Leiden, The Netherlands, 22 June 2023 - VarmX, a biotech company focusing on the development of innovative approaches for the reversal of anticoagulation, today announces that it will present two abstracts at the International Society on Thrombosis and Haemostasis (ISTH) in Montreal, June 24-28, 2023.
The abstracts, which were selected by the conference organisers for an oral presentation and a poster, are available below.
Gerard Short, chief medical officer at VarmX, will discuss preliminary data demonstrating that the Company’s lead compound, VMX-C001, warrants further clinical development.
VarmX will also present a poster concluding that dRVVT and dPT assays can be used to monitor FX-a DOAC anticoagulation with a high degree of sensitivity and can serve as surrogate endpoints in studies of VMX-C001.
Dr. Jan Öhrström, CEO of VarmX, said: “We are pleased to present new promising data about VMX-C001 at the ISTH congress. Our lead compound is a modified recombinant human blood clotting factor X that enables blood to clot normally, even in the presence of a factor Xa blood clotting inhibitors. We look forward to further developing VMX-C001 as there are very limited treatment options against severe spontaneous bleeding for patients on blood thinning DOACs.”
Further details about the oral presentation and the poster are below:
Title: Phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of VMX-C001 in healthy subjects
Session: OC 31.3
Date: 26 June 2023
Time: 11.15-11:30 ET
Location: Room 516
Background: VMX-C001 is a recombinant variant of human coagulation factor X (FX) insensitive to inhibition by FXa direct oral anticoagulants (FXa-DOACs) under development for reversal of FXa-DOACs in patients with serious bleeding or requiring urgent surgery.
Aims: To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VMX-C001 in healthy subjects.
Methods: In Part 1 of this phase 1, single-center, double-blind, randomized, placebo-controlled, first-in-human study (NCT05152420), single ascending intravenous doses of VMX-C001 (100‒3000 IU; n=6) or placebo (n=2) were administered to 6 cohorts of 8 healthy subjects (age 18–49 years). In Part 2, 7 cohorts of 8 healthy older subjects (age 50‒79 years) who had received a 3.5-day course of treatment with apixaban (5 mg twice-daily) or rivaroxaban (20 mg once-daily) were given, 5 min after their last FXa-DOAC dose, a single intravenous dose of VMX-C001 or placebo administered over 5 min. The local ethics committee approved the study; all volunteers provided written informed consent. Blood samples were collected before and after study drug administration for determination of PK parameters, thrombin generation, diluted prothrombin time (dPT), and diluted Russell viper venom time (dRVVT). Safety assessments included adverse events, immunogenicity (antibodies against VMX-C001 or FX), and the levels of D-dimer, thrombin-antithrombin complexes, and prothrombin F1.2.
Results: Subject dosing is completed but the data are still blinded. Overall, 78 subjects received VMX-C001 either alone (n=36) or in combination with FXa-DOACs (n=42). There were no safety or tolerability concerns. Blinded PK data (Figure 1) revealed dose-proportional linear kinetics with a half-life (t½) of approximately 30 h and a volume of distribution of approximately 9 L. Preliminary PD data (Figure 2) suggest that VMX-C001 reverses the anticoagulant effects of apixaban and rivaroxaban. The complete results will be presented.
Conclusion(s): Preliminary data warrant further clinical development of VMX-C001 for the reversal of FXa-DOACs.
Title: Coagulation assays for assessing direct Factor Xa inhibitor oral anticoagulant reversal effect
Date: 27 June 2023
Time: 18.30-1:30 ET
Background: Factor Xa direct oral anticoagulants (FXa-DOACs) require rapid reversal in patients with serious bleeding or prior to urgent surgery. VMX-C001 is a recombinant variant of human FX under clinical development as a FXa-DOAC bypassing agent. Because standard laboratory coagulation tests lack sensitivity to assess the effects of FXa-DOAC, two commercially-available coagulation assays, dilute Russell’s viper venom time (dRVVT) and dilute prothrombin time (dPT), were modified to develop more sensitive assays.
Aims: To evaluate the modified dRVVT and dPT assays and their sensitivity to FXa-DOACs.
Methods: Citrated platelet-poor plasma samples were obtained from healthy volunteers (n=22). Assay validity was measured in 3x and 4x diluted plasma for dRVVT and in undiluted and 2.5x diluted plasma for dPT in the absence and presence of apixaban (100 or 250 ng/mL) and/or VMX-C001 (30 μg/mL; approximately 0.3 U/mL). Plasma samples from healthy volunteers were then spiked ex vivo with apixaban (n=22), edoxaban (n=3), or rivaroxaban (n=3) at 0‒400 ng/mL with and without VMX-C001 (0.3 U/mL) and dRVVT and dPT were measured. In vivo assay validation was performed using plasma samples taken from healthy volunteers who had received apixaban (n=8) or rivaroxaban (n=5) for 3.5 days before measuring dRVVT and dPT in samples taken before and after the FXa-DOAC dose on day 4.
Results: Both assays were validated and sensitive to FXa-DOACs, resulting in dose-dependent prolongation of dRVVT and dPT, which was reversed when VMX-C001 was present in plasma, resulting in normal dRVVT and dPT (Figure 1). Assay validity was also confirmed with the plasma samples taken from subjects treated with FXa-DOACs in vivo (Figure 2).
Conclusion(s): dRVVT and dPT assays can be used to monitor FXa-DOAC anticoagulation with a high degree of sensitivity and can serve as surrogate endpoints in studies of the FXa-DOAC reversal agent VMX-C001.
For further information, please contact:
Dr. Jan Öhrström, CEO
Instinctif Partners (media enquiries)Melanie Toyne-Sewell / Giulia Lasagni / Batoul Ali
Tel: +44 20 7457 2020
Notes to Editors
VarmX is a spin-off from the Leiden University Medical Center (LUMC), founded in 2016 by Professor Pieter Reitsma, a world leading expert in hemostasis and thrombosis. VarmX’s lead compound VMX-C001 is a modified recombinant blood factor X. The compound is being developed for the treatment of severe spontaneous bleeding and for the prevention of bleeding during urgent surgery in patients taking oral factor Xa inhibitors (FXa DOACs) as anticoagulation therapy. The Company is supported by a strong syndicate of investors including Sound Bioventures, EIC, EQT Life Sciences (formerly LSP), Inkef, Lundbeckfonden BioCapital, Ysios Capital, BioGeneration Ventures and InnovationQuarter.