Pharmacokinetic profiles of a SARS-COV-2 neutralizing antibody BD-604 in cynomolgus monkeys.

ABSTRACT

BACKGROUND: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread worldwide as a severe pandemic and effective therapeutic medications are urgently needed. As reported previously, BD-604 is a fully human monoclonal antibody with strong in vitro and in vivo neutralizing activity to SARS-COV-2. OBJECTIVE: The purpose of this study was to characterize the pharmacokinetic propertie of BD-604 in cynomolgus monkeys. METHODS: To analyze the concentration of BD-604 in cynomolgus monkey serum, an ELISA assay was established, and a systemic validation was performed including accuracy and precision, dilution linearity and hook effect, selectivity, specificity, stability, and parallelism tests. Then, six naïve cynomolgus monkeys (3/sex) were administered BD-604 at a single dose of 10 mg/kg via intravenous infusion (60 min). Blood samples were collected at various time points (0-672 h) and analyzed for serum concentrations of BD-604. RESULTS: The data from validation experiments assure the reproducibility and reliability of the established ELISA assay. Then, the validated method was used to measure BD-604 concentration in cynomolgus monkey serum. The pharmacokinetics parameters including terminal half-life (t1/2 ), peak serum concentration (Cmax ), area under curve from time zero to last timepoint or infinity (AUClast /AUCinf ), apparent volume of distribution (Vz ), clearance rate (CL), and mean residence time (MRT) were calculated and reported. BD-604 showed no marked sex differences at the dose of 10 mg/kg when comparing the AUC0-last and Cmax between female and male cynomolgus monkeys. CONCLUSION: In cynomolgus monkeys, BD-604 possesses pharmacokinetic properties similar to natural IgGs.