A Quantitative Modeling and Simulation Framework to Support Candidate and Dose Selection of Anti-SARS-CoV-2 Monoclonal Antibodies to Advance Bamlanivimab Into a First-in-Human Clinical Trial

Neutralizing monoclonal antibodies (mAb) have emerged as promising therapeutics for COVID-19, with research efforts accelerated through open-access in silico models. Innovative approaches, including a physiologically-based pharmacokinetic (PBPK) model and a longitudinal SARS-CoV-2 viral dynamic model, facilitated the selection of optimal mAb candidate and therapeutic dose. By utilizing these models, the first-in-human trial of bamlanivimab (NCT04411628) initiated with a conservative dose of 700 mg, aiming to achieve maximum therapeutic effect while ensuring safety and tolerability.