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.
"The voices—sometimes they whisper, sometimes they shout—tell me things I don’t want to hear. Sometimes they argue with me or mock me. But sometimes they warn me about dangers no one else can see. I try to ignore them, but it's exhausting. People say they’re not real, but I can hear them."
"Everything is connected. If you know what to look for, there are messages hidden in what people say or in the way they read the news on TV. I’m beginning to understand. I’m part of something bigger, but I don’t know if it’s good or bad. Sometimes, I can see things that others can’t."
"The people on the bus keep talking about me. They think I don’t know, but I see the way they look at me and I can tell. They’re in on it. Their agents have been following me for weeks. They put cameras in my house to spy on me."
“On my good days, there’s little background noise, so I can deal with it,” he said. “On my bad days, I have a hard time focusing on what I was doing. It takes a lot of energy to look calm”
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.
Dual M1/M4 agonism has clinical potential across multiple neuropsychiatric indications and symptom domains.
CLE-905 is currently in preclinical development. IND-enabling studies are ongoing.
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.)