Hepion Pharmaceuticals Announces CRV431 Shows Potential to Extend Multiple Organs and Fibrotic Diseases

Posted on February 19, 2020 by Medtech[y] Staff

Clinical stage biopharma company, Hepion Pharmaceuticals (NASDAQ:HEPA), announced results from in vitro studies showing that their lead drug candidate, CRV431, can decrease production of the extracellular matrix (ECM) molecules, collagen and fibronectin, from fibroblastic cells derived from five different organs. Collagen and fibronectin over-production from these types of cells cause fibrotic scarring of injured organs, and therefore these results suggest that CRV431 could exert anti-fibrotic activity across a range of diseases.

Hepion is primarily focused on the development of targeted therapies for liver disease arising from non-alcoholic steatohepatitis (NASH) and other types of hepatitis. CRV431 has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH.

"Fibrotic scarring is a major pathological feature and driver of organ dysfunction in many diseases, including liver cirrhosis, IPF, chronic kidney disease, and several heart conditions. Yet, there are very few treatments available that attenuate the scarring," said Dr. Daren Ure, Chief Scientific Officer of Hepion. "Most treatments attempt to reduce fibrosis by targeting the stimulation of fibroblastic cells, but these signaling events may vary by patient, type of fibrotic disease, or disease stage. The advantage of CRV431, based on our findings, is that its effects appear to be independent of the type of stimulatory signal. Therefore, CRV431 could be used to treat fibrosis without having to fully elucidate how the ECM-producing cells become over-activated."

Hepion Therapeutics Corporate Presentation - 2020

In the study, the five cell types were lung fibroblasts from a patient with idiopathic pulmonary fibrosis, cardiac fibroblasts, dermal (skin) fibroblasts, renal mesangial cells, and the LX2 hepatic stellate cell line.

The CRV431 dose-dependently decreased procollagen and fibronectin secretion from all cell types with similar magnitude, as measured by enzyme-linked immunosorbent assay (ELISA).

The extent of inhibition was similar whether or not the cells were stimulated with the profibrotic agent, transforming growth factor-beta (TGFβ), consistent with direct effects on ECM synthesis. CRV431 dose-dependently decreased ECM production by up to 55% at clinically relevant concentrations, without causing any reduction in cell viability. CRV431 is believed to reduce ECM production by inhibiting cyclophilin B, and consistent with this hypothesis, downregulation of cyclophilin B with small interfering RNA (siRNA) similarly decreased procollagen and fibronectin secretion.

According to Dr. Robert Foster, Hepion's Chief Executive Officer, "Liver fibrosis arising from NASH and other chronic insults continues to be Hepion's primary focus, but the results of these recent studies raise the intriguing possibility that CRV431 could be evaluated for a host of other disorders. IPF is one such example of an aggressive fibrotic disease in tremendous need of new treatments. In addition, our Phase 1 study in healthy volunteers continues to demonstrate a very good safety profile for CRV431, further supporting its possible use for other indications."