blarcamesine (Anavex 2-73) / Anavex - LARVOL DELTA

Investigating oral blarcamesine for treatment of early Alzheimer's disease. (PubMed, Expert Opin Pharmacother) - "Additionally, we discuss recent preclinical evidence supporting a preventive role for blarcamesine in AD. A Pubmed search was conducted for relevant literature regarding this topic using keywords including, but not limited to, 'blarcamesine,' 'disease-modifying therapy,' 'precision medicine,' 'sigma-1 receptor,' and 'SIGMAR1 agonist.' Blarcamesine is a potential oral disease-modifying therapeutic candidate for early-stage AD that acts upstream of amyloid-beta pathogenesis and could prevent AD progression very early on, with emerging preclinical evidence also supporting its potential for disease prevention."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Sigma-1 Receptor Stimulation Rescues FTD/ALS Mutant TDP43-Induced Disruption of the VAPB-PTPIP51 ER-Mitochondria Tethering Proteins via Inhibition of GSK3β. (PubMed, Cells) - "Finally, we show that ANAVEX2-73, a further Sigma-1 receptor agonist which is in clinical trials for Alzheimer's disease, also stimulates VAPB-PTPIP51 binding via GSK3β inhibition. Our findings provide novel insights into the mechanisms by which Sigma-1 receptor agonists influence defective ER-mitochondria signalling in FTD/ALS."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • RMDN3 • TARDBP

Anavex Life Sciences Reports Third Fiscal Quarter 2026 Financial Results and Business Update (The Manila Times) - "Anavex will be attending the following upcoming 2026 events...19th Clinical Trials on Alzheimer's Disease Conference as a Silver Sponsor with one poster presentation taking place on November 16-19 in Boston, MA...Anavex has submitted all data from its Alzheimer's disease clinical trials to its newly opened Alzheimer's IND...These data and feedback will serve as the foundation for planned discussions with the FDA regarding its U.S. clinical development program and design of a Phase 3 study (ANAVEX2-73-AD-005) for an Alzheimer’s indication...the ADME study and the DDI study - will provide critical support across the Company’s pipeline programs, with the first participant visit in the ADME study recently completed and the last participant in the DDI study expected to complete the last study visit by the end of September. This will then represent the completion of the clinical conduct of the DDI study."

New P3 trial • Trial status • Alzheimer's Disease

Sigma-1 Receptor Ligand Blarcamesine (ANAVEX 2-73) for Alzheimer's Disease: A Systematic Review. (PubMed, CNS Drugs) - P2, P2/3, P2a, P2b | "Current clinical evidence suggests that blarcamesine is a promising orally administered therapeutic candidate for early-stage AD with an acceptable safety profile and encouraging efficacy, particularly in genetically defined populations. However, the available evidence is derived from a limited number of clinical studies, including secondary analyses and conference reports. Additional independent randomised clinical trials are required to confirm these findings and further define the role of blarcamesine in the treatment of AD."

First-in-human • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia

Oral Blarcamesine Clinical Effect In a Phase 2b/3 Early AD Population For SIGMAR1 And Col24a1 Genotypes (CTAD 2026) - No abstract available

Clinical • P2/3 data • P2b data

Alzheimer’s Disease Program (The Manila Times) - "Two foundational clinical pharmacology studies are proceeding under this IND in the U.S.: an absorption, distribution, metabolism, and excretion (ADME) study and a drug-drug interaction (DDI) study with a goal to strengthen and support the Company’s regulatory pathway for all blarcamesine indications; The Company anticipates initiation of the ADME study to take place in the third quarter of the 2026 calendar year, and dosing in the DDI study is already underway...The Company intends to engage with the FDA on a U.S. clinical development strategy for early Alzheimer's disease. The Company continues to review the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) assessment report and intends to use it to inform and support its clinical development strategy with the FDA."

