383. Pharmacokinetics and Safety in Healthy Adults of RSM01, a Novel RSV Monoclonal Antibody, and Population PK Modeling to Support Pediatric Development
Authors: Levi Micha , Watson Shayne , Anderson Aparna B , Taylor Dale , White Joleen T , Stamm Luisa M , Dunne Michael W 
Published: November 2023

Abstract

Background
RSV is a common cause of infant respiratory infection and hospitalization. RSM01 is a novel anti-RSV mAb targeting the F glycoprotein essential for viral entry with a YTE mutation for half-life extension. Phase 1a PK and safety results are presented, along with an adult population PK model used to predict pediatric exposures via simulation.

Methods
In this double-blind Phase 1a study, healthy males and non-childbearing females aged 18-49 yrs were randomized 6:1 within dose cohorts to receive a single dose of RSM01 or placebo (PBO) in the following RSM01 dose sequence: 300mg IV, 300mg IM or 1000mg IV, 3000mg IV and cohort at 600mg IM. Serial serum samples were taken to measure RSM01 PK using a validated immunoassay method. A noncompartmental analysis (NCA) was conducted, and a population PK model was developed to characterize adult PK and predict pediatric PK using allometric scaling. Pediatric RSM01 PK was predicted for African infants at different IM doses.

Results
Overall, 56 participants received RSM01 (n=48) or PBO (n=8): median age 30 yrs (range 19-48), 52% male (n = 29), 66% White (n=37), median BMI 24.6 kg/m2 (range 18.1-29.4). 12/48 (25%) RSM01 recipients and 2/8 (25%) PBO recipients reported an AE, with no hypersensitivity reactions, serious AEs, or deaths reported. The median Tmax was ∼6–7 days after IM injection. Cmax and AUClast increased dose proportionally following IV administration. RSM01 adult PK was characterized using a two-compartment model with first-order elimination. IM absorption was described using a zero-order rate constant. Inter-individual variability was included for clearance (CL), central and peripheral volumes (V2 and V3). The RSM01 model estimated that distribution and a terminal half-life were 1.3 and 79.1 days, respectively, and IM bioavailability was ∼82%. The model predicted that following a 50 mg IM dose, median serum RSM01 concentration on day 150 in African infants 0-12 months old to be ∼ 28 mcg/mL, higher than the target exposure based on preclinical models (6.8 mcg/mL).
Serum RSM01 NCA PK summary
Note: AUClast and Cmax values are presented as geometric mean (CV). Tmax and Tlast are presented as median (min-max).
Arithmetic Mean (±SD) Serum RSM01 Concentration-Time Curve by Treatment
Note: Horizontal blue dashed line represents the target exposure based on preclinical models (6.8 mcg/mL).

Conclusion
RSM01 was shown to be well tolerated in healthy adults. Its long half-life and the predicted infant PK profiles support further pediatric development and indicate the potential for dosing once every RSV season.

Disclosures
Micha Levi, PhD, Bill & Melinda Gates Medical Research Institute: Salary as a full-time employee Shayne Watson, MSc, Bill & Melinda Gates Medical Research Institute: Salary as a full-time employee Dale Taylor, MD, Sanara Medtech Inc: Stocks/Bonds Luisa M. Stamm, MD, PhD, Bill & Melinda Gates Medical Research Institute: Salary as a full-time employee Michael W. Dunne, MD, Bill & Melinda Gates Medical Research Institute: Salary as a full-time employee