Lixudebart for organ fibrosis

Lead program in fibrosis

With lixudebart (formerly named ALE.F02) we aim to reverse organ fibrosis. The program is being developed for kidney, liver and lung fibrosis, in particular for ANCA-associated vasculitis, advanced liver fibrosis and idiopathic pulmonary fibrosis.

The role of Claudin-1 in fibrotic disease

In healthy cells, Claudin-1 is hidden within tight junctions where its normal function is to bind cells together. In fibrotic tissue Claudin-1 is overexpressed and exposed outside tight junctions. Exposed Claudin-1 activates fibrotic signaling, and over time, drives excessive accumulation of extracellular matrix components like collagen. The increasing amount of collagen creates a physical barrier that eventually causes organ failure in fibrosis.

What is Lixudebart (ALE.F02)

Lixudebart is an investigational first-in-class monoclonal antibody designed to reverse fibrosis by targeting exposed Claudin-1 in fibrotic tissue. By binding exposed Claudin-1, lixudebart blocks fibrotic signaling and opens the collagen barrier to preserve or restore organ function.

Lixudebart – a novel mechanism of action for fibrosis treatment

Lixudebart has been designed to specifically bind exposed Claudin-1 without interfering with the protein in tight junctions. Upon binding, the antibody blocks fibrotic signaling inside the cell and disrupts the physical interactions between exposed Claudin-1 and collagen-binding receptors. This leads to the breakdown of the collagen barrier around the organ.

Critical need for new fibrosis drugs

Severe fibrosis is estimated to account for up to 45% of deaths in developed countries. Fibrosis with exposed Claudin-1 frequently affects the kidney, liver and lung.

What is ANCA-associated vasculitis with rapidly progressive glomerulonephritis

ANCA-associated vasculitis (AAV) with renal involvement (rapidly progressive glomerulonephritis phenotype) is a rare, severe and potentially fatal disease. In up to 85% of AAV cases, the kidneys are affected by fibrosis within 2 years of disease onset. Despite anti-inflammatory treatment, most patients develop significant or total loss of renal function over time. Consequently, new treatments are needed to stop or reverse organ failure.

What is idiopathic pulmonary fibrosis

IPF is a progressive lung disease with a poor prognosis. On average patients live for 2.5–5 years after diagnosis. Current medicines merely slow progression, highlighting the pressing demand for new treatments that halt progression or improve the condition of IPF.

Clinical trials of lixudebart

Phase 2 in kidney fibrosis - recruiting

Lixudebart is being studied in a Phase 2 clinical trial called RENAL-F02 (NCT06047171). The study will enroll 60 patients with Antineutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis with Rapidly Progressive Glomerulonephritis (RPGN). The randomized, double-blind, placebo-controlled study evaluates the safety, tolerability, pharmacokinetics, and renal sparing efficacy of lixudebart.

Phase 1b in liver fibrosis - recruiting

We are currently testing lixudebart in a Phase 1b study called FEGATO-01 (NCT05939947). The randomized, double-blind, placebo-controlled trial is designed to study how the body processes lixudebart (pharmacokinetics) in 34 patients with advanced liver fibrosis and/or mild cirrhosis. Besides primary endpoint PK, secondary endpoints in the trial include safety, pharmacodynamics, target engagement, and further understanding of CLDN1 biology.

Phase 2 in lung fibrosis - planned

A Phase 2 trial of lixudebart in idiopathic pulmonary fibrosis is being planned.

Phase 1 in healthy volunteers - completed

A first-in-human clinical trial was completed in healthy volunteers. Lixudebart showed a good safety and tolerability profile at all dose levels. No severe or serious adverse events were observed.