Blocking Coagulation Factor XIIIa (FXIIIa) in risk patients

The physiological functions of coagulation factor XIIIa - also called plasma transglutaminase - are well known. Factor XIII is activated by thrombin to factor XIIIa and subsequently cross-links fibrin fibers. This covalent cross-linking reaction augments blood clot strength several fold and influences the visco-elastic properties. Further, the clot is covalently decorated by a2-antiplasmin increasing clot stability against fibrinolysis by plasmin. In summary, factor XIII is the major factor influencing clot stability, clot maturation and clot lysis.

Currently vitamin K antagonists and heparins, both used for decades in anticoagulation, face the appearance of novel direct acting oral drugs blocking either factor Xa or thrombin. Independently of the mode of action, all these drugs have one feature in common: a dramatically reduced thrombin activity. This leads to good anticoagulation efficiency but unfortunately increases the risk for severe bleeding events.

Safer medication is therefore still needed. Addressing factor XIIIa may open the gate to a “high efficiency - low bleeding” anticoagulation drug.

Factor XIIIa inhibition does not affect thrombin generation and therefore does not impair primary clot formation. This is the central difference compared to current anticoagulants, which affect both platelet aggregation and fibrin clot formation. By inhibiting factor XIIIa, the clot may form but be neither cross-linked nor decorated with antifibrinolytics like α2-antiplasmin. The resulting “soft” clot may rapidly be hydrolysed by plasmin, the major fibrinolytic protease. Thrombotic events will thus be drastically reduced, providing a reduced bleeding probability compared to current anticoagulation drugs.

Zedira’s factor XIIIa blockers have the highest efficacy demonstrated to date. We are currently on the way to developing a drug candidate for pre(clinical) development. Our compounds have the potential to provide a novel therapeutic option with a superior risk/benefit ratio.

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News  

  • Zedira publication: Microbial Transglutaminase Used in Bread Preparation at Standard Bakery Concentrations Does Not Increase Immunodetectable Amounts of Deamidated Gliadin
  • Pressemitteilung: Dr. Falk Pharma und Zedira geben den Abschluss der Phase 1b-Studie für ZED1227 zur Zöliakie-Therapie bekannt und planen Start der Wirksamkeitsstudie
  • Press release: Dr. Falk Pharma and Zedira announce completion of phase 1b clinical trial of ZED1227 for the treatment of celiac disease and move on to proof of concept study
  • Press Release: Dr. Falk Pharma GmbH and Zedira enter a phase 1b clinical trial for a celiac disease drug
  • Zedira publication: Microbial transglutaminase has a lower deamidation preference than human tissue transglutaminase on a celiac disease relevant wheat gliadin T-cell epitope
  • Press release: Additional subsidy funding for clinical development of a celiac disease drug
  • Pressemitteilung: Zusätzliche Fördermittel für die klinische Entwicklung eines Zöliakie-Medikamentes
  • Press Release: Cooperation between Zedira and Cardiff University - Transglutaminase 6 is the focus of new research into ataxia
  • Press Release: Dr. Falk Pharma and Zedira enter phase I clinical trials for a celiac disease drug
  • Press release: Zedira receives further funding to develop Factor XIIIa-blockers for safe anticoagulation

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Events  

  • MEDICA

    13.11.2017 - 16.11.2017
    Düsseldorf, Germany

  • Gordon Research Conference on: Transglutaminases in Human Disease Processes

    16.06.2018 - 17.06.2018
    Les Diablerets, Switzerland