Anavex Life Sciences Presented at the 6th Annual European Rett Syndrome Conference Preliminary Clinical Efficacy Data from the U.S. Rett Syndrome Phase 2 ANAVEX®2-73 Study
NEW YORK – September 27, 2019
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) disorders, today presented preliminary clinical efficacy data from the PK cohort (Part A) of the U.S. Phase 2 Rett syndrome clinical trial ANAVEX®2-73-RS-001.
“The data from the PK cohort (Part A, n=6) is very encouraging because of the (1) magnitude of change (large to very large effect sizes: Cohen’s d: RSBQ Total 1.47; Cohen’s d: Glutamate 1.11), (2) the efficacy signal on both caregiver- and clinician-based measures of severity and correlations with key biomarker related to disease pathogenesis (Glutamate), (3) the short duration of treatment with ANAVEX®2-73 (blarcamesine), (4) the relatively low dose, (5) the older age of participants, and (6) the clinical significance (RSBQ-CGI-I correlations),” said Walter E Kaufmann, MD, Principal Investigator of the study and Chief Medical Officer of Anavex. “The randomized, double-blind, placebo-controlled study (Part B, n=15) is currently ongoing.”
This is one of three clinical studies in Anavex’s Rett Syndrome Program: U.S. RTT (ANAVEX®2-73-RS-001), AVATAR (ANAVEX®2-73-RS-002) and EXCELLENCE (ANAVEX®2-73-RS-003).
PK cohort (Part A) ranging in age from 18 to 36 years, who completed the pharmacokinetic (PK) part of the study received a low dose of approx. 5 mg daily oral liquid dose of ANAVEX®2-73 (blarcamesine) for 7 weeks. Efficacy evaluations took place at Baseline (Week 0), Week 4 and Week 7.
In addition to the significant improvements of the two global efficacy endpoints, the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score and the Clinical Global Impression – Improvement (CGI-I), the RSBQ Hand Behaviours and the RSBQ Breathing Abnormalities improved during the trial. Efficacy signals on both caregiver- & clinician-based measures of severity correlated with a key biomarker related to disease pathogenesis (Glutamate). The biomarker correlation was also significant with the improvement in CSHQ (Children’s Sleep Habits Questionnaire). 
Christopher U Missling, PhD, President and Chief Executive Officer of Anavex stated, “We are intrigued by the biomarker correlation with the efficacy measures for ANAVEX®2-73 (blarcamesine) in patients with Rett syndrome and we are currently proceeding with Part B of the study. In addition to Rett syndrome, Anavex has ongoing clinical development programs for ANAVEX®2-73 (blarcamesine) for the treatment of Alzheimer’s disease and Parkinson’s disease dementia.”
About Rett Syndrome
Rett syndrome is a devastating, non-inherited genetic postnatal progressive neurodevelopmental disorder that occurs almost exclusively in girls and leads to severe impairments, affecting nearly every aspect of the child’s life: their ability to speak, walk, eat and even breathe easily. The hallmark of Rett syndrome is near constant repetitive hand movements while awake. It is characterized by normal early growth and development (6 to 18 months) followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, autistic features, slowed brain and head growth, ataxia, seizures and intellectual disability. There is currently no cure for Rett syndrome. Rett syndrome is caused by mutations in the MECP2 gene and strikes all racial and ethnic groups and occurs worldwide in approximately one in every 10,000 to 15,000 live female births.
About ANAVEX®2-73-RS-001 Clinical Study (NCT03758924)
The Phase 2 trial is a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic and efficacy study of oral liquid ANAVEX®2-73 (blarcamesine) to treat Rett syndrome. Pharmacokinetic and dose-finding elements in a total of 21 patients over a 7-week treatment period will be evaluated incorporating precision medicine biomarkers. Preceding the placebo-controlled randomization of 15 patients (Part B), a 6 patient cohort (Part A) underwent a 7-week pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73 (blarcamesine). All patients who participate in the study will be eligible to receive ANAVEX®2-73 (blarcamesine) under an open label extension protocol.
ANAVEX®2-73 (blarcamesine) activates the Sigma-1 receptor (S1R) protein, which serves as a molecular chaperone and functional modulator involved in restoring homeostasis. In a Phase 2a Alzheimer’s disease (AD) study, ANAVEX®2-73 (blarcamesine) has shown dose dependent improvement in exploratory endpoints of cognition (MMSE) and activities of daily living (ADCS-ADL). Full genomic analysis of ANAVEX®2-73 (blarcamesine) Phase 2a AD patients was performed. The ANAVEX®2-73 (blarcamesine) Phase 2 Rett syndrome study design includes genomic biomarkers identified in the ANAVEX®2-73 (blarcamesine) Phase 2a AD study. Studies of ANAVEX®2-73 (blarcamesine) in a mouse model with a heterozygous Mecp2-null mutation (HET) that causes neurological symptoms that mimic Rett syndrome, ANAXEX®2-73 (blarcamesine) was evaluated in automatic visual responses and breathing tests in 7-month old mice, an age at which advanced pathology is evident. Vehicle-treated HET mice demonstrated fewer automatic visual responses and more frequent expiratory apneas than wild-type mice. Treatment with ANAVEX®2-73 (blarcamesine) for four weeks significantly increased these visual responses in the HET mice (p<0.05). Additionally, chronic oral dosing daily for 3-6.5 weeks of ANAVEX®2-73 (blarcamesine) starting at ~5 weeks of age was also conducted in the HET mouse model of Rett syndrome, and dose-dependent improvements in a variety of sensory and motor deficits, including those involving motor coordination, balance, and learning, were also observed. Notably, one of the strongest effects was on hindlimb clasping, a postural response that resembles the characteristic hand stereotypies present in Rett syndrome. These experiments were sponsored by Rettsyndrome.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 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), recently completed a successful Phase 2a clinical trial for Alzheimer’s disease. ANAVEX®2-73 (blarcamesine) 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 (blarcamesine) 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 (blarcamesine) for the treatment of Parkinson’s disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising preclinical 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 neuroinflammation and mitochondrial dysfunction. Further information is available at www.anavex.com. You can also connect with the company on Twitter, Facebook 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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 Excitatory-inhibitory imbalances postulated in many neurologic disorders, including Rett syndrome, have been linked to imbalances between Glutamate and GABA: Kaufmann et al. Expert Opin Orphan Drugs 4:1043-1055, 2016; Banerjee et al. Brain 142:239-248, 2019.
 ClinicalTrials.gov Identifier: NCT03758924; NCT03941444
 ClinicalTrials.gov Identifier: NCT03790709
 ClinicalTrials.gov Identifier: NCT03774459