Abstract: INFO15-FR
Phase 1/2 Trial of PS-002, an Adeno-Associated Virus-Based Therapy Delivering the Complement Factor I Gene to Podocytes in IgAN
Session Information
- Informational Posters - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Harrison, Pille, Purespring Therapeutics Limited, London, England, United Kingdom
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Sinha, Smeeta, Northern Care Alliance NHS Foundation Trust, Salford, England, United Kingdom
- Roberts, Ian, Oxford University Hospitals NHS Foundation Trust, Oxford, England, United Kingdom
- Saleem, Moin A., University of Bristol, Bristol, England, United Kingdom
- Smerdon, Charlotte J, Purespring Therapeutics Limited, London, England, United Kingdom
- Rowland, Alicia, Purespring Therapeutics Limited, London, England, United Kingdom
- Erlandsson, Fredrik, Purespring Therapeutics Limited, London, England, United Kingdom
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Description
Recent drug development in IgA nephropathy (IgAN) has seen major advancements in addressing CKD and immunological dimensions. Next to systemic approaches, medical need remains to target the disease specific processes locally. In the grouped ddY mouse model of IgAN a PS-002 analogue clears glomerular C3 deposition and improves histopathological characteristics including fibrosis. In pigs, administration of PS-002 results in the highly localised expression of human complement factor I (CFI) within glomeruli. PS-002 therefore has potential to alleviate complement driven glomerular diseases locally without affecting systemic complement activation.
The phase 1/2 trial was designed to efficiently evaluate the safety, tolerability, optimal dose and early markers of efficacy of PS-002 in patients with IgAN. This is an open label multi-centre trial conducted in patients rather than healthy volunteers. Each participant will receive a single dose of PS-002 administered locally to both kidneys. A single PS-002 dose is expected to confer long-term benefits enabling non-dividing podocytes to produce complement modulating CFI locally.
Each phase 1 cohort will evaluate one dose of PS-002 in approximately 3 participants, and the dose is planned to be increased 2-3 fold between each cohort. Dose exploration and trial modifications are overseen by an independent data monitoring committee. A sentinel dosing strategy is utilized within and between each dose cohort to enable collection of sufficient safety data for dose exploration decisions. Participants receive a prophylactic corticosteroid over 8 weeks to minimize the risk of immune reactions to PS-002.
Key objectives include safety and tolerability, and effects on proteinuria and complement biomarkers. A biopsy is conducted at 6 months to assess C3 deposition, expression of the CFI gene in glomeruli, and histopathology.
Following identification of a biologically optimal dose in the phase 1 dose exploration portion, a phase 2 dose expansion cohort will be recruited to evaluate further safety and efficacy.
The trial will be conducted in the US and UK and will recruit up to 12 patients in the phase 1 exploration and 20 patients in the phase 2 expansion cohort.
Funding
- Purespring Therapeutics