Downing v. Anavex Life Sciences Corporation — Entry #23: DECLARATION of Theodore L

Case 1:24-cv-03529-CM   Document 23-9   Filed 08/23/24   Page 1 of 4


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Jun 6, 2023


Completion of ANAVEX®2-73 (blarcamesine)
EXCELLENCE Phase 2/3 Rett Syndrome Clinical
Trial


NEW YORK – June 6, 2023
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 announced the completion of dosing of all participants of the placebo-controlled EXCELLENCE Phase 2/3 study
ANAVEX®2-73-RS-003 in pediatric patients with Rett syndrome. The Company expects to announce topline results
from this study in the second half of this year.


ANAVEX®2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1) which,
data suggest, is pivotal to restoring cellular homeostasis and promoting neuroplasticity. [1]


The completion of the randomized, placebo-controlled EXCELLENCE Phase 2/3 study ANAVEX®2-73-RS-003 for the
treatment of 92 pediatric patients with Rett syndrome ages ≥ 5 years to 17 (inclusive) was preceded by the successful
completion of both placebo-controlled Phase 2 U.S. (ANAVEX®2-73-RS-001) [2], and Phase 3 AVATAR (ANAVEX®2-
73-RS-002)[3] studies in adult patients with Rett syndrome.


The multi-center, double-blind clinical EXCELLENCE study (ANAVEX®2-73-RS-003)[4] in pediatric patients is
measuring safety, tolerability, and efficacy of daily oral ANAVEX®2-73 (blarcamesine) doses or placebo. After


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completing the double-blind study, eligible participants are able to join a voluntary open-label extension study of
ANAVEX®2-73 (blarcamesine).


In communication with the FDA, the Company received the Agency’s input on the study endpoints, which were utilized
in this clinical study. The Rett Syndrome Behavior Questionnaire (RBSQ) total score and Clinical Global Impression
Improvement Scale (CGI-I) score are co-primary endpoints in the statistical analysis plan with specified linear mixed-
effects models for repeated measures (MMRM) as the primary analysis methods.


ANAVEX®2-73 (blarcamesine) had previously received Fast Track designation, Rare Pediatric Disease designation and
Orphan Drug designation from the FDA for the treatment of Rett syndrome.


“We would like to thank the investigators and clinical site coordinators as well as all the participating families for their
dedication to this clinical study completed with ANAVEX®2-73 (blarcamesine)”, said Christopher U. Missling, PhD,
President and Chief Executive Officer of Anavex. “Rett syndrome is a devastating, non-inherited genetic post-natal
progressive neurodevelopmental disorder that occurs almost exclusively in girls and leads to severe impairments,
affecting nearly every aspect of the child’s life, hence we continue our fast-paced development program of ANAVEX®2-
73 (blarcamesine) in Rett syndrome.”


About Rett Syndrome
Rett syndrome is a rare, 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, slowed brain and head growth, problems
with walking, seizures and intellectual disability. There is currently no cure for Rett syndrome and treatment of the
disorder is symptomatic. Management of symptoms is done through a multidisciplinary approach utilizing medication for
motor difficulties, breathing irregularities and control of seizures through anticonvulsant drugs. 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 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 and recently 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 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


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to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 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, 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.


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 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.


For Further Information:
Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
Email: [email protected]


Investors:
Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: [email protected]


[1]Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as
Therapeutic Targets.
[2] ClinicalTrials.gov Identifier: NCT03758924
[3] ClinicalTrials.gov Identifier: NCT03941444
[4] ClinicalTrials.gov Identifier: NCT04304482