GlobeNewswire Inc | Aug 26, 2021 07:00AM EDT

August 26, 2021

Published in Scientific Reports, Results Highlight Reversal of Hyperactivity and Restoration of Associative Learning and Reduction of Anxiety, Phenotypes Associated with Fragile X Syndrome

Positron emission tomography (PET) Establishes ANAVEX2-73s Dose Dependent SIGMAR1 Receptor Occupancy

Study Provides Proof-of-Concept for Advancing ANAVEX2-73 (blarcamesine) into Phase 2/3 Fragile X Syndrome Clinical Trial

NEW YORK, Aug. 26, 2021 (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 Alzheimers disease, Parkinsons disease, Rett syndrome and other central nervous system (CNS) diseases, today announced that preclinical data of ANAVEX2-73 (blarcamesine) in Fragile X Syndrome were published in the peer-reviewed journal, Scientific Reports.

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and the most frequent single gene cause of autism spectrum disorder with an estimated population of approximately 62,500 in the US and 1,088,500 worldwide.1 At present, there is no approved treatment for Fragile X Syndrome.

The study evaluated doses of ANAVEX2-73 in Fmr1 knockout (KO) mice, a validated animal model for the disease, which resulted in the reversal of hyperactivity and restoration of associative learning as well as reduction in anxiety-like and perseverative behaviors. Positron emission tomography (PET) and ex vivo autoradiographic studies, using the highly selective SIGMAR1 PET ligand [18F]FTC-146, demonstrated ANAVEX2-73s dose dependent receptor occupancy. Additionally, ANAVEX2-73 also restored pAkt and BDNF levels in the hippocampus, which are signaling pathways particularly affected in Fragile X Syndrome. ANAVEX2-73 also showed a good safety profile.

"Testing novel drugs that can safely improve the symptoms of Fragile X Syndrome is a high priority, said Walter E. Kaufmann, M.D., Chief Medical Officer of Anavex and corresponding author of the paper. The present findings support the viability of SIGMAR1 as a therapeutic target in Fragile X Syndrome, and the clinical potential of ANAVEX2-73 (blarcamesine) in Fragile X Syndrome and other neurodevelopmental disorders.

The study, Effects of the Sigma-1 Receptor Agonist Blarcamesine in a Murine Model of Fragile X Syndrome: Neurobehavioral Phenotypes and Receptor Occupancy, is the basis for a Phase 2/3 ANAVEX2-73 study in Fragile X Syndrome. The fact that the investigation involved chronic administration, as opposed to acute dosing, provides additional evidence in favor of the clinical use of ANAVEX2-73. Since the behavioral paradigms reflect the involvement of multiple cortical and subcortical regions, their marked improvement by ANAVEX2-73 suggest widespread activation of SIGMAR1 by the drug and modulation of multiple neural pathways. Indeed, the observation of normalization of pAkt and BDNF levels after ANAVEX2-73 administration, in a brain region critical for cognition and behavior, is also a finding with important implications for Fragile X Syndrome and other synaptic disorders.

Altogether, these neurobehavioral, biochemical, and imaging data demonstrate that corresponding doses of ANAVEX2-73 that yield measurable receptor occupancy are effective for substantially correcting key synaptic and behavioral phenotypes in Fmr1 KO mice. The data also suggest that these positive effects are mediated by SIGMAR1 activation in multiple brain regions, where ANAVEX2-73 binds to the receptor in a dose-dependent and genotype-independent manner. The study was supported by the FRAXA Research Foundation.

We look forward to initiating a double-blind, placebo-controlled Phase 2/3 ANAVEX2-73 study in Fragile X Syndrome, said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. We are intrigued about the clear preclinical data providing potential to expand the therapeutic profile of ANAVEX2-73 into the largest portion of addressable market of autism spectrum disorder, Fragile X Syndrome. This is further evidence of the potential of ANAVEX2-73 as a platform technology of precision medicine."

The full paper can be accessed online at: www.nature.com/articles/s41598-021-94079-7.

Anavex Life Sciences product portfolio platform includes orally available small molecule drug lead candidate ANAVEX2-73 for the treatment of Alzheimers disease, Parkinsons disease and Rett syndrome and ANAVEX3-71 for frontotemporal dementia.

About Fragile X Syndrome and Autism Spectrum Disorder

Fragile X Syndrome is the most common form of inherited intellectual disability and the most frequent single gene cause of autism, affecting approximately 1 in 4,000 males and 1 in 6,000 females. The disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene that leads to abnormal methylation and suppression of FMR1 transcription with the resulting decrease in protein levels in the brain and other tissues. The average age of Fragile X Syndrome diagnosis for boys and girls are 35 to 37 months and 42 months, respectively. Behavioral abnormalities, including autism spectrum disorder, are common.

Autism spectrum disorder is a behavioral diagnosis while Fragile X Syndrome is a medical/genetic diagnosis. Many studies have evaluated the link between Fragile X Syndrome and autism spectrum disorder over the last few decades. Since many children with Fragile X Syndrome are interested in social interactions, they may not meet the diagnostic criteria for autism spectrum disorder, even though they exhibit some features such as poor eye contact, shyness, social anxiety, hand-flapping and sensory issues. Autism is much more common in boys than in girls with Fragile X Syndrome. According to the CDC, a national parent survey found that 46% of males and 16% of females with Fragile X Syndrome have been diagnosed or treated for autism spectrum disorder.

About FRAXA Research Foundation

FRAXAs mission is to find effective treatments and ultimately a cure for Fragile X Syndrome. FRAXA directly funds research grants and fellowships at top universities around the world. FRAXA partners with biomedical and pharmaceutical companies, large and small, to bridge the gap between research discoveries and actual treatments. Treatments for Fragile X Syndrome are likely to help people affected by autism, Alzheimers, and other brain disorders. More information is available at www.fraxa.org.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimers disease, Parkinsons disease, Rett syndrome and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavexs lead drug candidate, ANAVEX2-73 (blarcamesine), successfully completed a Phase 2a clinical trial for Alzheimers disease and recently a Phase 2 proof-of-concept study in Parkinsons disease dementia and a Phase 2 study in adult patients with Rett syndrome. ANAVEX2-73 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 Alzheimers disease. ANAVEX2-73 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 Parkinsons Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX2-73 for the treatment of Parkinsons disease. ANAVEX3-71, which targets sigma-1 and muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimers disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX3-71 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 Companys 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 Relations

Tel: 516-662-9461Email: andrew@barwicki.com

1 https://fragilex.org/understanding-fragile-x/fragile-x-101/prevalence/