Hepion Pharmaceuticals, Inc.'s NASH Drug Candidate, CRV431, Demonstrates Superior Antifibrotic Efficacy in Expanded Human Liver Study
January 28, 2020 at 09:27 pm
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Hepion Pharmaceuticals, Inc. announced positive findings from an expanded study with human precision cut liver slices (“PCLS”). In this specialized experimental model using human liver tissue, Hepion’s drug candidate, CRV431, prevented experimentally induced liver fibrosis to a greater extent than four other leading NASH drug candidates: obeticholic acid (“OCA”, an FXR agonist), elafibranor (a PPARa/d agonist), resmetirom (a THR-ß agonist), and Aramchol (an SCD1 inhibitor). These results support the potential for CRV431 to exert potent antifibrotic activity in NASH. The study was conducted by FibroFind, a spin-out contract research company from the Fibrosis Research Group at Newcastle University, Newcastle Upon Tyne, UK. Liver tissue was obtained from three separate human donors and exposed to TGF-ß1 and PDGF-BB, which are potent biological inducers of inflammation and fibrosis. The study design and its findings were similar to a previous study conducted by Hepion and FibroFind in which CRV431 was tested on tissue from a single human donor. In a combined data analysis of all of four donor samples, CRV431 was the only one of the five drug candidates that, on average, completely prevented TGF-ß1- and PDGF-BB-induced fibrosis. The comparator compounds in these studies were administered at equimolar or higher concentrations than CRV431. Furthermore, CRV431 was also able to diminish endogenous fibrotic activity in diseased liver samples from three of four donors in the absence of added TGF-ß1 and PDGF-BB. In addition to the reductions in tissue fibrosis, as measured by Picrosirius Red staining, CRV431 decreased gene expression and secretion of several markers of inflammation and fibrosis, including IL-6, MCP-1, collagen 1a1, hyaluronic acid, and TIMP-1.
Hepion Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of drug therapy for treatment of chronic liver diseases. The Company is developing a treatment for non-alcoholic steatohepatitis (NASH), hepatocellular carcinoma (HCC), and other chronic liver diseases. Its cyclophilin inhibitor, rencofilstat, is being developed to offer benefits to address multiple complex pathologies related to the progression of liver disease. It is developing rencofilstat as its lead molecule. Rencofilstat is a compound that binds and inhibits the function of a specific class of isomerase enzymes called cyclophilins that regulate protein folding, in addition to other activities. It has developed and maintains an artificial intelligence deep machine learning (AI/ML) platform designed to understand disease processes and identify patients that are rencofilstat responders. In addition, its AI/ML can be used to further NASH and HCC clinical development programs.