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EASL International Liver Conference | June 2022


Complex diseases involve dysregulation of multiple biological pathways, limiting the effectiveness of single-targeted therapies. Endogenous metabolic modulators (EMMs) are naturally occurring compounds with signaling and regulatory properties that, when selectively combined, may elicit multifactorial effects in complex diseases. In a 16-week clinical study, administration of AXA1125, a novel EMM composition of 5 specific amino acids (AAs; leucine [L], isoleucine [I], valine [V], arginine [R], glutamine [Q]) and an AA derivative, N-acetylcysteine (Nac), resulted in a greater reduction of hepatic fat than placebo as one of its multifactorial effects in patients with nonalcoholic fatty liver disease. An analogous decrease in triglyceride accumulation has been observed in primary human hepatocytes (PHHs) treated with LIVRQNac, the nonclinical form of AXA1125 containing the same constituents; a mechanism explaining this effect might be promotion of fatty acid oxidation (FAO) in PHHs by LIVRQNac.