First clinical study in GSK-Oxford Experimental Medicine Collaboration starts in ulcerative colitis trial
The first patient in the PEGASUS clinical study, part of the GSK-University of Oxford Experimental Medicine Collaboration, received first dose today/this week.
The participant has received a first dose of an investigational anti-interleukin-18 (IL-18) monoclonal antibody, in as part of the PEGASUS programme, an experimental medicine clinical trial in adults with moderate-to-severely active ulcerative colitis.
The PEGASUS project is part of the GSK–University of Oxford Experimental Medicine Collaboration established in 2025. Backed by a £10 million investment over five years, this collaboration unites GSK’s drug-development expertise with Oxford’s experimental medicine capabilities to help inform early target-development decisions in a range of therapy areas.
The milestone marks the start of dosing under the PEGASUS master protocol (NCT07747467 and NCT07747480). Recruitment happened within only 72 hours of Oxford site activation. The Phase 1b, open-label, repeat-dose, single-centre mechanistic study is designed to characterise the safety, tolerability and biological effects of investigational interventions in people with active ulcerative colitis who have not previously received advanced therapy.
Alissa Walsh DPhil FRCP, Chief Investigator, Kennedy Institute of Rheumatology and John Radcliffe Hospital, Oxford, said: 'Dosing our first participant within days of opening is a real credit to the Oxford team. PEGASUS is off to a flying start, and we're grateful to the patients who participate in early phase research like this.'
Investigating a distinct inflammatory pathway
Ulcerative colitis is a chronic inflammatory disease of the colon that can substantially affect health and quality of life. Over 500,000 people in the UK have Inflammatory Bowel Disease (IBD), the two main forms of which are Crohn’s Disease and Ulcerative Colitis.
Although therapeutic options have expanded, a significant unmet need remains. Many patients still live with pain and discomfort which has an impact on how they lead fulfilling and independent lives. This study will help improve the mechanistic understanding of IL-18 on this inflammatory disease and inform potential therapeutic application.
About the PEGASUS study
PEGASUS uses a master-protocol design to enable the sequential evaluation of investigational therapies through individual sub-studies. Exploratory assessments will examine biological responses relevant to the IL-18 pathway and intestinal inflammation at a cellular level, including single cell, transcriptomic and proteomic analysis.
The platform study design is intended to support evidence-led decisions about whether emerging therapeutic mechanisms warrant further clinical development. Any evaluation within PEGASUS should be described only following the applicable regulatory, governance and operational approvals.
Professor Chris Buckley, Director of Research, Kennedy Institute of Rheumatology, said: 'By integrating longitudinal gut and blood sampling with single-cell and spatial technologies, we aim to define how inflammatory pathways are driven at cellular and tissue levels. Linking these cell-based readouts derived from the PEGASUS clinical study with other studies using standard of care therapies in ulcerative colitis offers a valuable opportunity to deepen biological understanding and inform future therapeutic development.'
Oxford research will map cellular and molecular responses
The biomarker research project aligned with PEGASUS at the Kennedy Institute of Rheumatology, University of Oxford, will assess the molecular and cellular effects of anti-IL-18 inhibition in advanced-therapy-naïve participants with moderate-to-severely active ulcerative colitis. Led by Calliope Dendrou and Matthias Friedrich, the project will analyse samples from the GSK-sponsored PEGASUS clinical trial to generate mechanistic evidence alongside the clinical study.
Dr Kaivan Khavandi MD PhD, Senior Vice President and Head of R&D Translational & Development Sciences, GSK, said: 'This is a significant milestone for the GSK-Oxford Experimental Medicine Collaboration. By combining forces with Oxford, we're able to unite deep characterisation of disease pathobiology, at a cellular level, and then understand whether pharmacological perturbation with IL18 inhibition is able to correct these signatures of disease towards health. This approach, called interventional genomics, is central to both our innovation and collaboration strategy: using technology and high dimensional data to make earlier and higher fidelity predictions for therapeutic success.'
Using state of the art molecular and cellular techniques, including single cell RNA analysis, spatial transcriptomics, proteomics and bioinformatic analysis, the Oxford team will investigate treatment-associated biological changes and compare them with responses to standard-of-care therapies, including anti-tumour necrosis factor treatments previously studied by Oxford in the TAURUS study (Thomas, T et al Nature Immunol 2024). The analyses will examine whether anti-IL-18 affects molecular signatures associated with response compared to response or non-response to anti-TNF therapy, and will also explore pharmacokinetics, target engagement, clinical disease activity and clinical biomarkers.
PEGASUS is sponsored by GSK, with Oxford University Hospitals serving as the clinical site.
