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Nathan Connell: Advancing Prophylaxis for von Willebrand Disease with HMB-002
Nathan Connell/LinkedIn
Feb 9, 2026, 14:19

Nathan Connell: Advancing Prophylaxis for von Willebrand Disease with HMB-002

Nathan Connell, Clinical Chief of Hematology at Brigham and Women’s Faulkner Hospital, shared on LinkedIn about a recent article by Mattias Häger et al, published in Blood Advances:

”Advancing Prophylaxis for von Willebrand Disease: Introducing HMB-002

Excited to learn more about a significant development in the treatment landscape for von Willebrand Disease (VWD), recently published in Blood Advances.

VWD is the most common inherited bleeding disorder, yet current prophylactic options remain burdensome, often requiring frequent intravenous infusions due to the short half-life of available therapies. Mattias Häger et al. introduce HMB-002, a first-in-class, human Fc-silenced monovalent IgG4 antibody designed to transform VWD management through subcutaneous prophylaxis.

How it works: Unlike traditional replacement therapies, HMB-002 targets the endogenous system. It binds with sub-nanomolar affinity to the C-terminal cysteine-knot (CK) domain of von Willebrand Factor (VWF). Because this domain is spatially distant from VWF’s hemostatic regions, the antibody extends the protein’s half-life without interfering with its vital functions.

Key Findings:

  • Significant Elevation: In non-human primates, HMB-002 achieved a sustained ~2-fold elevation of endogenous VWF and Factor VIII (FVIII) levels.
  • Functional Preservation: In vitro and ex vivo studies confirmed that HMB-002-bound VWF retains its ability to bind platelets (GPIbα), collagen, and FVIII, and remains susceptible to regulation by ADAMTS13.
  • Improved Hemostasis: In a type 1 VWD mouse model, a surrogate antibody recapitulated these results, leading to improved hemostatic control.
  • Subcutaneous Convenience: The study demonstrates the potential for a long-acting, subcutaneous treatment that could significantly reduce the treatment burden for patients.

This ‘passive engagement’ strategy represents a sophisticated shift in how we approach protein deficiencies—moving from replacement to half-life extension of the patient’s own hemostatic proteins.

Congratulations to Mattias Häger, Catherine Rea, Benny Sorensen, and the whole team at Hemab Therapeutics on this impactful research!”

Title: HMB-002: A Monovalent Antibody that Elevates Circulating VWF and FVIII Levels for Treatment of Von Willebrand Disease

Authors: Mattias Häger, Minka Zivkovic, Prafull S Gandhi, Caroline Rasmussen, Cécile Bonvoisin, Rane A Harrison, Emil Poulsen, Dana Huskens, Mark Roest, Fortunato Ferrara, Anais Naretto, Lionel Renaud, Ole H Olsen, Nicolas O Eskesen, Lars Holten-Andersen, Ruthvik Malladi, Catherine J Rea, Benny Sørensen, Rolf T Urbanus, Henrik Ostergaard

Read the Full Article on Blood Advances

Nathan Connell: Advancing Prophylaxis for von Willebrand Disease with HMB-002

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Anais Naretto Benny Sørensen bleeding disorders Blood Advances Caroline Rasmussen Catherine J Rea Cécile Bonvoisin Dana Huskens Emil Poulsen Fortunato Ferrara Health Hematology Hemostasis Hemostasis News Hemostasis Today Henrik Ostergaard Lars Holten-Andersen Lionel Renaud Mark Roest Mattias Häger Medicine Minka Zivkovic Nathan Connell Nicolas O Eskesen Ole H Olsen Prafull S Gandhi Rane A Harrison Rolf T. Urbanus Ruthvik Malladi VWD VWF
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