AVXL Anavex Life Sciences Corporation

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 announced that The Journal of Prevention of Alzheimer’s Disease (JPAD) has published peer-reviewed detailed results from the Phase IIb/III study evaluating oral blarcamesine (ANAVEX®2-73) for the treatment of early Alzheimer’s Disease (AD).

Once daily oral blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the prespecified SIGMAR1 wild-type gene group by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13.

Oral once daily blarcamesine could represent a novel treatment in early Alzheimer’s disease and be complementary or alternative to injectable anti-beta amyloid drugs.

“The Alzheimer’s disease community has been actively pursuing new medicines for decades. To have data like these published in JPAD gives us energy and hope. We are now seeing in the data what we suspected about blarcamesine for a long time – that it has the potential to make a clinical difference for people living with early Alzheimer’s disease,” said senior author behavioral neurologist Professor Dr. Marwan Noel Sabbagh MD, Chairman of the Scientific Advisory Board. “The advantage of blarcamesine lies in its small oral formulation, which offers clinical benefits for cognition and neurodegeneration. Its ease of administration and favorable safety profile make it an appealing option.”

Data from the Phase IIb/III trial demonstrated oral once daily blarcamesine pre-specified clinical efficacy through upstream SIGMAR1 activation. SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis.

“The results from the Phase IIb/III blarcamesine study show real promise for patients living with early Alzheimer’s disease,” said lead author Associate Professor Dr. Stephen Macfarlane, FRANZCP, Head of Clinical Services at the Dementia Centre, HammondCare and Principal Investigator. “Early Alzheimer’s disease can progress swiftly, and the potential for blarcamesine to target on a constitutional level of the pathology should bring hope and excitement to persons living with Alzheimer’s disease and those of us who care for them.”

Impaired autophagy precedes both amyloid beta and tau tangles, and therefore anticipates the neurodegenerative process in Alzheimer’s disease.1 Hence, stabilization or restoration of autophagy can be seen as an early preventative measure countering the Alzheimer’s disease pathology.

“Publication of the pivotal placebo-controlled Phase IIb/III blarcamesine early Alzheimer’s disease trial allows for a broader dissemination of these important data and highlights blarcamesine’s impressive and consistent clinical profile that has led to meaningful results for these patients,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “These data serve as the foundation for the MAA filing that is currently being reviewed by the EMA. We are aiming to potentially advance an important medicine to patients in need.”

Blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than 2 points.2 This suggests superior numerical clinical efficacy compared to approved therapies while also slowing neurodegeneration in early Alzheimer’s disease patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, oral blarcamesine could represent a novel treatment that could be complementary or an alternative to injectable anti-beta amyloid monoclonal antibody drugs.

“The peer-reviewed publication of these data underscores the significance of the findings for both the scientific community and those focused on Alzheimer's disease,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “Alzheimer's disease is a highly complex condition, and this dataset plays a crucial role in advancing our understanding of the Phase IIb/III results. We are grateful to the dedication from participants, their families, and the sites for taking part in this important study.”

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.

The publication may be accessed here.

About Alzheimer’s Disease

There are an estimated 7 million people in Europe with Alzheimer’s disease, a number expected to double by 2030, according to the European Brain Council.3 The World Health Organization (WHO) estimated the cost in Europe of caring for people with dementia, including Alzheimer's disease, at $439 billion, or $31,144 per person in 2019. That includes hospital care, medicines, diagnostics, informal caregiver time, community services and long-term care facility costs.4,5

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 DevelopmentToll-free: 1-844-689-3939Email: info@anavex.com

Investors:Andrew J. BarwickiInvestor RelationsTel: 516-662-9461Email: andrew@barwicki.com

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1 Christ MG, Clement AM, Behl C. The Sigma-1 Receptor at the Crossroad of Proteostasis, Neurodegeneration, and Autophagy. Trends Neurosci. 2020 Feb;43(2):79-81; Chen, J., He, HJ., Ye, Q. et al. Defective Autophagy and Mitophagy in Alzheimer’s Disease: Mechanisms and Translational Implications. Mol Neurobiol 58, 5289–5302 (2021).2 Muir RT, Hill MD, Black SE, Smith EE. Minimal clinically important difference in Alzheimer's disease: Rapid review. Alzheimers Dement. 2024;20(5):3352-3363. doi:10.1002/alz.137703 https://www.braincouncil.eu/projects/rethinking-alzheimers-disease/4 Jönsson L. The personal economic burden of dementia in Europe. Lancet Reg Health Eur. 2022 Jul 25;20:100472. doi: 10.1016/j.lanepe.2022.100472. PMID: 35910037; PMCID: PMC9326307.5 World Health Organization (WHO); 2021. Global status report on the public health response to dementia.