– Data demonstrate ATH434 slows disease progression and stabilizes orthostatic hypotension – – New analysis increases overall confidence in the Phase 2 trial results – – State-of-the-art neuroimaging and biomarker analysis advance understanding of MSA diagnosis – MELBOURNE, Australia and SAN FRANCISCO, Oct. 09, 2025 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerati ...

– Data demonstrate ATH434 slows disease progression and stabilizes orthostatic hypotension – – New analysis increases overall confidence in the Phase 2 trial results – – State-of-the-art neuroimaging and biomarker analysis advance understanding of MSA diagnosis – MELBOURNE, Australia and SAN FRANCISCO, Oct. 09, 2025 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerati ...

Core Insights - Alterity Therapeutics is set to present data from its ATH434-201 Phase 2 clinical trial for Multiple System Atrophy (MSA) at the 2025 International Congress of Parkinson's Disease and Movement Disorders [1][2] Company Overview - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly MSA and Parkinson's disease [4][8] - The company has demonstrated clinically meaningful efficacy for its lead asset, ATH434, in a randomized, double-blind, placebo-controlled Phase 2 clinical trial [8] ATH434 Details - ATH434 is an oral agent designed to inhibit the aggregation of pathological proteins involved in neurodegeneration, specifically targeting α-synuclein pathology [4] - Preclinical studies have shown that ATH434 can reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain [4] - The drug has received Fast Track Designation and Orphan Drug Designation from the FDA for the treatment of MSA [4] ATH434-201 Phase 2 Clinical Trial - The ATH434-201 trial was a randomized, double-blind, placebo-controlled study involving 77 adults, assessing the efficacy, safety, and pharmacokinetics of ATH434 over 12 months [5][6] - Results indicated that ATH434 led to clinically and statistically significant improvements on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I compared to placebo [6] - Wearable sensors were used to evaluate motor activities, showing increased activity in outpatient settings for those receiving ATH434 [6] Presentation Details - The data will be presented in an oral session titled "ATH434 Slowed Disease Progression in a Phase 2 Study in Multiple System Atrophy" by CEO David Stamler on October 8, 2025 [3] - Additional poster presentations will cover topics such as the relationship between α-synuclein aggregation profiles and disease severity, and differences between clinical and imaging phenotypes in MSA [3]

– Data from ATH434-201 double-blind Phase 2 trial to be featured in oral session and multiple poster presentations – MELBOURNE, Australia and SAN FRANCISCO, Oct. 02, 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 data from the ATH434-201 randomized, double-blind Phase 2 clinical trial in Multiple System Atrophy (MSA) will b ...

Core Insights - Alterity Therapeutics announced positive results from the ATH434-201 Phase 2 clinical trial for Multiple System Atrophy (MSA), demonstrating clinically meaningful efficacy in modifying disease progression at both 50 mg and 75 mg doses [1][2][3] Company Overview - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly MSA and Parkinson's disease [4][8] - The lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration, showing preclinical efficacy in reducing α-synuclein pathology and restoring normal iron balance in the brain [4][8] Clinical Trial Details - The ATH434-201 Phase 2 clinical trial was a randomized, double-blind, placebo-controlled study involving 77 adults, assessing the efficacy, safety, and pharmacokinetics of ATH434 over 12 months [5][6] - Results indicated that ATH434 produced clinically and statistically significant improvements on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, with additional positive trends in motor performance and patient-reported outcomes [5][6] Efficacy and Safety - ATH434 demonstrated target engagement by reducing iron accumulation in MSA-affected brain regions, with both dose levels showing a favorable safety profile comparable to placebo [2][5] - The study reported no serious adverse events attributed to ATH434, reinforcing its tolerability [2][6] Regulatory Status - ATH434 has received Fast Track Designation and Orphan Drug Designation from the U.S. FDA and the European Commission for the treatment of MSA, highlighting its potential as a significant therapeutic option in a market with currently no approved disease-modifying treatments [4][8]

