OC 43.1 - A novel bleeding model in monkeys to assess efficacy of VMX-C001 for bypassing of FXa-DOAC anticoagulation

Monday, June 24, 2024

14:45 – 15:00 ICT

Room: Ballroom B3

Presenting Author(s)

Daniël Verhoef

Research Director
Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

PR

Pieter Reitsma

Chief Scientific Officer
Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
VS

Viola Strijbis

R&D Scientist
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
TG

Tainá Gomes

R&D Scientist
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
J�

Jan Öhrström

Chairman
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Ged Short

Chief Medical Officer
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
MZ

Michael Zörer

Head of Clinical Operations
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
JL

Jeffrey Lawson

Chief Executive Officer
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands

Background: VMX-C001 is a modified recombinant human factor X (FX) in clinical development for bypassing FXa direct oral anticoagulants (FXa-DOAC) in patients who are bleeding or require surgery.

Aims: To study the effects of VMX-C001 alone and in combination with a FXa-DOAC (rivaroxaban) on post-injury bleeding in monkeys, and determine how clotting assays correlate with bleeding.

Methods: Male monkeys were anesthetized, baseline blood samples collected, the liver exposed, and a 4 mm diameter/2 mm depth injury inflicted using a punch biopsy tool. Post-injury bleeding time was measured and blood loss by weighing gauze used to absorb blood from the injury. In stage 1, monkeys received two IV bolus doses of VMX-C001 (1.3 mg/kg), 20 minutes apart. Post-injury bleeding time and blood loss were assessed at baseline and 20 minutes after each dose. Blood samples were taken to evaluate clotting (PT, aPTT) and VMX-C001 plasma level. In stage 2, post-injury bleeding outcomes were measured in monkeys before and after rivaroxaban (IV bolus followed by continuous infusion) alone and then after VMX-C001 (1.3 mg/kg) or placebo. The surgery team and assessors were blinded to treatment (VMX-C001 or placebo).

Results: In monkeys administered VMX-C001 alone, PT and, particularly, aPTT increased versus baseline. These increases were not associated with altered bleeding outcome post-injury (Fig 1). In animals pre-treated with rivaroxaban, PT and aPTT were prolonged (PT from 9.8±0.5 to 20.9±5.7 seconds; aPTT from 23.0±1.25 to 36.7±4.9 seconds); VMX-C001 administration shortened PT to 14.2±1.2 seconds and further prolonged aPTT to 52.0±6.6 seconds; however, VMX-C001 reversed the rivaroxaban-induced increases in bleeding time and blood loss post-injury to baseline levels (Fig 2).

Conclusion(s): VMX-C001 alone has no impact on bleeding outcomes, despite prolonging PT and aPTT. VMX-C001 completely reverses rivaroxaban-induced increased bleeding time and blood loss, despite prolonging aPTT. Changes in PT/aPTT appear not to predict the effect of VMX-C001 on bleeding.