Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the
Company”), a biotechnology company dedicated to developing disease
modifying treatments for neurodegenerative diseases, today
announced that three posters were presented at the American Academy
of Neurology (AAN) 2024 Annual Meeting taking place April 13-18,
2024, in Denver, Colorado, USA. Featured presentations described
the Company’s work in Parkinson’s disease and Multiple System
Atrophy (MSA), including initial biomarker data and baseline
characteristics from the ATH434-201 Phase 2 clinical trial.
David Stamler, M.D., Chief Executive Officer of
Alterity, commented, “We are excited to present the Parkinson’s
disease primate study to an international audience because we have
shown that ATH434 can reduce Parkinsonism in a higher order animal
with symptoms that closely parallel human disease. Importantly, the
improvements in motor skills and general functioning that parallel
human parkinsonism were associated with reductions in abnormal iron
in affected brain regions, validating the approach we are using in
our ongoing clinical trials. The data from this study improve our
ability to predict clinical outcomes and increases our confidence
level in our ongoing Phase 2 clinical trials in Multiple System
Atrophy, a parkinsonian disorder with similar underlying pathology
to Parkinson’s disease.”
Dr. Stamler continued, “Through our
collaboration with our partners at Vanderbilt University, we have
gained a deeper understanding of MSA, and we are now seeing the
fruits of this labor in both our bioMUSE natural history study and
our Phase 2 clinical trial. At AAN we reported the baseline
characteristics from our ATH434-201 Phase 2 trial including fluid
biomarkers and neuroimaging data. The data showed increased iron in
areas of pathology and elevated plasma Neurofilament Light Chain
(NfL) levels at baseline that correlated significantly with disease
severity. These data give us confidence in our approach of using
ATH434 to target the labile cellular iron known to promote
neurodegeneration, inhibit α‐synuclein aggregation, and improve
outcomes.”
Dr. Daniel Claassen, Professor of Neurology at
Vanderbilt University Medical Center and coordinating investigator
for the ATH434-201 Phase 2 study, commented, “The specialized
neuroimaging and biomarker assessments evaluated and refined in the
bioMUSE study were used to select and track patients in the Phase 2
study, making this program unique among current MSA clinical
studies. It is vital to select study patients with a high degree of
accuracy. The biomarkers being tested in the Alterity program hold
promise for assessing the potential disease modifying benefits of
ATH434.”
Presentation Summaries:
Title: A Phase 2
Study of ATH434, a Novel Inhibitor of α-Synuclein Aggregation, for
the Treatment of Multiple System Atrophy Lead
Author: David Stamler, M.D., Chief Executive Officer
of Alterity TherapeuticsResults: The poster
describes the baseline characteristics for the 65 evaluable
participants from Alterity’s ATH434-201 randomized, double-blind
Phase 2 clinical trial, with a focus on baseline fluid biomarkers,
neuroimaging and clinical data. The participants met the strict
criteria designed to confirm that participants were diagnosed with
early-stage MSA and had a mean of two years of motor symptoms.
ATH434 is a potential disease modifying therapy based on its
ability to redistribute excess labile iron without impairing normal
iron storage, inhibit α‐synuclein aggregation and reduce oxidative
stress. Importantly, the increased iron levels in the trial
participants were evident in multiple subcortical brain regions
with two distinct patterns of iron accumulations observed. In
addition, MSA participants with less than four years of motor
symptoms have elevated plasma Neurofilament Light Chain (NfL)
levels at baseline which correlate significantly with disease
severity.
Title: Neurofilament Light Chain and
Clinical Progression in Early Multiple System
AtrophyLead Author: Daniel O.
Claassen, M.D., M.S., Professor of Neurology, Vanderbilt University
Medical CenterResults: The poster describes
results from the bioMUSE Natural History Study in which changes in
clinical severity of 15 patients across a span of 12 months were
compared with plasma biomarkers with a goal of establishing
meaningful correlations. The advancement of MSA is profoundly
aggressive, highlighting the critical need for biomarkers to
delineate its progression over time. Emerging interest surrounds
the use of the fluid biomarker NfL, found in both cerebrospinal
fluid (CSF) and plasma, as an indicator of axonal damage in MSA.
