Alterity Therapeutics Prominently Featured at the International MSA Congress
Alterity Therapeutics (NASDAQ: ATHE) presented significant findings at the 2025 International MSA Congress regarding their ATH434 Phase 2 clinical trial and related MSA research. The ATH434-201 trial demonstrated promising results, with the 50mg dose showing a 48% relative treatment effect (p=0.02) and the 75mg dose showing a 30% effect (p=0.16) in reducing disease severity on the UMSARS I scale. The drug was well-tolerated with no serious adverse events.
Key research presentations included the development of the MSA Atrophy Index (MSAai), a new imaging biomarker for improved MSA diagnosis and monitoring, and findings from the bioMUSE Natural History Study showing increased α-synuclein levels in skin correlating with greater orthostatic symptoms. The study also demonstrated ATH434's ability to stabilize or reduce iron accumulation in affected brain regions and showed trends in reducing brain atrophy at both dose levels.
Alterity Therapeutics (NASDAQ: ATHE) ha presentato risultati significativi al Congresso Internazionale MSA 2025 riguardanti la loro sperimentazione clinica di Fase 2 ATH434 e la ricerca correlata sulla MSA. Lo studio ATH434-201 ha mostrato risultati promettenti, con la dose da 50 mg che ha evidenziato un effetto terapeutico relativo del 48% (p=0,02) e la dose da 75 mg un effetto del 30% (p=0,16) nella riduzione della gravità della malattia sulla scala UMSARS I. Il farmaco è stato ben tollerato senza eventi avversi gravi.
Le presentazioni chiave della ricerca hanno incluso lo sviluppo dell'Indice di Atrofia MSA (MSAai), un nuovo biomarcatore di imaging per una diagnosi e un monitoraggio migliorati della MSA, e i risultati dello studio bioMUSE sulla storia naturale che mostrano livelli aumentati di α-sinucleina nella pelle, correlati a sintomi ortostatici più gravi. Lo studio ha inoltre dimostrato la capacità di ATH434 di stabilizzare o ridurre l'accumulo di ferro nelle aree cerebrali colpite e ha evidenziato tendenze nella riduzione dell'atrofia cerebrale a entrambe le dosi.
Alterity Therapeutics (NASDAQ: ATHE) presentó hallazgos significativos en el Congreso Internacional MSA 2025 sobre su ensayo clínico de fase 2 ATH434 y la investigación relacionada con la MSA. El ensayo ATH434-201 mostró resultados prometedores, con la dosis de 50 mg mostrando un efecto terapéutico relativo del 48% (p=0,02) y la dosis de 75 mg un efecto del 30% (p=0,16) en la reducción de la gravedad de la enfermedad según la escala UMSARS I. El medicamento fue bien tolerado sin eventos adversos graves.
Las presentaciones clave incluyeron el desarrollo del Índice de Atrofia MSA (MSAai), un nuevo biomarcador de imagen para mejorar el diagnóstico y monitoreo de la MSA, y hallazgos del estudio bioMUSE sobre historia natural que muestran niveles aumentados de α-sinucleína en la piel, correlacionados con síntomas ortostáticos más severos. El estudio también demostró la capacidad de ATH434 para estabilizar o reducir la acumulación de hierro en regiones cerebrales afectadas y mostró tendencias en la reducción de la atrofia cerebral en ambas dosis.
Alterity Therapeutics(NASDAQ: ATHE)는 2025 국제 MSA 학회에서 ATH434 2상 임상시험과 관련 MSA 연구에 관한 중요한 결과를 발표했습니다. ATH434-201 시험은 유망한 결과를 보였습니다. 50mg 용량은 UMSARS I 척도에서 질병 중증도 감소에 대해 48%의 상대적 치료 효과(p=0.02)를 나타냈고, 75mg 용량은 30%(p=0.16)의 효과를 보였습니다. 약물은 심각한 부작용 없이 잘 견뎌졌습니다.
주요 연구 발표에는 MSA 진단 및 모니터링 개선을 위한 새로운 영상 바이오마커인 MSA 위축 지수(MSAai) 개발과, bioMUSE 자연사 연구에서 피부 내 α-시누클레인 수치가 증가하며 기립성 증상 악화와 연관됨을 보여준 결과가 포함되었습니다. 연구는 또한 ATH434가 영향을 받은 뇌 영역의 철 축적을 안정시키거나 감소시키는 능력을 입증했으며, 두 용량 모두에서 뇌 위축 감소 경향을 보였습니다.
