Targeting Bile Salt Hydrolase with the Oral Small Molecule VT-6382 as a Novel and Differentiated Approach to Treating MASH and Liver Fibrosis
- Bile acid homeostasis is dysregulated in MASH and liver fibrosis, with progressive increases in secondary bile acids occurring across the MAFLD-MASH-fibrosis continuum. Targeting bile salt hyrdrolase (BSH), an essential nodal enzyme in bile acid regulation, has the potential to restore bile acid homeostasis and associated signaling.
- VT-6382 is an orally administered, gut-restricted small molecule inhibitor of BSH
- Chronic administration of VT-6382 to hyperphagic mice in the foz/foz model of progressive MASH and liver fibrosis lead to significant, dose-dependent improvements in several key MASH- and fibrosis-related endpoints as well as significant appetite suppression and weight loss. VT-6382 is being developed as a promising new approach to management of cardiometabolic disease.