Cyclerion Therapeutics, Inc. announced positive topline data from its clinical study of CY6463 for the treatment of Cognitive Impairment Associated with Schizophrenia (CIAS) in individuals with stable schizophrenia on a stable, single, atypical antipsychotic regimen. Data from the 14-day, double-blind, randomized, placebo-controlled, multiple-ascending-dose study demonstrate that once-daily CY6463 was safe and well tolerated, with no reports of serious adverse events (SAEs), severe adverse events (AEs), or treatment discontinuation due to AEs. Study data demonstrate a strong effect on cognitive performance after two weeks of 15mg once-daily dosing.

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. CY6463 is a positive allosteric modulator of soluble guanylate cyclase (sGC) that amplifies endogenous nitric oxide (NO) signaling, a pathway that has been linked to schizophrenia.

The clinical study enrolled 48 participants with stable schizophrenia with no more than moderate positive symptoms and on a stable, single, atypical antipsychotic regimen. Topline results include: CY6463 was safe and well tolerated. There were no reports of SAEs, severe AEs, or treatment discontinuation due to AEs.

All AEs were transient. The pharmacokinetic profile of once-daily CY6463 is consistent with earlier clinical studies in healthy volunteers and MELAS patients, and demonstrated linear, dose-proportional exposure and low intersubject variability. The general cognition composite score from the Cogstate Schizophrenia Battery increased with 14 days of once-daily dosing with CY6463 15 mg, compared to placebo, with an effect size of 0.60.

An effect size of approximately 0.3 is generally considered clinically relevant in neuropsychiatry. Favorable changes were observed in a broad panel of plasma inflammatory biomarkers, including biomarkers with links to schizophrenia and cognition, after 14 days of once-daily dosing with CY6463 15 mg. These anti-inflammatory effects extend results observed in preclinical and earlier clinical studies of CY6463.

Analysis of data from exploratory EEG assessments (resting state, qEEG, ERP, sleep EEG,) are ongoing. Data from these assessments will be shared in future scientific forums. At the two higher dose levels evaluated in this multiple-ascending-dose study (30 and 60 mg), CY6463 was observed to be safe and well tolerated; however, higher doses did not demonstrate an effect on the general cognition composite at Day 14, a finding consistent with preclinical experiments.