FDA event • New trial • Alzheimer's Disease

Do sigma-1 receptor agonists offer therapeutic promise for Alzheimer's disease? (PubMed, Expert Opin Pharmacother) - "We discussed clinical-stage compounds, including blarcamesine, evaluating their potential effects on both cognitive decline and neuropsychiatric symptoms...However, challenges remained, including incomplete understanding of receptor biology in aging and disease, variability in clinical response, and the need for robust biomarkers of target engagement. Future research should prioritize well-designed clinical trials and integrative biomarker strategies to define their role in AD treatment paradigms."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Psychiatry

Advancing Alzheimer's Disease Care: Convenience For Both Patients AndFamilies With Oral Blarcamesine With Long-term Time Saved (AAIC 2026) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

Sigma-1 Receptor Stimulation Rescues FTD/ALS Mutant TDP43-Induced Disruption Of The VAPB-PTPIP51 ER-Mitochondria Tethering Proteins Via Inhibition Of GSK3b (ENCALS 2026) - "Similarly, treatment with ANAVEX2-73, a Sigma-1 receptor agonist currently in clinical trials for Alzheimer's disease, also enhanced VAPB–PTPIP51 binding through inhibition of GSK3β.Conclusion Sigma-1 receptor agonists restore ER–mitochondria signaling by promoting VAPB–PTPIP51 interactions via inhibition of GSK3β. Our findings provide mechanistic insight into the therapeutic role of Sigma-1 receptor agonists in FTD/ALS."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • RMDN3 • TARDBP

Anavex Life Sciences Teases New Pivotal Blarcamesine Trials, Maps Regulatory Path at Needham Conference (MarketBeat) - "In the Q&A, Fadia asked about the company’s presentation of open-label extension results alongside a matched cohort from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Missling said the ADNI cohort served as an approximation of how patients might be expected to progress under standard of care beyond the placebo-controlled phase...Missling said that by week 144, the delta versus the ADNI comparison cohort reached 'over 12 points' on ADAS-Cog-13, which he characterized as clinically meaningful."

P2/3 data • Alzheimer's Disease

Regulatory path and next studies (MarketBeat) - "Regarding Europe, he said the company had a 'very productive interaction' with the European Medicines Agency (EMA) and that Anavex understands 'a pivotal study will be needed for full approval for blarcamesine in Europe.' He added that the company expects a similar path in other jurisdictions, including the U.S...On trial design, Missling said a new early Alzheimer’s pivotal study would be consistent with other trials in the space: approximately '18 months' in duration, with CDR-Sum of Boxes as the company’s preferred primary endpoint. He said the company has begun preparation and site engagement and is reviewing feedback aimed at optimizing protocol design, including visit schedules and frequency."

New trial • Alzheimer's Disease

Anavex Life Sciences Presents New Data from its AD-004 Phase IIb/III Trial at AD/PD 2026 Conference Demonstrating Consistent Correlation Between the Treatment Effect of Oral Blarcamesine and Preservation of Brain Volume in Early Alzheimer’s Disease (Anavex Press Release) - "A dedicated analysis of MRI biomarkers demonstrated a highly consistent correlation between slowing of atrophy and improvements across primary and secondary clinical endpoints, including: ADAS-Cog13 (cognition); ADCS-ADL (activities of daily living); CDR-SB (global clinical cognitive and functional outcome)...In the genetically defined ABCLEAR32 precision medicine population, the correlation (R²) strength improved markedly, with R² increasing by 78% for ADAS-Cog13 (from R²=0.23 to R²=0.41)—firmly within the 'very suggestive' range for clinical relevance."

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Highlights New Scientific Findings on Shared Biology Between Autism and Alzheimer’s Disease (Anavex Press Release) - "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...The brain’s extracellular matrix (ECM) is pathologically altered in ASD and is bidirectionally coupled to autophagy....Collectively, these data provide a scientific basis for advancing blarcamesine into pivotal clinical studies, subject to further evaluation and regulatory considerations."

