Unique Fat-Inhibiting Approach Targets Multiple Pathways in Metabolic Liver Disease with David Happel Sagimet Biosciences

David Happel is President and CEO of Sagimet Biosciences, a company developing drugs to treat metabolic diseases by targeting the underlying cause of fat accumulation in the liver. The drug denifanstat limits the activity of fatty acid synthase (FASN), an enzyme that regulates fat accumulation. This approach is a fat inhibitor, not a fat burner, the focus of other MASH drugs.  David explains, "Sagimet was founded back in 2007 as a private company with a group of medicinal chemists that had a particular target in mind, and this particular target was called fatty acid synthase, or FASN. FASN is a rather ubiquitous enzyme throughout the body that functions as a regulating enzyme in many organs. When FASN becomes overactive or overexpressed, it sort of throws things out of balance and, in particular, certain cardiometabolic diseases, such as MASH and in the liver. So, this group of chemists, in order to resolve this overactivity, developed a portfolio of FASN inhibitors, led by our lead program denifanstat, that seek to target the underlying cause of MASH and, therefore, really work to limit the activity of FASN, try to normalize it essentially is what we do." "For us and this particular molecule, it offers a differentiated approach to treating the disease. Our molecule, denifanstat, is the only fat synthesis inhibitor in development for MASH, making it rather unique. All the rest of the molecules are fat burners, fat oxidizers, and fat mobilizers, including GLPs, FGF, and THR-beta. They all function by trying to burn fat peripherally and in the liver to a degree. They rely on that fat-burning mechanism to translate into downstream reductions in inflammation and fibrosis, which is important to treating MASH, but they've had varying degrees of success. Our molecule targets each pathway independently: fat, inflammation, and fibrosis, and has had a rather pronounced treatment effect as a result."  #SagimetBiosciences #MASH #FattyLiverDisease #FASN #FASNInhibitor #Fibrosis #Obesity #NASH #GLP1Agonists sagimet.com Download the transcript here