Programs

Program Discovery Lead
Optimization
Pre-clinical Phase 1 Phase 2 Phase 3 Anticipated Next Milestone
FXR
(MET409)

NASH

Phase 1b
Initiate 4Q 2018

IBS-D

Phase 2
Initiate 1H 2019

IBD (UC and Crohn’s)

Phase 2
Initiate 1H 2019
Inflammation and Fibrosis

Development candidate
YE 2019

Program Phase Anticipated Next Milestone
FXR (Met409)
NASH
Ph 1 Phase 1b
Initiate 4Q 2018
FXR (Met409)
IBS-D
Ph 1 Phase 2
Initiate 1H 2019
FXR (Met409)
IBD (UC and Chron’s)
Ph 1 Phase 2
Initiate 1H 2019
New Targets Discovery Development candidate
YE 2019

Our Approach

We have invested in building a foundation of chemistry and biology expertise to drive
innovative drug discovery and development. We believe these internal capabilities allow us to gain insights into disease targets and mechanisms and more quickly and purposefully design drugs with characteristics that we view as key to safety and efficacy.

With this systematic approach, we have designed our lead product candidate MET409 as a novel farnesoid X receptor (FXR) agonist and have identified a potential role for it in the treatment of non-alcoholic steatohepatitis (NASH), irritable bowel syndrome with diarrhea (IBS-D), and inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (Crohn’s). Beyond our FXR program, we are building a pipeline of novel drug candidates by taking advantage of our drug discovery and development capabilities.

FXR Biology

FXR is a nuclear hormone receptor expressed selectively in various tissues, including the liver and gastrointestinal (GI) tract, and implicated in multiple cellular processes that regulate bile acids, lipid metabolism and inflammation. FXR activation in the GI tract leads to release of fibroblast growth factor 19 (FGF19) which signals through receptors in the liver. Preclinical and clinical studies have shown that targeting FXR directly in the liver has advantages beyond FGF19 signaling alone.

Step 1 of 4

The FXR drug (agonist) is taken orally and travels through the stomach to the intestine. In the intestine the FXR agonist binds to and activates the FXR receptor.

Step 2 of 4

FXR receptor activation causes cells in the intestine to release a protein called FGF19 which travels to the liver

Step 3 of 4

Once in the liver FGF19, binds to its receptor and causes a decrease in the synthesis of bile acids.

Step 4 of 4

In addition to the intestine, the FXR agonist also activates FXR receptors in the liver which can provide additional regulation of bile acid synthesis and maintenance of the bile acid pool.

Metacrine FXR Legend

We have purposefully designed MET409 to be a non-bile acid, with sustained FXR engagement and high potency, dosed orally, once-a-day. With this profile, we believe MET409 has the potential to be a best-in-class drug with a key differentiated safety and efficacy profile from other FXR agonists in development.

Inflammation and Fibrosis

In addition to our FXR program, we have continued to invest in drug discovery on other drug targets, particularly in NASH. We have sought to identify drug targets that have effects on inflammation and/or fibrosis for which we believe we could develop proprietary small molecule drugs.