Kynos Therapeutics Ltd, a clinical stage biotechnology company developing small molecule kynurenine 3-monooxygenase (KMO) inhibitors for acute and chronic inflammatory disorders, has announced the key findings from the first in human Phase I trial of its lead drug candidate, KNS366.
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 in order to prevent excess tissue damage and dysregulation of the immune system occurring during inflammation.
The study
The Phase I study of KNS366 was a randomised, double-blind, placebo-controlled dose escalation study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of KNS366 in healthy adult participants.
During the multiple dose segment, KNS366 was administered over seven days.
All doses of KNS366 were safe and the molecule showed excellent tolerability. Pharmacodynamic measures clearly demonstrated 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.”