Clinical • Preclinical • Alzheimer's Disease

Anavex Life Sciences Provides Comprehensive Regulatory Update (Anavex Press Release) - "Following the withdrawal of the application for the marketing authorization of blarcamesine in the EU, Anavex will continue to gather additional data and conduct further analyses to advance the development program in early Alzheimer’s disease. The dialogue continues with the EMA to address the points raised by the Committee for Medicinal Products for Human Use (CHMP). As part of our ongoing interactions with the FDA, Anavex has submitted additional data to the regulatory agency with the objective of reaching alignment on the Alzheimer’s disease development program for blarcamesine in the U.S. Anavex is also advancing regulatory engagement with EU authorities for blarcamesine in Parkinson’s disease and rare neurological conditions, including Rett syndrome, underscoring the breadth of the Company’s clinical development portfolio."

European regulatory • FDA event • Alzheimer's Disease • Parkinson's Disease

Anavex Life Sciences Corp…announced that it has withdrawn its application for the marketing authorization of blarcamesine in the EU as an add-on therapy for the treatment of early Alzheimer’s disease in adults, which had been under review by the European Medicines Agency (EMA) (Anavex Press Release) - "The decision to withdraw the application follows feedback from the EMA’s Committee for Medicinal Products for Human Use (CHMP) indicating that it would not be in a position to issue a positive opinion for the application at this time."

European regulatory • Alzheimer's Disease

STUDY OF BLARCAMESINE IN A NEW PARKINSON'S MODEL OF COMBINED ΑLPHA-SYNUCLEIN PATHOLOGY AND NORADRENERGIC DYSFUNCTION (ADPD 2026) - "The motor deficit caused by alpha-synuclein pathology combined with noradrenergic dysfunction was significantly attenuated after 6 weeks of blarcamesine treatment. This was accompanied by a restoration of DA fibers in the most denervated striatal regions, without any significant change in number of nigral DA neurons or pSyn inclusions. We conclude that blarcamesine has restorative effects on nigrostriatal dopaminergic neurons even in the presence of alpha-synuclein aggregates formation."

CNS Disorders • Movement Disorders • Parkinson's Disease

ADVANCING ALZHEIMER'S DISEASE CARE: CONVENIENCE FOR BOTH PATIENTS AND FAMILIES WITH ORAL BLARCAMESINE WITH LONG-TERM TIME SAVED (ADPD 2026) - "The impact on daily life is extended by time saved with oral Alzheimer's treatment blarcamesine¾here 17.8 months¾allowing for longer independence of loved ones¾with safer and better outcome¾while allowing efficiency, accessibility, and ease for patients and families."

Clinical • Alzheimer's Disease • CNS Disorders

New Scientific Findings Highlight Hypothesis of Autophagy Failure as a Precursor of Amyloid Beta and Tau Pathology in Alzheimer’s Disease (GlobeNewswire) - "The authors further provide an explanation why amyloid plaques, or oligomers of Aβ, do not play a primary role, which allows for accommodation of the disconnect between the prevalence of plaques within the brain and cognitive status. Also, the role of apolipoprotein E (APOE) expression, being the largest genetic risk factor in sporadic Alzheimer’s disease could be explained. APOE is thought to influence Aβ trafficking, which could play an important role by increasing neuronal uptake of extracellular Aβ—thus defeating or competing with beneficial secretion....These findings directly align with Anavex’s clinical and mechanistic data showing that blarcamesine..."

Preclinical • Alzheimer's Disease

Anavex Life Sciences Presents Significant Treatment Effects of Blarcamesine in New Advanced Alpha-Synuclein Model of Parkinson’s Disease at AD/PD 2026 Conference (The Manila Times) - "New Parkinson’s model of combined alpha-synuclein pathology and noradrenergic degeneration...Significant treatment effects of blarcamesine were detected using both a test of impaired motor function and a biomarker of dopaminergic nerve fiber density, indicating fiber regrowth in striatum after 6 weeks of blarcamesine treatment."

