A Study Assessing HMB-002 in Participants With Von Willebrand Disease

Inclusion criteria

• Weight 50 to 120 kg, inclusive.
• Documented diagnosis of Congenital VWD, confirmed by laboratory testing consistent with ISTH/ASH) diagnostic guidelines).
• Vital signs are within normal ranges at Screening.
• Participants must meet the following baseline organ function, indicated by laboratory criteria as Screening:
• Renal: Estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73m\^2.
• Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin ≤1.5 upper limit of normal (ULN) at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN.
• Hematology \>85 g/L and platelet count \>120 x 10\^9/L. Part A Only:
• Age: ≥18 and \<70 years of age at the time of informed consent.
• VWD Subtype Eligibility:
• Cohorts A1 and A2: Participants with Type 1 VWD, only.
• Cohorts A3 and A4: Participants with Type 1 VWD (including Type 1C) and Type 2A VWD
• Residual VWF activity of ≤ 50 IU/dL and FVIII activity ≤ 70 IU/dL during screening. Part B Only:
• Age: ≥16 and \<70 years of age at the time of informed consent.
• VWD Subtype Eligibility: Participants with Type 1 VWD (including Type 1C) and Type 2A.
• Residual VWF activity of ≤50 IU/dL and FVIII activity ≤70 IU/dL during screening.
• Symptomatic Disease: Participants must be symptomatic, typically reporting bleeding events on a monthly basis.
• Bleeding History (must meet one of the following):
• Prior Observational Study Participation: The participant must have participated in the observational study HMB-002-101\_SCR (VELORA Discover), have a minimum annualized treated bleeding event (ATBR) of 3; OR
• Medical Record-Documented Bleeding History: The Investigator confirms that ≥3 treated bleeding events have been documented in the participant's medical record within the preceding 12 months. Part C Only:
• Age: ≥18 and \<70 years of age at the time of informed consent.
• Participants with Type 3 VWD or Type 1 VWD with low residual VWF and FVIII activity levels (VWF activity \<5 IU/dL and FVIII activity \<10 IU/dL).
• Receives regular VWF concentrate (at least 1/week) as part of their routine care (usual dose ≤50 IU/kg). Key

Exclusion criteria

• Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
• High risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/Prothrombin gene mutation, Antithrombin deficiency with activity \<50%. Congenital Protein C and Protein S deficiency with levels \<50%.
• Body mass index (BMI) \>35 kg/m\^2 (obese, adjusted for ethnicity).
• Presence of other conditions that substantially increase risk of thrombosis either individually (for participants \>65 years of age) or in combination (for participants ≤65 years of age), at the discretion of the Investigator or Medical Monitor.
• Clinically significant cardiovascular disease.
• Other known severe bleeding disorder(s) other than VWD.
• Requirement for concomitant medications that affect hemostasis (including, but not limited to anticoagulation, antiplatelet agents, certain non-steroidal anti-inflammatory drugs) and cannot refrain from use for 14 days prior to the first dose of study drug and throughout the study. Exclusion Criteria for Part A and Part B Only
• Requirement for ongoing hemostatic treatment to prevent bleeding (bleed prophylaxis). Prophylaxis administered intermittently for procedures or surgery to reduce bleeding risk is permitted.