eXIthera Announces Publication of EP-7041 Data Demonstrating Safe Antithrombotic Activity in ECMO
Clinical and preclinical data published in Critical Care Explorations demonstrate that EP-7041 has the ability to inhibit ECMO-related thrombosis while minimizing the risk of unwanted bleeding
Westborough, Mass., Sept. 17, 2020 – eXIthera Pharmaceuticals, a clinical-stage biotechnology company focused on addressing bleeding complications associated with currently available antithrombotic agents through the inhibition of coagulation Factor XIa, today announced the publication of data in Critical Care Explorations. The publication describes the pharmacodynamic, pharmacokinetic and safety profile of EP-7041, a parenteral, potent, and selective small-molecule Factor XIa inhibitor, as seen in multiple preclinical studies and a Phase 1 study. The manuscript, titled “EP-7041, a Factor XIa Inhibitor as a Potential Antithrombotic Strategy in Extracorporeal Membrane Oxygenation: A Brief Report,” explores the challenges of current systemic antithrombotic therapies in support of extracorporeal membrane oxygenation (ECMO) and proposes an alternative approach through the inhibition of Factor XIa, such as with EP-7041.
“These data demonstrate that EP-7041 has the ability to inhibit thrombosis while minimizing the risk of unwanted bleeding,” said Charles Pollack, Jr., M.D., Medical Director of eXIthera and lead author on the publication. “By preferentially inhibiting thrombosis but not normal hemostasis, EP-7041 holds the promise of preventing circuit and vascular thromboembolism with substantially less inhibition of the local hemostasis required for bleeding control in trauma or surgical procedures. This will potentially enable safer use of ECMO or other interventions employing vascular circuits (cardiac surgery, ventricular assist devices, etc.) in critically ill patients.”
The compelling EP-7041 data as a selective inhibitor of Factor XIa represent not only an appealing strategy for antithrombic therapy during ECMO, but also show promise in the treatment of thromboprophylaxis in patients managed in the intensive care unit (ICU) for COVID-19 syndrome. Inhibition of Factor XIa may represent a unique target to safely prevent and treat thromboinflammatory complications due to COVID-19, including the cytokine response and coagulopathy, and to reduce the associate mortality. eXIthera plans to explore the safety and tolerability of two doses of EP-7041 for the prevention of thromboembolism in the management of COVID-19 patients, compared to control patients managed with institutional standard thromboprophylaxis regimens.
Regarding the exploration of EP-7041 into multiple indications, Neil Hayward, Ph.D., Chief Executive Officer of eXIthera, stated, “the strong data we have seen in both our preclinical and clinical studies support our pursuit of two parallel indications for EP-7041: one in ECMO and one in COVID-19. We look forward to continuing our studies of EP-7041 in the ECMO setting and sharing additional efficacy data comparing EP-7041 to UFH.”
Unfractionated heparin (UFH) remains the standard antithrombotic agent for ECMO support. However, bleeding remains the most common complication of ECMO when using UFH, which can also be complicated by the activation of PF4 antibodies and resulting heparin-induced thrombocytopenia (HIT), heparin resistance, and unreliability of laboratory measures of anticoagulation. Factor XI or XIa is an appealing target in ECMO owing to its role in activation of thrombin production and its lack of contribution to normal homeostasis.
EP-7041 is a highly selective, potent Factor XIa inhibitor, which has been found to be safe and well tolerated in humans. EP-7041 inhibits human Factor XIa with an IC50 of 7.1 nM in humans and has a half-life of only about 45 minutes following parenteral administration, as determined with its pharmacodynamic efficacy marker (aPTT). In healthy volunteers, at a dose of 0.6 mg/kg/hour of EP-7041, the aPTT decreased from 1.8 × baseline just prior to the end of a 5-day continuous infusion to just 1.2 × baseline within 1 hour of terminating the infusion.
The data were initially presented during a virtual poster session at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Congress in July 2020. The abstract (number PB0166) can be found online here.
eXIthera is a clinical-stage biotech company developing small molecule inhibitors of Factor XIa which offer the potential of thrombosis prevention without the bleeding liabilities which exist for all current treatment options. eXIthera’s lead IV candidate, EP-7041, is a novel, potent and selective small-molecule Factor XIa inhibitor. EP-7041 was found to be safe and well tolerated in sixty healthy volunteers following single or multiple ascending doses in a recent Phase 1 clinical study. In addition, the pharmacokinetic and pharmacodynamic profile indicated desired efficacy with minimal potential for bleeding. For more information, visit eXIthera’s website at www.eXIthera.com
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 Shatzel JJ, DeLoughery EP, Lorentz CU. , et al. The contact activation system as a potential therapeutic target in patients with COVID-19. Res Pract Thromb Haemost 2020 . Doi: 10.1002/rth2.12349