Summary of Alterity Therapeutics Conference Call Company Overview - **Company**: Alterity Therapeutics (ATHE) - **Focus**: Development of therapies for neurodegenerative disorders, specifically targeting multiple system atrophy (MSA) and other Parkinsonian disorders [10][11] Industry Context - **Biotech Sector**: The conference is part of the Pink Asset Management Monsoon Communications Biotech Showcase 2025, highlighting the growing interest in biotech investments [1][2] - **Market Potential**: There are approximately 175 listed life sciences companies on the ASX, making it the third largest biotech exchange globally [2] Core Points and Arguments - **Therapeutic Development**: Alterity's lead asset, ATH434, is a first-in-class oral therapy for MSA, which has received FDA fast-track designation and EU orphan designation [10][17] - **Clinical Trials**: Positive phase two data was disclosed, showing significant efficacy in slowing disease progression in MSA patients [11][27] - **Mechanism of Action**: ATH434 targets the misfolding of alpha-synuclein and imbalanced iron in the central nervous system, which are critical in the pathology of neurodegenerative diseases [15][16] - **Patient Population**: MSA affects up to 50,000 patients in the U.S., with a median survival of seven to eight years post-symptom onset [17][18] Clinical Trial Results - **201 Study**: A randomized double-blind placebo-controlled study with 75 patients showed that the 50 mg dose declined by 48% less than placebo, while the 75 mg dose declined by 30% less than placebo [23][24] - **Orthostatic Hypotension**: A significant symptom in MSA, the placebo group deteriorated by six points, while both active treatment groups stabilized or improved slightly [24] - **Safety Profile**: ATH434 demonstrated a clean safety profile with no serious adverse events related to the study drug [25][27] Future Plans - **Upcoming Presentations**: Alterity plans to present at the International Congress on Parkinson's Disease and Movement Disorders and target an end-of-phase two meeting with the FDA by the end of the year [28] - **Funding**: The company raised $40 million following the positive phase two data in February [31] Additional Insights - **Investor Engagement**: The event emphasized the importance of networking among biotech investors and companies, highlighting the collaborative nature of the sector [5][6] - **Historical Context**: The narrative included a historical perspective on Australian biotech, referencing early challenges faced by companies like Circadian [2][3] This summary encapsulates the key points discussed during the Alterity Therapeutics conference call, focusing on the company's advancements, clinical trial results, and future directions within the biotech industry.

Core Insights - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly Parkinson's disease and related disorders [2][4] - The company will present a corporate update at the Biotech Showcase on September 3, 2025, in Australia and September 2, 2025, in the United States [1][2] Company Overview - Alterity Therapeutics is a clinical-stage biotechnology firm based in Melbourne, Australia, and San Francisco, California, dedicated to creating therapies for neurodegenerative diseases [2] - The company has shown clinically meaningful efficacy for its lead asset, ATH434, in a Phase 2 clinical trial for Multiple System Atrophy (MSA), a rare and rapidly progressive Parkinsonian disorder [2] - ATH434 has recently reported positive data in an open-label Phase 2 clinical trial for advanced MSA [2] - Alterity has a broad drug discovery platform that generates patentable chemical compounds aimed at treating the underlying pathology of neurological diseases [2]

ATH434 Clinical Development and Efficacy - Alterity is developing treatments for neurodegenerative diseases, focusing on slowing disease progression and improving patient quality of life[5] - ATH434 has shown positive Phase 2 data in Multiple System Atrophy (MSA), demonstrating efficacy on a functional endpoint endorsed by the FDA/EMA[6] - The ATH434-201 trial achieved clinically significant efficacy on modified UMSARS Part I, with a -38 (16)% relative treatment effect at 50 mg and a -24 (17)% relative treatment effect at 75 mg compared to placebo[68] - In the ATH434-201 trial, 50 mg dosage showed statistically significant improvement in Clinical Global Impression of Severity (CGI-S) scale (p=0009)[72] - Wearable sensor data from the ATH434-201 trial indicated that ATH434 preserved activity in an outpatient setting, with statistically significant improvement in step count at 50 mg (p=00437)[79] MSA and Market Opportunity - Multiple System Atrophy (MSA) is a Parkinsonian disorder with no approved treatment, affecting up to 50000 patients in the US[40, 42] - Over 50% of MSA patients require a wheelchair within 5 years, and the median survival is 75 years after symptom onset[42] - ATH434 has the potential to achieve over $US11 billion in annual peak sales in the U S for MSA[101] ATH434 Mechanism and Safety - ATH434 redistributes excess labile iron in the CNS, reduces α-synuclein aggregation and oxidative injury, and preserves neurons and oligodendrocyte support cells[29] - ATH434 is an orally administered iron chaperone with the potential to treat various neurodegenerative diseases[33] - The ATH434-201 trial showed similar rates of adverse events in ATH434 and placebo participants, with no treatment-associated effects on hemoglobin or iron parameters[84]

