Positive Phase I results for KMO inhibitor in inflammatory disorders

Cancer research

Kynos Therapeutics has announced positive top line results from the first in human Phase I trial of its lead drug candidate, KMO inhibitor KNS366, for acute and chronic inflammatory disorders.

KMO is an enzyme that acts at a key point in the kynurenine pathway of tryptophan metabolism, converting kynurenine into 3-hydroxykynurenine (3-HK).

By inhibiting KMO activity, KNS366 is designed to reduce elevated 3-HK to prevent excess tissue damage and dysregulation of the immune system occurring during inflammation.

In the Phase I study, all doses of KNS366 were safe and well tolerated. Pharmacodynamic measures indicated KNS366 is a potent inhibitor of the KMO enzyme, with a high level of inhibition achieved as demonstrated by a substantial reduction in the enzyme product 3-HK.

Kynos Therapeutics Founder and CSO Damian Mole said: “The headline data from this Phase I study have demonstrated KNS366 is safe and well tolerated at exposures that resulted in a high level of KMO enzyme inhibition. Information from the study, including pharmacodynamic measures, enables the selection of doses for future clinical studies in patients.

“To our knowledge, this is the first time a KMO inhibitor has been administered across multiple days resulting in sustained KMO inhibition in humans. We are therefore also able to generate information on the biological pathways impacted by this mechanism in humans, through an ongoing exploratory biomarker analysis as a valuable tool to inform further clinical development.”

Spun out from the University of Edinburgh, Kynos applies drug discovery research on KMO inhibitors originally co-developed through a collaboration between GSK and the University of Edinburgh.

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