Hemab Therapeutics (Nasdaq: COAG) presented Phase I/II data from its HMB-002 program in Von Willebrand Disease at the ISTH 2026 Congress, reporting dose-dependent increases in endogenous VWF and Factor VIII alongside a preliminary bleeding signal that, while descriptive in nature, suggests the subcutaneous antibody may reduce treated bleeds in a population with substantial baseline disease burden.
In the single ascending dose portion of the VELORA Pioneer trial (NCT06754852), the 150 mg cohort (A3) achieved at least 2.4-fold peak elevations in both VWF and FVIII, accompanied by restoration of thrombin generation, shortening of activated partial thromboplastin time, and stable multimer distribution. Pharmacokinetic data showed a dose-dependent increase in Cmax with prolonged duration, and the company said the PK/PD profile supports the potential for monthly subcutaneous dosing. Across all SAD cohorts, 8 of 9 evaluable patients recorded zero treated bleeds in the 28 days following a single dose, with a mean annualized treated bleed rate of 1.6 compared to a pre-treatment baseline of 20.1, based on bleed data collected over up to 5.5 months. Safety was characterized as favorable: most treatment-emergent adverse events were mild to moderate, no serious adverse events occurred, no events were attributed to HMB-002, and no thromboembolic events, injection site reactions, thrombocytopenia, or hypersensitivity reactions were observed.
The VELORA Pioneer study is an open-label, dose-escalation Phase I/II trial enrolling adults with VWD; the SAD portion was not designed to measure efficacy, and the company explicitly characterized the bleeding observations as descriptive. Data were reported from 9 evaluable patients, and no controlled comparison was made. The bleed rate reduction should be interpreted cautiously given the small sample, unblinded design, and the absence of a concurrent control arm.
HMB-002 is a monovalent human antibody that targets the C-terminal CK domain of VWF, shielding the protein from degradation and thereby raising endogenous VWF and FVIII levels without replacing them exogenously. The non-replacement approach contrasts with the current standard of care, which includes recombinant VWF replacement with vonicog alfa (Vonvendi/Veyvondi), approved for adults with severe VWD and associated in a Phase III prophylaxis study with a 91.5% reduction in spontaneous annualized bleeding rate versus historical on-demand baselines, and plasma-derived VWF/FVIII concentrate wilate, which demonstrated an 84.4% reduction in mean total annualized bleeding rate during prophylaxis in the WIL-31 Phase III study. Both approved therapies require intravenous administration. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.