Abstract 1663 | The Liver Meeting® 2020, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
Authors: Seth J. Baum, Stephen A. Harrison, Nadege T. Gunn, Ziad H. Younes, Anita Kohli, Rashmee Patil, Harinder Chera, Jeff Zhao, Manu V. Chakravarthy, and Margaret J. Koziel
Nonalcoholic fatty liver disease (NAFLD) is multifactorial, mediated by dysregulated metabolic and fibroinflammatory pathways. Because NAFLD and type 2 diabetes (T2D) have a well-established bidirectional link, with insulin resistance serving as a common metabolic driver, targeting insulin resistance is a potential strategy for managing NAFLD. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families that include amino acids (AAs), fatty acids and other lipids, bile acids, ketone bodies, hormones, and other molecules. EMMs can be selectively combined to form EMM compositions to simultaneously support multiple metabolic nodes and pathways key to liver health and multifactorial diseases. As novel, orally administered EMM compositions of AAs and related metabolites and precursors, AXA1125 and AXA1957 are specifically designed to support pathways related to liver metabolism, inflammation, and fibrosis in a multitargeted manner. AXA1125 is composed of leucine, isoleucine, valine, arginine, glutamine, and N-acetylcysteine (LIVRQNac). A previous non-IND clinical study (AXA1125-002) assessed the safety, tolerability, and biological activity of AXA1125 on liver structure and function in subjects with NAFLD and T2D and demonstrated positive directional changes in biomarkers related to liver fat, insulin sensitivity, inflammation, and fibrosis, results that were supported by targeted plasma metabolomic and lipidomic data. Composed of leucine, isoleucine, arginine, glutamine, N-acetylcysteine, carnitine, and serine (LIRQNacCarS), AXA1957 is isonitrogenous to AXA1125 and was developed to examine additional biological activity.