Developing And Validating Clinical Receptor Occupancy Pharmacodynamic Biomarker Assays

Receptor occupancy (RO) assays are essential pharmacodynamic markers used to assess target engagement and support pharmacokinetic/pharmacodynamic (PK/PD) modeling in first-in-human clinical studies. Accurate RO measurement often requires fresh whole blood samples, as receptor binding can be disrupted by cell isolation or cryopreservation, and biological factors such as receptor downregulation, internalization, or cell trafficking can further complicate interpretation. Given these challenges, RO assays must be carefully customized to the drug and receptor biology to accurately measure receptor stability and engagement.

This case study involves an immuno-modulatory therapy for autoimmune and inflammatory diseases, where the sponsor needed to monitor CD6 receptor occupancy and modulation on T cells. The assay needed to quantify receptor engagement and support dose optimization while allowing batched flow cytometry testing on stabilized whole blood samples. Effective RO assays provide critical insights into drug activity and enable precise PK/PD modeling, facilitating dose selection and better understanding of therapeutic effects in patients under treatment.