Clexio is developing CLE-905, a potent M1/M4 preferential muscarinic agonist for the treatment of Schizophrenia.
CLE-905 is an investigational drug that has not been previously approved for commercial distribution.
Schizophrenia is a chronic and debilitating disorder with onset typically occurring in late-teens / early adulthood. An estimated 2.7 million people live with Schizophrenia in the U.S., and more than 24 million worldwide
It is characterized by positive (psychotic) symptoms including hallucinations, delusions, disorganized speech and behavior, as well as negative symptoms such as diminished emotional expression and inability or lack of energy to engage in routine activities. Schizophrenia can also lead to some degree of cognitive impairment, including poor executive function and impaired memory and attention.
Despite advancements in treatment, many people with Schizophrenia do not fully respond to their medication: 50% experience only partial improvement in positive symptoms or unacceptable adverse effects. Current antipsychotic medications treat positive symptoms, but do not treat negative symptoms well.
• As a result of the medication I took, I gained 66 pounds. At that time I was twenty years old and it really affected my self-confidence. Together with the stigma about taking psychiatric drugs, it made it really hard for me to adhere to taking the medication.
• In one of the hospitalizations they gave me medicine to try to stabilize me. The medicine made me feel really bad. I could barely function. I would fall asleep all the time. I couldn't handle conversations. In the end I insisted on stopping the medication.
CLE-905 targets M1/M4 receptors in the brain: M1 and M4 muscarinic receptors are expressed in brain regions linked to schizophrenia symptoms: the associative and limbic striatum (positive symptoms) and the prefrontal cortex (negative and cognitive symptoms).
Agonism of these receptors modulates neurotransmitters like acetylcholine, dopamine, GABA, and glutamate, potentially improving positive, negative, and cognitive symptoms of schizophrenia.
CLE-905 is currently in preclinical development.
Paul et al. 2024 Muscarinic Receptor Activators as Novel Treatments for Schizophrenia, Biol Psychiatry. 2024 Mar 25:S0006-3223(24)01173-9.
Yohn et al. 2022 Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic, Trends Pharmacol Sci. 2022 Dec;43(12):1098-1112
American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.)