Alterity Therapeutics (NASDAQ : ATHE) a présenté des résultats significatifs lors du Congrès international MSA 2025 concernant leur essai clinique de phase 2 ATH434 et les recherches associées sur la MSA. L'essai ATH434-201 a montré des résultats prometteurs, avec une dose de 50 mg affichant un effet thérapeutique relatif de 48 % (p=0,02) et une dose de 75 mg un effet de 30 % (p=0,16) dans la réduction de la gravité de la maladie selon l'échelle UMSARS I. Le médicament a été bien toléré sans événements indésirables graves.
Les présentations clés comprenaient le développement de l'Indice d'Atrophie MSA (MSAai), un nouveau biomarqueur d'imagerie pour améliorer le diagnostic et le suivi de la MSA, ainsi que les résultats de l'étude bioMUSE sur l'histoire naturelle montrant une augmentation des niveaux d’α-synucléine dans la peau, corrélée à des symptômes orthostatiques plus marqués. L'étude a également démontré la capacité d’ATH434 à stabiliser ou réduire l’accumulation de fer dans les régions cérébrales affectées et a montré des tendances à réduire l’atrophie cérébrale à ces deux doses.
Alterity Therapeutics (NASDAQ: ATHE) präsentierte beim Internationalen MSA-Kongress 2025 bedeutende Ergebnisse zu ihrer Phase-2-Studie ATH434 und verwandten MSA-Forschungen. Die ATH434-201-Studie zeigte vielversprechende Resultate, wobei die 50 mg-Dosis eine relative Behandlungseffektstärke von 48 % (p=0,02) und die 75 mg-Dosis eine von 30 % (p=0,16) bei der Verringerung der Krankheitsintensität auf der UMSARS-I-Skala zeigte. Das Medikament wurde gut vertragen, ohne schwerwiegende Nebenwirkungen.
Wichtige Forschungsbeiträge umfassten die Entwicklung des MSA-Atrophie-Index (MSAai), eines neuen bildgebenden Biomarkers zur verbesserten Diagnose und Überwachung von MSA, sowie Ergebnisse der bioMUSE-Studie zur natürlichen Krankheitsgeschichte, die erhöhte α-Synuclein-Spiegel in der Haut zeigten, welche mit stärkeren orthostatischen Symptomen korrelieren. Die Studie zeigte außerdem, dass ATH434 die Eisenansammlung in betroffenen Hirnregionen stabilisieren oder reduzieren kann und Trends zur Verringerung der Gehirnatrophie bei beiden Dosierungen aufwies.
- ATH434 showed 48% reduction in disease severity at 50mg dose (p=0.02)
- Drug demonstrated improvement in Clinical Global Impression of Severity Scale
- ATH434 showed increased patient activity levels in outpatient setting
- Drug was well-tolerated with no serious adverse events
- ATH434 demonstrated target engagement by reducing iron accumulation in affected brain regions
- 75mg dose showed lower efficacy (30% effect) than 50mg dose
- Baseline differences in disease severity affected response rates between dose groups
Insights
ATH434 shows promising Phase 2 results with 48% disease reduction at 50mg dose and good safety profile in MSA patients.
The Phase 2 data for ATH434 in Multiple System Atrophy represents a significant clinical breakthrough in a disease with no approved disease-modifying therapies. The 48% relative treatment effect at 50mg (p=0.02) on the UMSARS I activities of daily living scale is clinically meaningful and substantially exceeds the typical threshold of 20-30% improvement generally considered significant in neurodegenerative conditions.
What's particularly compelling is the consistency across multiple endpoints. The improvements in the Clinical Global Impression of Severity Scale (p=0.0088 at 50mg) and the Orthostatic Hypotension Symptom Assessment support the primary findings. Even more impressive is the objective evidence from wearable sensors showing increased physical activity in real-world settings – a crucial functional outcome that matters to patients.
