candidates to be used in combination therapies with anti-diabetic medications; and the potential for its FXR product candidates to be therapies for patients with both NASH and type 2 diabetes. 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.

    Contact:

    Chelcie Lister

    THRUST Strategic Communications

    910.777.3049



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  3. SAN DIEGO, Jan. 19, 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 the U.S. Food & Drug Administration (FDA) has granted Fast Track designation to MET642, the company's second farnesoid X receptor (FXR) agonist, for the treatment of non-alcoholic steatohepatitis (NASH).

    "We are pleased to have received a second fast track designation for product candidates from our proprietary FXR platform and believe this further demonstrates the recognition of significant unmet needs in patients with NASH by regulatory authorities," said Hubert C. Chen, M.D., chief…

    SAN DIEGO, Jan. 19, 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 the U.S. Food & Drug Administration (FDA) has granted Fast Track designation to MET642, the company's second farnesoid X receptor (FXR) agonist, for the treatment of non-alcoholic steatohepatitis (NASH).

    "We are pleased to have received a second fast track designation for product candidates from our proprietary FXR platform and believe this further demonstrates the recognition of significant unmet needs in patients with NASH by regulatory authorities," said Hubert C. Chen, M.D., chief medical officer of Metacrine. "Given our recently reported, favorable Phase 1 data for MET642, we are excited about its potential and look forward to advancing it into the Phase 2a study in the first half of this year."

    Fast Track is a process designed to facilitate the development and expedite the review of drugs designed to treat serious diseases or conditions that have the potential to fill an unmet medical need for such diseases or conditions. Through the Fast Track designation, the company may be eligible to submit sections of its New Drug Application on a rolling basis, and there are opportunities for more frequent interactions and written communications with the FDA around the drug's development plan. A Fast Track-designated product may also be eligible for accelerated approval and priority review if the criteria for those programs are satisfied.

    Metacrine recently completed a Phase 1 clinical trial of MET642 in healthy volunteers, in which MET642 was safe and generally well-tolerated and demonstrated a sustained pharmacokinetic profile and robust FXR target engagement after 14 days of daily oral dosing. Importantly, pruritus and LDL-cholesterol increases were not seen at any dose level. The company plans to further evaluate MET642 in a Phase 2a, 16-week, randomized, placebo-controlled trial in patients with NASH, which is expected to begin in the first half of 2021.

    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. 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 advanced into a 16-week monotherapy trial in patients with NASH.

    Forward-Looking Statements

    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; statements regarding Metacrine's timelines; the differentiated nature of Metacrine's FXR program; plans underlying Metacrine's clinical trials; plans for advancing the clinical development of MET642; 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," "look forward," "will," "expect," "plan," "estimate," "intend," "potential," 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.

    Contact:

    Chelcie Lister

    THRUST Strategic Communications

    910.777.3049



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  4. SAN DIEGO, Jan. 05, 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 the first patient has been treated in the company's Phase 2a trial evaluating MET409 (50 mg) in combination with empagliflozin (Jardiance®), a sodium-glucose cotransport-2 (SGLT2) inhibitor, in patients with both type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). T2DM and NASH co-exist in many patients, with abnormal liver fat content seen in up to approximately 70% of patients with T2DM and biopsy-proven NASH in up to approximately 25% of patients.

    "NASH is a…

    SAN DIEGO, Jan. 05, 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 the first patient has been treated in the company's Phase 2a trial evaluating MET409 (50 mg) in combination with empagliflozin (Jardiance®), a sodium-glucose cotransport-2 (SGLT2) inhibitor, in patients with both type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). T2DM and NASH co-exist in many patients, with abnormal liver fat content seen in up to approximately 70% of patients with T2DM and biopsy-proven NASH in up to approximately 25% of patients.

    "NASH is a multifactorial liver disease associated with a number of co-morbidities, including type 2 diabetes," said Eric J. Lawitz, M.D., vice president of scientific and research development at The Texas Liver Institute, clinical professor of medicine at the University of Texas Health San Antonio and primary investigator for the Phase 2a trial. "Even though patients with T2DM are perceived to have a more aggressive form of NASH and fibrosis, there has been a lack of innovative treatments for these patients. I am encouraged by MET409's monotherapy clinical data in patients with NASH, as well as its potential to combine with a SGLT2 inhibitor. I look forward to evaluating MET409 in this combination, potentially enabling its clinical use in the future."