Core Viewpoint - Alterity Therapeutics has made significant progress in the development of ATH434 for the treatment of Multiple System Atrophy (MSA), highlighted by the U.S. FDA granting Fast Track designation, which underscores the potential of this therapy to address unmet medical needs in MSA patients [2][4]. Financial Summary - As of June 30, 2025, Alterity's cash position was A$40.66 million, with operating cash outflows for the quarter amounting to A$2.35 million [3]. - The company raised A$26.3 million in gross proceeds from a two-tranche placement and received a refund of A$3.98 million from the Australian Taxation Office under the Research and Development Tax Incentive Scheme [16]. Clinical Developments - The Fast Track designation for ATH434 was granted in May 2025, aimed at accelerating its development and review process due to its potential as an innovative treatment for MSA, a disease currently without approved therapies [4][5]. - Positive results from the ATH434-201 Phase 2 clinical trial were presented, showing a 48% relative treatment effect at the 50 mg dose and a 30% effect at the 75 mg dose on the modified UMSARS I scale [7][8]. - The ATH434-202 open-label Phase 2 trial also reported positive topline data, indicating clinical benefits and stabilization of key biomarkers in a more advanced MSA patient population [10][11]. Efficacy and Safety - ATH434 demonstrated a favorable safety profile, with no serious adverse events reported and similar adverse event rates compared to placebo [14]. - Neuroimaging data indicated that ATH434 stabilized or reduced iron accumulation in MSA-affected brain regions and showed trends in reducing brain atrophy [9][12]. Research and Innovation - The MSA Atrophy Index (MSA-AI), developed in the bioMUSE Natural History Study, was featured in a peer-reviewed journal, providing a novel measure for tracking disease progression in MSA patients [15]. - The use of deep learning methods in defining neuroanatomy and developing the MSA-AI can enhance understanding of MSA progression and support the evaluation of disease-modifying therapies [15].

Core Insights - ATH434 demonstrated clinical benefits in patients with multiple system atrophy (MSA), showing stabilization of neurological symptoms and a favorable safety profile [1][3][5] Clinical Trial Results - The ATH434-202 Phase 2 trial involved 10 participants with advanced MSA, treated with 75 mg of ATH434 twice daily for 12 months [6] - Over the treatment period, disease progression as measured by the Modified Unified MSA Rating Scale Part I (UMSARS I) was reduced by approximately 50% compared to historical controls [3] - 30% of participants reported stable neurological symptoms, which is notable given the advanced stage of their disease [3][11] Biomarker Outcomes - Neuroimaging results indicated that ATH434 slowed brain atrophy in MSA-affected areas, as measured by the MSA Atrophy Index (MSA-AI) [4][12] - There was a reduction in iron accumulation in the putamen and globus pallidus compared to placebo-treated patients, providing evidence of target engagement [4][12] Safety Profile - ATH434 was well-tolerated, with most adverse events being mild to moderate in severity, and no serious adverse events related to the treatment reported [12][19] Expert Commentary - The CEO of Alterity expressed encouragement regarding the positive results, reinforcing the efficacy observed in previous studies and emphasizing the potential of ATH434 to slow disease progression [5] - The principal investigator noted that the consistent changes in UMSARS and imaging measures support the continued development of ATH434 for MSA treatment [5]