Anavex Life Sciences Corp. announced the initiation of the U.S. FDA cleared placebo-controlled Phase 2 trial of ANAVEX®3-71 for the treatment of schizophrenia, which is expected to begin in Second Quarter 2024. ANAVEX®3-71 positive initial Phase 1 results in healthy volunteers were previously reported ANAVEX®3-71 (formerly AF710B) is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects.

This novel mechanism of action offers the potential to treat all symptom domains (positive, negative, and cognitive) of schizophrenia without the side effects of standard of care antipsychotics. The selective nature of ANAVEX®3-71?s dual synergistic mechanism of action has previously demonstrated long-lasting, pro-cognitive effects and behavioral improvements in animal models of neurodegenerative diseases. ANAVEX®3-71 has also previously demonstrated the ability to prevent cognitive decline in an animal model of Alzheimer?s disease.

New research into the genetic underpinnings of schizophrenia has revealed links between this psychiatric disorder and Alzheimer?s disease, suggesting the disorders may share certain mechanisms. A recent successful trial of Karuna Therapeutic?s dual M1/M4 muscarinic receptor agonist KarXT in individuals with schizophrenia demonstrated efficacy in treating both positive and negative symptoms. Muscarinic agonists have previously been investigated in Alzheimer?s disease and schizophrenia. Positive, negative, and cognitive symptoms associated with schizophrenia are strongly associated with poor social and functional outcomes. As currently approved treatments only control a subset of symptoms, patients continue to exhibit severe impairments in social and occupational functioning and poor quality of life.

ANAVEX®3-71?s ability to modulate both SIGMAR1 and M1 receptors synergistically are expected to address disruptions to neuronal homeostasis observed in individuals with schizophrenia, upstream of the targets leveraged by standard of care medications which do not adequately address all domains of symptoms in schizophrenia. The placebo-controlled Phase 2 ANAVEX®3-71-SZ-001 study, will consist of two-parts to explore multiple ascending doses in individuals with schizophrenia followed by a 28-day treatment period in a larger cohort. The study will utilize standard clinical outcome measures for schizophrenia including the Positive and Negative Symptoms Scale (PANSS) and novel electrophysiological biomarkers identified by the ERP Biomarker Qualification Consortium for use in schizophrenia clinical trials.

Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects.