Basel, Switzerland – 21 December 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 in the peer-reviewed journal Science Translational Medicine providing preclinical proof-of-concept for Claudin-1-specific monoclonal antibodies for the treatment of fibrosis and cancer prevention across organs.
Severe tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries, and there is currently a large unmet need for effective antifibrotic therapies1.
In this study, highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed non-junctional Claudin-1 were tested in patient-derived liver 3D fibrosis and human liver chimeric mouse models, and showed that Claudin-1 is a previously unknown mediator and target for liver fibrosis. Targeting Claudin-1 reverted inflammation-induced hepatocyte pro-fibrogenic signaling and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies did not reveal any significant adverse events even at high steady-state concentrations.
In addition, the use of Claudin-1-specific monoclonal antibodies in lung and kidney fibrosis models demonstrated clear antifibrotic effects, further indicating a role of Claudin-1 as a therapeutic target for tissue fibrosis across organs.
Separately, in a further demonstration of the role of CLDN1 as a therapeutic target, an article was published recently in the Journal of Hepatology which provided preclinical proof-of-concept for Claudin-1-specific monoclonal antibodies as potential first-in-class therapies for hepatocellular carcinoma (https://doi.org/10.1016/j.jhep.2022.10.011).
Professor Thomas Baumert commented: “Fibrosis causes organ tissue scarring and thickening over time, which can lead to organ malfunction and cancer. This study provides valuable new evidence of the role of non-junctional Claudin-1 in the progression of fibrosis and proof-of-concept to treat fibrotic diseases with Claudin-1 specific monoclonal antibodies discovered by our research unit. Moreover, our study paves the way for further exploration of Claudin-1-targeting therapies for fibrotic diseases in patients.”
Roberto Iacone, CEO at Alentis Therapeutics, added: “Since anti-Claudin-1 monoclonal antibodies target exposed non-junctional Claudin-1 they exhibit an excellent safety profile. Using this innovative approach which now has entered clinical development, Alentis Therapeutics aims to reverse the course of fibrosis and sensitize solid tumors to immuno-oncologic and chemotherapeutic medication. The important data published in Science Translational Medicine provide further validation for our approach and we look forward to progressing our candidates in clinical development.”
This study was led by Professor Thomas Baumert at Inserm and the University of Strasbourg and conducted as a collaboration between Inserm, University of Strasbourg, Alentis Therapeutics, Novo Nordisk, German Cancer Research Center, IRB Bellizona, University of Texas Southwestern Medical Center Dallas, the Universities of Aalborg, Geneva, Leuven and Copenhagen, Massachusetts General Hospital Cancer Center and Harvard Medical School.
The full paper can be accessed here: http://www.science.org/doi/10.1126/scitranslmed.abj4221
References
- Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004; 4(8):583–594. doi: 10.1038/nri1412.
- Roehlen N et al. Treatment of HCC with Claudin-1 specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment. Journal of Hepatology 2022; https://doi.org/10.1016/j.jhep.2022.10.011
- http://www.science.org/doi/10.1126/scitranslmed.abj4221
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About Alentis Therapeutics
Alentis Therapeutics, the Claudin-1 company, is a clinical stage biotechnology company that focuses on developing breakthrough treatments for CLDN1+ tumors and organ fibrosis.
Alentis is pioneering a novel approach to modify and reverse the course of disease progression targeting Claudin-1 (CLDN1), a previously unexploited target that plays a key role in the pathology of tumors with immune evasive properties and fibrotic disease across multiple organs. Alentis is the only company developing potential treatments for solid cancers and fibrosis targeting Claudin-1.
Alentis’ portfolio of anti-CLDN1 monoclonal antibodies includes a novel class of anti-cancer therapies designed to reprogram the tumor microenvironment (TME). The interplay between cancer cells and their surrounding microenvironment is highly promising for drug development as many cancers use the TME to build barriers that shield against immune system attack. Alentis’ lead oncology asset, ALE.C04, is the first potential treatment to target CLDN1 to open up the mechanical barrier that characterizes immune-excluded CLDN1+ tumors, thus making the tumors vulnerable to treatment.
In addition, Alentis’ pipeline includes a first-in-class therapy designed to modify and reverse the course of advanced organ fibrosis. ALE.F02, which is currently in Phase 1 clinical trials, is designed to target pathological overexpression of CLDN1 outside of the tight junction to resolve and reverse organ fibrosis, and is being investigated for the treatment of fibrotic disease in the kidney, lung and liver.
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 headquartered in Basel’s pharma-biotech hub in Switzerland with a subsidiary for R&D in Strasbourg, France.
For more information, visit https://alentis.ch
For more information please contact:
Alentis Therapeutics
Nathalie Graf-Tschupp
info@alentis.ch
Consilium Strategic Communications (International)
Mary-Jane Elliott / Matthew Cole / Ashley Tapp
alentis@consilium-comms.com
Tel: +44 (0) 20 3709 5700