Liver Disease

The liver is one of the most complex organs in the body. Diseases of the liver impact the body’s ability to digest food, metabolize nutrients and fats, filter the blood and fight infections. Driven by a wide range of environmental, viral and genetic causes, liver diseases impact a broad swath of society. NGM leveraged expertise in cardio-metabolic disease to initially focus on liver diseases that are metabolically driven. An estimated 75-100 million Americans have Nonalcoholic Fatty Liver Disease (NAFLD), a condition characterized by excessive fat deposits in the liver. Frequently correlated with poor diet and obesity, NAFLD can also have genetic components. An asymptomatic condition, NAFLD often progresses to a more serious inflammatory disease called Nonalcoholic Steatohepatitis (NASH), which can lead to liver scarring, liver cancer, organ failure and, absent a liver transplant, death.

With contributions from both environmental and genetic factors, the pathogenesis and progression of NAFLD and NASH are complex and not well understood. In order to develop meaningful new medicines for the treatment of NASH, NGM is leveraging our expertise in metabolic disorders to better understand the underlying biology of the disease. Focusing on the identification of new drug targets, we have pursued investigations into both the metabolic dysfunction in hepatocytes and the activation of pro-fibrotic hepatic stellate cells. As a result of these efforts, we are now positioned to discover experimental medicines that impact multiple biological mechanisms and resolve the essential pathophysiological conditions that lead to NASH and resulting liver dysfunctions. We are also pursuing research on the mechanisms of bile acid synthesis and the diseases driven by dysregulation of those mechanisms, including cholestatic liver diseases.