Study data demonstrates positive effects of CY6463 on cognition and inflammation

Cyclerion Therapeutics has announced positive top line data from its clinical study of CY6463 for the treatment of Cognitive Impairment Associated with Schizophrenia (CIAS). It concerns individuals with stable schizophrenia on a stable, single, atypical antipsychotic regimen.

CY6463 is a positive allosteric modulator of soluble guanylate cyclase that amplifies endogenous nitric oxide signalling – a pathway that has been linked to schizophrenia.

The clinical trial enrolled 48 participants with stable schizophrenia. Data from the 14-day, double-blind, placebo-controlled, multiple-ascending-dose study demonstrate that once-daily CY6463 was safe and well tolerated, with no reports of serious adverse events, severe adverse events or treatment discontinuation.

Furthermore, the study data demonstrated a strong effect on cognitive performance after two weeks of 15mg once-daily dosing, while a broad positive movement on inflammatory biomarkers was also observed. These signals on exploratory endpoints provide further evidence of the pro-cognitive and anti-inflammatory effects of CY6463 observed in preclinical studies and prior clinical trials.

“Cognitive impairment is a central debilitating, and untreated facet of schizophrenia, and there is a significant need for a treatment option that improves cognition,” noted Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute.

“I am encouraged by the promising cognition signals observed after only two weeks of CY6463 dosing in patients with stable schizophrenia. This data demonstrates the positive effects on cognition and inflammation, and supports further development of CY6463 in diseases characterised by cognitive impairment.”

“This is the second clinical study successfully demonstrating safety, pharmacokinetics, and therapeutic activity in a patient population where previous drug development has been very challenging,” explained Andreas Busch, chief scientific officer at Cyclerion Therapeutics.

“These exciting results confirm previous clinical and preclinical findings, adding to a strong data package that supports the advancement of CY6463 in CNS diseases where cognition is impaired, including CIAS and MELAS. We are eager to build on the momentum from these positive data and continue to assess opportunities to accelerate development, refine patient selection and improve endpoint assessment,” he added.