This fluid biomarker holds promise for measuring the extent of
disease, tracking its progression, and forecasting the onset of
clinical manifestations associated with MSA. In this observational
study, the plasma NfL and CSF NfL were highly correlated,
indicating that the more easily obtained plasma values have a
meaningful relationship with brain pathology. Plasma NfL
significantly increased over 12 months, and both plasma and CSF NfL
were associated with disease progression in MSA. These data suggest
that NfL may be a marker of disease modification in studies of
MSA.
Title: Effects of
ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for
Iron, in Hemiparkinsonian MacaquesLead
Author: Margaret Bradbury, Vice President,
Research and Nonclinical Development, Alterity
TherapeuticsResults: The presentation demonstrated
that ATH434 treatment led to lower iron levels in the affected area
of the brain, the substantia nigra, and improved motor performance
and general function in monkeys with experimentally induced
Parkinson’s disease. At week 12, all 6 ATH434-treated macaques had
stable or improving scores from Baseline while two of three
vehicle-treated macaques did not demonstrate improvement. The
improved general behavior was well-correlated with reduced motor
impairment. These favorable parkinsonian outcomes observed in each
of the ATH434-treated monkeys were also associated with increased
levels of striatal synaptophysin, a protein marker that reflects
functional connections between neurons, suggesting functional
recovery of nerve endings in this critical motor pathway. These
results support further investigation of ATH434 for the treatment
of Parkinson’s disease.
The poster presentations can be found on
Alterity’s website here.
About ATH434
Alterity’s lead candidate, ATH434, is an oral
agent designed to inhibit the aggregation of pathological proteins
implicated in neurodegeneration. ATH434 has been shown
preclinically to reduce α-synuclein pathology and preserve neuronal
function by restoring normal iron balance in the brain. As an iron
chaperone, it has excellent potential to treat Parkinson’s disease
as well as various Parkinsonian disorders such as Multiple System
Atrophy (MSA). ATH434 successfully completed Phase 1 studies
demonstrating the agent is well tolerated and achieved brain levels
comparable to efficacious levels in animal models of MSA. ATH434 is
currently being studied in two clinical trials: Study ATH434-201 is
a randomized, double-blind, placebo-controlled Phase 2 clinical
trial in patients with early-stage MSA and Study ATH434-202 is an
open-label Phase 2 Biomarker trial in patients with more advanced
MSA. ATH434 has been granted Orphan drug designation for the
treatment of MSA by the U.S. FDA and the European Commission.
About ATH434-201 Phase 2 Clinical
Trial
The ATH434-201 Phase 2 clinical trial is a
randomized, double-blind, placebo-controlled investigation of
ATH434 in patients with early-stage MSA. The study will evaluate
the effect of ATH434 treatment on neuroimaging and protein
biomarkers to demonstrate target engagement and clinical endpoints
to demonstrate efficacy, in addition to assessments of safety and
pharmacokinetics. Selected biomarkers, such as brain iron and
aggregating α-synuclein, are important contributors to MSA
pathology and are therefore appropriate targets to demonstrate drug
activity. Wearable sensors have also been employed to evaluate
motor activities that are important to patients with MSA. The study
enrolled 77 adults who were randomly assigned to receive one of two
dose levels of ATH434 or placebo. Participants will receive
treatment for 12 months which will provide an opportunity to detect
changes in efficacy endpoints to optimize design of a definitive
Phase 3 study. Additional information on the Phase 2 trial can be
found by ClinicalTrials.gov Identifier: NCT05109091.
About bioMUSE
Biomarkers of progression in Multiple System
Atrophy (bioMUSE) is a natural history study that aims to track the
progression of individuals with MSA, a parkinsonian disorder
without approved therapy. The study is being conducted in
collaboration with Vanderbilt University Medical Center in the U.S.
under the direction of Daniel Claassen, M.D., M.S., Professor of
Neurology and Principal Investigator. Natural history studies are
important for characterizing disease progression in selected
patient populations. The study has provided rich data for
optimizing the design of Alterity’s randomized ATH434-201 Phase 2
clinical trial and enrolled approximately 20 individuals with
clinically probable or clinically established MSA. BioMUSE
continues to provide vital information on early stage MSA patients,
informs the selection of biomarkers suitable to evaluate target
engagement and preliminary efficacy, and delivers clinical data to
characterize disease progression in a patient population that
mirrors those currently enrolling in the Phase 2 clinical
trial.
