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  • 3 March 2020
    Genkyotex’s setanaxib significantly improves immunotherapy including checkpoint inhibitors in multiple preclinical cancer models

    Genkyotex (Euronext Paris & Brussels: FR0013399474 – GKTX), a biopharmaceutical company and the leader in NOX therapies, announced today that setanaxib, the Company’s NOX1 and NOX4 inhibitor, was shown to significantly improve immunotherapy in multiple preclinical cancer models. Results from this preclinical study were published in Cancer Research, a peer-reviewed journal of the American Association for Cancer Research.

    In this study, conducted by Professor Gareth Thomas and his colleagues at the University of Southampton, United Kingdom, setanaxib was able to overcome immune cell exclusion and enhance response to multiple immunotherapies. Immune exclusion, the inability of effector T-cells to penetrate the tumor and kill cancer cells, is emerging as one of the key causes of resistance to immunotherapies such as checkpoint inhibitors, adoptive T-cell therapy, and therapeutic vaccines. This study showed that the exclusion effect is caused by activated cancer associated fibroblasts (CAFs), making CAFs a promising therapeutic target, but as yet, there are no clinically available CAF-specific inhibitors.

    The Southampton team had previously identified the enzyme NOX4 as a key regulator of CAF activation in multiple solid cancers. In the present study, they tested the effect of setanaxib, Genkyotex’s NOX1 and NOX4 inhibitor, and found that it reverses CAF activation, overcomes immune exclusion and promotes infiltration of CD8+ T-cells into tumors. Importantly, setanaxib abolished treatment resistance and enhanced immunotherapeutic responses to anti-PD1 antibodies and therapeutic vaccination.

    This work is supported by a Small Molecule Drug Discovery grant from Cancer Research UK (CRUK) to evaluate the optimal clinical development strategy for setanaxib in oncology. Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. The objective of the funded program is to inform the design of a potential clinical trial of setanaxib in combination with an available immunotherapy.

    “Immunotherapy has been the most important advance in cancer treatment for several decades, and overcoming the tumor immune exclusion effect is now a major goal, since it significantly limits its effectiveness. These new results provide evidence that setanaxib improves immunotherapy response in CAF-rich tumors, and this could help a significant proportion of patients who are currently resistant to this type of treatment” said Professor Gareth Thomas.

    “These results are consistent with setanaxib’s anti-fibrotic mechanism and suggest that setanaxib could become an important adjunctive therapy used in combination with several types of immunotherapies. Clinical proof of concept for its anti-fibrotic effect and favorable safety profile has been demonstrated in our recent trial in liver fibrosis. These results pave the way for the clinical evaluation of setanaxib in oncology” said Philippe Wiesel, M.D., Executive Vice President and Chief Medical Officer of Genkyotex. The original research article, entitled “NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumors” is currently available on the website of Cancer Research.