Preclinical • Parkinson's Disease

Upcoming milestones, pipeline breadth, and financial position (Yahoo Finance) - "Looking ahead, Missling said the company expects a review of its re-examination with the EMA in the first half of the year...Participation in ACCESS-AD, described as a European-funded initiative, and planning for an Alzheimer’s study; A planned Phase IIb/III Parkinson’s disease dementia study, described as likely around 12 months in duration...Three expected publications: a precision medicine analysis from the Alzheimer’s study, a GWAS/COL24A1 publication..."

New trial • Alzheimer's Disease • Parkinson's Disease

New scientific findings to be presented at upcoming conferences or publications (Anavex Press Release) - "Oral Presentation at 16th Intrinsic Capacity, Frailty and Sarcopenia Research Conference for Healthy Longevity (ICFSR26)...Clinical relationship with biomarker: Correlation between clinical endpoints and reduced brain region atrophy with blarcamesine in early Alzheimer’s disease; Publication Alzheimer’s disease: Precision Medicine ABCLEAR populations of the ANAVEX2-73-AD-004 Phase 2b/3 trial; Publication Alzheimer’s disease: Precision Medicine gene, COL24A1, with estimated >70% prevalence in the early AD population has the potential to establish effective treatment of early Alzheimer’s disease through effectiveness of autophagy-enhancing blarcamesine."

Clinical data • Alzheimer's Disease • Sarcopenia

Expected Development Milestones (Anavex Press Release) - "Update on regulatory pathway for blarcamesine in early Alzheimer’s disease; Progress on clinical development program in Parkinson’s disease through targeted approach, potentially addressing the highest disease burden in Parkinson’s disease; Regulatory and clinical trial update for blarcamesine in Parkinson’s disease....Progressing collaborative initiatives and strategic partnership activities."

Pipeline update • Alzheimer's Disease

Emerging neurobiological targets in psychiatric treatment. (PubMed, Eur Neuropsychopharmacol) - "Recent evidence suggests that sodium channel modulators, such as evenamide, may offer therapeutic benefits for treatment-resistant schizophrenia by stabilizing glutamatergic neurotransmission...Additionally, Sigma-1 receptor agonists, including Blarcamesine and Pridopidine, have shown neuroprotective and cognitive-enhancing properties, making them attractive candidates for psychiatric and neurodegenerative disorders. Orexin receptor antagonists, such as suvorexant and seltorexant, have potential in mood disorders and substance dependence, highlighting the broader therapeutic applications of targeting the orexinergic system...The identification of biomarkers for patient stratification will be critical in the hitherto elusive goal of developing precision medicine approaches. Targeted pharmacological interventions offer a path toward more effective, well-tolerated, and potentially individualized treatment options for patients with severe mental illness."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Anavex Joins ACCESS-AD, a Major Initiative Funded by the European Commission, Through the Clinical Evaluation of Blarcamesine as Part of a Precision Medicine Approach in Alzheimer’s Disease (The Manila Times) - "As part of the consortium, blarcamesine, the once-daily orally administered investigational small-molecule therapy designed to target autophagy through SIGMAR1 activation, a central regulator of cellular homeostasis, will be evaluated in a clinical prediction study....The blarcamesine study will examine patient characteristics, treatment response predictors and real-world feasibility within both specialty and community-based clinical environments."

Financing • New trial • Alzheimer's Disease

Anavex Life Sciences Receives FDA Feedback on Alzheimer’s Disease Program (The Manila Times) - "During the Type C meeting, the FDA shared their interest and collaborative approach to Anavex’ development plans. The Company provided information related to the scientific rationale and profile of blarcamesine as an oral administration being convenient to dispense and the absence of significant safety concerns in clinical trials of blarcamesine conducted so far extending to the lack of amyloid-related imaging abnormalities (ARIA)...In order to move forward, existing data from the Phase IIb/III ANAVEX2-73-AD-004 program requested by the Agency will be submitted."

FDA event • Alzheimer's Disease