631. Preliminary safety and pharmacokinetic profile of VIR-2482: a monoclonal antibody for the prevention of influenza A illness

BACKGROUND: VIR-2482 is a fully human immunoglobulin G1(IgG) monoclonal antibody (mAb) directed against a highly-conserved epitope in the influenza A hemagglutinin stem region and is in clinical development for the prevention of influenza A illness. The Fc region of VIR-2482 has been modified to provide an extended half-life. METHODS: This is a randomized, placebo-controlled, Phase 1/2 study of VIR-2482 administered intramuscularly (IM) to healthy adult volunteers aged 18-64 years old who have not received a current influenza vaccine. The Phase 1 portion of the study will evaluate the safety, tolerability, pharmacokinetic (PK), and immunogenicity profile of VIR-2482 following single (Part A) or multiple doses (Part B). The Phase 2 study will evaluate the efficacy of VIR-2482 in the prevention of influenza A illness as well as safety, tolerability, and PK. Part A is ongoing and consists of four single dose cohorts (N=25/cohort) randomized (4:1) to a single dose of VIR-2482 or placebo at 60, 300, 1200, or 1800 mg. Safety, tolerability, PK and immunogenicity will be evaluated for at least 52 weeks post-dose. RESULTS: In Part A, all 100 subjects received a single dose of VIR-2482 (N=80) or placebo (N=20). Preliminary blinded safety data for all cohorts and PK data for the 300 and 1200 mg cohorts are reported here. Dosing was well tolerated; 6% (6/100) of subjects experienced mild injection site reactions, which generally resolved within 48 hrs. Through 12 weeks post-dosing, the majority (124/126; 98.4%) of adverse events (AEs) were mild to moderate in nature, no serious AEs were reported, and no subjects discontinued due to an AE. Based on available data, exposure (C(max) and AUC) between 300 and 1200 mg of VIR-2482 increased in a dose proportional manner. The PK profile of VIR-2482 is consistent with a half-life extended IgG. CONCLUSION: Based on available data, VIR-2482 has been well tolerated following single IM doses of up to 1800 mg in healthy subjects. The preliminary PK profile of VIR-2482 enables once per season dosing. Overall, these data support initiation of a Phase 2 study to evaluate efficacy of VIR-2482 for the prevention of influenza A illness. DISCLOSURES: Jennifer Sager, PharmD, Vir Biotechnology (Employee) David K. Hong, MD, Vir Biotechnology (Employee) Aurelio Bonavia, PhD, Vir Biotechnology (Employee) Lynn Connolly, MD, PhD, Vir Biotechnology (Employee) Deborah Cebrik, PhD, Vir Biotechnology (Independent Contractor) Marie Christine Fanget, MS, Vir Biotechnology (Employee) Erik Mogalian, PharmD, PhD, Vir Biotechnology (Employee)