Cerenis Therapeutics featured prominently at the 25th Conference of the ASIAN PACIFIC ASSOCIATION FOR THE STUDY OF THE LIVER (APASL)
Experimental results demonstrate an active role to treat atherosclerosis and non-alcoholic steatohepatitis (NASH) for CER-209 as an agonist of the P2Y13 receptor
Toulouse, FRANCE, Ann Arbor, UNITED STATES, February 25, 2016 – Cerenis Therapeutics (FR0012616852- CEREN), an international biopharmaceutical company dedicated to the discovery and development of innovative HDL therapies (“good cholesterol”) for treating cardiovascular and metabolic diseases, today reported two poster presentations featuring Cerenis Therapeutics’ innovative HDL therapy, CER-209, during the 25th Conference of the APASL held in Tokyo, February 20-24, 2016.
• CER-209, an agonist of the P2Y13 receptor, is potentially well suited to the treatment of atherosclerosis and non-alcoholic steatohepatitis (NASH)
In a poster presentation (“P2Y13 receptor agonist CER-209 decreases both atherosclerosis and liver steatosis in vivo”), Cerenis presented results of CER-209, a selective novel agonist of the P2Y13 receptor (P2Y13R) that caused an increased uptake of high-density lipoprotein-cholesterol (HDL-c) in the liver which is associated with stimulation of bile acid secretion. Repeated dose administration of CER-209 stimulated the apoA-I synthesis and formation of small HDL particles, known to be atheroprotective. CER-209-treated plasma samples had high cholesterol efflux capacity for the mobilization of cellular cholesterol in vitro compared with the placebo group. CER-209 induced a decrease in atherosclerotic plaques in aorta and carotids as well as a remarkable decrease in the steatosis in a validated preclinical model.
HDL is known to protect against atherosclerosis by promoting the reverse lipid transport. A new pathway for the regulation of HDL-c recognition by the liver involving F1-ATPase and P2Y13 receptor (P2Y13R) has been described in vitro, and recently in mice. An increase in the expression of liver mRNA coding for apoA-I and plasma apoA-I concentration of treated animals was observed. The uptake of large, mature HDL particles loaded with cholesterol by the liver also stimulates de novo synthesis of nascent HDL particles, thereby enhancing the cholesterol efflux capacity of the serum. The overall implication of this increase is not only to allow the removal of cholesterol from atherosclerotic plaques, but also to regulate lipid homeostasis in the liver.
In another poster presentation (“P2Y13 receptor agonist CER-209, an anti-atherosclerotic compound, decreases liver steatosis in vivo”), Cerenis presented further results with the selective novel agonist of the P2Y13R, CER-209. In this preclinical model, CER-209 resulted in a marked reduction in overall steatohepatitis as determined by reductions in cholesterol, trigylcerides and fatty acids compared with placebo. Furthermore, CER-209 produced considerable decreases in liver enzymes (ALT and AST) in the plasma. These effects suggest the restoration of liver integrity and indicate a strong potential for CER-209 to treat liver disease such as NASH and non-alcoholic fatty liver disease (NAFLD) associated with cardiovascular disease.
These are important findings given the current lack of treatment options for NASH and introduces P2Y13R as a new therapeutic target for this disorder. CER-209 exerts its beneficial effect on liver steatosis via a specific action on the cholesterol elimination pathways. Therefore, CER-209 has a strong potential for the treatment of NASH and NAFLD.
Dr. Jean-Louis Dasseux, Founder and CEO of Cerenis comments: “These results show that CER-209 has the potential to be an effective treatment for atherosclerosis and associated non-alcoholic steatohepatitis (NASH). They also demonstrate the ability of the Cerenis scientists to advance critically our understanding of HDL metabolism which could lead to several entirely new classes of therapeutic agents”.