July 2025 For personal use only Corporate Presentation Forward looking statements This presentation may contain some statements that may be considered "Forward -Looking Statements", within the meaning of the US Securities Laws. Thus, any forward -looking statement relating to financial projections or other statements relating to the Company's plans, objectives, expectations or intentions involve risks and uncertainties that may cause actual results to differ materially. For a discussion of such risks and un ...

Highlights Granted U.S. FDA Fast Track Designation for ATH434 to treat Multiple System Atrophy (MSA)Reported positive topline data from open-label Phase 2 clinical trial of ATH434 in MSAPresented additional analyses from the ATH434-201 trial demonstrating continued robust efficacy for the treatment of MSACash balance on 30 June 2025 of A$40.66M MELBOURNE, Australia and SAN FRANCISCO, July 30, 2025 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnolo ...

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]

Core Insights - The article highlights the development and validation of the MSA Atrophy Index (MSA-AI) as a significant advancement in diagnosing and tracking disease progression in Multiple System Atrophy (MSA) patients [1][2][3] Company Overview - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly MSA [1][10] - The company has reported positive data for its lead asset, ATH434, in a Phase 2 clinical trial for MSA [10] Research Findings - The MSA-AI utilizes deep learning methods to define neuroanatomy and track brain atrophy in MSA patients over one year, correlating with clinical measures of disease severity [2][3] - Statistically significant reductions in brain volume over 12 months were observed, correlating with clinical worsening of the disease [3] - The MSA-AI provides an objective measure of brain atrophy, aiding in the differentiation of MSA from related disorders like Parkinson's disease and Dementia with Lewy Bodies [4][5] Clinical Implications - The MSA-AI enhances understanding of MSA progression and supports the evaluation of disease-modifying therapies, potentially improving diagnosis and clinical trial participant selection [3][4] - The study design included both longitudinal and cross-sectional cohorts, capturing a broad spectrum of clinical severity and atrophy patterns, which strengthens the generalizability of the findings [5][8] About bioMUSE - The bioMUSE study aims to track MSA progression and is conducted in collaboration with Vanderbilt University Medical Center, providing vital data for optimizing clinical trial designs [7][8] - Approximately 20 individuals with clinically probable or established MSA have been enrolled in the bioMUSE study [8] Disease Context - MSA is a rare neurodegenerative disease characterized by autonomic nervous system failure and impaired movement, affecting at least 15,000 individuals in the U.S. [9] - Currently, there are no approved therapies to slow disease progression, highlighting the need for innovative diagnostic and treatment approaches [9]

Core Viewpoint - Alterity Therapeutics is advancing its development program for ATH434, a treatment for Multiple System Atrophy, following positive Phase 2 trial results released in January 2025 [1][4]. Group 1: Corporate Update - David Stamler, M.D., CEO of Alterity, will provide a corporate update during a Fireside Chat hosted by MST Access on June 25, 2025, in Australia and June 24, 2025, in the United States [1]. - The focus of the update will be on the progress made in the ATH434 development program since the positive Phase 2 data announcement [1]. Group 2: Webcast Details - The webcast will take place on June 25, 2025, at 9:00 a.m. AEST for Australian participants and on June 24, 2025, at 4:00 p.m. Pacific Time for U.S. participants [2]. - Registration for the Zoom webcast is required, and details will be sent directly upon registration [2]. Group 3: Company Overview - Alterity Therapeutics is a clinical-stage biotechnology company focused on developing disease-modifying therapies for neurodegenerative diseases, particularly Parkinson's disease and related disorders [4]. - The company has reported positive data for its lead asset, ATH434, in a Phase 2 clinical trial for Multiple System Atrophy, a rare and rapidly progressive disorder [4]. - Alterity is also conducting a Phase 2 clinical trial for ATH434 in advanced MSA and has a drug discovery platform aimed at generating patentable compounds for neurological diseases [4].