About Multiple System
Atrophy
Multiple System Atrophy (MSA) is a rare,
neurodegenerative disease characterized by failure of the autonomic
nervous system and impaired movement. The symptoms reflect the
progressive loss of function and death of different types of nerve
cells in the brain and spinal cord. It is a rapidly progressive
disease and causes profound disability. MSA is a Parkinsonian
disorder characterized by a variable combination of slowed movement
and/or rigidity, autonomic instability that affects involuntary
functions such as blood pressure maintenance and bladder control,
and impaired balance and/or coordination that predisposes to falls.
A pathological hallmark of MSA is the accumulation of the protein
α-synuclein within glia, the support cells of the central nervous
system, and neuron loss in multiple brain regions. MSA affects at
least 15,000 individuals in the U.S., and while some of the
symptoms of MSA can be treated with medications, currently there
are no drugs that are able to slow disease progression and there is
no cure.1
1Multiple System Atrophy | National Institute of Neurological
Disorders and Stroke (nih.gov)
About Parkinson’s Disease
Parkinson’s disease (PD) is the second most
common neurodegenerative disorder and causes unintended or
uncontrollable movements of the body along with neuropsychiatric
and other nonmotor features. The precise cause of PD is
unknown, but some cases are hereditary while others are thought to
occur from a combination of genetics and environmental factors that
trigger the disease. In PD, brain cells become damaged or die
in the substantia nigra, the part of the brain that produces
dopamine--a chemical needed to produce smooth, purposeful movement.
The cardinal symptoms of PD are tremors, rigidity, slowing of
movements, and later in disease, impaired balance. Other symptoms
may include difficulty swallowing, chewing, or speaking; emotional
changes; urinary problems or constipation; dementia or other
cognitive problems; fatigue; and problems sleeping.1
Nearly one million people in the U.S. and more than 10 million
people worldwide are living with PD. Approximately 60,000 Americans
are diagnosed with PD each year.2
1National Institute of Health: Neurological
Disorders and Stroke, Parkinson’s Disease Information Page;
2Parkinson’s Foundation
About Alterity Therapeutics
Limited
Alterity Therapeutics is a clinical stage
biotechnology company dedicated to creating an alternate future for
people living with neurodegenerative diseases. The Company’s
lead asset, ATH434, has the potential to treat various Parkinsonian
disorders and is currently being evaluated in two Phase 2 clinical
trials in Multiple System Atrophy. Alterity also has a broad drug
discovery platform generating patentable chemical compounds to
treat the underlying pathology of neurological diseases. The
Company is based in Melbourne, Australia, and San Francisco,
California, USA. For further information please visit the Company’s
web site at www.alteritytherapeutics.com.
Authorisation & Additional informationThis
announcement was authorized by David Stamler, CEO of Alterity
Therapeutics Limited.
Investor and Media Contacts:
AustraliaHannah
Howlettwe-aualteritytherapeutics@we-worldwide.com+61 450 648
064
U.S.Remy Bernardaremy.bernarda@iradvisory.com
+1 (415) 203-6386
Forward Looking Statements
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statements" within the meaning of section 27A of the Securities Act
of 1933 and section 21E of the Securities Exchange Act of 1934. The
Company has tried to identify such forward-looking statements by
use of such words as "expects," "intends," "hopes," "anticipates,"
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Important factors that could cause actual
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including its most recent Annual Report on Form 20-F as well as
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including, but not limited to the initiation, progress and outcomes
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including, but not limited to, ATH434, and any other statements
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uncertainties relating to the difficulties or delays in financing,
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ATH434, the ability of the Company to procure additional future
sources of financing, unexpected adverse side effects or inadequate
therapeutic efficacy of the Company's drug compounds, including,
but not limited to, ATH434, that could slow or prevent products
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whether as a result of new information, future developments or
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