lixudebart (ALE.F02) / Alentis Therap - LARVOL DELTA

Targeting of CLDN1 Reduces Kidney Injury and Macrophage Infiltration in FSGS (KIDNEY WEEK 2025) - "Lixudebart (ALE.F02), a first-in-class monoclonal antibody (mAb) developed by Alentis, selectively targets exposed CLDN1 on activated renal epithelial cells...In vitro and ex vivo studies linked aberrant CLDN1 exposure to immune cell recruitment and ECM remodeling. These findings support CLDN1 inhibition as a novel therapeutic strategy in FSGS."

Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Inflammation • Renal Disease • CD44 • CD68 • CLDN1 • MMP14

Therapeutic Targeting of CLDN1 Reduces Glomerular Crescent Formation and Fibrosis and Preserves Renal Function in ANCA-Associated Glomerulonephritis (KIDNEY WEEK 2025) - P2 | "Lixudebart (ALE.F02), a first-in-class monoclonal antibody (mAb) developed by Alentis, selectively targets and blocks exposed CLDN1 on activated renal epithelial cells...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."

Fibrosis • Glomerulonephritis • Immunology • Lupus Nephritis • Nephrology • CLDN1 • MMP14 • MPO

Rescue of Nephrons With ALE.F02 (RENAL-F02) (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Alentis Therapeutics AG | Active, not recruiting ➔ Recruiting | Trial completion date: Sep 2025 ➔ Jun 2027 | Trial primary completion date: Sep 2025 ➔ Jun 2027

Enrollment open • Trial completion date • Trial primary completion date • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis • Nephrology • Vasculitis

Targeting CLDN1 in IPF: A Pathogenic Driver in Aberrant Epithelium and a Potential Therapeutic Avenue (ATS 2025) - "Our findings suggest a functional role for CLDN1 in IPF progression, as CLDN1 is prominently localized within aberrant epithelial populations in regions of active matrix deposition and tissue remodeling. GRN analysis and in vivo studies further support a link between CLDN1 and the regulation of ECM organization and inflammatory pathways. Finally, anti-CLDN1 mAb treatment significantly improved lung fibrosis and function in a bleomycin-induced mouse model, providing a strong preclinical proof-of-concept for Lixudebart as a novel therapy for IPF."

Late-breaking abstract • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • CLDN1

Alentis Announces Positive Topline Results from Two Studies of Lixudebart (ALE.F02) in Patients with ANCA-RPGN and Advanced Liver Fibrosis (Businesswire) - P2 | N=80 | RENAL-F02 (NCT06047171) | P1 | N=41 | FEGATO-01 (NCT05939947) | Sponsor: Alentis Therapeutics AG | "'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.' '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.' In both clinical trials, lixudebart demonstrated a favorable safety profile, both as a monotherapy and in combination with standard of care (n=51 active patients across the two trials)."

P1 data • P2 data • ANCA Vasculitis • Fibrosis

Rescue of Nephrons With ALE.F02 (RENAL-F02) (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Alentis Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis • Nephrology • Vasculitis

FEGATO-01: A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: Alentis Therapeutics AG | Recruiting ➔ Completed

Metastases • Trial completion • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Novel therapeutic for crescentic glomerulonephritis through targeting CLDN1 in parietal epithelial cells (ESPN 2024) - P2 | "Lixudebart (formerly ALE.F02) is a first-in-class monoclonal antibody that specifically targets and blocks exposed CLDN1 in injured epithelial cells... Our results suggest a functional role of CLDN1 in the pathogenesis of CrGN, providing preclinical proof-of-concept for anti-CLDN1 antibodies as a novel therapeutic approach in patients with CrGN."

ANCA Vasculitis • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis • CD44 • CLDN1

Lixudebart for IPF receives orphan drug status from FDA (Pulmonary Fibrosis News) - "'Alentis is doing important work on developing lixudebart as a treatment targeting the root causes of disease,' Nathan said. 'This molecule has shown a very favorable safety profile in Phase 1, and I would be thrilled to see lixudebart tested in IPF patients in the future.'"

Media quote • Regulatory • Idiopathic Pulmonary Fibrosis

Alentis Receives FDA Orphan Drug Designation for Lixudebart to Treat Idiopathic Pulmonary Fibrosis - "'IPF patients do not have transformative treatment options and often experience tolerability challenges with the current standard of care drugs. Alentis is doing important work on developing lixudebart as a treatment targeting the root causes of disease,' added Prof. Steven Nathan...'This molecule has shown a very favorable safety profile in Phase 1, and I would be thrilled to see lixudebart tested in IPF patients in the future.'"

Media quote • Regulatory • Idiopathic Pulmonary Fibrosis

Alentis Receives FDA Orphan Drug Designation for Lixudebart to Treat Idiopathic Pulmonary Fibrosis (Businesswire) - "Alentis Therapeutics...announced today that the U.S. Food and Drug Administration (FDA) has granted lixudebart (ALE.F02) Orphan Drug designation for the treatment of Idiopathic Pulmonary Fibrosis (IPF)."

Orphan drug • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Novel therapeutic for crescentic glomerulonephritis through targeting CLDN1 in parietal epithelial cells (ERA-EDTA 2024) - P2 | "Lixudebart (formerly ALE.F02) is a first-in-class monoclonal antibody that specifically targets and blocks exposed CLDN1 in injured epithelial cells... Our results suggest a functional role of CLDN1 in the pathogenesis of CrGN, providing preclinical proof-of-concept for anti-CLDN1 antibodies as a novel therapeutic approach in patients with CrGN."

