Alterity Therapeutics Presents ATH434-201 Phase 2 Clinical Trial Results at European MSA Symposium

Rhea-AI Summary

Alterity Therapeutics (NASDAQ: ATHE) presented Phase 2 clinical trial results for ATH434-201 at the MSA Research Symposium. The double-blind study, involving 71 patients, demonstrated significant efficacy in treating Multiple System Atrophy (MSA).

Key findings include:

• 48% relative treatment effect at 50mg dose (p=0.02) and 30% at 75mg dose (p=0.16) on UMSARS I scale
• Improvement in Clinical Global Impression of Severity Scale at both doses
• Enhanced patient mobility metrics including step count and walking time
• Positive results in reducing brain atrophy and stabilizing iron levels in affected brain regions

The treatment was well-tolerated with similar adverse event rates to placebo, with no serious adverse events attributed to ATH434. The strong clinical efficacy data and novel mechanism support continued advancement of ATH434 for MSA treatment.

Positive

• Significant 48% treatment effect at 50mg dose (p=0.02)
• Improved patient mobility metrics across multiple measures
• Successful target engagement shown in neuroimaging
• Strong safety profile with no serious adverse events
• Demonstrated reduction in brain atrophy

Negative

• Lower efficacy at 75mg dose (30% effect, p=0.16)
• Statistical significance not reached for some secondary endpoints

Insights

Biotechnology Analyst

ATH434 Phase 2 trial shows statistically significant 48% improvement in MSA symptoms with favorable safety profile, advancing a potential first disease-modifying treatment.

Alterity's Phase 2 results for ATH434 mark a significant milestone in the development of a treatment for Multiple System Atrophy (MSA), a rare neurodegenerative disorder with no approved disease-modifying therapies. The data demonstrates a 48% relative treatment effect at the 50mg dose with statistical significance (p=0.02), which represents meaningful clinical benefit in this aggressive neurological condition.

The robustness of these findings is strengthened by improvements across multiple secondary endpoints. The Clinical Global Impression of Severity Scale showed improvement at both dose levels, with the 50mg dose achieving statistical significance (p=0.0088). The Orthostatic Hypotension Symptom Assessment revealed that placebo patients worsened by approximately 6% over 52 weeks while both ATH434 treatment groups showed improvement.

Particularly compelling is the objective evidence from wearable sensors showing increased activity in ATH434-treated patients, with improvements in step count, walking time, and standing time. The drug's mechanism of action is validated by neuroimaging data confirming target engagement through iron stabilization or reduction in MSA-affected brain regions.

The favorable safety profile, with similar adverse event rates to placebo and no serious adverse events attributed to ATH434, is critical for a chronic progressive disorder requiring long-term treatment. While the lower dose demonstrated superior efficacy to the higher dose (50mg: 48% vs 75mg: 30%), such non-linear dose responses aren't uncommon in CNS drug development.

These comprehensive positive results across clinical, patient-reported, and biological measures provide strong justification for advancing ATH434 toward late-stage clinical development for this devastating disorder with high unmet medical need.

Neurologist

ATH434 shows significant 48% functional improvement in MSA patients with supporting neuroimaging evidence, representing a breakthrough for this devastating disease.

The ATH434 Phase 2 trial results represent one of the most promising advances in MSA treatment development to date. The statistically significant 48% relative treatment effect on the UMSARS I activities of daily living scale at the 50mg dose (p=0.02) directly translates to preserved functional independence for patients. This magnitude of effect is clinically meaningful in MSA, a rapidly progressive disorder where patients typically become severely disabled within 3-5 years of diagnosis.

The multi-modal evidence supporting efficacy is particularly compelling. The concordance between clinician-rated measures (UMSARS I, CGI-S), patient-reported outcomes (orthostatic hypotension symptoms), and objective digital biomarkers (wearable sensor mobility data) strengthens confidence in the therapeutic benefit. While the 75mg dose showed a 30% treatment effect that didn't reach statistical significance (p=0.16), it still demonstrates a trend toward benefit.

The improvement in orthostatic hypotension symptoms deserves special attention, as autonomic dysfunction severely impacts quality of life in MSA patients. While placebo patients worsened by approximately 6 points over 52 weeks, both ATH434 treatment groups showed improvement.

From a mechanistic perspective, the neuroimaging data confirming target engagement through iron stabilization or reduction in affected brain regions provides biological validation of the therapeutic approach. The trends toward reduced brain atrophy further suggest potential neuroprotection.

The favorable safety profile, with adverse event rates similar to placebo and no serious adverse events attributed to ATH434, is essential for this vulnerable patient population. These comprehensive positive results across multiple domains provide strong justification for continued development of this promising approach for a disorder with significant unmet medical need.

MELBOURNE, Australia and SAN FRANCISCO, April 28, 2025 (GLOBE NEWSWIRE) -- 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 David Stamler, M.D., Chief Executive Officer presented the ATH434-201 Phase 2 clinical trial results at the annual MSA Research Symposium hosted by University College London, Institute of Neurology in partnership with the MSA Trust of the U.K.

“We were honoured to be selected to present the recent data from our double-blind Phase 2 trial,” said, Dr. Stamler. “The Symposium brought together prominent clinicians and researchers from both Europe and the US along with industry scientists, all of whom are focused on increasing their understanding of MSA and advancing new therapies for this aggressive disorder. The strong clinical efficacy data and novel mechanism of ATH434 was well received by this esteemed group of clinicians and academics, as we collectively seek solutions to improve the lives of individuals living with MSA.”

