KMO

The company has unveiled significant findings from its first-in-human phase 1 trial of KNS366, its leading drug candidate. The trial focused on assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of KNS366 in healthy adult participants. KMO, an enzyme pivotal in the kynurenine pathway of tryptophan metabolism, plays a crucial role in converting kynurenine into 3-hydroxykynurenine (3-HK). By inhibiting KMO activity, KNS366 aims to mitigate elevated 3-HK levels, thereby averting excessive tissue damage and immune system dysregulation during inflammation. According to the results, all doses of KNS366 were deemed safe and exhibited excellent tolerability. Moreover, pharmacodynamic measures showcased KNS366's potency as a KMO enzyme inhibitor, with a notable reduction in the enzyme product 3-HK. Dr. Damian Mole, is the founder and chief scientific officer (CSO) of Kynos Therapeutics, told OSP about the significance of the phase 1 data. He 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.” Kynos says this phase 1 trial represents a crucial step forward in advancing KNS366 as a potential therapeutic option for inflammatory disorders. With promising safety and efficacy profiles, KNS366 holds promise for future clinical studies aimed at addressing unmet medical needs in patients with acute and chronic inflammatory conditions. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Jonathan Savidge, CEO of Kynos Therapeutics, is optimistic about the trial's outcomes: He said: “The successful completion of this Phase I study is a significant milestone for Kynos and the results provide an excellent basis for further development of KNS366. The full analysis of the wealth of data from the study will generate invaluable information on this first-in-class mechanism to enable the optimization of the further clinical development pathway. We appreciate the funding contribution from Innovate UK to conduct this important clinical trial.” Manifesting across various bodily systems, chronic inflammatory diseases encompass afflictions affecting the digestive system, joints, skin, respiratory tract, and internal organs. While these conditions lack a definitive cure, treatment strategies typically involve the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and lifestyle interventions. Although incurable, effective management of symptoms and complications through tailored treatment regimens remains pivotal in enhancing the quality of life for individuals grappling with chronic inflammatory diseases. Chronic inflammatory diseases encompass a diverse array of conditions characterized by persistent inflammation within the body. These diseases can extend their reach beyond localized inflammation to affect vital organs, including segments of the digestive tract, the cardiovascular system, and the respiratory system. Certain inflammatory disorders, such as specific forms of arthritis, may manifest with additional complications, including vision impairment.

EDINBURGH, United Kingdom, April 22, 2024 (GLOBE NEWSWIRE) -- Kynos Therapeutics Ltd, a clinical-stage biotechnology company developing first-in-class small molecule kynurenine 3-monooxygenase (KMO) inhibitors for acute and chronic inflammatory disorders, today announces 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 Phase I study of KNS366 was a randomized, 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 part, 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.” Kynos Therapeutics CEO Jonathan Savidge said, “The successful completion of this Phase I study is a significant milestone for Kynos and the results provide an excellent basis for further development of KNS366. The full analysis of the wealth of data from the study will generate invaluable information on this first-in-class mechanism to enable optimization of the further clinical development pathway. We appreciate the funding contribution from Innovate UK to conduct this important clinical trial.” About Kynos Therapeutics – Kynos Therapeutics is a clinical-stage private company developing an innovative pipeline of first-in-class kynurenine 3-monooxygenase (KMO) inhibitors. KMO plays a major role in the regulation of inflammation, acting at the interface between inflammation, immunity and metabolism, and inhibition of KMO has therapeutic potential in both acute inflammatory conditions such as acute kidney injury and acute pancreatitis and in chronic immuno-inflammatory disorders. Spun out from the University of Edinburgh, Kynos leverages a decade of drug discovery research on KMO inhibitors originally co-developed through a collaboration between GSK and the University of Edinburgh and now exclusively licensed to Kynos. Based in Edinburgh, UK, the company is backed by founding investor Epidarex Capital as well as IP Group plc and Scottish Enterprise with additional non-dilutive funding from Innovate UK. Follow us on LinkedIn - For further information please contact: At the Company Jonathan Savidge, CEO, Kynos Therapeutics E: admin@kynostx.com Media enquiries: Sue Charles, Charles Consultants T: +44 (0)7968 726585 E: sue@charles-consultants.com

Edinburgh UK, 18 May 2023 - Kynos Therapeutics Ltd, a biotechnology company developing a portfolio of first in class kynurenine 3-monooxygenase (KMO) inhibitors, today announces that dosing is underway in a first in human phase I trial of its lead drug candidate, KNS366. The first-in-human study of KNS366 is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses in healthy adult participants. The study is being conducted at a single site in the UK. Full results from the study are expected in early 2024. KMO plays a major role in the regulation of inflammation, acting at the interface between inflammation, immunity and metabolism, and inhibition of KMO has therapeutic potential in a range of indications. Kynos Therapeutics founder and CSO Damian Mole said, “KMO is a target of increasing interest for the development of new medicines and it is fantastic to see our highly selective KMO inhibitor, KNS366, moving into clinical development. The data generated from the advanced analysis of biomarkers will allow measurement of KMO inhibition and the impact that has on inflammatory mechanisms important in human disease. This information will be invaluable for designing the next stage of clinical trials in patients.” Kynos Therapeutics CEO Jonathan Savidge said, “Progressing our lead KMO inhibitor rapidly into Phase I is a major milestone for Kynos. We are not aware of any other KMO inhibitors in clinical development and look forward to generating data in humans with this first-in-class mechanism. We appreciate the support of Innovate UK for its contribution to the financing of this trial.” -ENDS- About Kynos Therapeutics – www.kynostx.com Kynos Therapeutics is a clinical-stage private company developing an innovative pipeline of first-in-class kynurenine 3-monooxygenase (KMO) inhibitors. KMO plays a major role in the regulation of inflammation, acting at the interface between inflammation, immunity and metabolism, and inhibition of KMO has therapeutic potential in a range of indications. Spun out from the University of Edinburgh, Kynos leverages a decade of drug discovery research on KMO inhibitors originally co-developed through a collaboration between GSK and the University of Edinburgh and now exclusively licensed to Kynos. Based in Edinburgh, UK, the company is backed by founding investor Epidarex Capital as well as IP Group plc and Scottish Enterprise with additional non-dilutive funding from Innovate UK. Follow us on LinkedIn and Twitter For further information please contact: At the Company Jonathan Savidge, CEO, Kynos Therapeutics E: info@kynostx.com Media enquiries Sue Charles, Charles Consultants T: +44 (0)7968 726585 E: sue@charles-consultants.com