    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 the clinic. MET409, Metacrine's lead product candidate, is a once-daily, orally administered FXR agonist that is being evaluated as both a monotherapy and a combination therapy for the treatment of NASH. In a 12-week trial in patients with NASH, MET409 (50 mg) achieved approximately 38% mean relative liver fat reduction and was associated with a 16% overall pruritus rate, with no discontinuations due to pruritus, and a 7% LDL-cholesterol increase, findings that are favorable and perceived as class-leading for FXR agonists.

    SGLT2 inhibitors, such as empagliflozin, are once-daily, oral anti-diabetic medications that are increasingly viewed as a paradigm-shifting therapeutic class for T2DM. In addition to beneficial effects on metabolic control and cardio-renal protection, SGLT2 inhibitors have demonstrated positive effects on liver fat reduction. In a proof-of-concept trial in patients with NASH and T2DM, empagliflozin (10 mg) achieved approximately 30% relative liver fat reduction after 20 weeks of treatment. SGLT2 inhibitors therefore have the potential to complement the liver-targeting therapeutic effects of FXR agonism on hepatic steatosis, inflammation and fibrosis.

    "We are pleased to begin this trial, given the meaningful impact this combination could demonstrate in patients affected by these challenging and often overlapping conditions," said Hubert C. Chen, M.D., chief medical officer of Metacrine. "MET409 has already shown significant liver fat reductions and a differentiated tolerability profile as a monotherapy in patients with NASH. Importantly, as a once-daily, oral therapy, MET409 has the potential to be an ideal backbone for use in combination treatment. We look forward to advancing the trial in a key segment of the NASH patient population."

    The Phase 2a clinical trial is a 12-week, randomized, placebo-controlled, multi-center trial evaluating the safety, tolerability and pharmacological activity (as measured by reductions in liver fat content with magnetic resonance imaging-derived proton density fat fraction) of MET409 in combination with empagliflozin in patients with T2DM and NASH. Eligible patients will be randomized into one of four cohorts: MET409 (50 mg), MET409 (50 mg) plus empagliflozin (10 mg), placebo alone or placebo plus empagliflozin (10 mg). Each trial drug will be given once-daily by oral administration. The trial will enroll up to 120 patients in the United States. Metacrine expects to report topline data in the first half of 2022.

    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. 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 advanced into a 16-week monotherapy trial in patients with NASH.

    Forward-Looking Statements

    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 MET409; statements regarding Metacrine's timelines; 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; the potential for its FXR product candidates to be long-term therapies for NASH; the potential for its FXR product candidates to be used in combination therapies; and the potential for its FXR product candidates to be therapies for patients with both NASH and T2DM. 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.

    Contact:

    Chelcie Lister

    THRUST Strategic Communications

    910.777.3049

     



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  5. MET642 Demonstrated Sustained Pharmacokinetic Profile and Robust FXR Target Engagement with Once-Daily Oral Dosing, without Pruritis or LDL-Cholesterol Increase

    Doses Selected for Phase 2a Trial in Patients with NASH; On-Track to Initiate in 1H21

    SAN DIEGO, Dec. 17, 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 reported preliminary results from its Phase 1 trial of MET642, a farnesoid X receptor (FXR) agonist being developed for the treatment of non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease. Findings show that treatment with MET642 was safe and…

    MET642 Demonstrated Sustained Pharmacokinetic Profile and Robust FXR Target Engagement with Once-Daily Oral Dosing, without Pruritis or LDL-Cholesterol Increase

    Doses Selected for Phase 2a Trial in Patients with NASH; On-Track to Initiate in 1H21

    SAN DIEGO, Dec. 17, 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 reported preliminary results from its Phase 1 trial of MET642, a farnesoid X receptor (FXR) agonist being developed for the treatment of non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease. Findings show that treatment with MET642 was safe and generally well-tolerated and demonstrated a sustained pharmacokinetic (PK) profile and robust FXR target engagement after 14 days of daily oral dosing in healthy volunteers.

    "There are no treatments currently available for NASH patients, and given FXR agonism works through multiple mechanisms to improve NASH and fibrosis, I believe that an optimized FXR agonist could become both a first-line monotherapy and foundation for combination therapies in the future," said Stephen A. Harrison, M.D., Visiting Professor of Hepatology at University of Oxford's Radcliffe Department of Medicine, Medical Director of Pinnacle Clinical Research and President of Summit Clinical Research. "I am encouraged by the sustained activity and safety demonstrated with MET642, in particular the lack of pruritis and LDL-cholesterol increases, which support its continued evaluation in patients with NASH."  

