Benzinga | Aug 26, 2021 07:08AM EDT

Anavex Life Sciences Announces Publication of Foundational Data for ANAVEX 2-73 in Fragile X Syndrome

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 that preclinical data of ANAVEX(r)2-73 (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 ANAVEX(r)2-73 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 ANAVEX(r)2-73's dose dependent receptor occupancy. Additionally, ANAVEX(r)2-73 also restored pAkt and BDNF levels in the hippocampus, which are signaling pathways particularly affected in Fragile X Syndrome. ANAVEX(r)2-73 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 ANAVEX(r)2-73 (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 ANAVEX(r)2-73 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 ANAVEX(r)2-73. Since the behavioral paradigms reflect the involvement of multiple cortical and subcortical regions, their marked improvement by ANAVEX(r)2-73 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 ANAVEX(r)2-73 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 ANAVEX(r)2-73 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 ANAVEX(r)2-73 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 ANAVEX(r)2-73 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 ANAVEX(r)2-73 into the largest portion of addressable market of autism spectrum disorder, Fragile X Syndrome. This is further evidence of the potential of ANAVEX(r)2-73 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 ANAVEX(r)2-73 for the treatment of Alzheimer's disease, Parkinson's disease and Rett syndrome and ANAVEX(r)3-71 for frontotemporal dementia.