Kynexis, a clinical-stage biotechnology company focused on precision therapeutics for brain diseases, has announced the first patient dosing in its Phase 2 clinical trial evaluating KYN-5356 for cognitive impairment associated with schizophrenia (CIAS). The trial represents a significant milestone in addressing one of the most debilitating aspects of schizophrenia, for which no approved treatments currently exist.
Novel Mechanism Targets Kynurenine Pathway
KYN-5356 is a first-in-class small molecule inhibitor of KAT-II, a key enzyme in the kynurenine pathway. The drug candidate is described as the most advanced clinical candidate in development for CIAS and is designed to establish proof of clinical concept by demonstrating efficacy in improving cognitive performance.
"Advancing KYN-5356 into Phase 2 is a critical milestone in our mission to address cognitive impairment associated with schizophrenia, which is one of the most debilitating and overlooked aspects of the disease," said Kees Been, Chief Executive Officer of Kynexis. "Because schizophrenia often emerges early in life, these cognitive challenges can impact nearly every facet of a person's daily living for decades."
Phase 2 Trial Design and Objectives
The randomized, double-blind, placebo-controlled Phase 2 trial will enroll approximately 150 adults with schizophrenia across 13 clinical sites in the United States. Over a 28-day treatment period, the study will assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of KYN-5356 as an adjunctive treatment for CIAS.
Dr. David Walling, Chief Clinical Officer at CenExel and Lead Investigator of the Phase 2 trial, explained the study's comprehensive approach: "This Phase 2 trial is designed to rigorously evaluate the potential of KYN-5356 to improve cognitive function in people with schizophrenia. By combining standardized cognitive performance measures with pharmacokinetic and pharmacodynamic analyses to link clinical benefits with underlying biological effects, this study will generate the data needed to bring forward a therapy that could transform care for people living with CIAS."
Promising Phase 1 Results Support Advancement
The Phase 2 trial builds on positive results from Kynexis's first-in-human Phase 1 trial, where KYN-5356 demonstrated several encouraging characteristics. The drug showed an excellent safety and tolerability profile, adequate CNS penetration, and dose-dependent reductions in kynurenic acid in the cerebrospinal fluid. Additionally, the Phase 1 study provided exploratory evidence of cognitive benefit in healthy volunteers.
Addressing Significant Unmet Medical Need
The advancement of KYN-5356 addresses a critical gap in schizophrenia treatment. According to Kees Been, existing therapies fail to address cognitive deficits associated with the condition, creating a profound unmet medical need. The company's precision approach targets the underlying biology of the disease using a biomarker-based strategy to identify and stratify patients based on the causal human biology of CIAS.
Timeline and Next Steps
Topline results from the Phase 2 trial are expected by Q4 2026. The study is registered at clinicaltrials.gov under the identifier NCT07191483. Kynexis operates with a subsidiary in the United States based in Cambridge, Massachusetts, and continues to advance its precision therapeutics platform for brain diseases through its biomarker-based approach targeting the kynurenine pathway.
