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 together with our partner CSL, for rare kidney and liver diseases, in particular for ANCA-associated vasculitis, focal segmental glomerulosclerosis and primary sclerosing cholangitis.
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.
CSL partnership
Alentis and CSL are in a global partnership to co-develop and co-promote lixudebart in rare kidney and liver diseases, including AAV-RPGN, FSGS and PSC. The collaboration brings together Alentis’ scientific expertise as the leading clinical-stage biopharmaceutical company targeting claudin-1 and CSL’s global development and commercialization capabilities in nephrology.
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 (AAV-RPGN)
ANCA-associated vasculitis (AAV) with renal involvement (RPGN phenotype) is a rare, life-threatening autoimmune disease that can rapidly impair kidney function. Patients are at risk of irreversible kidney damage, kidney failure, dialysis and transplantation. While current treatment approaches rely on broad immunosuppression, significant unmet medical need remains.
What is focal segmental glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is a rare, progressive disease affecting the kidneys. The disease can lead to significant proteinuria, declining kidney function and, ultimately, kidney failure. Despite the serious burden of disease, treatment options remain limited, highlighting the substantial unmet medical need for patients living with FSGS.
What is primary sclerosing cholangitis (PSC)
Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease. As the disease advances, patients may develop fibrosis, cirrhosis, liver failure and an increased risk of hepatobiliary cancers. Besides liver transplantation, there are currently no treatment options for patients living with PSC, underscoring the high unmet medical need for patients.
Clinical trials of lixudebart
Phase 2 in AAV-RPGN - ongoing
Lixudebart is being studied in a Phase 2 clinical trial called RENAL-F02 (NCT06047171). The study is planned to 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.
Interim results showed dose-dependent target engagement, a favorable safety profile and preliminary evidence of improved kidney function (as measured by eGFR and proteinuria).
Phase 2 in FSGS - planned
A Phase 2 trial of lixudebart in focal segmental glomerulosclerosis is being planned.
Phase 2 in PSC - planned
A Phase 2 trial of lixudebart in primary sclerosing cholangitis is being planned.
Phase 1b in liver fibrosis - completed
Lixudebart was tested in a Phase 1b study called FEGATO-01 (NCT05939947). The randomized, double-blind, placebo-controlled trial studied lixudebart in 41 patients with advanced liver fibrosis and/or mild cirrhosis.
Topline results showed dose-dependent target engagement, a favorable safety profile and preliminary evidence of improved liver function (as measured by ALT/ AST).
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.