KMO

Freiburg, 29. October 2024: Today, Dr. Falk Pharma GmbH announces the successful acquisition of Kynos Therapeutics Ltd., a clinical stage biopharmaceutical company focusing on the development of novel treatments for patients suffering from acute and chronic inflammatory diseases. The company was founded as a spin-out of the University of Edinburgh, Scotland, together with lead investor Epidarex Capital, a leading early-stage transatlantic venture fund, along with IP Group, and Scottish Enterprise. Effective immediately, Kynos Therapeutics will be integrated into the Falk Group. Kynos Therapeutics’ lead investigational asset is KNS366, a highly potent and selective first-in-class inhibitor of the enzyme kynurenine 3-monooxygenase (KMO). In a Phase I clinical trial, KNS366 was shown to be safe and well-tolerated at multiple doses. The compound also led to a dose-dependent inhibition of the enzyme KMO and modulation of its downstream metabolites. Dr. Falk Pharma is excited about the addition of KNS366 to its R&D pipeline and will further explore the potential of KNS366 in future clinical trials, initially focusing on acute pancreatitis. This new asset will enhance Dr. Falk Pharma´s expansion into rare digestive and metabolic diseases and conditions. About KNS366 Kynos Therapeutics’ lead investigational asset KNS366 selectively inhibits the enzyme kynurenine 3-monooxygenase (KMO). KMO is a key enzyme in the tryptophan metabolic pathway and has also been shown to play an important role in modulating immune processes. By inhibiting KMO activity, KNS366 interferes with inflammation and other immune system pathologies by lowering levels of its downstream metabolite – 3- hydroxykynurenine (3HK) – high levels of which have been linked to tissue damage and dysregulation of the immune system during inflammation. Inflammatory diseases including acute pancreatitis trigger an exacerbated, systemic pro-inflammatory response, making KMO inhibitors a promising next-generation treatment option for disorders characterized by severe inflammation. About acute pancreatitis Acute pancreatitis is a sudden inflammation of the pancreas that can be triggered by a number of factors. In its severe form, this acute inflammation can cascade to a reaction in the entire body over several days to weeks that can result in systemic inflammation, organ failure, and death. Accordingly, acute pancreatitis requires immediate medical intervention to manage patients’ symptoms and prevent worsening of their condition, often necessitating prolonged hospitalization. Currently, acute pancreatitis occurs in about 240,000 people in Europe and 300,000 people in the United States each year, with 1 in 5 acute pancreatitis patients requiring intensive care. To date, there are no proven or approved treatment options to prevent organ failure and death resulting from severe acute pancreatitis, meaning there is an urgent need for effective treatments. About partnering with Dr. Falk Pharma Dr. Falk Pharma engages in a variety of collaboration and partnership models to develop and deliver innovative treatment concepts with great potential. These treatments can be based on any type of pharmacological approach, from small molecules to biologics to novel drug delivery technologies. The company is involved in partnership projects across the range of phases and partners, from all stages of pre-clinical/clinical development and marketing as well as with academic researchers, start-ups, and established companies. Dr. Falk Pharma is an industry leader in innovative pharmaceutical formulations that deliver active substances to specific functional segments of the gastrointestinal tract. Many of their products have attained standard-of-care status. The company enjoys strong, long-standing collaborations with renowned clinical centres and with academic and clinical key opinion leaders in the fields of gastroenterology, hepatology and metabolic diseases. About Dr. Falk Pharma GmbH Dr. Falk Pharma GmbH has been developing and marketing innovative medicines to treat a wide range of gastrointestinal disorders like inflammatory bowel disease or eosinophilic esophagitis as well as hepatobiliary disorders such as primary biliary cholangitis for over 60 years. As the international experts in digestive and metabolic medicine, the company brings together physicians, scientists, and patients to devise new and powerful approaches to patient care. Dr. Falk Pharma engages in pre-clinical and clinical stage research that aims to meaningfully improve therapeutic practice as well as patient health and well-being. A family-owned business with a global presence, Dr. Falk Pharma has ten affiliates in Europe and Australia and is continuously growing. The company has its headquarters and R&D facilities in Freiburg, Germany, its pharmaceutical products are manufactured in Europe, mainly at sites in Germany, France, Italy and Switzerland. Dr. Falk Pharma GmbH employs approximately 1250 individuals globally and 323 in Freiburg.

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

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.