Anavex Life Sciences Announces U.S. Phase 2 Clinical Trial of ANAVEX®3-71 in Schizophrenia

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

NEW YORK, Jan. 16, 2024 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and schizophrenia, today 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 Q2 2024. ANAVEX^®3-71 positive initial Phase 1 results in healthy volunteers were previously reported.¹

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 ERP Biomarker Qualification Consortium for use in schizophrenia clinical trials.¹⁰

“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 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.

About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX^®2-73 (blarcamesine), has successfully completed a Phase 2a and recently a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX^®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX^®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX^®2-73 for the treatment of Parkinson's disease. ANAVEX^®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX^®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.

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 SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

For Further Information:
Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
Email: info@anavex.com

Investors:
Andrew J. Barwicki
Investor Relations

Tel: 516-662-9461
Email: andrew@barwicki.com

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