Kynexis Reports Promising Phase 1 Results for KYN-5356 in Treating Schizophrenia-Related Cognitive Impairment

Kynexis, a biotechnology firm from Naarden, The Netherlands, has announced encouraging results from an initial phase 1 clinical trial of its novel drug, KYN-5356. This drug is designed as a first-in-class small molecule inhibitor targeting KAT-II, an enzyme in the kynurenine pathway linked to cognitive impairment in schizophrenia (CIAS).

The recent study aimed to assess the safety, tolerability, and pharmacokinetics of KYN-5356 in healthy volunteers, administering both single and multiple escalating doses orally. The research also examined various central pharmacodynamic biomarkers as well as cognitive performance to evaluate target engagement. Results revealed that KYN-5356 was both safe and well-tolerated, showing excellent pharmacokinetic properties in plasma and cerebrospinal fluid (CSF). This indicates that KYN-5356 penetrates effectively into the central nervous system, offering proper exposure.

Additionally, the study explored pharmacodynamic endpoints, where KYN-5356 showed statistically significant improvements in electroencephalography (EEG) activity related to cognitive pathways. There was also early evidence suggesting cognitive enhancement. A dose-dependent reduction in kynurenic acid levels within the CSF was observed, which is vital as elevated kynurenic acid is often seen in schizophrenia patients and is believed to contribute significantly to CIAS.

Kees Been, CEO of Kynexis, emphasized the importance of these findings, stating, "Cognitive impairment is a major cause of disability in schizophrenia, affecting the majority of individuals with the condition. Although preliminary, these findings are a significant milestone for Kynexis as we strive to develop an innovative treatment for CIAS. As the first KAT-II inhibitor tested in humans, KYN-5356 has exhibited a strong safety profile and promising pharmacokinetics, including substantial evidence of brain penetration. The reductions in CSF kynurenic acid, effects on EEG activity, and initial cognitive benefits further validate our precision-medicine approach aimed at the kynurenine pathway."

Dr. Jens Wendland, Chief Medical Officer at Kynexis, added, "All participants successfully completed the study, and the data provide essential insights into the effects of KYN-5356 on the brain. These findings, which include evident target engagement across multiple biomarker modalities, reinforce the potential of this drug to treat cognitive impairment associated with schizophrenia. We are eager to present the complete phase 1 results at a scientific conference next year and are moving quickly towards launching our first clinical study involving patients in 2025."

Kynexis is committed to advancing precision therapeutics for brain diseases through a biomarker-driven strategy to develop a potential treatment for CIAS. By utilizing extensive data to identify and categorize patients based on the underlying biological causes of the disease, Kynexis is targeting KAT-II, a crucial enzyme in the kynurenine pathway. The company's leading candidate, KYN-5356, is a highly selective, potent, first-in-class small molecule for KAT-II. Kynexis has a subsidiary in Cambridge, Massachusetts, named Kynexis Therapeutics Inc.