First dose in human / MABEL

First in human dose estimation is a classical problem where PK/PD modeling is key for biologics. Pharmacokinetics, target kinetics and binding to the target and their differences between the toxicology species and human must be factored in to determine a safe starting dose. Modeling helps here to factor in all data for a robust starting dose based on the MABEL (Minimal Anticipated Biological effect Level) as required by EMA: EMEA/CHMP/SWP/28367/07 “Wherever possible, the above data should be integrated in a PK/PD modelling approach for the determination of the MABEL. While the FIH dose is critical for safety another important aspect is the efficacious dose and dose regimen in human by translation of preclinical data.