On December 21, 2022 Alentis Therapeutics ("Alentis" or "the Company"), the biotechnology company developing breakthrough treatments for organ fibrosis and fibrotic-associated cancers, reported 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 (Press release, Alentis Therapeutics, DEC 21, 2022, View Source [SID1234625481]).

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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 (View Source).

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: View Source

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; View Source
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