    Metacrine has developed a proprietary FXR platform utilizing a unique chemical scaffold, which has demonstrated a clinically differentiated and improved therapeutic profile. The company's lead FXR clinical candidate, MET409, has successfully completed a 12-week trial in patients with NASH. MET642, Metacrine's second clinical candidate, is derived from the same chemical scaffold as MET409 and has shown comparable FXR target engagement and pharmacology in preclinical studies, as well as increased potency and differentiated pharmaceutical properties.

    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 once-daily MET642 doses ranging from 10 mg to 300 mg in the SAD cohorts and 2.5 mg to 10 mg in the MAD cohorts for 14 days. The primary objective of the trial was to evaluate safety and tolerability, and the secondary objectives were to assess PK parameters and FXR target engagement, the latter through the measurement of 7α-hydroxy-4-cholesten-3-one (C4), a blood biomarker of bile acid synthesis that decreases with FXR activation.

    Safety Findings

    MET642 was safe and generally well-tolerated, with no serious adverse events reported, and all adverse events were mild to moderate in severity. Importantly, pruritus and LDL-cholesterol increases were not seen at any dose level.

    PK and Target Engagement Findings

    MET642 exhibited a sustained PK profile as well as robust FXR target engagement throughout 24 hours after once-daily oral dosing, with notable C4 repression – up to an approximately 95% decrease in area-under-the-curve (AUC) relative to placebo – observed after the last dose in all MAD cohorts of the trial. The magnitude of C4 decrease can be used to project potential levels of liver fat reduction in NASH patients, with ≥30% relative liver fat reduction being associated with increased likelihood of histological benefits upon liver biopsy.

    "We are encouraged by the overall safety profile of MET642, and with meaningful target engagement seen at as low as the 2.5 mg dose level, we intend to evaluate the 3 mg and 6 mg dose levels in our upcoming Phase 2a trial in NASH patients," said Hubert C. Chen, M.D., chief medical officer of Metacrine. "With the benefit of greater potency and improved pharmaceutical properties, we believe MET642 has the potential to be another best-in-class FXR agonist in our proprietary portfolio."

    Summary of MET642 Phase 1 Trial Results

    Number of subjects32 total in SAD cohorts

    32 total in MAD cohorts
    Serious adverse eventsNone
    Severity of treatment-related adverse eventsMild to moderate only
    PruritusNone1
    LDL-cholesterolMean change from baseline to Day 14:

    -0.12 to -0.57 mmol/L for MET642 subjects

    -0.10 mmol/L for pooled placebo subjects
    Liver function testsSporadic, isolated ALT/AST increases in MAD cohorts; resolved with continued MET642 dosing/exposure
    PharmacokineticsMean elimination half-life:

    ~40-68 hours after 14 days of dosing
    FXR target engagementMean repression of C4 AUC after last multiple-dose administration:

    ~55% (2.5 mg) to ~95% (10 mg) relative to placebo

    1One case of localized, overnight itch was reported on Day 7 by one MET642 subject in the 5 mg cohort, a finding that is atypical of FXR-associated pruritus; dosing was continued without subsequent events.

    Based on the Phase 1 findings, Metacrine plans to advance two dose levels of MET642 – 3 mg and 6 mg – in a 16-week, randomized, placebo-controlled Phase 2a monotherapy trial enrolling up to 180 patients with NASH. The two doses are projected to repress C4 to levels that are likely to result in meaningful reductions in liver fat content. The trial is scheduled to start in the first half of 2021, with an interim analysis planned in the second half of 2021, after approximately 60 patients have completed 16 weeks of treatment.

    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. 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 MET409 and MET642; Metacrine's timelines; the differentiated nature of Metacrine's FXR program; plans underlying Metacrine's clinical trials; plans underlying Metacrine's clinical trials in NASH; plans for advancing the clinical development of Metacrine's FXR program; and the potential best-in-class nature of Metacrine's FXR program; and the potential for its FXR product candidates to be long-term therapies for NASH. Words such as "may," "will," "expect," "likely," "plan," "aim," "anticipate," "estimate," "intend," "potential," "preliminary," "prepare," "projected," "scheduled," 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: the risk that the preliminary analysis may change upon further evaluation or may not be able to be replicated in a larger patient sample and other risks and uncertainties inherent in early-stage clinical trials; risks and uncertainties regarding regulatory approvals for MET409 or MET642; potential delays in initiating, enrolling or completing any clinical trials; unexpected safety or efficacy data observed during preclinical or clinical studies, 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.

    Contact:

    Chelcie Lister

    THRUST Strategic Communications

    910.777.3049



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