Alterity Presents New Analysis of ATH434 Phase 2 Data at AAN
Released
Released
Announcement PDF
Alterity Therapeutics Presents New Analysis of ATH434 Phase 2 Trial Data in
Late Breaking Science Session of the American Academy of Neurology
- ATH434 reduced functional decline vs placebo at Week 52 on MuSyCA, a newly described MSA
composite scale -
- Effects seen on both daily function and neurological examination, consistent with previously
reported activity on modified UMSARS Part I -
- Presentation reinforces ATH434's clinical profile ahead of Phase 3 engagement with regulators -
MELBOURNE, AUSTRALIA AND SAN FRANCISCO, USA – 22 April 2026: Alterity Therapeutics (ASX:
ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to
developing disease modifying treatments for neurodegenerative diseases, today announced the
presentation of new data analyses from the Phase 2 trial of ATH434, demonstrating clinical efficacy
in patients with Multiple System Atrophy (MSA). The analysis was delivered in an oral presentation
during a Late Breaking Science Session at the American Academy of Neurology (AAN) Annual
Meeting taking place in Chicago, IL, USA.
The presentation, entitled, “ATH434 Demonstrates Disease-Modifying Signal in Multiple System
Atrophy Using the MuSyCA Composite Scale,” described an analysis from the ATH434-201 Phase 2
clinical trial in MSA utilizing the MSA Combined Outcome Assessment (MuSyCA). The MuSyCA is a
newly developed scale that includes 11 items from both the UMSARS1 I (activities of daily
living/functional assessment) and UMSARS II (motor exam) with highest standardized effect sizes
across four MSA cohorts and is intended to improve detection of disease progression in clinical
trials.2
Assessment of the ATH434-201 trial showed meaningful results utilizing MuSyCA. MuSyCA
demonstrated robust sensitivity to disease progression with placebo participants worsening by
approximately +9.7 points over 52 weeks, confirming the scale is sensitive to change over the study
period. Consistent with prior data, ATH434 slowed disease progression on the MuSyCA assessment
with a treatment effect of −1.9 (75 mg dose) to −4.0 points (50 mg dose, p=0.034, relative treatment
effect 41%) at Week 52. In contrast, when utilizing a MMRM3 statistical analysis, ATH434 slowed
disease progression on the modified UMSARS I versus placebo by -3.1 points at 75 mg (relative
treatment effect of 35%) and -4.7 points at 50 mg (relative treatment effect of 53%, p=0.029).
David Stamler, M.D., Chief Executive Officer of Alterity, commented, “In this rapidly progressive
disease, ATH434 shows consistent evidence of efficacy by slowing functional decline on the newly
described MuSyCA scale, which reinforces the efficacy observed on the established UMSARS Part I
scale. In aggregate, these data reinforce the potential of ATH434 as a disease-modifying therapy for
MSA."
MuSyCA represents a new framework for MSA outcome assessment by integrating patient-reported
function with clinical assessment, with a pathway to incorporate neurofilament light chain (NfL),
imaging, and objective performance tests as a comprehensive platform for detecting clinically
meaningful changes over time. It is being developed by the NIH-funded “Clinical Trial Readiness for
MSA Study Group” in a collaborative effort with four academic centers in the US and Europe, patient
advocacy groups, and pharmaceutical companies.
The presentation and poster are available on the Alterity Therapeutics website here.
About ATH434
Alterity’s lead candidate, ATH434, is an oral agent designed to reduce iron accumulation and inhibit
abnormal protein aggregation associated with neurodegeneration. ATH434 has been shown to
reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in
the brain in preclinical models. 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). Positive
results from the randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with
MSA demonstrated robust clinical efficacy, target engagement as indicated by key biomarkers, and
a favorable safety profile. Positive data from a second Phase 2 open-label biomarker trial in patients
with more advanced MSA reinforced these results. ATH434 has been granted Fast Track Designation
by the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation by the FDA and the
European Commission for the treatment of MSA.
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 up to 50,000 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.4
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 is focused on developing
disease modifying therapies in Multiple System Atrophy (MSA) and related Parkinsonian disorders.
Alterity is preparing to initiate a Phase 3 pivotal trial in MSA, a rare and rapidly progressive disease.
ATH434, the Company’s lead asset, has demonstrated clinically meaningful efficacy in a randomized,
double-blind, placebo-controlled Phase 2 clinical trial in participants with MSA. Alterity has further
reported positive data in its open label Phase 2 clinical trial in participants with advanced MSA. In
addition, Alterity 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
website at https://alteritytx.com.
References:
1 UMSARS: Unified Multiple System Atrophy Rating Scale, Parts I & II
2 For the MuSyCa MSA Combined Outcome assessment: UMSARS I items were swallowing, handwriting, utensils,
dressing, hygiene, walking; UMSARS I items were speech, leg agility, arising from chair,
body sway, gait
3
Mixed Models for Repeated Measures (MMRM) with fixed effects for treatment group (3 levels), visit (4 levels),
treatment visit interaction, and sex. Covariates: age, baseline CSF NfL, baseline orthostatic hypotension, baseline
outcome score. Unstructured covariance; missing data not imputed (mITT).
4
Multiple System Atrophy | National Institute of Neurological Disorders and Stroke (nih.gov)
Authorisation & Additional information
This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited.
Contacts:
Investors:
Elyse Shapiro
ir@alteritytx.com
Remy Bernarda
Investor Relations Advisory Solutions
ir@alteritytx.com
+1 (415) 203-6386
Media
Casey McDonald
Tiberend Strategic Advisors, Inc.
cmcdonald@tiberend.com
+1 (646) 577-8520
Forward Looking Statements
This press release contains "forward-looking 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," "believes," "could," "may," "evidences" and "estimates," and other similar
expressions, but these words are not the exclusive means of identifying such statements.
Important factors that could cause actual results to differ materially from those indicated by such
forward-looking statements are described in the sections titled “Risk Factors” in the Company’s
filings with the SEC, including its most recent Annual Report on Form 20-F as well as reports on
Form 6-K, including, but not limited to the following: statements relating to the Company's drug
development program, including, but not limited to the initiation, progress and outcomes of
clinical trials of the Company's drug development program, including, but not limited to, ATH434,
and any other statements that are not historical facts. Such statements involve risks and
uncertainties, including, but not limited to, those risks and uncertainties relating to the difficulties
or delays in financing, development, testing, regulatory approval, production and marketing of the
Company’s drug components, including, but not limited to, 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 coming to market, the uncertainty of obtaining patent protection
for the Company's intellectual property or trade secrets, the uncertainty of successfully enforcing
the Company’s patent rights and the uncertainty of the Company freedom to operate.
Any forward-looking statement made by us in this press release is based only on information
currently available to us and speaks only as of the date on which it is made. We undertake no
obligation to publicly update any forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information, future developments or
otherwise.
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