Non-alcoholic steatohepatitis (NASH) is a liver disease characterized by excess liver fat, inflammation and fibrosis. In 2015, an estimated 17 million people in the United States had NASH, which is expected to increase to an estimated 27 million people by 2030. Left untreated, the disease may progress to liver failure, which is a life-threatening condition. NASH is now the leading cause for liver transplants in the United States. In addition, patients with NASH often have metabolic disease and other co-morbidities including type 2 diabetes.
NASH is a complex and chronic disease that we believe will likely require combination regimes to effectively treat patients. Our FXR program can potentially serve as an important part of these novel combination approaches.
We are also developing hydroxysteroid dehydrogenase 17β13 (HSD17β13 or HSD) as a potential treatment for NASH and other liver diseases. HSD is a genetically-validated target for advanced liver disease. People with one or two alleles of the HSD17β13 variant rs72613567 are less likely to develop NASH, alcoholic liver disease (ALD), cirrhosis and hepatocellular carcinoma(1). The protective genetic variant results in impaired activity of the HSD17β13 enzyme, suggesting that inhibitors of the enzyme may provide similar protection(1, 2). Based upon the results of this research and our own discovery work, we are developing small molecule inhibitors of HSD17β13(3).
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Wang et al Eur Rev Med Pharmacol Sci 2020;24:8997-9907