Anavex Life Sciences Corp. ("Anavex" or the "Company") (NASDAQ:AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today presented new data from the Phase IIb/III study showing that blarcamesine (ANAVEX2-73), once daily orally, demonstrates pre-specified clinical efficacy through upstream SIGMAR1 activation.

Clinical data confirmed the mechanism of action (MoA) by pre-specified SIGMAR1 gene analysis in people with early Alzheimer's disease (AD). The data were presented by Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Anavex Scientific Advisory Board at the Clinical Trials on Alzheimer's Disease (CTAD) conference, which is taking place October 29 - November 1, 2024, in Madrid, Spain.

SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. In Alzheimer's disease patients, mutations (variants) of genes have generally been identified as disease risk factors. Likewise, impaired SIGMAR1 function (gene mutation, variants) leads to potential suboptimal function. Hence, patients who carry the non-mutated, common SIGMAR1 wild type (WT)1 gene, are expected to have stronger beneficial response to blarcamesine than patients with a SIGMAR1 mutation (variant), who nevertheless also benefited from treatment.2

This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; P=0.008] in the ITT analysis. This signal was even stronger in the pre-specified common SIGMAR1 wild type (WT) group with slowed clinical progression by 49.8% at 48 weeks in the active group vs. placebo, respectively [LS mean ADAS-Cog13 difference of -2.317; P=0.015]. Equal analysis with CDR-SB led to comparable consistent results.