Alentis Therapeutics has announced positive topline results from two clinical trials evaluating lixudebart (ALE.F02), a monoclonal antibody targeting Claudin-1 (CLDN1), for the treatment of organ fibrosis. The trials, RENAL-F02 in ANCA-Associated Vasculitis (AAV) with Rapidly Progressive Glomerulonephritis (RPGN) and FEGATO-01 in advanced liver fibrosis, showed promising signs of target engagement, safety, and preliminary efficacy.
Dose-Dependent Target Engagement and Safety
Lixudebart demonstrated robust dose-dependent target engagement in both the RENAL-F02 and FEGATO-01 studies. The drug also exhibited a favorable safety profile, both as a monotherapy and in combination with standard of care. These findings align with previous Phase 1 trial results in healthy volunteers, reinforcing the drug's tolerability.
RENAL-F02: ANCA-RPGN Trial
The ongoing Phase 2 RENAL-F02 trial (NCT06047171) enrolled 26 patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis (AAV) with Rapidly Progressive Glomerulonephritis (RPGN). Patients were dosed for up to 24 weeks. Interim results indicate beneficial effects of lixudebart on Glomerular Filtration Rate (GFR) recovery and proteinuria reduction.
According to David Jayne, Professor of Clinical Autoimmunity at Cambridge University, "Interim results from the RENAL-F02 study in ANCA-RPGN indicate beneficial effects of lixudebart on Glomerular Filtration Rate (GFR) recovery and proteinuria reduction. These observations were further supported by reductions of CD163, a validated urinary biomarker, also indicating an impact on immune cell homing and trafficking to the kidney."
FEGATO-01: Advanced Liver Fibrosis Trial
The Phase 1b FEGATO-01 trial (NCT05939947) included 41 patients with mainly advanced F3/F4 liver fibrosis and/or mild cirrhosis. These patients were dosed for up to 4 weeks. Preliminary data showed an initial decrease in ALT/AST levels in liver fibrosis patients treated with lixudebart.
Luigi Manenti, Chief Medical Officer of Alentis, stated, "The results from the two studies are very encouraging, particularly given the dose-dependent target engagement and favorable safety profile. We also observed an initial decrease in ALT/AST in liver fibrosis patients treated with lixudebart."
Lixudebart: A Novel Approach to Fibrosis
Lixudebart is a first-in-class monoclonal antibody designed to reverse organ fibrosis by specifically targeting a unique CLDN1 epitope exposed in fibrotic tissue. The investigational antibody is being developed for liver, lung, and kidney fibrosis. The FDA has granted Orphan Drug designation to lixudebart for the treatment of Idiopathic Pulmonary Fibrosis (IPF).
About Alentis Therapeutics
Alentis Therapeutics is a clinical-stage biotechnology company focused on developing first-in-class antibody-drug conjugates (ADCs) and antibodies targeting Claudin-1 (CLDN1) for oncology and multi-organ fibrosis. Their lead ADC program, ALE.P02, has received Fast Track designation from the FDA for the treatment of advanced or metastatic CLDN1+ squamous cancers.
