Programs

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Our Approach

Since our founding in 2014, we have invested in building a foundation of chemistry and biology expertise to drive drug discovery and development. We believe these internal capabilities allow us to gain insights into disease targets and mechanisms and more purposefully design therapies.

Our most advanced program targets the farnesoid X receptor (FXR) which is central to modulating GI and liver diseases. We believe that potency, sustained exposure and continuous target engagement are key to optimizing therapeutic benefit with an FXR targeted therapy. Leveraging our extensive chemistry and biology expertise, we have built a proprietary library of over 2,500 FXR compounds and have selected MET642 to advance into a Phase 2 study in ulcerative colitis.

We plan to develop MET642 as a potential treatment for GI diseases affecting large patient populations with high unmet need. We intend to pursue development of MET642 for the treatment of inflammatory bowel disease (IBD) including ulcerative colitis (UC), as we believe FXR plays a key role in the disease process of IBD. We believe an oral, once-daily therapy with FXR agonists could be an attractive treatment option for UC patients that may prefer oral administration instead of injectable biologics that are cumbersome to administer chronically. In preclinical studies of our FXR agonists, we have observed improvement in colon inflammation on a level similar to that of injectable biologics currently used for treatment. We intend to initiate a Phase 2 proof-of-concept clinical trial for MET642 in UC in the first half of 2022.

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