Core Insights - Alterity Therapeutics presented significant findings on ATH434, demonstrating clinically meaningful efficacy in treating Multiple System Atrophy (MSA) during the 2025 International MSA Congress [1][2][3] Group 1: ATH434 Clinical Trial Results - The Phase 2 double-blind trial of ATH434 involved 71 patients, 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 activities of daily living scale at 52 weeks [3][4] - ATH434 improved key symptoms of MSA, with statistically significant results on the Clinical Global Impression of Severity Scale (p=0.0088) and positive trends in the Orthostatic Hypotension Symptom Assessment [3][4][9] - Increased outpatient activity was observed with wearable sensors, indicating improvements in step count and total walking time compared to placebo [4][9] Group 2: MSA Atrophy Index (MSAai) - The MSA Atrophy Index (MSAai) was introduced as a novel imaging biomarker to enhance MSA diagnosis and monitoring, correlating with clinical presentation and tracking disease progression [5][6] - The bioMUSE study indicated that MSA patients had significantly lower MSAai values compared to healthy controls and other movement disorders, with strong correlations to UMSARS scores [5][6] Group 3: α-Synuclein Research Findings - The bioMUSE study revealed that higher concentrations of α-synuclein in skin biopsies were associated with greater burden of orthostatic symptoms, providing insights into disease progression [2][6] - Cutaneous α-synuclein deposition increased significantly over 12 months, with a mean increase from 6.59 to 7.71 (p=0.042) [6] Group 4: Company Overview and Future Directions - Alterity Therapeutics is focused on developing disease-modifying therapies for neurodegenerative diseases, with ATH434 being a lead candidate showing robust clinical efficacy and a favorable safety profile [7][12] - The company has received Fast Track Designation and Orphan Drug Designation from the U.S. FDA for ATH434, indicating its potential in treating MSA [7][12]

Core Insights - Alterity Therapeutics is set to present multiple clinical program findings related to ATH434 for Multiple System Atrophy (MSA) at the 2025 International MSA Congress in Boston, MA, from May 9 to 11, 2025 [1][2] - The company has received Fast Track Designation from the US FDA for ATH434, indicating significant interest in its clinical advancements [2][4] Company Overview - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly MSA and Parkinson's disease [3][9] - The lead candidate, ATH434, is designed to inhibit the aggregation of pathological proteins and has shown preclinical efficacy in reducing α-synuclein pathology [3][4] Clinical Trial Details - The ATH434-201 Phase 2 clinical trial involved 77 adults and demonstrated statistically significant improvements in the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I compared to placebo [5] - The trial also indicated that ATH434 stabilized or reduced iron accumulation in MSA-affected brain regions and was well tolerated with no serious adverse events attributed to the drug [5][4] Research Collaborations - The bioMUSE natural history study, conducted in collaboration with Vanderbilt University Medical Center, aims to track MSA progression and has enrolled approximately 20 individuals [6] - This study provides valuable data for optimizing clinical trial designs and evaluating biomarkers for target engagement and efficacy [6] Disease Context - MSA is a rare, rapidly progressive neurodegenerative disease affecting at least 15,000 individuals in the U.S., characterized by autonomic dysfunction and impaired movement [7] - Currently, there are no approved therapies that can slow the progression of MSA, highlighting the significance of Alterity's efforts in this area [7]

