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Anavex Life Sciences Announces Oral Blarcamesine Cognitive Resilience Results Approximating Normal Aging in New Precision Medicine Clinical Data from Phase IIb/III Alzheimer’s Disease Trial

September 9, 2025

https://www.globenewswire.com/news-rele ... -Dise.html

• New clinical Precision Medicine population 48-week data demonstrates unprecedented cognitive stabilization in early Alzheimer’s disease

• Cognitive outcomes observed in the oral blarcamesine 30 mg Precision Medicine cohort move toward normal aging profiles across validated clinical scales, supporting its relevance in early-stage Alzheimer’s care

• 84.7% reduction in decline at 48 weeks of blarcamesine treatment vs placebo on the primary cognitive endpoint ADAS-Cog13

• Blarcamesine could represent a novel treatment option for up to ~70% of early Alzheimer’s patients benefiting from further improved outcomes using directed Precision Medicine to alleviate significant medical and economic burden

NEW YORK, Sept. 09, 2025 (GLOBE NEWSWIRE) -- 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, announced today the latest findings for blarcamesine, an oral small molecule for the potential treatment of early Alzheimer’s disease (AD).

On all standard scales for measuring Alzheimer’s disease and cognitive decline, after 48 weeks, the defined Precision Medicine population ABCLEAR31 consisting of early AD patients with confirmed and progressed pathology taking 30 mg once-daily oral blarcamesine demonstrated barely detectable decline. This was comparable to minimally perceptible decline in prodromal (pre-dementia) aging adults.

• For ADAS-Cog13 (the standardized neuropsychological test used in Alzheimer's disease research to measure cognitive function and track disease progression), blarcamesine showed a 48-week change from baseline of 0.853 compared to ~1 point typical annual decline in prodromal (pre-dementia) aging adults.

• For CDR-SB (Clinical Dementia Rating, standard test that evaluates the severity of cognitive impairment and functional decline in individuals with AD), blarcamesine demonstrated a change from baseline of 0.465, aligning with the 0-0.5 point annual range seen in prodromal aging.

These data are similar to referenced barely detectable prodromal AD decline, in spite of the more advanced stage of AD impairment at baseline of the blarcamesine population.

Oral blarcamesine treatment over 48 weeks in a Precision Medicine population, including up to ~70% of the global population, indicate the ability to shift the cognitive decline of a MCI or mild AD patient population to that of a prodromal AD population.

In comparison, the respective placebo group in the ANAVEX2-73-AD-004 Phase IIb/III ABCLEAR34 population, ADAS-Cog13 LS mean declined by 5.592 points resulting in an ADAS-Cog13 LS mean difference of -4.739 [95% CI -7.370, -2.108]; P=0.0004. This represents a 84.7% reduction in decline at 48 weeks of blarcamesine treatment vs placebo on the cognitive endpoint ADAS-Cog13.

"Given the strong interest in living a longer life without Alzheimer’s dementia, novel therapeutic directions are required. Blarcamesine’s mechanism of autophagy restoration via SIGMAR1 activation addresses a non-amyloid, upstream target, representing such a highly transformative clinical innovation,” said Marwan Noel Sabbagh, MD, Professor of Neurology, and Chairman of the Anavex Scientific Advisory Board. “We are thrilled that today's findings show the superior effect of blarcamesine Precision Medicine population shifting the previous cognitive decline of Alzheimer’s disease to barely detectable decline resembling prodromal older cognitive decline.”

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Anavex Life Sciences Highlights New Scientific Findings on Shared Biology Between Autism and Alzheimer’s Disease

April 14, 2026 07:30 ET

https://www.globenewswire.com/news-rele ... sease.html

NEW YORK, April 14, 2026 (GLOBE NEWSWIRE) -- 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 new findings on the shared biology between autism spectrum disorder (ASD) and Alzheimer’s disease (AD), a core area of Anavex’ development plans with its autophagy enhancing orally administered blarcamesine.

Key Highlights:

• Multiple peer-reviewed publications point to biological link between autism spectrum disorder (ASD) and Alzheimer’s disease (AD), including shared disruptions in autophagy.

• Epidemiological data show that autistic adults may be diagnosed with Alzheimer’s and related dementias at rates up to 8 times higher than the general population, with onset occurring years or decades earlier than typical.

• Converging human genetic evidence links numerous high-confidence ASD risk genes — including TSC1/TSC2, PTEN, SHANK3, and FMRP — to impaired cellular autophagy, establishing autophagy dysfunction as a shared molecular substrate across genetically diverse forms of ASD.

• Synaptic dysfunction in ASD is now understood to arise, in substantial part, from a failure of autophagy-dependent synaptic pruning — causing an excess of poorly regulated synaptic connections and disrupted excitatory–inhibitory balance in neural circuits.

• The brain’s extracellular matrix (ECM) is pathologically altered in ASD and is bidirectionally coupled to autophagy.

• Restoration of autophagy impairment, now emerging as a central shared pathway in both ASD and AD, is precisely the biological system targeted by blarcamesine through its activation of SIGMAR1.

• Blarcamesine has demonstrated restoration of autophagy through SIGMAR1 activation in preclinical models and has shown clinical effects in Phase IIb/III trials in early Alzheimer’s disease, Phase II/III in Rett syndrome (a neurodevelopmental disorder caused by MECP2 mutation), and Phase II in Parkinson’s disease dementia.

