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  • 8 October 2018
    Preclinical Efficacy of Genkyotex’s GKT831 in Prostate Cancer Presented at ESUR18 Meeting

    Genkyotex (Euronext Paris & Brussels: FR00011790542 – GKTX), a biopharmaceutical company and the leader in NOX therapies, announced today the presentation of preclinical data showing that GKT831, the Company’s clinical stage NOX1 and NOX4 inhibitor, efficiently targeted cancer associated fibroblasts (CAFs) in prostate cancer and abrogated the pro-tumorigenic influence of the tumor micro-environment. The results were presented by Dr. Natalie Sampson, Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Austria, at ESUR18 – the 25th Meeting of the European Association of Urology, taking place October 4-6, 2018, in Athens, Greece (ESUR18, October 5, Poster #P-23). 

    CAFs are an essential component of the tumor-associated stromal microenvironment, which is a primary driver of prostate cancer progression. The new preclinical data demonstrated that elevated NOX4 expression in prostate cancer correlates with disease relapse and shortened disease-free survival. Furthermore, NOX4 inhibition with GKT831 reverts primary prostate CAFs to a benign-like phenotype and abrogates their paracrine-mediated pro-tumorigenic effects on prostate cancer cells in vitro & ex vivo. Additional recent data suggest that specific CAF subtypes may have distinct tumor promoting roles. In this study, a dominant NOX4-expressing CAF subtype was identified. In these NOX4 expressing CAFs, GKT831 reduced the production of reactive oxygen species and suppressed CAF activation markers. GKT831 also blocked the onco-supportive effects of CAFs, including prostate cancer cell proliferation and migration.

    "These new data further support our previous findings that NOX4 in the tumor microenvironment/CAFs plays a key role in driving progression towards aggressive prostate cancer. In addition, the results of this preclinical study are indicative of the therapeutic potential of GKT831 in targeting NOX4 in prostate cancer” said Dr. Sampson.

    “Together with previously published results, these studies indicate that GKT831 has the potential to block the multiple tumor promoting effects of CAFs, including tumor growth, invasion and resistance to immunooncology therapies. Accordingly, we continue to evaluate potential clinical development strategies with GKT831 in order to address significant unmet medical needs in cancer patients” said Philippe Wiesel, M.D., Executive Vice President and Chief Medical Officer of Genkyotex.

    The role of NOX4 in the activation of CAFs is similar to its function in the activation of myofibroblasts, a key characteristic of fibrogenesis in many fibrotic diseases. GKT831 has also demonstrated potent antifibrotic activity in multiple preclinical models of liver, lung, skin, and renal fibrosis. The safety and efficacy of GKT831 is currently being assessed in two separate Phase 2 trials in patients with primary biliary cholangitis (PBC) and diabetic kidney disease, two progressive fibrotic disorders. As previously announced, the interim results from the PBC study are expected in early November 2018 and the final results should be available in Spring 2019. A third phase 2 trial, funded by the US National Institutes of Health, in patients with idiopathic pulmonary fibrosis, is expected to be initiated in H1 2019.