Experimental VWD treatment HMB-002 shows promise in animal models
Study: Therapy addresses protein deficiency that drives the disease
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HMB-002, an antibody-based experimental treatment for von Willebrand disease (VWD) currently in early clinical testing, boosted levels of the protein whose deficiency causes VWD, according to a new study in animal models.
The study, “HMB-002: A Monovalent Antibody that Elevates Circulating VWF and FVIII Levels for Treatment of Von Willebrand Disease,” was published in Blood Advances.
The work was funded by Hemab Therapeutics, which is now sponsoring a Phase 1/2 clinical trial (NCT06754852) testing HMB-002 in adults with VWD. Participants in the Phase 1/2 study will receive one or multiple doses of HMB-002 by injection under the skin, with the main goal of evaluating the therapy’s safety. The study is recruiting at sites in the U.K. and Australia.
HMB-002 designed to bind to and stabilize VWF protein
VWD is caused by mutations in the gene that encodes von Willebrand factor (VWF), a protein essential for normal blood clotting. In type 1 VWD, the most common form of the disease, patients produce less VWF protein than normal. As a result, blood doesn’t clot correctly, leading to symptoms such as unusually easy or prolonged bleeding.
HMB-002 is an antibody designed to bind to the VWF protein and stabilize it, with the aim of boosting blood levels of the protein to help restore clotting.
In their study, scientists at Hemab and their collaborators reported preclinical experiments showing that the antibody is able to bind to the VWF protein tightly without interfering with its binding to other proteins and platelets that form clots.
The scientists then tested HMB-002 in healthy monkeys. They found that HMB-002 injections increased VWF protein levels by roughly twofold.
These findings support the potential of HMB-002 as a prophylactic [preventive] agent addressing current limitations in VWD management.
One current treatment strategy for VWD is replacement therapy, in which a version of the VWF protein is administered as medicine. The researchers found that when they gave monkeys a replacement therapy in combination with HMB-002, the replacement therapy’s half-life was tripled. In other words, the therapeutic VWF protein stayed in the body for substantially longer, suggesting that HMB-002 may be able to act in synergy with currently available VWD treatments.
The researchers also conducted experiments in mice engineered to have low VWF protein levels, a model that mimics VWD type 1. HMB-002 is explicitly designed to stick to the human version of the VWF protein. The monkey version is similar enough to the human version, but the mouse form is different, so the researchers used a different antibody engineered to recognize a part of the protein that overlaps with HMB-002’s binding site.
These mouse experiments showed that the therapeutic antibody treatment increased VWF protein levels and that treated mice tended to lose less blood during bleeding assessments.
The researchers concluded that their study “demonstrates the mechanistically novel ability of HMB-002 to bind and extend the half-life of VWF,” adding that “these findings support the potential of HMB-002 as a prophylactic [preventive] agent addressing current limitations in VWD management.”