Presentation: A Randomized, Double Blind, Placebo Controlled Study of ATH434 in MSA
The oral presentation included data from Alterity’s ATH434-201 Phase 2 clinical trial. The clinical analysis included 71 patients who had at least one post-baseline assessment of the key clinical endpoint, the modified UMSARS¹ I activities of daily living scale. On this endpoint, ATH434 demonstrated a clinically significant reduction in disease severity versus placebo, with a 48% relative treatment effect at the 50 mg dose (p=0.02)^{^} and a 30% relative treatment effect at the 75 mg dose (p=0.16) at 52 weeks. Additional efficacy assessments showed improvement consistent with the UMSARS I findings: the Clinical Global Impression of Severity Scale² demonstrated improvement compared to placebo at both dose levels, with difference at 50 mg achieving nominal statistical significance (p=0.0088). On the Orthostatic Hypotension Symptom Assessment (a patient reported outcome), on average placebo patients worsened by approximately 6 points over 52 weeks whereas both ATH434 treatment groups improved over the same period (p=0.08 at 50 mg, p=0.14 at 75 mg). Increased activity in the outpatient setting was observed at both dose levels as compared to placebo with wearable sensors, with clinically meaningful improvements in step count, bouts of walking, total walking time, and total standing time. ATH434 was well tolerated with similar adverse event rates compared to placebo and no serious adverse events attributed to ATH434. Regarding neuroimaging, ATH434 demonstrated target engagement by stabilizing or reducing iron at both dose levels compared to placebo in MSA affected brain regions. In addition, ATH434 demonstrated trends in reducing brain atrophy at both dose levels compared to placebo. Overall, the study results support continued advancement of ATH434 for the treatment of MSA.

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 recently announced positive results from the randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA. A second Phase 2 open-label 2 Biomarker trial in patients with more advanced MSA is ongoing. 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 12 months treatment with ATH434 in patients with MSA. The study evaluated the efficacy, safety and pharmacokinetics of ATH434 as well as the effect of ATH434 on neuroimaging and protein biomarkers. Wearable sensors were employed to evaluate motor activities outside of the clinic. The study enrolled 77 adults who were randomly assigned to receive ATH434 50 mg or 75 mg twice daily or matching placebo. The topline data showed that ATH434 produced clinically and statistically significant improvement on the modified UMSARS Part I, a functional rating scale that assesses disability on activities of daily living affected in MSA. In addition to the robust efficacy demonstrated on the UMSARS Part I, trends in improved motor performance were observed on the Parkinson’s Plus rating scale and overall benefit was shown on the Clinical Global Impression of Severity at the 50 mg dose. Wearable sensor data indicated that both dose levels of ATH434 led to increased activity in an outpatient setting as compared to placebo. Biomarkers were used to evaluate potential drug effect and target engagement. Both dose levels reduced iron accumulation in MSA affected brain regions and trends in preservation of brain volume were observed relative to placebo. Additional information on the Phase 2 trial can be found by ClinicalTrials.gov Identifier: NCT05109091.

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.³

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 initially focused on developing disease modifying therapies in Parkinson’s disease and related disorders. Alterity recently reported positive data for its lead asset, ATH434, in a Phase 2 clinical trial in participants with Multiple System Atrophy (MSA), a rare and rapidly progressive Parkinsonian disorder. ATH434 is also being evaluated in a Phase 2 clinical trial in 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 www.alteritytherapeutics.com.

References:
¹ UMSARS: Unified Multiple System Atrophy Rating Scale
^ All p-values are uncorrected
² Clinical Global Impression of Severity: a clinician assessment of the total picture of the subject including the impact of the illness on function and level of distress
³ 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.

Investor and Media Contacts:

Australia
Millie Macdonald
Head of Investor Relations and Business Development
mmacdonald@alteritytherapeutics.com
+61 468 304 742

Ana Luiza Harrop
we-aualteritytherapeutics@we-worldwide.com
+61 452 510 255

U.S.
Remy Bernarda
remy.bernarda@iradvisory.com
+1 (415) 203-6386

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.

FAQ

What were the key results of Alterity's ATH434-201 Phase 2 trial for MSA treatment?

The trial showed a 48% relative treatment effect at 50mg dose and 30% at 75mg dose, with improvements in daily living activities, severity scale, and patient mobility metrics.

How did ATHE's ATH434 perform in terms of safety during the Phase 2 trial?

ATH434 was well-tolerated with adverse event rates similar to placebo and no serious adverse events attributed to the treatment.

What neuroimaging results were observed in ATHE's ATH434 Phase 2 trial?

ATH434 demonstrated target engagement by stabilizing or reducing iron levels in MSA-affected brain regions and showed trends in reducing brain atrophy at both dose levels compared to placebo.

How many patients were included in Alterity's ATH434-201 Phase 2 MSA trial?

The clinical analysis included 71 patients who had at least one post-baseline assessment of the key clinical endpoint.

What improvements in mobility were observed in ATHE's ATH434 trial?

Patients showed clinically meaningful improvements in step count, bouts of walking, total walking time, and total standing time compared to placebo.