Full Press Release Details
Therapeutics Parkinson's Disease and Multiple System Atrophy Data
Featured at the American Academy of Neurology (AAN) 2024 Annual
ATH434 Improved Motor Performance and General Function in a Primate Model of Parkinson's Disease -
ATH434-201 Phase 2 Baseline Data Confirm Approach to Target Biomarkers for Slowing Disease Progression -
12-Month Data from bioMUSE Study Shows Key Biomarker is Associated with Disease Progression in MSA -
AUSTRALIA AND SAN FRANCISCO, USA - 17 April 2024: 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.
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."
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 -synuclein aggregation, and improve
Daniel Classen, 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."
A Phase 2 Study of ATH434, a Novel Inhibitor of -Synuclein Aggregation, for the Treatment of Multiple System Atrophy
Author: David Stamler, M.D., Chief Executive Officer of Alterity Therapeutics
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 -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.
Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy
Lead Author: Daniel O.Claassen, M.D.,
M.S., Professor of Neurology, Vanderbilt University Medical Center
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.
Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in Hemiparkinsonian Macaques
Author: Margaret Bradbury, Vice President, Research and Nonclinical Development, Alterity Therapeutics
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.
poster presentations can be found on Alterity's website here.
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 -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.
ATH434-201 Phase 2 Clinical Trial
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 -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.
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.
Multiple System Atrophy
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 -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
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;