•

MET409 NASH Proof-of-Concept Trial Results Published in the Journal of Hepatology: In February 2021, results from a 12-week, randomized, placebo-controlled Phase 1b trial of MET409, one of two novel farnesoid X receptor (FXR) agonists developed by Metacrine, in patients with non-alcoholic steatohepatitis (NASH) were published in the Journal of Hepatology. In the trial, MET409, at 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.

•

MET409 Phase 2a Combination Trial with Empagliflozin in Patients with Type 2 Diabetes and NASH Initiated: In January 2021, the first patient was treated in Metacrine’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 and NASH. 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 (MRI-PDFF). The trial will enroll up to 120 patients in the United States. Metacrine expects to report topline data in the first half of 2022.

•

MET642 Phase 1 Data Presented at the 2021 NASH-TAG Conference: A poster highlighting the final results from Metacrine’s Phase 1 trial of MET642, the company’s second FXR agonist, in healthy volunteers was presented at the 2021 NASH-TAG Conference. These data build upon the preliminary Phase 1 results reported in December 2020, which showed that treatment with MET642 was generally well-tolerated, with no incidence of pruritus or increases in LDL cholesterol at all doses evaluated. MET642 also demonstrated a sustained pharmacokinetic profile and robust FXR target engagement after 14 days of daily oral dosing in healthy volunteers.

•

Initiated a Phase 2a Monotherapy Trial of MET642 in Patients with NASH: In March 2021, the first patient was treated in Metacrine’s Phase 2a trial evaluating MET642 in patients with NASH. The Phase 2a clinical trial is a 16-week, randomized, placebo-controlled, multi-center trial evaluating the safety, tolerability and pharmacological activity, as measured by MRI-PDFF, at 3 mg and 6 mg dose levels. The two doses are projected to suppress 7α-hydroxy-4-cholesten-3-one (C4), a blood biomarker of bile acid synthesis that decreases with FXR activation, to levels that are likely to result in meaningful reductions in liver fat content. The trial will enroll up to 180 patients in the United States. An interim analysis is planned in the fourth quarter of 2021, after approximately 60 patients have completed 16 weeks of treatment, with topline trial results of up to 180 patients expected to be reported in the first half of 2022.

•

MET642 Granted Fast Track Designation as a Treatment for NASH: In January 2021, the U.S. Food & Drug Administration (FDA) granted Fast Track designation to MET642 for the treatment of NASH. 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.

•

Industry Veteran, Jeff Jonker, Appointed to Board of Directors: In March 2021, Metacrine appointed Jeff Jonker to its board of directors. Mr. Jonker currently serves as a senior advisor for Ambys Medicines, where he was previously the

president and chief executive officer and a director. During his tenure at Ambys Medicines, Mr. Jonker leveraged the company’s $140 million Series A financing and strategic partnership with Takeda to establish a pioneering cell therapy platform, including the build out of a cGMP cell therapy manufacturing facility to enable clinical and commercial supply of human hepatocytes. Prior to Ambys Medicines, Mr. Jonker served as president of NGM Biopharmaceuticals, where he led the advancement of the company’s robust pipeline, including therapeutics for immune-oncology, retinal, liver and metabolic diseases. Mr. Jonker holds a J.D. from Columbia University School of Law, an M.LITT. from the University of St. Andrews and a B.A. from Claremont McKenna College.

•

Metacrine expects to report topline data of an interim analysis from its Phase 2a, 16-week, randomized, placebo-controlled trial evaluating MET642 in patients with NASH in the fourth quarter of 2021 after approximately 60 patients have completed 16 weeks of treatment, with topline trial results of up to 180 patients expected to be reported in the first half of 2022.

•

Metacrine expects to report topline data from its Phase 2a trial evaluating MET409 in combination with empagliflozin in patients with both type 2 diabetes mellitus and NASH in the first half of 2022.

•

Capital Position: Cash, cash equivalents and short-term investments were $96.2 million as of December 31, 2020. The company believes that its cash, cash equivalents and short-term investments as of December 31, 2020 will be sufficient to fund its current operating plan through 2022.

•

R&D Expenses: Research and development expenses were $6.8 million for the fourth quarter of 2020 and $26.8 million for the full year ended December 31, 2020, compared to $6.5 million for the fourth quarter of 2019 and $26.0 million for the full year ended December 31, 2019. The increase in research and development expenses was primarily attributable to the continued investment in the clinical development and manufacturing activities associated with the advancement of MET409 and MET642.  

•

G&A Expenses: General and administrative expenses were $3.8 million for the fourth quarter of 2020 and $9.9 million for the full year ended December 31, 2020, compared to $1.0 million for the fourth quarter of 2019 and $4.0 million for the full year ended December 31, 2019. The increase in general and administrative expenses was primarily attributable to increased headcount, non-cash stock-based compensation and costs associated with operating as a publicly traded company upon completion of the company’s initial public offering in September 2020.

•

Net Loss: Net loss was $10.8 million for the fourth quarter of 2020 and $37.3 million for the full year ended December 31, 2020, compared to $7.4 million for the fourth quarter of 2019 and $28.9 million for the full year ended December 31, 2019.