The favorable safety profile is noteworthy, as many CNS drugs fail in late-stage development due to tolerability issues. The neuroimaging data confirming target engagement through reduction of iron accumulation in MSA-affected brain regions validates the mechanism of action and provides a plausible explanation for the clinical benefits.
The differential response between the 50mg and 75mg doses (48% vs 30% improvement) likely reflects baseline differences in disease severity rather than a dose-response relationship. This phenomenon is common in heterogeneous neurodegenerative populations and underscores the importance of patient stratification in future trials.
These results position ATH434 as a potential first-in-class treatment for MSA, addressing a significant unmet need in this rapidly progressive, fatal condition. The data quality and consistency across multiple endpoints strengthen the case for advancement to pivotal trials.
The biomarker advancements reported here represent critical complementary assets to Alterity's therapeutic development program. The MSA Atrophy Index (MSAai) addresses a fundamental challenge in MSA research: accurate diagnosis and objective progression monitoring.
The MSAai's ability to distinguish MSA from similar disorders with high discriminatory power (p<0.001) compared to healthy controls and related conditions (PD, DLB, PAF) represents a diagnostic breakthrough. More importantly, its correlation with clinical measures (UMSARS scores, ρ=-0.46, p=0.038) and predictive value for clinical progression (ρ=0.58, p=0.022) establishes its validity as a progression biomarker.
The cutaneous phosphorylated α-synuclein findings further strengthen Alterity's biomarker portfolio. The 100% detection rate in MSA patients provides exceptional sensitivity, while the significant increase in deposition over 12 months (p=0.042) offers a potential longitudinal biomarker. The correlation with autonomic symptoms (OHQ: coefficient=0.579, p=0.015; COMPASS-31: coefficient=0.560, p=0.024) links the biomarker directly to clinical manifestations.
These biomarkers offer three strategic advantages for Alterity: 1) improved patient selection for future trials, enhancing statistical power; 2) objective progression measures that could serve as surrogate endpoints; and 3) companion diagnostic potential to identify patients most likely to benefit from ATH434.
The synergy between Alterity's therapeutic agent and diagnostic biomarkers creates a comprehensive approach to MSA management, positioning the company advantageously in this orphan disease space. These tools could significantly accelerate clinical development timelines and enhance the value proposition of ATH434.
– ATH434 Phase 2 data demonstrated clinically meaningful efficacy on multiple clinical endpoints –
– MSA Atrophy Index (MSAai) enhances MSA diagnosis and monitoring –
– bioMUSE Study shows higher α- synuclein concentration is associated with greater burden of orthostatic symptoms –
MELBOURNE, Australia and SAN FRANCISCO, May 12, 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 several oral and poster presentations related to Alterity’s clinical programs in Multiple System Atrophy (MSA) were featured at the 2025 International MSA Congress. The Congress was presented by Mission MSA, a non-profit organization dedicated to improving the quality of life and building hope for people affected by MSA through support services, educational resources, research funding, and community engagement.
“The MSA Congress gave us an opportunity to share the results of our Phase 2 double-blind trial of ATH434 with prominent MSA clinicians and scientists as well as community members affected by MSA,” said David Stamler, M.D., Chief Executive Officer of Alterity. “The robust efficacy of ATH434, as indicated by reduced disease severity on the MSA activities of daily living scale along with improvement in key symptoms of MSA and preserved activity in the outpatient setting, continue to generate enthusiasm. Our clinical progress is generating significant excitement, and we are focused on bringing this therapy to patients as quickly as possible.”
“In addition, our colleagues at Vanderbilt University Medical Center presented data from our bioMUSE Natural History Study that highlights the understanding of MSA we have brought to our development program. Because of the variability in MSA presentation and progression and its similarity to Parkinson’s disease, it is critical to improve diagnostic and monitoring tools. Through development of a novel imaging biomarker known as the MSA Atrophy Index (MSAai), we have a new tool to measure and track brain volume in individuals with MSA. In a separate presentation, the bioMUSE study demonstrated that α-synuclein levels in the skin increased over the 12-month follow-up period, and that a higher concentration of α-synuclein in skin is associated with greater burden of orthostatic symptoms, a valuable finding that confers insight into disease progression.”