Core Viewpoint - Alterity Therapeutics has received Fast Track designation from the U.S. FDA for its drug candidate ATH434, aimed at treating Multiple System Atrophy (MSA), highlighting its potential to address a significant unmet medical need in this area [1][2]. Group 1: FDA Designation and Implications - The Fast Track designation is intended to expedite the development and review of drugs for serious conditions with unmet medical needs, such as MSA, and provides benefits like more frequent communication with the FDA and rolling review of the New Drug Application (NDA) [3][6]. - The designation underscores the promise of ATH434 as a disease-modifying therapy for MSA, supported by recent scientific findings and positive results from a Phase 2 clinical trial [2][4]. Group 2: ATH434 Overview - ATH434 is an oral agent designed to inhibit the aggregation of pathological proteins involved in neurodegeneration, showing preclinical efficacy in reducing α-synuclein pathology and preserving neuronal function [4]. - The drug has demonstrated robust clinical efficacy in a randomized, double-blind Phase 2 clinical trial, with a favorable safety profile and evidence of target engagement on key biomarkers [4][5]. Group 3: Clinical Trial Details - The ATH434-201 Phase 2 clinical trial involved 77 adults and assessed the efficacy, safety, and pharmacokinetics of ATH434 over 12 months, showing significant improvements on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I compared to placebo [5][7]. - The trial also indicated that ATH434 stabilized or reduced iron accumulation in MSA-affected brain regions, with trends in preserving brain volume and no serious adverse events attributed to the drug [7]. Group 4: MSA Background - Multiple System Atrophy (MSA) is a rare, rapidly progressive neurodegenerative disease affecting at least 15,000 individuals in the U.S., characterized by autonomic dysfunction and impaired movement, with no current approved therapies to slow disease progression [8]. - The disease is marked by the accumulation of α-synuclein protein and leads to significant disability, emphasizing the urgent need for effective treatments like ATH434 [8]. Group 5: Company Overview - Alterity Therapeutics is focused on developing disease-modifying therapies for neurodegenerative diseases, with ATH434 as its lead asset currently in clinical trials for MSA [9]. - The company is based in Melbourne, Australia, and San Francisco, California, and aims to create innovative treatments for conditions like Parkinson's disease and related disorders [9].

Core Viewpoint - Alterity Therapeutics reported significant progress in its clinical trials for ATH434, a treatment for Multiple System Atrophy (MSA), highlighting its potential to change the treatment landscape for this condition [3][8]. Financial Summary - As of March 31, 2025, Alterity's cash position was A$17.96 million, with operating cash outflows of A$0.73 million for the quarter [4]. - The company raised approximately A$15.0 million during the period and an additional A$27.1 million after the quarter ended [11]. Clinical Trial Updates - The ATH434-201 Phase 2 trial demonstrated a 48% relative treatment effect at the 50 mg dose and a 30% effect at the 75 mg dose, indicating significant efficacy in reducing disease severity compared to placebo [7]. - The ATH434-202 open-label trial in advanced MSA was completed, with topline data expected to be reported mid-year 2025 [10]. Operational Activities - The ATH434-201 trial involved 77 participants and utilized wearable sensors to assess outpatient activity levels, showing clinically meaningful improvements in various metrics [6][9]. - The company plans to engage with regulatory authorities to advance ATH434's development for MSA [3]. Corporate Activities - Alterity received a refund of A$1.65 million from the Australian Taxation Office under the Research and Development Tax Incentive Scheme for eligible activities conducted in the financial year ending June 30, 2020 [11].

Core Insights - Alterity Therapeutics announced positive results from the ATH434-201 Phase 2 clinical trial for Multiple System Atrophy (MSA) at the MSA Research Symposium [1][2] - The trial demonstrated significant clinical efficacy of ATH434, with a 48% relative treatment effect at the 50 mg dose and a 30% effect at the 75 mg dose [3][5] - ATH434 is designed to inhibit the aggregation of pathological proteins and has shown potential in treating neurodegenerative diseases [4][8] Company Overview - Alterity Therapeutics is focused on developing disease-modifying therapies for neurodegenerative diseases, particularly Parkinson's disease and related disorders [8] - The company is based in Melbourne, Australia, and San Francisco, California, and is advancing its lead candidate, ATH434, through clinical trials [8] Clinical Trial Details - The ATH434-201 Phase 2 trial involved 77 patients and assessed the efficacy, safety, and pharmacokinetics of ATH434 over 12 months [5][6] - Key findings included a clinically significant reduction in disease severity on the modified UMSARS I scale and improvements in motor activities measured by wearable sensors [3][5] - ATH434 was well tolerated, with no serious adverse events reported, and showed trends in reducing iron accumulation in MSA-affected brain regions [3][4][6] Disease Context - Multiple System Atrophy (MSA) is a rare, rapidly progressive neurodegenerative disease affecting the autonomic nervous system and movement [7] - MSA currently has no approved treatments that can slow disease progression, highlighting the potential impact of successful therapies like ATH434 [7]