GSK and the University of Oxford have dosed the first patient in a Phase Ib ulcerative colitis study of aletekitug (GSK1070806), an anti-interleukin-18 (IL-18) antibody, pairing treatment with detailed analysis of gut and blood samples to investigate how blocking the pathway affects intestinal inflammation. PEGASUS is the first clinical study under their five-year, GBP 10 million experimental medicine collaboration.
IL-18 is an immune-signaling protein implicated in inflammation. By examining cellular and tissue changes during treatment, the researchers aim to establish whether inhibiting it alters disease-associated biological activity in ulcerative colitis, providing evidence to guide further therapeutic development.
The GSK-sponsored, open-label, repeat-dose study is being conducted at Oxford University Hospitals in adults with moderately to severely active ulcerative colitis who have not previously received advanced therapy. It will assess safety, tolerability, and biological effects under the PEGASUS master protocol, which allows investigational treatments to be evaluated sequentially through separate sub-studies. Aletekitug is the first treatment being tested, as identified in the UK Health Research Authority’s study summary.
A parallel research project at Oxford’s Kennedy Institute of Rheumatology, led by Calliope Dendrou and Matthias Friedrich, will investigate which cells and molecular pathways respond to treatment. Single-cell RNA analysis, spatial transcriptomics, and proteomics will help map these changes and their location within intestinal tissue, alongside assessments of drug exposure, target engagement, clinical disease activity, and biomarkers.