Are Ticks the Answer to Medical Device-Associated Clotting?
Bioxodes has just published major preclinical results in the renowned Journal of the American College of Cardiology.
Bioxodes SA, a dynamic clinical stage Belgian biotech company specialized in developing novel generation of antithrombotics for cardiovascular setting, has just published major preclinical results in the renowned Journal of the American College of Cardiology.
The company’s lead product, Ir-CPI, is intended to be used as an alternative to the current gold standard treatment used to prevent medical device-associated clotting, the Unfractionated Heparin (UFH). Heparin, while efficacious, increases bleeding risk in many patients and can be associated to allergy, to heparin resistance and to a life-threatening reduction of platelets.
Ir CPI, first identified in the tick, is a small protein with a wide-range of potential indications where blood is in contact with medical devices known to activate the coagulation processes leading to clot formation. Several blood-contacting devices such as catheters, extracorporeal membrane oxygenation (ECMO), hemodialysis, and cardiopulmonary bypass (CPB) are routinely used. At the blood-contacting surface of these devices, coagulation is triggered through activation of two molecules belonging to the coagulation pathway, the Factors XII (FXII) and Factors XI (FXI). Ir-CPI is a unique compound targeting both activated forms of these molecules, namely FXIIa and FXIa. Using preclinical models, Ir-CPI was proven to be a highly efficient antithrombotic moleculewhich does not promote bleeding or impair blood coagulation parameters.
Bioxodes has just published these major preclinical results in the renowned Journal of the American College of Cardiology.
“This publication clearly validates the scientific results of Bioxodes, emphasizing their relevancy and scientific interest. It represents a tremendous support for the ongoing clinical studies” said the KOL Prof. Cédric Hermans, Head of Haemostasis and Thrombosis at St-Luc University Hospital, Brussels, Belgium.
Anticoagulation with an inhibitor of Factors XIa and XIIa during cardiopulmonary bypass
In a nutshell, the authors evaluated the antithrombotic activity of Ir-CPI by using 3 different animal models of medical device-associated clotting.
They showed that Ir-CPI:
1) attenuates catheter thrombosis in a rabbit model;
2) decreases thrombus formation in a rabbit arteriovenous shunt model;
3) is as effective as heparin for preventing clotting in an ovine cardiopulmonary bypass (CPB) model with cardiac surgery on beating-heart.
Furthermore, in the latter model, treatment with Ir-CPI had no clinical impact on the recovery of animals during a 7-day period.
Same antithrombotic efficacy as Heparin, with less bleeding
Taking advantage of the similar hemostatic properties of pigs and humans, pig liver bleeding assays were performed to evaluate the safety of Ir-CPI. Whereas heparin increased blood loss compared with saline, Ir-CPI did not.
This is the first time that an inhibitor of both FXIa and FXIIa has been shown to provide thromboprotection during CPB in cardiac surgery, to have no clinical impact on the recovery of animals, and to be safer than UFH in terms of bleeding. Such preclinical results indicate that Ir-CPI might be an important therapeutic agent by protecting patients from thrombosis in highly thrombogenic clinical situations involving blood-contacting medical devices.
Bioxodes obtains authorization to launch phase I trial of its antithrombotic drug, Ir-CPI, in healthy male volunteers
In June 2019, the company completed an EUR 7.65 million capital increase. A repayable advance of EUR 2.65 million was granted by the Walloon Region which has been actively supportive since the creation of the company. With this capital increase, Bioxodes wishes to demonstrate the safety of Ir-CPI in humans (Phase I) but also to obtain first proofs of efficacy in patients.
The company announced on October, 15 obtaining the authorization to launch a double blind, placebo controlled, single ascending dose phase I trial of its antithrombotic drug, Ir-CPI, in healthy male volunteers. The objectives of this phase I study are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug candidate, Ir-CPI. The clinical trial has already been launched in Belgium, early October.