ANAVEX®3-71 effect is supported by biomarkers: Decrease of extracellular A (Abeta) deposition and reduced pathological inflammatory glial cell recruitment towards hippocampal neurons (p ≤ 0.01)
NEW YORK, Aug. 02, 2022 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced long-lasting effect of clinical drug candidate ANAVEX®3-71 in preventing cognitive decline in a transgenic rat model of Alzheimer’s disease at the Alzheimer’s Association International Conference (AAIC), taking place in San Diego, CA and virtually on July 31 – August 4, 2022.
The poster presentation titled, “An M1/sigma-1 receptor agonist prevents cognitive deficits, reduces amyloid plaques and neuroinflammation in a transgenic rat model of Alzheimer’s amyloid pathology” is being presented by Chiara Orciani, Sonia Do Carmo, Morgan K Foret, Helene Hall, Quentin Bonomo, Agustina Lavagna, Chunwei Huang and A. Claudio Cuello from McGill University, Montreal, Canada.
ANAVEX®3-71 (10 μg/kg) or control (saline) was administered orally once daily in pre-plaque McGill-R-Thy1-APP transgenic (Tg) rats (n=22) and wild-type (wt) rats (n=22) divided into four groups, for seven months. Subsequently, after one month of drug interruption, behavioral tests were performed: Novel Object Recognition, Morris Water Maze, and Social Preference.
Biomarker analysis revealed that ANAVEX®3-71 prevents McGill-APP transgenic rats from increasing cortical (p ≤ 0.05) and hippocampal (p ≤ 0.01) extracellular Aβ deposition. ANAVEX®3-71 also significantly reduces microglia (p ≤ 0.05) and astrocytes (p ≤ 0.05) recruitment towards Aβ-burdened neurons in the hippocampus.
In the Novel Object Recognition behavioral test, Tg control rats explored the novel object significantly less than wt control rats (p ≤ 0.01). The impairment in Tg rats was completely reversed with ANAVEX®3-71 (p ≤ 0.01).
In the Morris Water Maze behavioral test, the rats showed significant differences in learning. Tg control rats required more time to find the hidden platform than wt control rats (p ≤ 0.01). Conversely, ANAVEX®3-71-treated Tg rats performed significantly better than Tg control rats (p ≤ 0.05).
In the Social Preference behavioral test, Tg control rats showed less interaction time with a “stranger rat” than wt control rats (p ≤ 0.001). This deficit in Tg rats was entirely reversed with ANAVEX®3-71 (p ≤ 0.0001).
This new data strengthens the importance and applicability of Anavex’s Precision Medicine SIGMAR1 platform and is consistent with previously reported therapeutic significant and dose-dependent preclinical prevention of Aβ (Abeta) induced biomarker-correlated cognitive impairments with ANAVEX®2-73.1
Both clinical drug candidates ANAVEX®2-73 and ANAVEX®3-71 activate the sigma-1 receptor (SIGMAR1). Data suggests that activation of SIGMAR1 results in the restoration of homeostatic function within the body and is pivotal to restoring neural cell balance and the promotion of neuroplasticity.2 Recent independent findings strengthen the understanding of the beneficial effects of SIGMAR1 activation as a compensatory mechanism to chronic CNS diseases.3
“These results strengthen our SIGMAR1 product platform and validate Anavex’s approach to CNS target selection and drug discovery,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “This data increases Anavex’ confidence in the potential of our Precision Medicine technology to address serious neurodegenerative diseases.”
ANAVEX®3-71, previously AF710B, represents Anavex’s 2nd novel clinical sigma-1 and muscarinic receptor program parallel to ANAVEX®2-73 (blarcamesine). Anavex is developing ANAVEX®3-71 initially for the treatment of Frontotemporal Dementia (FTD), for which ANAVEX®3-71 was previously granted orphan drug designation by the FDA. ANAVEX®3-71 demonstrated disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, as well as beneficial effects on mitochondrial dysfunction and neuroinflammation.4 ANAVEX®3-71 recently completed a placebo-controlled Phase 1 clinical trial (ANAVEX®3-71-001). The study successfully reached primary and secondary safety endpoints.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 and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, 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 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 with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 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. ANAVEX®3-71, which targets sigma-1 and muscarinic M1 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.
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.
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2 Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.
3 Prasanth MI, Malar DS, Tencomnao T, Brimson JM. The emerging role of the sigma-1 receptor in autophagy: Hand-in-hand targets for the treatment of Alzheimer's. Expert Opin Ther Targets. 2021 Jun 10. doi: 10.1080/14728222.2021.1939681. Epub ahead of print. PMID: 34110944.
4 Fisher, A., Bezprozvanny, I., Wu, L., Ryskamp, D. A., Bar-Ner, N., Natan, N., Brandeis, R., Elkon, H., Nahum, V., Gershonov, E., LaFerla, F. M., & Medeiros, R. (2016). AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neuro-degenerative diseases, 16(1-2), 95–110. https://doi.org/10.1159/000440864