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

Area of Science:

• Bioanalytical Chemistry
• Pharmacokinetics
• Immunochemistry

Background:

• Endogenous interferents in biological samples can compromise the accuracy of ligand binding assays.
• Nonselective quantification of drug concentrations leads to unreliable pharmacokinetic data.

Purpose of the Study:

• To develop a selective Gyrolab immunoassay for quantifying the novel modality CB307.
• To address and mitigate matrix effects impacting assay accuracy and sensitivity.

Main Methods:

• Implemented strategies to overcome matrix effects, including increasing minimum required dilution (MRD) and lower limit of quantification.
• Optimized antibody orientation, assay buffer, and solid phase for enhanced selectivity.
• Utilized Gyrolab immunoassay technology for high-throughput quantification.

Main Results:

• Successfully mitigated matrix effects through strategic assay optimization.
• Achieved desired sensitivity and selectivity for CB307 quantification in disease state matrix.
• The developed method met bioanalytical method validation (BMV) guidance.

Conclusions:

• The developed Gyrolab immunoassay provides a selective and sensitive method for CB307 quantification.
• This validated assay is crucial for supporting pharmacokinetic analysis in clinical studies.
• The method is currently employed in the first-in-human POTENTIA clinical study (NCT04839991).