{
  "abstract": "Background: Anticoagulation therapy confers increased risk of potentially life-threatening bleeding events. Limited options exist for anticoagulation reversal in patients treated with direct oral factor Xa (FXa) anticoagulants (aka FXa inhibitors). Clinical development of reltodecacog alfa (VMX-C001), a modified form of human zymogen FX, as an FXa inhibitor-bypassing agent is ongoing. We report non-clinical pharmacology, toxicokinetic and pharmacodynamic studies of VMX-C001. Methods: Dose-ranging and 2-week toxicity studies were conducted in which Sprague-Dawley rats and cynomolgus monkeys received VMX-C001 at various doses for ≤2 weeks. Safety, pharmacologic, toxicokinetic and pharmacodynamic parameters were assessed. The anticoagulation-bypassing ability of VMX-C001 against edoxaban (ex vivo spiking) and rivaroxaban (in vivo) in monkeys was also evaluated. Results: No safety concerns were noted in either species at VMX-C001 doses up to 10 mg/kg; no VMX-C001-related adverse clinical signs were observed. VMX-C001 exhibited approximately dose-proportional kinetics, with no accumulation after repeat dosing. Changes in thrombin-generation parameters in both species were mild and non-adverse. VMX-C001 restored rivaroxaban-induced decreases in thrombin generation toward pre-rivaroxaban levels. In blood samples spiked ex vivo with edoxaban, the ability of VMX-C001 to support thrombin generation was maintained, even after repeat dosing. Conclusions: Treatment with VMX-C001 for 2 weeks was well tolerated at all tested doses. VMX-C001 had an approximately dose-proportional toxicokinetic profile, and accumulation was not observed upon repeat dosing. VMX-C001 also displayed a favourable pharmacodynamic profile and supported thrombin generation in the presence of FXa inhibitors.",
  "abstract_shown": true,
  "affiliations": [
    "VarmX, Emmy Noetherweg 2, Plus Ultra Building, 2333 BK Leiden, The Netherlands.",
    "Division of Thrombosis and Haemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.",
    "DGr Pharma, Hoge Mosten 2c1, 4822 NH Breda, The Netherlands.",
    "Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.",
    "Thrombosis Expertise Center, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniël Verhoef",
      "orcid": "0000-0002-1604-6965"
    },
    {
      "affs": [
        0
      ],
      "name": "Gerard Short"
    },
    {
      "affs": [
        0
      ],
      "name": "Tainá Gomes",
      "orcid": "0000-0003-3987-2490"
    },
    {
      "affs": [
        2
      ],
      "name": "Kees Groen"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Henri Spronk"
    },
    {
      "affs": [
        0
      ],
      "name": "Jan Ohrstrom"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pieter H Reitsma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c2bvt4bbgvsh8.bib",
  "cited_by": 0,
  "doi": "10.3390/pharmaceutics18101210",
  "fulltext_url": "https://europepmc.org/articles/PMC13708372",
  "id": "c2bvt4bbgvsh8",
  "issns": [
    "1999-4923"
  ],
  "landing_url": "https://europepmc.org/article/MED/42942742",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Blood Coagulation and Thrombosis Mechanisms"
    ]
  ],
  "openalex": "W7214077233",
  "pdf_url": "https://europepmc.org/articles/PMC13708372?pdf=render",
  "pmcid": "PMC13708372",
  "pmid": "42942742",
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c2bvt4bbgvsh8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42942742",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42942742"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Blood Coagulation and Thrombosis Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models.",
  "title_text": "Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/c2bvt4bbgvsh8",
  "venue": "Pharmaceutics",
  "versions": []
}