FREMONT, Calif.--(EON: Enhanced Online News)--While NOACs are increasingly replacing warfarin to treat thromboembolism – blood clots – they have an increased risk of bleeding and bleeding complications, which can be life-threatening1. Preclinical research presented at the ASH (American Society of Hematology) Annual Meeting on Monday demonstrated that multiple novel anticoagulants from Verseon are as effective as the NOACs at preventing thrombosis, but with a much-reduced bleeding risk.
“This unique feature of our novel class of thrombin inhibitors provides a biological explanation for their low bleeding liability”
The research presented by Verseon’s Dr Mohan Sivaraja, Associate Director of Discovery Biology, showed that Verseon’s new class of direct thrombin inhibitors (VE-DTIs) are able to preserve platelet function while still blocking fibrinogen cleavage, a primary event in blood clot formation2.
Platelet function plays an important role in wound healing, healthy tissue growth, and hemostasis (stopping of bleeding). The observed preservation of platelet function indicates a reason why the VE-DTIs have a significantly reduced bleeding risk when compared to current NOACs.
The presentation detailed a number of in vivo tests, including the arteriovenous shunt and thrombin-induced thromboembolism models, which demonstrate that the VE-DTIs effectively prevent thrombosis while preserving platelet function. This is further reinforced by in vitro research in which both animal and human blood was put through a number of assays, which confirm that Verseon’s compounds leave platelet function almost unaffected.
NOACs, currently the most commonly used anticoagulants, are associated with a high bleeding risk and are known to strongly inhibit thrombin-mediated platelet activation, which affects platelet function3. Verseon’s drug candidates are up to 900-fold less potent in the in vitro inhibition of platelet activation when compared to the NOACs, while they effectively block fibrinogen cleavage.
“This unique feature of our novel class of thrombin inhibitors provides a biological explanation for their low bleeding liability,” said Dr. Mohan Sivaraja. “These encouraging results further establish the distinctive pharmacology of our compounds and could lead to improved blood thinners.”
Verseon’s new class of anticoagulants has been developed using its proprietary, computationally driven drug discovery platform. This platform can generate better drugs through the design of novel chemical matter. In addition to its anticoagulant program, Verseon currently also has programs on diabetic macular edema and oncology in preclinical testing, all with multiple novel drug candidates.
1 “Risk of Fatal Bleeding in Episodes of Major Bleeding with New Oral Anticoagulants and Vitamin K Antagonists: A Systematic Review and Meta-Analysis” http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137444
2 “Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms” http://www.bloodjournal.org/content/100/3/743?sso-checked=true
3 “Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding.” https://www.ncbi.nlm.nih.gov/pubmed/27693274