Anavex Life Sciences Announces Translational Biomarker Data for ANAVEX2-73 in Fragile X Syndrome (Major Cause of Autism)

Anavex Life Sciences Corp. recently reported positive preclinical results in directly to humans’ translatable biomarkers for individuals with FXS for ANAVEX2-73 (blarcamesine), in a disease model of Fragile X syndrome (FXS).

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. It is characterized by a range of cognitive, behavioral, and sensory challenges, including learning difficulties, anxiety, hyperactivity, and sensitivity to sensory stimuli. At present, there is no approved treatment for Fragile X syndrome.

The findings presented at the 19th NFXF International Fragile X Conference reports positive results in directly to humans’ translatable electroencephalogram (EEG) biomarkers present in both individuals with FXS and animal models of FXS.

The study presented investigated the effects of ANAVEX2-73 on brain activity in a mouse model of FXS using electroencephalography (EEG), a non-invasive technique that measures electrical signals in the brain. EEG recordings from mice treated with ANAVEX2-73 showed significant dose-dependent improvements in several key biomarkers of brain function compared to untreated mice.

Key results were found in the auditory steady state response (ASSR) EEG test, which are of particular importance to the treatment of CNS disorders. In FXS and other CNS disorders, the brain is unable to synchronize sensory stimuli like sounds appropriately, driving sensory overload and hypersensitivity in affected individuals. In the current study, ANAVEX2-73 robustly enhances neural synchrony in response to sounds in the frontal and auditory cortices of the brain in a dose dependent manner.

Dysfunction of cells that regulate the balance of excitatory-inhibitory signaling has been implicated in these characteristic hypersensitivities of various neurodevelopmental disorders, including FXS. This new data demonstrates that ANAVEX2-73 restores this balance and improves neuronal connectivity, which is directly translatable to humans and demonstrates the therapeutic potential of ANAVEX2-73 to address behavioral, sensory, and cognitive abnormalities in individuals with FXS.

ANAVEX2-73 has previously demonstrated preclinical efficacy in an animal model of FXS published in the scientific journals Nature Scientific Reports and the American Journal of Medical Genetics. These previous studies highlighted the ability of ANAVEX2-73 to ameliorate behavioral deficits and fluid biomarker features of FXS. Dose-dependent treatment effect of ANAVEX2-73 resulted in reversal of hyperactivity, restoration of associative learning and reduction of anxiety in a mouse model of Fragile X syndrome, which were also associated with improvements in key blood signaling biomarkers, which are measurable in patients with Fragile X syndrome as well.

Based on these results, the company plans to initiate a clinical trial to evaluate the safety and efficacy of ANAVEX2-73 in individuals with FXS.

“These additional non-invasive biomarker findings in Fragile X syndrome provide further evidence of potential to expand the therapeutic profile of ANAVEX2-73 into the largest portion of addressable market of autism spectrum disorder, Fragile X syndrome,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We look forward to initiating a double-blind, placebo-controlled ANAVEX2-73 study in Fragile X syndrome. This is further evidence of the potential of ANAVEX2-73 as a platform technology of precision medicine.”

Anavex Life Sciences’ product portfolio platform includes orally available small molecule drug candidate ANAVEX2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease, Rett syndrome and ANAVEX3-71 for schizophrenia.

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.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel 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, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 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 and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX2-73 is an orally available drug candidate that restores cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s 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 Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX2-73 for the treatment of Parkinson’s disease. We believe that ANAVEX3-71, which targets SIGMAR1 and M1 muscarinic 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, ANAVEX3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. For more information, visit www.anavex.com.