Metacrine

Metacrine, Inc. is a clinical-stage biopharmaceutical company headquartered in San Diego, California, focused on discovering and developing therapies for patients with liver and gastrointestinal diseases. The company built a proprietary portfolio of non-bile acid farnesoid X receptor (FXR) agonists through an internal chemistry and biology platform based on a chemical scaffold that it described as showing an improved therapeutic profile in clinical trials [1][4].

Its lead program, MET409, is a next-generation FXR agonist that was pursued for non-alcoholic steatohepatitis (NASH), diarrhea-predominant irritable bowel syndrome (IBS-D) and inflammatory bowel diseases including ulcerative colitis and Crohn's disease [1][3]. A second candidate, MET642, is an orally delivered FXR agonist that completed Phase 1 and was described in 2022 as Phase 2 ready for ulcerative colitis, positioned as a potential first-in-class, non-immunosuppressive treatment for inflammatory bowel disease intended to address epithelial barrier function and reduce bacterial translocation [0][4]. Metacrine also described a pipeline of drug candidates addressing inflammation and fibrosis [1]. At an earlier stage the company also worked on an injectable protein drug intended to resensitize the body to insulin for type 2 diabetes and obesity, alongside an orally administered compound for NASH and weight loss [6].

The company had no approved products and remained in clinical development [4]. In August 2020 it filed a Form S-1 registration statement for an initial public offering of common stock, applying to list on The Nasdaq Global Market under the ticker MTCR, with Jefferies, Evercore ISI and RBC Capital Markets as joint book-running managers and Canaccord Genuity as lead manager [2].

Founding story

Metacrine's technology was licensed from the laboratory of Ronald Evans at the Salk Institute / Howard Hughes Medical Institute; Evans is known for the discovery of nuclear hormone receptors and mechanisms of hormone signaling [3][6]. The company was founded by a team including Evans and biotech investor/entrepreneur Richard Heyman, who had previously worked in Evans' laboratory and continued to attend its scientific meetings, one of which reportedly gave him the idea for Metacrine [6]. One account lists founders as Michael Downes, Richard Heyman and Ronald M. Evans [4]. Heyman was previously behind Aragon Pharmaceuticals, sold to Johnson & Johnson in 2013 for up to $1 billion, and Seragon Pharmaceuticals, sold to Roche's Genentech in 2014 for up to $1.7 billion [5][6]. Metacrine was officially established in September and began operating in earnest in May 2015 according to then-CEO Neil McDonnell, and initially occupied Seragon's former facility in Carmel Valley, San Diego, hiring three former Aragon and Seragon officials: CFO Trisha Millican, SVP of chemistry Nicholas Smith and VP of business operations Eric Bischoff [6]. Sources differ on the founding year, citing incorporation in 2014 [4] and founding in 2015 [3][4].

Business model

Metacrine operated as a clinical-stage biopharmaceutical developer, funding internal discovery and clinical development of proprietary small-molecule FXR agonists through venture equity, debt financing and public equity markets rather than product revenue [2][3][4]. It had no approved products [4].

Traction

MET409 was expected to enter a Phase 1 clinical trial in June 2018 [3]. MET642 completed Phase 1 in ulcerative colitis and was characterized as Phase 2 ready as of September 2022 [0][4]. The company had 14 employees in August 2015 and planned to add more [6]. In connection with the proposed 2022 merger, Metacrine was expected to deliver net cash of approximately $26 million and minimum net cash of $23 million at closing, and carried term debt with an outstanding principal of $15 million from lender K2 HealthVentures LLC [0].

Latest developments

On September 6, 2022, Equillium, Inc. and Metacrine announced a definitive merger agreement under which Equillium would acquire Metacrine in an all-stock transaction; consideration was to be stock valued at a 25% premium over net cash delivered at closing (estimated at approximately $26 million), with Equillium expecting to add roughly $33 million of cash to its balance sheet, assuming Metacrine's $15 million K2 HealthVentures loan, and appointing Metacrine CEO Preston Klassen to its board. Equillium stated it did not plan to retain any Metacrine employees and would seek a strategic partner for MET642 [0]. On December 23, 2022, the two companies announced mutual termination of the merger agreement, with Equillium citing an intervening strategic partnership with Ono Pharmaceutical that extended its cash runway [7]. One third-party profile cites a share price of $0.58 as of mid-2023 [4].