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  • 17 July 2019
    Genkyotex Announces FDA Approval of Phase 2 InvestigatorInitiated Trial with GKT831 in IPF

    Genkyotex (Euronext Paris & Brussels: FR0013399474 – GKTX) a biopharmaceutical company and the leader in NOX therapies, announced today that the United States Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application allowing the initiation of a Phase 2 trial of the Company’s lead product candidate, GKT831, in patients with idiopathic pulmonary fibrosis (IPF). 

    This will be the third Phase 2 clinical trial of GKT831 in a fibrotic disease, adding lung fibrosis to liver fibrosis and kidney fibrosis as potential clinical indications for this compound. GKT831 recently demonstrated clinical evidence of anti-fibrotic and anti-inflammatory activity in patients with primary biliary cholangitis (PBC), a fibrotic liver disease.

    The Company had previously announced that the United States National Institutes of Health (NIH) awarded an $8.9 million grant1 to Professor Victor Thannickal at the University of Alabama at Birmingham (UAB), to fund a multi-year research program evaluating the role of NOX enzymes in IPF, a chronic lung disease that results in fibrosis of the lungs. The investigator-initiated 24-week Phase 2 trial of GKT831 in patients with IPF is the core component of the program.

    “This is an important step forward in translating seminal preclinical discoveries to patients with fibrotic lung disease,” said Professor Thannickal. “NOX1/4 inhibition may have profound disease modifying effects on the fibrotic and vascular remodeling, which drives disease progression in IPF. Based on the preclinical data generated to date, we believe GKT831 has the potential to be an effective treatment in IPF. GKT831 has previously shown marked anti-fibrotic activity in preclinical models and now in patients with liver fibrosis, and we look forward to further evaluating this promising candidate in IPF patients”

    “We congratulate Professor Victor Thannickal and his colleagues for obtaining FDA approval for this important trial,” said Dr. Philippe Wiesel, Chief Medical Officer of Genkyotex. “The clear efficacy, excellent safety, and quality of life improvement achieved by GKT831 in our recently reported PBC trial suggest that GKT831 may provide important therapeutic benefits in patients with IPF.”

    About the Phase 2 clinical trial of GKT831 in IPF

    The academic consortium also includes Dr. Steven Duncan at UAB, Dr. Gerard Criner at Temple University, Dr. Hyun Kim at the University of Minnesota, Dr. Kevin Flaherty at the University of Michigan, and Dr. Joseph Lasky at Tulane University. Professor Thannickal and his colleagues previously published a seminal study in Nature Medicine identifying NOX4 as a key driver of lung fibrosis. In a subsequent publication in Science Translational Medicine, the researchers demonstrated that pharmacological inhibition of NOX1/4 with GKT831 achieved marked anti-fibrotic effects and prolonged survival in a stringent model of lung fibrosis in aged mice. Separately, NOX1 has been shown to drive vascular remodeling, a critical factor contributing to disease progression in IPF, in several preclinical models of lung disease. In these preclinical models, GKT831 was shown to efficiently reduce vascular remodeling and secondary right heart disease.

    The investigator-initiated Phase 2 trial will be a placebo-controlled, double-blind, randomized, parallel group study to evaluate the safety and efficacy of oral GKT831 in patients with IPF receiving standard of care therapies. A total of 60 patients will be allocated to a 24-week treatment with oral GKT831 or matching placebo. GKT831 will be dosed at 400mg twice a day, the dose which achieved statistically significant improvements in multiple efficacy endpoints and demonstrated an excellent safety profile in the recently completed Phase 2 trial in patients with primary biliary cholangitis (PBC), a fibrotic liver disease. The primary endpoint of the IPF trial will be the change in plasma levels, at the end of the 24- week treatment period, of o,o’-dityrosine, which is an oxidized covalent modification of protein tyrosine residues that has been shown to be a marker of pulmonary oxidative stress and is markedly elevated in patients with interstitial lung disease. Key secondary endpoints include changes in 6-minute walk distance, forced vital capacity and high-resolution CT imaging.