Abstract: TH-PO0659
Therapeutic Targeting of CLDN1 Reduces Glomerular Crescent Formation and Fibrosis and Preserves Renal Function in ANCA-Associated Glomerulonephritis
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Teixeira, Geoffrey, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Dang, Minh Huan, Monash University, Melbourne, Victoria, Australia
- Prakongtham, Peemapat, Monash University, Melbourne, Victoria, Australia
- Lu, Chunni, Monash University, Melbourne, Victoria, Australia
- Polini, Elisa, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Chanemouga, Isabelle, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Cavadini, Silvia, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Anquetil, Vincent, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Herbert, Corentin, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Iacone, Roberto, Alentis Therapeutics AG, Allschwil, BL, Switzerland
- Kitching, A. Richard, Monash University, Melbourne, Victoria, Australia
Background
Despite immunosuppression, glomerular crescents in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (crGN) can progress to fibrosis and glomerulosclerosis, underscoring the need for adjunctive therapies targeting fibrotic pathways. In crGN, claudin-1 (CLDN1), a transmembrane tight junction protein, becomes aberrantly exposed outside tight junctions, where it promotes pro-fibrotic signaling, immune cell homing and extracellular matrix (ECM) remodeling. Lixudebart (ALE.F02), a first-in-class monoclonal antibody (mAb) developed by Alentis, selectively targets and blocks exposed CLDN1 on activated renal epithelial cells. A Phase II clinical trial is currently underway in patients with crGN due to AAV (NCT06047171). This study investigates whether CLDN1 inhibition modulates established ANCA-induced crGN.
Methods
A new 21 day model of crGN in mice induced by ANCA (mouse anti-mouse myeloperoxidase mAbs) tested anti-CLDN1 mAb therapy, commenced 6 days post disease induction (d6 crescents 31.6±3.7%). Mechanistic studies used in vitro/ex vivo epithelial cell models to explore interactions between CLDN1 and pro-inflammatory/pro-fibrotic mediators.
Results
In murine MPO-AAV, anti-CLDN1 mAb treatment reduced glomerular crescents (d21 Ctrl 31.4±2.6%, anti-CLDN1 mAb 19.1±1.7% p<0.001), limited glomerular segmental necrosis, decreased glomerular fibrosis (d21 Ctrl 12.5±0.6%, anti-CLDN1 mAb 9.7±0.7% p=0.0210) and improved renal function. Ex vivo, Lixudebart disrupted CLDN1 interactions with CD44 and MMP14, key mediators of immune cell recruitment and ECM remodeling.
Conclusion
Lixudebart commenced in established experimental MPO-ANCA induced crGN improved histology and kidney function. In vitro/ex vivo studies link CLDN1’s aberrant exposure to immune cell recruitment and ECM remodeling. These studies support CLDN1 inhibition as a novel therapeutic strategy in crGN.