Table II.

Utilities of Drug and Target Concentration Data at Preclinical Development Stage

Concentration dataa	Intended use
mAbfree or mAbtotal	To characterize in vivo PK behavior and to project human PK
	To assess PK and PD response relationships in animal models
	To calculate safety margin and determine the safe starting dose and/or efficacious dose in FIH study
Lfree	To assess the inhibition of Lfree following drug treatment and provide proof of concept information; to understand the dynamics of Lfree
Ltotal	To assess the re-distribution/modulation of Ltotal following drug treatment and provide proof of concept information; understand the dynamics of Ltotal
Lfree/Ltotal ratio	To compare in vivo and in vitro binding affinities
mAb and L dynamic relationship	To understand the underlying dynamic relationship between mAb and L to facilitate dose and dosing schedule selection

mAb monoclonal antibody drugs, L target ligand, PK pharmacokinetics, PD pharmacodynamics, FIH first in human

^aThe concentration data required for a specific analyte depend on many factors as discussed in the text