Article published in The Journal of Hepatology highlights potential of Claudin-1 as a novel target for the treatment of hepatocellular carcinoma

Breakthrough results provide robust pre-clinical proof-of-concept for Claudin-1 monoclonal antibodies as potential first in-class compounds for HCC

Potential shown to break the plateau of limited treatment response in advanced HCC

These results pave the way for the clinical development of Claudin-1 specific antibodies for treatment of patients with HCC

Basel, Switzerland – 2 November 2022 Alentis Therapeutics (“Alentis” or “the Company”), the biotechnology company developing breakthrough treatments for organ fibrosis and fibrotic-associated cancers, today announces that Scientific Founder Professor Thomas Baumert’s team has published an article on the role of Claudin-1 (CLDN1) in the treatment of hepatocellular carcinoma (HCC) The Journal of Hepatology.

Despite new treatment approvals, treatment response and prognosis of patients with advanced HCC remain poor. CLDN1 is a membrane protein expressed not only at tight junctions but also non-junctionally such as the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored.

Using humanized monoclonal antibodies (mAbs) targeting specifically the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems, the study investigated the role of CLDN1 as a therapeutic target for HCC.

The study found that mAbs targeting CLDN1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. The results provide clear evidence of the efficiency of targeting CLDN1 for HCC and paves the way for the development of novel therapeutic interventions with CLDN1 mAbs, aimed at improving the limited efficacy of current therapies.

Moreover, given the differentiated mechanism of action, the identification of CLDN1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response, especially in advanced HCC.

Professor Thomas Baumert commented: “Hepatocellular carcinoma (HCC) is a leading cause of cancer worldwide with rising incidence and long-term survival rates are poor. These data unravel a previously undiscovered functional role of CLDN1 in HCC signaling and microenvironment and provide compelling preclinical evidence on CLDN1 as a target for drug development using monoclonal antibodies.”

Roberto Iacone, CEO at Alentis Therapeutics, added: “The role of CLDN1 in cancer has long been established and these data provide robust pre-clinical proof-of-concept for CLDN1 mAbs as potential first in-class compounds for hepatocellular carcinoma. We look forward to capitalizing on this exciting data and progressing ALE.C04, our development programme targeting CLDN1 for fibrotic-associated cancers, into the clinic.”

This study was led by Prof. Thomas Baumert at Inserm and the University of Strasbourg and conducted as a collaboration between Inserm, University of Strasbourg, Alentis Therapeutics, German Cancer Research Center, University of Texas Southwestern Medical Center Dallas, Massachusetts General Hospital Cancer Center and Harvard Medical School.

The full paper can be accessed here:

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About Alentis Therapeutics

Alentis Therapeutics is a biotechnology company that focuses on developing breakthrough treatments for fibrotic and rare diseases and associated cancers.  The company was founded in 2019 based on ground-breaking research in the laboratory of Prof. Thomas Baumert MD at the University of Strasbourg and the French National Institute of Health (Inserm).

Alentis is using its portfolio of unique monoclonal antibodies that are highly selective for exposed and non-junctional Claudin-1, a previously unexploited target that plays a key role in the pathology of fibrosis across organs as well as solid tumors, to develop a pipeline of novel mechanisms targeting advanced fibrosis and cancer. Unlike current therapies in fibrosis, which mostly address the disease indirectly, Alentis’ pioneering approach has the potential to directly modify and reverse the course of disease progression by targeting the epithelial injury. Furthermore, the unique mechanism of action of the antibodies provide the opportunity to treat solid tumors.  

Alentis’s lead therapeutic candidate, Claudin-1 specific mAb ALE.F02, is in Phase 1 clinical studies for the treatment of advanced kidney, liver and lung fibrosis which are expected to read out in Q1 2023. These represent very large and expanding markets with high unmet need. The company is also developing monoclonal antibody ALE-C04 for solid tumors that is currently in pre-clinical development. In addition, Alentis’s proprietary discovery platform allows the identification of new targets and supports the fast development of new compounds for other CLDN-driven diseases.

Alentis is headquartered in Basel’s pharma-biotech hub in Switzerland with a subsidiary for R&D in Strasbourg, France.

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Alentis Therapeutics
Nathalie Graf-Tschupp

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