A Phase 1/2, First-in-Human, Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia

Background & Significance: Glanzmann thrombasthenia (GT) is a rare bleeding disorder resulting from a deficiency of integrin αIIbβ3 (also known as glycoprotein [GP] IIb/IIIa), a receptor for fibrinogen on platelets. Fibrinogen binding to αIIbβ3 bridges platelets and is a required step for normal platelet aggregation and hemostasis. GT is considered a severe bleeding disorder with approximately 50% of the patients reporting 1 bleed every day, and 13% reporting over 500 bleeds per year. The current standard of care for bleeding in patients with GT is reactive and on-demand, with no approved therapies for primary prophylaxis. HMB-001 is a bispecific antibody being developed by Hemab for prophylactic treatment to prevent and reduce bleeding events in patients with GT that can be administered subcutaneously. One arm of HMB-001 binds to and accumulates endogenous activated coagulation factor VII (FVIIa) while the second arm binds to the TREM-like transcript 1 receptor (TLT-1) on activated platelets. The combined effect of FVIIa accumulation and targeting to the surface of activated platelets via HMB-001 brings the activity of FVIIa to levels that are considered therapeutically effective based on clinical experience with recombinant FVIIa (rFVIIa). This is a first-in-human, Phase 1/2, dose escalation, safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy study of HMB-001 in participants with Glanzmann thrombasthenia.

Study Design and Methods:

The study consists of 3 parts.

• Part A is a Phase 1, open-label, single ascending dose study, which will evaluate the safety, tolerability, PK, and PD of HMB-001 in participants with GT.

• Part B is a Phase 2, open-label, multiple ascending dose study evaluating the safety, tolerability, PK, PD, and preliminary effects on bleeding of repeat doses of HMB-001 monotherapy.

• Part C is a Phase 2, open-label, treatment extension portion study. It will be open to participants who have fulfilled the requirements of Part B and are considered eligible to continue by the Investigator. Part C will evaluate longer term safety, and preliminary efficacy of repeat doses of HMB-001 monotherapy for 9 months.

Study Population: Male and female participants 18 to 65 years of age with GT. Part A is single-center, while Part B/C will be a multicenter study in various countries.

Major inclusion and exclusion criteria include:

Criteria for Inclusion:

• Part A and B

  • Age 18 to 65

  • Diagnosis of GT

  • Vital signs within normal range

  • Negative pregnancy test

  • Must meet the following baseline organ function

    • eGFR >45 mL/min/1.73m ²

    • LFTs within normal range

    • Hgb >85 g/L and platelet count >150 x 10 ⁹/L

Part B only

• 2 bleeding events per week on average of any severity and type and at least 1 spontaneous or traumatic bleed within the last 12 months requiring treatment with rFVIIa, platelets, medical or surgical procedure

Criteria for Exclusion:

• Part A

  • Active severe infection or inflammation

  • History of clinically significant hypersensitivity associated with monoclonal antibody therapies.

  • Personal or family history of venous or arterial thrombosis or thromboembolic disease.

  • Other risk factors that substantially increase risk of venous or arterial thrombosis

  • Congenital or acquired bleeding disorders other than GT

  • Concurrent disease, treatment, medications, or abnormality in clinical laboratory tests that may pose additional risk

  • Addiction or other diseases that prevent the participant from appropriately assessing the nature and scope of the clinical study or participating in study procedures

Participants included in Part B are eligible for Part C following completion of their dosing in Part B.