Diets high in saturated fats and processed carbohydrates drive the accumulation of fats (lipids) in peripheral organs. Altered levels (quantity) and abundance (quality) of key bioactive lipids can induce tissue inflammation. This is referred to as ‘lipotoxicity’, where tissue fibrosis can compromise organ function. Lipotoxicity contributes to the high prevalence of conditions such as Metabolic Syndrome or Type 2 diabetes and more serious co-morbidities such as CKD (chronic kidney disease) and non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD is globally estimated at ~25% (and rising) and is a continuum of liver abnormalities from NASH (non-alcoholic steatohepatitis) to cirrhosis and end-stage liver disease (necessitating liver transplantation) and liver cancer.
Cincera Therapeutics (Cincera) is developing range of potent and orally available inhibitors of a key enzymatic target in a lipid metabolism pathway as medicaments for the treatment of NAFLD/NASH and other indications ranging from insulin resistance to CKD and cancer. Our novel agents have shown potent cell mediated anti-inflammatory/anti-fibrotic properties and display a broad mechanism of action founded in the modulation of the relative abundance of key bioactive lipids (i.e. quality), rather than directly affecting total lipid levels (i.e. quantity). This orthogonal approach supports single agent efficacy but is also highly compatible for combination therapies with incumbent or leading metabolic disease therapies targeting NASH and associated indications. Cincera has potent and selective compounds currently under optimisation and pre-clinical efficacy assessment in key disease models. The Company is aiming to have drug candidates ready for clinical trials by 2020/21.