Receptor Occupancy In The Era Of Multispecific Therapeutics

By Deborah Phippard, PhD, and Jenny Zilberberg

Receptor occupancy has become more than a measure of target engagement as multispecific therapeutics introduce new biological and analytical complexities. Bispecific antibodies, T-cell engagers, ADCs, and other next-generation modalities can alter receptor expression, trafficking, and cellular interactions in ways that complicate conventional occupancy measurements.

This article examines the practical considerations that shape meaningful RO studies, from sample collection, stabilization, processing, and shipping to assay design and cellular resolution. It also explores when peripheral blood can serve as a surrogate for tissue-resident target populations, how receptor internalization and shedding affect interpretation, and why occupancy may need to be considered alongside total receptor, pharmacodynamic, biomarker, and mechanistic endpoints.

Examine how evolving therapeutic modalities are changing the questions RO assays need to answer and the strategies used to address them.