PB1110 - VGA039, a novel anti-Protein S antibody, enhances ex vivo coagulation with hemophilia A blood as assessed by thromboelastometry

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

MM

Miriam M. Moser

Medical Resident
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Wien, Austria

Co-Author(s)

LL

Lilley Leong

Principal Scientist
Vega Therapeutics, South San Francisco
South San Francisco, California, United States
KK

Katarina Kovacevic-Miljevic

Postdoctoral Researcher
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Wien, Austria
MW

Matthias Weiss-Tessbach

Medical Resident
Department of Clinical Pharmacology, Medical University Vienna
Vienna, Wien, Austria
Sandip Panicker

Chief Scientific Officer
Vega Therapeutics, Inc.
South San Francisco, California, United States
Benjamin Kim

Vice President, Clinical Development
Vega Therapeutics Inc.
South San Francisco, California, United States
Daniel Kraemmer, MD

PhD Student
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
Vienna, Wien, Austria
KT

Katharina Thom

Medical Resident
Department of Pediatrics, Medical University of Vienna
Vienna, Wien, Austria
Christoph Male

Consultant, Associate professor
Department of Paediatrics, Medical University Hospital of Vienna, Vienna, Austria
Wien, Wien, Austria
Cihan Ay, MD

Professor
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
Vienna, Wien, Austria
Bernd Jilma, MD

Professor
Department of Clinical Pharmacology, Medical University Vienna
Vienna, Wien, Austria
Christian Schoergenhofer, MD, PHD

Associate Professor
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Wien, Austria

Background: VGA039 is a first-in-class, fully human IgG4 monoclonal antibody directed against protein S. Protein S is a cofactor for activated protein C (APC) and tissue factor pathway inhibitor-alpha (TFPIa). In TFPIa- or APC-pretreated human plasma, VGA039 augmented thrombin generation. In an experimentally induced non-human primate model of von Willebrand disease featuring administration of caplacizumab and neutralizing anti-factor VIII antibody (FVIII nAb), VGA039 reduced bleeding time from mucosal cuts and prevented blood loss.

Aims: To investigate the effects of VGA039 on coagulation ex vivo as measured by thromboelastometry in whole blood from people with hemophilia A.

Methods: Whole blood samples were collected from people with severe hemophilia A (n=10) and spiked with increasing concentrations of VGA039 (range 3.125 to 200µg/mL). Based on preclinical studies, effects on thrombin generation were expected for VGA039 concentrations exceeding ~10µg/mL. Clotting time (CT), clot formation time (CFT), and the sum of CT and CFT at increasing VGA039 concentrations were compared to baseline using the Wilcoxon test for related samples, with a two-sided alpha of 0.05.

Results: The median age of the included people with hemophilia A was 28 (range 14–52) years, median factor VIII activity was 3.5 (range < 1-27) IU/dL. The mean ± SD baseline CT was 698 ± 160 seconds, and the mean ± SD CFT 301 ± 58 seconds. VGA039 significantly reduced the CT at the concentrations 6.25, 50, 100, and 200µg/mL by ~9 to 13% and significantly reduced the CFT at concentrations 6.25, 50, 100, and 200µg/mL by ~7 to 13%. The sum of CT and CFT was significantly reduced by ~8 to 14% at the concentrations 6.25, 50, 100, and 200µg/mL

Conclusion(s): The non-factor replacement therapy VGA039 improved clotting at concentrations 6.25 and ≥ 50µg/mL using thromboelastometry in whole blood from patients with an inherited bleeding disorder, namely hemophilia A.