FASN is a key enzyme in the pathway that our bodies use to make lipids. In diseases such as NASH and in certain tumors this pathway does not function properly and overproduces lipids, causing unfavorable metabolic and inflammatory problems to occur.
Our preclinical programs have shown the therapeutic benefit of FASN inhibition in diet-induced mouse models of NASH. Mice fed a “Western diet” containing high amounts of fat and sugar will develop liver damage characterized by excessive fat, inflammation and eventually fibrosis. Our inhibitors reduce the build up of damaging liver fat as well as reduce inflammation and fibrosis, even while the animals continue to eat an unhealthy high fat, high sugar diet.
In cancer models, our compounds have demonstrated significant anti-tumor effects, especially in tumor cells that are dependent on FASN for their survival. Breast, ovarian, and a special subset of non-small cell lung cancer cells (those with a mutation in the KRas gene) are particularly susceptible to our compounds.