Anavex Life Sciences Announces New Publication in Medical Journal: Blarcamesine Prevented Cognitive Impairment in Animal Model of Alzheimer's Disease

Pre-Treatment with blarcamesine entirely prevented Abeta-induced cognitive decline

Confirmed significant biomarker-response in hippocampus

Anavex Life Sciences Corp. ("Anavex" or the "Company") (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, today reported a peer-reviewed publication in the journal Neuroscience Letters titled " Prevention of memory impairment and hippocampal injury with blarcamesine in an Alzheimer's disease model. " 1

This study shows that a pre-treatment with blarcamesine prevented Amyloid beta-induced memory impairment and brain oxidative injury suggesting that blarcamesine is an attractive candidate for Alzheimer's disease pharmacological prevention.

"This preclinical study is exciting since it clearly demonstrates a preventative effect of blarcamesine in Alzheimer's pathology and potentially might be able to prevent onset of Alzheimer's disease in healthy individuals," said Tangui Maurice, PhD, Research Director at University of Montpellier, France and author of the publication. "These findings support the future direction of clinical trials with the objective of addressing blarcamesine's potential as a safe and effective pharmacologic agent — applied as convenient once-daily oral pill — for the prevention of Alzheimer's disease."

While placebo-controlled mice developed significant amyloid toxicity in the brains after the toxic Aβ _25-35 peptide injection, in animals pre-treated with blarcamesine, significant protection was observed with less vulnerability to Aβ _25-35 -induced oxidative stress and less vulnerability to develop learning and memory deficits.

The mechanistic confirmation that blarcamesine particularly restores impaired autophagy through SIGMAR1 activation by acting upstream of amyloid and tau pathologies at the molecular level was previously established both in vitro and in vivo. Specifically, blarcamesine's studies demonstrated effect of enhanced autophagic flux in human cells and in C. elegans as well as increased proteostasis capacity and ability to promote autophagosome biogenesis, autophagic cargo reception, and lysosome fusion. ²

SIGMAR1 has emerged as a key therapeutic target in the treatment of neurodegenerative disorders. Its activation enhances autophagy, facilitating the degradation of amyloid-beta precursor protein (APP) and helping to normalize Aβ production. ³ Beyond its role in amyloid regulation, SIGMAR1 activation supports neurogenesis, mitigates oxidative stress by reducing reactive oxygen species (ROS), suppresses neuroinflammatory responses, and alleviates Aβ-induced toxicity. It also plays a critical role in maintaining endoplasmic reticulum (ER) integrity and modulating intracellular calcium signaling. ⁴ Collectively, these effects contribute to the restoration of cellular homeostasis, rebalancing neural function, and promoting neuroplasticity. ⁵

"The findings in this publication further support the potential beneficial effect of blarcamesine in Alzheimer's disease prevention. With once daily oral blarcamesine administration and hence retaining autophagy strength through upstream SIGMAR1 activation, the downstream potentially pathological manifestations of Amyloid beta might be prevented," said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.

The paper can be accessed online at: https://pubmed.ncbi.nlm.nih.gov/40784611/ .

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.

About Alzheimer's Disease

Alzheimer's disease is a progressive degenerative brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate and carry out daily activities. An estimated 7.2 million Americans currently have Alzheimer's dementia. Alzheimer's is the most common cause of dementia among older adults and is estimated to rank as the third leading cause of death for older people in the United States, just behind heart disease and cancer. In 2020, Alzheimer's and other dementias cost the nation approximately $781 billion. By 2050, these costs could rise as high as $1.1 trillion. ⁶ There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 2050. ⁷ Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families. ⁸

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, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, 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 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 and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore 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. We believe that 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

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_{¹ Maurice, Tangui. "Prevention of memory impairment and hippocampal injury with blarcamesine in an Alzheimer's disease model." Neuroscience letters, 138349. Aug. 2025.
² Christ, M G et al. "Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo." Cells vol. 8,3 211. 2 Mar. 2019.
³ Jaeger PA, Pickford F, Sun C-H, et al. Regulation of amyloid precursor protein processing by the Beclin 1 complex. PloS one. 2010;5(6):e11102.
⁴ Nguyen L, Lucke-Wold BP, Mookerjee SA, et al. Role of sigma-1 receptors in neurodegenerative diseases. Journal of pharmacological sciences. 2015;127(1):17-29; Moriguchi S, Shinoda Y, Yamamoto Y, et al. Stimulation of the sigma-1 receptor by DHEA enhances synaptic efficacy and neurogenesis in the hippocampal dentate gyrus of olfactory bulbectomized mice. PloS one. 2013;8(4):e60863-e60863; Rosen DA, Seki SM, Fernández-Castañeda A, et al. Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Science Translational Medicine. 2019;11(478):eaau5266; Maurice T, Volle J-N, Strehaiano M, et al. Neuroprotection in non-transgenic and transgenic mouse models of Alzheimer's disease by positive modulation of σ1 receptors. Pharmacological research. 2019;144:315-330.
⁵ Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.
⁶ https://www.nia.nih.gov/health/alzheimers ; https://www.alz.org/alzheimers-dementia/facts-figures .
⁷ Alzheimer's Disease International. World Alzheimer Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf .
⁸ AARP. 2020 Report: Caregiving in the U.S. https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf .}