TARGETING UNMET DISEASE THROUGH DEVELOPMENT of Best-in-class Therapies

Metacrine is a biotech company developing innovative therapeutics for liver, gastrointestinal, and metabolic diseases. The company is led by an experienced management team and backed by leading institutional investors. Metacrine’s management team has a distinguished track record in the life sciences industry and was instrumental in the successful development and commercialization of products from companies such as Aragon Pharmaceuticals, Seragon Pharmaceuticals, and Ariosa Diagnostics.

Founded in 2015, Metacrine’s initial technology was licensed from the laboratory of Dr. Ronald Evans, a world leader in nuclear hormone receptors and Howard Hughes Medical Institute Investigator at the Salk Institute. Metacrine’s lead program is centered around the Farnesoid X Receptor (FXR). FXR is a nuclear hormone receptor that has been clinically validated as a key drug target in hepatobiliary diseases such as primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH). NASH is reaching epidemic proportions in the US and worldwide, with approximately 10-15 million Americans having various stages of NASH. Currently, there is no approved therapy for NASH, and left untreated, patients with NASH can progress to cirrhosis. NASH is projected to become the leading cause of liver transplantation in the U.S. within the next few years.

Metacrine has identified key aspects as it relates to FXR engagement and has developed a robust small molecule non-bile acid portfolio originating from a unique chemical scaffold. Key insights around FXR has allowed Metacrine to develop a best-in-class portfolio of FXR agonists with the lead molecule entering clinical development in early 2018. In addition to hepatobiliary indications, FXR is being explored in other human diseases.

In addition to FXR, Metacrine has discovery efforts against novel inflammatory and fibrosis targets. These targets can complement the activities of FXR as it relates to NASH and NASH related fibrosis as well as having potential utility in other diseases.

Metacrine is also developing a novel first-in-class insulin sensitizing protein therapeutic. Fibroblast growth factor 1 (FGF1) was recently demonstrated to have unexpected metabolic benefit when administered to various diabetic animal models. There are over 30 million type 2 diabetics in the United States and despite numerous available drug classes, close to 50% of patients are unable to achieve target HbA1c levels and glucose control. Most therapies do not address the core issue of insulin resistance in diabetes. FGF1 appears to not only lower glucose, but also improve insulin sensitivity. In 2017, Metacrine established a research collaboration with Novo Nordisk to further develop FGF1 analogs.