TLC-1180 + TLC-3595

TLC-1180 + TLC-3595 is a novel combination therapy being developed by OrsoBio for the treatment of obesity and associated metabolic disorders. The combination consists of TLC-1180, a mitochondrial protonophore (MP), and TLC-3595, a selective inhibitor of acetyl-CoA carboxylase 2 (ACC2). These two agents enhance fatty acid oxidation through complementary mechanisms: TLC-1180 increases energy expenditure by uncoupling oxidative phosphorylation, while TLC-3595 promotes fatty acid oxidation by reducing malonyl-CoA levels in the mitochondria. Preclinical data in diet-induced obese (DIO) mice demonstrate that the combination induces weight loss comparable to GLP-1 receptor agonists like semaglutide, but with the distinct advantage of preserving lean mass, whereas incretin-based therapies often lead to a reduction in lean mass.