OR13 - Subcutaneous Four-Week Dosing of the Novel Protein S Antibody VGA039 Demonstrates Safety and Clinically Meaningful Bleed Reduction in Patients with Von Willebrand Disease: Phase 1/2 Multi-Dose Study Results

OR13

Subcutaneous Four-Week Dosing of the Novel Protein S Antibody VGA039 Demonstrates Safety and Clinically Meaningful Bleed Reduction in Patients with Von Willebrand Disease: Phase 1/2 Multi-Dose Study Results

G. Yamaguti-Hayakawa^1,*, N. C. Machin², S. Kshirsagar³, J. Mason⁴, A. Giermasz⁵, M. Sholzberg⁶, J. Mahlangu⁷, C. Kempton⁸, P. Villaca⁹, G. Moyer¹⁰, A. Tercero¹¹, P. Sims¹¹, S. Panicker¹¹, C. Foo¹¹, E. K. Sawyer¹¹, C. DelNagro¹¹, G. Patou¹¹, B. Kim¹¹, S. Rangarajan¹², A. P. Wheeler¹³

¹Hemocentro UNICAMP, University of Campinas, Campinas, Brazil, ²Division of Classical Hematology, Department of Medicine, University of Pittsburgh and Hemophilia Center of Western Pennsylvania, Pittsburgh, United States, ³Advanced Center for Oncology, Haematology & Rare Disorders (ACOHRD), K. J. Somaiya Medical College & Research Center, Somaiya Ayurvihar, Mumbai, India, ⁴Queensland Haemophilia Centre, Department of Haematology and BMT, Royal Brisbane and Women’s Hospital, Brisbane, Australia, ⁵Division of Hematology/Oncology, Department of Medicine, University of California Davis, Sacramento, United States, ⁶Departments of Medicine, and Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Canada, ⁷Haemophilia Comprehensive Care Centre, Charlotte Maxeke Johannesburg Hospital, University of the Witwatersrand, Johannesburg, South Africa, ⁸Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, United States, ⁹Hospital das Clínicas-University of São Paulo , São Paulo, Brazil, ¹⁰The University of Colorado Hemophilia and Thrombosis Center, Aurora, ¹¹Star Therapeutics, Inc., South San Francisco, United States, ¹²University Hospital Southampton NHS Foundation Trust, South Hamton, United Kingdom, ¹³Washington Center for Bleeding Disorders and Divisions of Pediatric Hematology/Oncology and Hematology/Oncology, University of Washington, Seattle, United States

 

Introduction: Von Willebrand disease (VWD) causes recurrent and prolonged bleeding, leading to clinical sequelae and high treatment burden due to the need for frequent infusions. VGA039 is a fully human IgG4 monoclonal antibody that inhibits Protein S cofactor activity, thereby enhancing thrombin generation and promoting primary and secondary hemostasis. In a prior single-ascending-dose study, VGA039 showed safety and a reduction in bleeding events. This multi-dose study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneous (SC) VGA039 prophylaxis in patients with all types of VWD.

Methods: This open-label, phase 1/2 study (NCT05776069) was conducted in symptomatic participants (pts) aged 12-75 years with any type of VWD. Key eligibility criteria included baseline FVIII activity < the lower limit of normal and no laboratory evidence of thrombophilia or history of thromboembolism. Pts received scheduled doses of SC VGA039 over 120 days with up to 42-day follow-up and optional participation in an open-label extension study. Safety, efficacy, pharmacokinetic, and pharmacodynamic parameters were collected.

Results: As of October 13, 2025, a total of 16 pts (aged 15-53 years, weighing 45-160.5 kg) with various VWD types/subtypes received a single SC loading dose on Day 1, followed by 5 SC maintenance doses every 4 weeks starting on Day 8. Six pts in Cohort MD-1 received a flat dose of 225 mg SC VGA039. Ten pts in Cohort MD-2 received weight-banded doses of SC VGA039 per the following criteria: 187.5 mg (45–<60 kg; n=0), 262.5 mg (60–100 kg; n=7), or 450 mg (>100 kg; n=3). There were no serious drug-related AEs or clinically significant elevations in D-dimer levels. All 3 pts with historical annualized bleed rates ≥12 who had completed the study had reductions of 72-80% and elected to continue in the open-label extension study. 

Discussion/Conclusion: VGA039 administered subcutaneously every four weeks was safe, well tolerated, and associated with clinically meaningful reductions in bleeding across VWD subtypes. These findings support dose regimen optimization for consistent bleed control and inform dose selection in the ongoing Phase 3 trial (NCT07115004), which includes adolescents and adults.

Disclosure of Interest: G. Yamaguti-Hayakawa: None declared, N. Machin: None declared, S. Kshirsagar: None declared, J. Mason: None declared, A. Giermasz: None declared, M. Sholzberg: None declared, J. Mahlangu: None declared, C. Kempton: None declared, P. Villaca: None declared, G. Moyer: None declared, A. Tercero Employee of: Star Therapeutics, P. Sims Employee of: Star Therapeutics, S. Panicker Employee of: Star Therapeutics, C. Foo Employee of: Star Therapeutics, E. Sawyer Employee of: Star Therapeutics, C. DelNagro Employee of: Star Therapeutics, G. Patou Employee of: Star Therapeutics, B. Kim Employee of: Star Therapeutics, S. Rangarajan: None declared, A. Wheeler Consultant for: Star Therapeutics