OC 73.3 - VGA039, a Protein S-targeting monoclonal antibody, demonstrates in a Phase Ia healthy volunteer trial the potential of subcutaneous weekly or less frequent prophylactic dosing for bleeding disorders

Wednesday, June 26, 2024

10:45 – 11:00 ICT

Room: Ballroom B4

Presenting Author(s)

Christian Schoergenhofer, MD, PHD

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

Co-Author(s)

MM

Miriam M. Moser

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

Christa Firbas

Research Associate
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Wien, Austria
TL

Timothy S. Leach

Medical Monitor
Vega Therapeutics, Inc.
South San Francisco, California, United States
AT

Almudena Tercero

Director, Clinical Operations
Vega Therapeutics, Inc.
South San Francisco, California, United States
KC

Kelly Covert

Senior Manager, Translational Sciences
Vega Therapeutics, Inc.
South San Francisco, California, United States
GP

Graham C. Parry

Executive Vice President, Translational Sciences
Vega Therapeutics, Inc.
South San Francisco, California, United States
HL

Hayley Lane

Vice President, Clinical Operations
Vega Therapeutics, Inc.
South San Francisco, California, United States
Bernd Jilma, MD

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

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

Gary Patou

Chief Medical 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

Background: Non-factor replacement therapies have the potential to rebalance coagulation in various bleeding disorders with less frequent dosing than factor concentrate prophylaxis. Preclinical studies of VGA039 have demonstrated its ability to increase thrombin generation across multiple inherited bleeding disorders, including von Willebrand disease (VWD), and prevent blood loss in vivo in a novel, non-human primate (NHP) VWD model.

Aims: To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses (SADs) of intravenous (IV) or subcutaneous (SC) VGA039.

Methods: This is an unevenly randomized (3 VGA039:2 placebo), double-blind, placebo-controlled, first-in-human, phase Ia trial conducted in healthy volunteers aged ≥18 years and approved by the local ethics committee. Informed consent was obtained. The starting IV SAD was less than the 10% effective concentration value for in vivo thrombin generation in NHPs, with dose escalations up to a pre-specified maximum of 1.0 mg/kg in the absence of dose limiting toxicity (DLT). The starting SC SAD was the maximally tolerated/tested IV dose, with continued dose escalations up to 3.0 mg/kg.

Results: To date, a total of 30 healthy volunteers in 4 IV and 2 SC SAD cohorts have been dosed. No adverse events related to VGA039, including thromboembolic events, DLTs, or infusion-related/injection-site reactions, have occurred. Plasma concentrations of VGA039 have increased dose dependently across the IV and SC cohorts (Figure 1). SC bioavailability is ~98%, with drug concentrations of 1.0 mg/kg IV and SC VGA039 converging after 1 week (Figure 2). At higher tested doses, VGA039 increases ex vivo thrombin generation compared to baseline (presented for all cohorts at the meeting).

Conclusion(s): Emerging data suggest VGA039 is well tolerated and increases thrombin generation in healthy volunteers. Drug concentration profiles demonstrate suitability for weekly or less frequent SC prophylactic dosing for various bleeding disorders. Further investigation of VGA039 is underway in VWD patients.

Funded by Vega Therapeutics.