Benzinga | Dec 2, 2020 07:36AM EST

Hepion Highlights Results From CRV431 Study

EDISON, NJ / ACCESSWIRE / December 2, 2020 / Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence ("AI")-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis ("NASH") and liver disease, today announced results from a translational research study in which its lead drug candidate, CRV431, decreased formation of a novel class of human blood platelets, called 'procoagulant platelets.' High levels of procoagulant platelets have been associated with transient ischemic attack and stroke.1

Patients with advanced liver disease often have coagulopathy disorders, diabetes, and dyslipidemia, and may develop hemorrhagic and ischemic diseases including stroke.2 For example, patients with nonalcoholic fatty liver disease ("NAFLD") and NASH have an increased risk for ischemic stroke, which accounts for 87% of strokes in the United States and is the second leading cause of death globally.3 Additionally, patients with NAFLD may experience more severe stroke which may require more aggressive management of liver disease.4 Nonclinical studies have reported that cyclophilins, the enzymes inhibited by CRV431, contribute to platelet activities, which prompted Hepion to undertake the present in vitro study to examine the effects of CRV431 on platelets.

The study was conducted by Dr. Paul Jurasz, Associate Professor in the Faculty of Pharmacy & Pharmaceutical Sciences at University of Alberta (Edmonton, Canada). Human blood platelets were collected from 8 human donors and experimentally activated with collagen and thrombin to simulate the propagation phase of blood clotting. Treatment with CRV431 at pharmacologically relevant concentrations decreased membrane exposure of phosphatidylserine, a marker of procoagulant platelets, by up to 49% (mean 29% reduction; p<0.001). Importantly, CRV431 seemingly had no significant effect on platelet aggregation.

"NASH and NAFLD are well-established risk factors for cardiovascular disease," stated Dr. Patrick Mayo, Hepion's Senior Vice-President of Clinical Pharmacology and Analytics. "And, we know that the risks for ischemic stroke and the severity and prognosis of stroke appear to be linked to liver diseases such as NASH. In turn, high levels of procoagulant platelets are noted in ischemic stroke. The reduction in procoagulant platelets by CRV431 appears to occur at least in part by inhibiting the specific isoform, cyclophilin D, based on other experimental studies."

Dr. Jurasz added, "The results of this study are quite intriguing, as blocking procoagulant platelet formation may provide for a novel anti-thrombotic strategy, particularly in the prevention of certain types of strokes in which elevated levels of procoagulant platelets have been observed."

"The findings of this study further add to our belief that CRV431 will emerge as a leading therapeutic drug in the treatment of NASH and other liver disease," stated Dr. Robert Foster, Hepion's CEO. "CRV431 is a multi-modal agent that is now demonstrating an additional potential benefit in reducing the downstream negative consequences of NASH: a possible link to cardiovascular risk. Thus far, we have generated both in vitro and in vivo data confirming CRV431 reduces fibrosis, inflammation, hepatocellular carcinoma, and now, the potential to reduce procoagulant platelets. Each one of these events may lead to increased morbidity and mortality, but may be treated by CRV431, an inhibitor of many isoforms of cyclophilins in humans. To date, CRV431 appears safe and well-tolerated in our phase 1 and 2 clinical trials."

1Blood 2017;130(20):2171-2179

2JAMA Neurol. 2017;74(8):927-932

3Medscape 2018

4World J Hepatol. 2018;10(7):474-478