Using skin biopsies to measure target occupancy of anti-fibrotic molecules: assay development and application for zampilimab in a primate model of chronic kidney disease and in healthy human volunteers.

ABSTRACT:

Background

Assessing target engagement (TE) and target occupancy (TO) of novel antifibrotic molecules is challenging, as the target organs are inaccessible. In clinical trials, this often requires biopsies of internal organs, which increases both risk and discomfort for participants. Zampilimab (UCB7858) is a humanized monoclonal antibody that specifically inhibits the extracellular activity of transglutaminase 2 (TG2). Blocking TG2 activity reduces fibrosis in experimental models of chronic kidney disease. Here, a low-risk skin 'biopsy-on-biopsy' approach has been developed as a surrogate to assess TO of zampilimab in the kidney, ahead of further investigation of zampilimab in clinical studies.

Methods

A dual-antibody competitive immunofluorescence assay was developed to as

SUBMITTER: Huang L 

PROVIDER: S-EPMC12829241 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature