Establishing a flow cytometry-based tissue receptor occupancy assay for an anti-oncostatin M receptor beta subunit therapeutic candidate in inflammatory bowel disease

Abstract

This article details the development of a tissue-based receptor occupancy (RO) assay using colonic pinch biopsies to enable the evaluation of vixarelimab target coverage in a Phase 1c study for inflammatory bowel disease (IBD). Vixarelimab, a monoclonal antibody targeting Oncostatin M Receptor Beta subunit (OSMRβ), has demonstrated clinical efficacy in treating inflammatory conditions such as prurigo nodularis and chronic pruritus. It was more recently studied in patients with ulcerative colitis (UC). Understanding the drug's distribution and retention in gut tissues is essential for assessing its therapeutic potential for IBD. While RO assays are powerful tools for evaluating drug target engagement, there are gaps in best practices for their development, especially when applied to sample types not readily available as single-cell suspensions. This article addresses challenges associated with tissue processing, cell recovery, and accurate interpretation of RO results, offering insights into overcoming limitations in sample availability and variability in drug-target interactions during assay development.