• Collectively, these data provide a scientific basis for advancing blarcamesine into pivotal clinical studies, subject to further evaluation and regulatory considerations.

Reframing Brain Disorders: Converging Pathways in Neurodevelopment and Neurodegeneration

For decades, autism and Alzheimer’s disease were treated as conditions on opposite ends of the lifespan — one affecting brain development in early childhood, the other driving decline in old age. New research is adding a critical new twist. A landmark April 2025 study published in JAMA analyzed Medicare and Medicaid records covering more than 114,000 autistic adults and found that dementia prevalence among this population was dramatically elevated compared to the general population.¹ A separate recent 2026 paper in Frontiers in Neuroscience identified convergent disruptions in two critical systems shared by both conditions: The autophagy network and the synaptic regulation machinery.²

Autophagy is the cell’s natural process for clearing misfolded proteins, damaged organelles, lipids, and other cellular waste. In autism, excess synaptic connections form which are not properly pruned during development. In Alzheimer’s disease, impaired autophagy, worsened by ApoE4 lipoproteins, allows toxic protein aggregates — including amyloid-beta and fibrillary tau — to accumulate unchecked. Both conditions, in essence, share a common driver of disease pathogenesis: A failure of the brain’s housekeeping system.

Synaptic Dysfunction in ASD: When the Brain’s Pruning Mechanism Fails

The human brain is sculpted by a process of exuberant synapse formation followed by selective elimination — synaptic pruning — that removes excess connections and renders neural circuits fully functional. Autophagy is a core cellular mechanism enabling this pruning. A landmark Neuron study³ found excess dendritic spines in postmortem ASD cortical tissue compared to controls — direct evidence of failed pruning correlating with impaired autophagy. Blocking neural autophagy genetically reproduced core ASD features: Excess synapse density, impaired social behavior, and repetitive behaviors; restoring autophagy normalized both synaptic architecture and behavior. Microglia, the brain’s resident immune cells, depend equally on autophagy for synapse elimination.⁴ The downstream consequence of both failures is a disruption of excitatory–inhibitory balance — a core pathobiological signature of ASD.⁵,⁶

The Genetic Architecture of ASD Converges on Autophagy

ASD is genetically heterogeneous, yet genome analyses repeatedly converge on a common theme: Mutations and copy-number variants in genes whose protein products regulate autophagy. Among the most studied are mutations in TSC1/TSC2 and PTEN genes, whose loss of function suppresses autophagy and is associated with high rates of ASD alongside epilepsy and intellectual disability.⁷ Fragile-X syndrome — the most common inherited cause of intellectual disability and autism — likewise involves reduced autophagic flux in hippocampal neurons, with activation of autophagy rescuing aberrant spine morphology, synaptic plasticity, and cognition in preclinical models.⁵ SHANK3 mutations further alter autophagy-dependent protein homeostasis at the synapse.⁸ Whole-exome sequencing has additionally identified copy-number variants in core autophagy genes in sporadic ASD cases.⁹ This genetic convergence is not coincidental; it is pathobiologically instructive.

The Brain’s Extracellular Matrix and Autophagy: A Bidirectional Relationship

A third dimension of ASD biology is receiving growing attention: The extracellular matrix (ECM) — the structural scaffold of proteins and proteoglycans surrounding all brain cells. Its most specialized form, the perineuronal net (PNN), enwraps key inhibitory interneurons and governs critical-period synaptic plasticity and circuit stability.¹⁰ PNN architecture is consistently altered in genetic ASD mouse models and in postmortem human ASD brain tissue.¹¹,¹² The ECM and autophagy are bidirectionally coupled: The ECM modulates intracellular autophagic activity, while autophagic flux is required for normal ECM remodeling and synaptic structural integrity.¹³,¹⁴,¹⁵ PNN disruption has also been identified as relevant for Alzheimer’s disease,¹⁶ reinforcing that the brain’s ECM is not a passive structural scaffold but an active participant in the same homeostatic networks that autophagy governs — and that blarcamesine targets through SIGMAR1 activation.

Why This Matters for Anavex and Blarcamesine

Blarcamesine is an investigational oral therapy that activates SIGMAR1, a key intracellular chaperone protein that sits at a critical junction of cellular homeostasis. Peer-reviewed research has established that SIGMAR1 activation by blarcamesine restores impaired autophagy by stimulating ULK1 phosphorylation — a central signaling node that initiates the formation of autophagosomes, the cellular organelles responsible for engulfing and recycling damaged proteins and organelles.

This mechanism was first demonstrated at the molecular level in a 2019 publication in Cells, which showed that blarcamesine enhances autophagic flux in human cells and increases proteostasis capacity in the roundworm C. elegans, ultimately rescuing the organism from paralysis caused by protein aggregation.¹⁷ A 2025 iScience publication further elucidated the molecular protein binding mechanism of blarcamesine to SIGMAR1 and GABARAP, a core autophagy protein.¹⁸

The emerging picture of ASD — as a condition with co-contribution of autophagy failure, synaptic pruning deficits, convergent genetic disruption of protein homeostasis pathways, and ECM dysregulation — maps directly onto the disease biology that blarcamesine is designed to address. The therapeutic rationale is not inferential; it is mechanistically grounded in the same autophagic machinery that blarcamesine has been shown to restore across multiple model systems and in human clinical trials.

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