Anavex Announces First Entire Clinical Gene Pathway Data of ANAVEX®2-73 from AVATAR Study in Patients with Rett Syndrome
20 Dicembre 2023 - 1:30PM
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 the first entire clinical gene
pathway data from the ANAVEX®2-73-RS-002 AVATAR Rett syndrome
trial.
A whole genome and exome analysis comparing drug
and placebo in patients with Rett syndrome was performed. We
believe the results confirm that Rett syndrome is indeed a
neurodevelopmental disorder with a key metabolic component, which
can be addressed with therapeutic intervention and is likely
relevant for other neurodevelopmental disease indications.
AVATAR study was a randomized,
placebo-controlled clinical trial in 33 patients with Rett syndrome
which included prespecified biomarkers of response as well as Whole
Exome Sequencing (WES) DNA data and full RNA exome expression
(RNA-seq) data collection. The study included analysis of gene
expression changes in each treatment group as well as analysis of
the impact of single nucleotide polymorphisms/variants (SNPs/SNVs)
on treatment response.
ANAVEX®2-73 transcriptomics analysis (RNAseq)
identified gene networks that are differentially expressed in Rett
syndrome patients treated with ANAVEX®2-73 compared to placebo.
Patient samples that were analyzed contained on average over 20
million unique reads in both placebo and ANAVEX®2-73 treated
patients. Biological relevance of this pool of genes was assessed
through pathway analysis and confirmed the impact of ANAVEX®2-73
treatment on pathways involved in neurodevelopmental diseases.
The results highlight many significant
differences between active treatment group and placebo, such as the
differential expression of several genes in response to ANAVEX®2-73
treatment as shown in the following heatmap figure:
Pathway analysis of the differentially expressed
genes suggests ANAVEX®2-73 may, among other functions, correct
metabolic alterations in patients with Rett syndrome through
enhanced mitochondrial energy production and increased expression
of genes involved in oxidative phosphorylation, fatty acid
metabolism, developmental signaling pathways,
transcription/translation, membrane trafficking, and branched-chain
amino acid catabolism as shown in the following table:
ANAVEX®2-73
Treatment-enriched Pathways |
Pathway Name |
Category |
p-value |
Oxidative phosphorylation |
Energy Metabolism |
2.84E-04 |
Valine leucine and isoleucine degradation |
Metabolism |
6.85E-04 |
Adipogenesis |
Energy Metabolism |
1.48E-03 |
Fatty acid degradation |
Energy Metabolism |
5.52E-03 |
Amino acid metabolism |
Metabolism |
7.14E-03 |
Cysteine and methionine metabolism |
Metabolism |
8.41E-03 |
Acyl chain remodeling of phosphatidylserine |
Metabolism |
1.43E-02 |
Mitochondrial protein import |
Energy Metabolism |
1.71E-02 |
α-Linolenic acid metabolism |
Metabolism |
1.83E-02 |
PPAR-α pathway |
Signaling |
1.98E-02 |
Acyl chain remodeling of phosphatidylethanolamine |
Metabolism |
2.43E-02 |
TGF-β signaling pathway |
Signaling |
2.49E-02 |
Deubiquitination |
Metabolism |
2.99E-02 |
NOD1/2 signaling pathway |
Signaling |
3.09E-02 |
Fatty acid β-oxidation |
Energy Metabolism |
3.26E-02 |
Detoxification of reactive oxygen species |
Metabolism |
3.26E-02 |
N-glycan trimming in ER and calnexin/calreticulin cycle |
Metabolism |
3.44E-02 |
miRNAs involvement in the immune response in sepsis |
Transcription / Translation |
3.81E-02 |
RHOV GTPase cycle |
Signaling |
3.81E-02 |
Formation of xylulose-5-phosphate |
Metabolism |
4.11E-02 |
NR1H2 and NR1H3 regulate gene expression linked to
gluconeogenesis |
Transcription / Translation |
4.11E-02 |
RHOU GTPase cycle |
Signaling |
4.20E-02 |
Fatty acid metabolism |
Energy Metabolism |
4.36E-02 |
Nucleotide-binding oligomerization domain (NOD) pathway |
Transcription / Translation |
4.60E-02 |
Protein localization |
Membrane Trafficking |
4.89E-02 |
Glycerophospholipid metabolism |
Metabolism |
4.89E-02 |
The scope of these detected gene expression
changes identified through ANAVEX®2-73 effect may represent
additional potential biomarkers of disease pathology and
response.
Christopher U Missling, PhD, President and Chief
Executive Officer of Anavex, stated, "We believe, this represents
an extensive transcriptomics analysis (RNAseq) of a therapeutic
agent in patients with Rett syndrome and it is very exciting to
witness ANAVEX®2-73’s demonstration of its platform Precision
Medicine potential for Rett syndrome with ability to compensate for
expression levels of dysregulated developmental and metabolic
genes, apparent within the Rett syndrome pathology. We are steadily
making progress to learn more about this debilitating disorder and
further analysis will be dedicated to evaluating the significance
of each identified gene and gene variant and should deepen the
understanding of the underlying signaling pathways involved in
response to ANAVEX®2-73 treatment in patients with Rett
syndrome.”
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 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 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 DevelopmentToll-free:
1-844-689-3939Email: info@anavex.com
Investors:Andrew J.
BarwickiInvestor RelationsTel: 516-662-9461Email:
andrew@barwicki.com
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/a70a64c6-9af5-487a-91dd-ff744924b733.
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