Solving selectivity issues in LBAs: case study using Gyrolab to quantify CB307, a bispecific Humabody in human serum.

ABSTRACT

Aim: Endogenous interferents can cause nonselectivity in ligand binding pharmacokinetic assays, leading to inaccurate quantification of drug concentrations. We describe the development of a Gyrolab immunoassay to quantify a new modality, CB307 and discuss strategies implemented to overcome matrix effects and achieve selectivity at the desired sensitivity.Results: Matrix effects were mitigated using strategies including increasing minimum required dilution (MRD) and lower limit of quantification, optimization of antibody orientation, assay buffer and solid phase.Conclusion: The strategies described resulted in a selective method for CB307 in disease state matrix that met bioanalytical method validation (BMV) guidance and is currently used to support clinical pharmacokinetic sample analysis in the first-in-human POTENTIA clinical study (NCT04839991) as a secondary clinical end point.

[Box see text].