ANCA Vasculitis • Fibrosis • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Vasculitis • CD44 • CLDN1

Expression of Exposed CLDN1 Is Linked to Early Pathological Lesions in Idiopathic Pulmonary Fibrosis (ATS 2024) - "Our results may imply a functional role for CLDN1 in IPF pathogenesis. Exposed CLDN1 is present in areas of active matrix deposition, even in mild disease areas, suggesting a direct involvement of exposed CLDN1 in the maturation of the fibroblastic scars in IPF. Importantly, we provided a preclinical proof-of-concept for Lixudebart as a novel therapeutic approach based on the enrichment of exposed CLDN1 during disease progression and its association with epithelial injury and active fibrotic lesions in IPF lungs."

Late-breaking abstract • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation • CLDN1 • TGFB1 • TNFA

Orphan Designation: treatment of idiopathic pulmonary fibrosis (FDA) - Date Designated: 05/24/2024

Orphan drug • Idiopathic Pulmonary Fibrosis • Immunology

Rescue of Nephrons With ALE.F02 (RENAL-F02) (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Alentis Therapeutics AG | N=60 ➔ 80

Enrollment change • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis • Nephrology • Vasculitis

Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development. (PubMed, Am J Physiol Endocrinol Metab) - "Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Oncology • Renal Disease

FEGATO-01: A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis (clinicaltrials.gov) - P1 | N=38 | Recruiting | Sponsor: Alentis Therapeutics AG | Phase classification: P1b ➔ P1 | N=28 ➔ 38 | Trial completion date: Jun 2024 ➔ Nov 2024 | Trial primary completion date: Jun 2024 ➔ Nov 2024

Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Claudin-1 Is a Therapeutic Target for Crescentic Glomerulonephritis (KIDNEY WEEK 2023) - "Our results suggest a functional role for CLDN1 in the pathogenesis of CGN, providing preclinical proof-of-concept for ALE.F02 as a novel therapeutic approach in patients with CGN."

ANCA Vasculitis • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis • CD44 • CLDN1 • CXCL12 • MMP7

FEGATO-01: A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis (clinicaltrials.gov) - P1b | N=28 | Recruiting | Sponsor: Alentis Therapeutics AG | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Jan 2024 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • TIMP1

REscue of Nephrons With ALe.F02 (RENAL-F02) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Alentis Therapeutics AG | Not yet recruiting ➔ Recruiting

Enrollment open • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis • Nephrology • Vasculitis

Alentis Therapeutics Appoints Lung Experts Professors Tony Mok and Steven Nathan to its Scientific Advisory Board (BioSpace) - "Prof. Tony Mok said, 'I am excited to be working with Alentis on the development plan for their first in class antibody ALE.C04 in squamous cell lung cancer as well as their Claudin Technology Platform, specifically antibody-drug conjugates, for use in Claudin-1 positive squamous cell lung cancer and Claudin-1 histology agnostic clinical trials.'...'There is a huge unmet medical need for idiopathic pulmonary fibrosis patients, and Alentis is doing important work on ALE.F02, a new treatment for organ fibrosis that has the potential to help IPF patients,' said Prof. Steven Nathan. 'I am looking forward to our broad research collaboration using Alentis' Claudin Technology Platform to develop next-generation lung fibrosis therapies including bispecific antibodies.'"

Announcement • Media quote • Idiopathic Pulmonary Fibrosis

REscue of Nephrons With ALe.F02 (RENAL-F02) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Alentis Therapeutics AG

New P2 trial • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis • Nephrology • Vasculitis

Late Breaking Abstract - Claudin-1 is a potential airway-centric therapeutic target for pulmonary fibrosis (ERS 2023) - "Using preclinical animal models of IPF and precision-cut lung slices (PCLS) generated from IPF lung explants, we investigated the individual and combined effects of ALE.F02 and Nintedanib or Pirfenidone on parameters related to the pathogenesis of IPF...Preclinical studies in aged bleomycin mouse model showed that therapeutic treatment with anti-CLDN1 mAb reduced fibrosis and improved lung function. Our results suggest a functional role for CLDN1 in the pathogenesis of IPF, providing preclinical proof-of-concept for ALE.F02 as a novel airway-centric therapeutic approach in patients with pulmonary fibrosis.; Physiology; Cell and molecular biology; Imaging"

Late-breaking abstract • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CLDN1 • COL1A1 • MMP7 • TIMP1

Alentis Therapeutics to Present at the European Respiratory Society (ERS) International Congress (Businesswire) - "Alentis Therapeutics...announced today an oral presentation during the ERS International Congress to be held September 9-13 in Milan, Italy....'Our studies suggest that exposed Claudin-1 plays a functional role in the pathogenesis of idiopathic pulmonary fibrosis and provide preclinical proof-of-concept for ALE.F02 as a potential treatment for pulmonary fibrosis.'"

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology

FEGATO-01: A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis (clinicaltrials.gov) - P1b | N=34 | Recruiting | Sponsor: Alentis Therapeutics AG

Metastases • New P1 trial • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • TIMP1