Cognitive impairment associated with schizophrenia is a core and disabling facet of the disease.

Cognitive Impairment Associated with Schizophrenia (CIAS)

Schizophrenia is a complex, chronic, and disabling disorder. People with schizophrenia experience a spectrum of positive symptoms (eg, hallucinations, delusions, and disorganized thinking), negative symptoms (eg, blunted affect, alogia, avolition, asociality, and anhedonia), and impaired cognition, including impairments in attention, memory, and executive function.

Cognitive impairment is a debilitating core element of schizophrenia—yet no approved therapy exists.

Cognitive impairment is a core facet of schizophrenia

  • Nearly all people with schizophrenia (98%) have cognitive deficits.

  • Worldwide, at least 21M people suffer from schizophrenia, including 2.7M in the US.

  • Deficits in perception and cognition in schizophrenia are associated with poor social and vocational functioning.

  • Over three-quarters of the estimated US annual cost of schizophrenia ($281B in 2020) is attributable to indirect costs including costs due to unemployment and productivity loss.

CY6463 may help improve CIAS symptoms by:

Improving cognition

Enabling functional recovery

  • Increasing the ability to participate fully in the community and live independently.

The NO-sGC-cGMP pathway plays a critical role in multiple physiological processes underlying overall brain health and function, including processes involved in learning and memory.

Deficient NO-sGC-cGMP signaling has been linked to cognitive impairment, including in people with schizophrenia.

Overexpression of NOS1AP leads to sequestering of NOS-1 from NMDA receptor

Reduced NO-sGC-cGMP signaling alterations in dendritic spine number and morphology

Reduced synaptic plasticity disturbance of prefrontal cortex and hippocampal function, detectable by EEG

Cognitive Impairment

As an sGC stimulator that amplifies endogenous NO-sGC-cGMP signaling, CY6463 may restore deficient signaling and thereby improve cognition in people with schizophrenia.

Enrollment in Study C6463-103 is ongoing

  • Evaluate safety, tolerability, and explore CY6463 effects on brain neurophysiology and cognitive performance
  • Efficiently assess the near-term impact on disease-specific biomarkers
  • Inform selection of dose, patient profile, and biomarkers for subsequent larger and longer trials
  • 14-day, in-clinic, randomized, placebo-controlled, blinded
  • Once-daily CY6463 dosing across sequential cohorts
Patient Population
  • Up to 60 psychiatrically stable adults with schizophrenia
  • Must be on stable antipsychotic regimen

To learn more about the study,
see the study listing on


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