Placebo-controlled Phase 2 trial cleared by the FDA – Trial to begin in Q2 2024
Trial to include Schizophrenia validated clinical outcomes PANSS and EEG/ERP biomarkers
Trial to study positive, negative, and cognitive domains of Schizophrenia based on ANAVEX®3-71’s ability to synergistically activate both SIGMAR1 and M1 muscarinic receptors
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.2
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.3 ANAVEX®3-71 has also previously demonstrated the ability to prevent cognitive decline in an animal model of Alzheimer’s disease.4
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.5
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.6,7 Muscarinic agonists have previously been investigated in Alzheimer’s disease8 and schizophrenia.9
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
“Schizophrenia is a serious mental illness affecting 24 million people worldwide. While current antipsychotic therapies can be effective in managing positive symptoms, like hallucinations and delusions, they may not fully address persistent negative symptoms or cognitive difficulties. Often, available treatments are limited by side effects, e.g., movement disorders, sedation, weight gain, and other metabolic side effects,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We are excited to build on our diverse Precision Medicine Platform, which advanced blarcamesine (ANAVEX®2-73) onto a regulatory pathway for potential treatment of Alzheimer’s disease and to now also study ANAVEX®3-71, another small molecule from our drug portfolio with selective SIGMAR1 receptor activity as a novel pharmacological approach to potentially provide a new schizophrenia treatment option for patients and their physicians.”
About Schizophrenia
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
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Forward-Looking Statements
Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the
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1 Fadiran EO, Hammond E, Tran J, et al. Concentration-QTc Relationship from a Single Ascending Dose Study of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for the Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease. Clin Pharmacol Drug Dev. 2023;12(9):888-901. doi:10.1002/cpdd.1303
2 Fisher A, Bezprozvanny I, Wu L, et al. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neurodegener Dis. 2016;16(1-2):95-110. doi:10.1159/000440864
3 Hall H, Iulita MF, Gubert P, et al. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease. Alzheimers Dement. 2018;14(6):811-823. doi:10.1016/j.jalz.2017.11.009
4 Orciani C, Do Carmo S, Foret MK, et al. Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology [published online ahead of print, 2023 Sep 26]. Neurobiol Aging. 2023;132:220-232. doi:10.1016/j.neurobiolaging.2023.09.010
5 Guo P, Meng C, Zhang S, et al. Network-based analysis on the genes and their interactions reveals link between schizophrenia and Alzheimer's disease. Neuropharmacology. 2024;244:109802. doi:10.1016/j.neuropharm.2023.109802
6 Weiden PJ, Breier A, Kavanagh S, Miller AC, Brannan SK, Paul SM. Antipsychotic Efficacy of KarXT (Xanomeline-Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study. J Clin Psychiatry. 2022;83(3):21m14316. Published 2022 May 11. doi:10.4088/JCP.21m14316
7 Kidambi N, Elsayed OH, El-Mallakh RS. Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. Neuropsychiatr Dis Treat. 2023 May 10;19:1145-1151. doi: 10.2147/NDT.S406371. PMID: 37193547; PMCID: PMC10183173.
8 Bodick NC, Offen WW, Levey AI, et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997;54(4):465-473. doi:10.1001/archneur.1997.00550160091022
9 Shekhar A, Potter WZ, Lightfoot J, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008;165(8):1033-1039. doi:10.1176/appi.ajp.2008.06091591
10 Cecchi M, Adachi M, Basile A, et al. Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers. Schizophr Res. 2023;254:178-189. doi:10.1016/j.schres.2023.02.018
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