Presentation Highlights:
ATH434 Slowed Disease Progression in a Phase 2 Study in Multiple System Atrophy
Presenter: David Stamler, M.D., Chief Executive Officer of Alterity
The oral and poster presentation highlighted 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
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 in 61 participants, ATH434 demonstrated target engagement by stabilizing or reducing iron accumulation 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.
MSA Atrophy Index (MSAai): A Quantitative Imaging Marker for Diagnosis and Monitoring of Multiple System Atrophy
Presenter: Amy Brown, M.D., M.S., Assistant Professor, Movement Disorders Division, Department of Neurology, Vanderbilt University Medical Center
This oral presentation described the MSA Atrophy Index (MSAai) as a promising imaging biomarker that distinguishes MSA from related disorders, correlates with clinical presentation, and tracks disease progression. Its implementation has the potential to enhance MSA diagnosis and monitoring in both clinical trials and clinical practice. The MSAai imaging tool was developed by the team at Vanderbilt University Medical Center as part of the bioMUSE Natural History Study. The study evaluated the utility of volumetric measures and the MSAai in distinguishing early MSA from other movement-related disorders, correlating with clinical presentation, and tracking longitudinal changes in brain structure. The study results showed that fluid biomarkers classified bioMUSE participants into MSA (n=10), Lewy body disorders (n=5; PD or DLB), and α-synuclein-negative (n=2) groups. At baseline, MSA patients had significantly lower LN, brainstem, cerebellum, and MSAai values compared to HC, PD, DLB, and PAF (all p<0.001). The MSAai demonstrated strong group discrimination, correlated with UMSARS scores (ρ=-0.46, p=0.038), and predicted clinical progression (ρ=0.58, p=0.022). Longitudinally, reductions in LN, brainstem, and MSAai volumes were strongly associated with UMSARS progression.
Cutaneous Phosphorylated Alpha-Synuclein Deposition Informs Autonomic Function in Individuals with Early-Stage Multiple System Atrophy
Presenter: Leah Mann, PhD, Postdoctoral Research Fellow, Vanderbilt University Medical Center
This poster presentation evaluated 17 participants from the bioMUSE Natural History Study who met criteria for clinically probable MSA. The study compared α-synuclein deposition in skin at baseline and 12 months later and examined associations between clinical measures and α-synuclein quantitation over the year. The analysis described the relationship between α-synuclein and autonomic function and revealed that cutaneous α-synuclein detection may serve as an effective diagnostic biomarker that can additionally track progression of MSA. Importantly, deposition of α-synuclein may confer insight into symptomatology, as higher α- synuclein concentration is associated with greater burden of orthostatic symptoms. In the analysis,
Presentations will be available on the Alterity Therapeutics 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 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). Phase 1 studies have demonstrated the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. Positive results from the randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with MSA demonstrated robust clinical efficacy, target engagement on key biomarkers, and a favorable safety profile. A second Phase 2 open-label biomarker trial in patients with more advanced MSA is ongoing. ATH434 has been granted Fast Track Designation by the U.S. FDA, and Orphan Drug Designation by the U.S. FDA and the European Commission for the treatment of MSA.
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 data showed that, compared to placebo, ATH434 produced clinically and statistically significant improvement on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, a functional rating scale that assesses disability on activities of daily living affected in MSA. Additional efficacy assessments demonstrated improvement consistent with the positive UMSARS Part I findings including trends in improved motor performance on the Parkinson’s Plus rating scale, the Clinical Global Impression of Severity Scale, and the Orthostatic Hypotension Symptom Assessment (a patient reported outcome). Wearable sensor data indicated that ATH434 also led to increased activity in an outpatient setting. Biomarkers were used to evaluate potential drug effect and target engagement relative to placebo. Both dose levels reduced iron accumulation in MSA affected brain regions with trends in preservation of brain volume. ATH434 was well tolerated with similar adverse event rates compared to placebo and no serious adverse events attributed to ATH434. 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 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.
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 (ATHE) ATH434 Phase 2 trial for MSA?
How effective was ATHE's ATH434 in treating Multiple System Atrophy symptoms?
What is the MSA Atrophy Index (MSAai) developed through Alterity's research?
What did the bioMUSE study reveal about α-synuclein levels in MSA patients?
