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 ...

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 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 Insights - Alterity Therapeutics is advancing its lead drug candidate, ATH434, aimed at treating neurodegenerative diseases, specifically targeting Multiple System Atrophy (MSA) [1][4] - The last patient in the ATH434-202 Phase 2 trial has completed the study, with topline data expected to be reported in mid-2025 [1][2] 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 [7] - The company is based in Melbourne, Australia, and San Francisco, California, and has a drug discovery platform aimed at creating treatments for neurological diseases [7] ATH434-202 Phase 2 Clinical Trial - The ATH434-202 trial is an open-label study involving 10 participants with advanced MSA, where participants received a 75 mg dose of ATH434 for 12 months [3] - The study aims to evaluate the effects of ATH434 on neuroimaging and protein biomarkers, alongside clinical measures, safety, and pharmacokinetics [3] - The primary objective is to assess the impact of ATH434 on brain volume in a more advanced patient population compared to previous trials [3] Drug Mechanism and Efficacy - ATH434 is designed to inhibit the aggregation of pathological proteins associated with 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 Orphan Drug Designation for MSA treatment from the U.S. FDA and the European Commission [4] Disease Context - 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 [5] - Currently, there are no approved drugs that can slow the progression of MSA, highlighting the potential significance of ATH434 in the treatment landscape [5]

[Appendix 4D: Half-Year Report Summary](index=4&type=section&id=Appendix%204D) [Results for Announcement to the Market](index=4&type=section&id=Results%20for%20announcement%20to%20the%20market) Alterity Therapeutics reported decreased revenue and increased net loss for H1 FY2025, with net tangible assets per share significantly declining Financial Performance Summary (vs. 31 Dec 2023) | Metric | Change | Value (A$) | | :--- | :--- | :--- | | Revenue from ordinary activities | Down 6.0% | 111,299 | | Net loss after tax | Up 10.2% | 7,173,335 | Net Tangible Assets per Security | Date | Cents per Share | | :--- | :--- | | 31 December 2024 | 0.14 | | 31 December 2023 | 0.62 | - The reported income of **$111,299** for the half-year was entirely from interest received on the Group's bank accounts[7](index=7&type=chunk) - No dividends have been paid or declared by the Group for the current or previous financial period[8](index=8&type=chunk) [Directors' Report](index=8&type=section&id=Directors'%20report) [Review of Operations](index=8&type=section&id=Review%20of%20Operations) The company achieved significant progress with positive ATH434-201 Phase 2 trial results for MSA, followed by a successful A$42 million capital raise [Lead Compound - ATH434](index=8&type=section&id=Lead%20Compound%20-%20ATH434) ATH434 is the company's lead oral agent, inhibiting pathological protein aggregation by redistributing iron, with potential for MSA and other neurodegenerative diseases - **ATH434** is an oral agent designed to inhibit pathological protein aggregation by redistributing excess iron in the brain, thereby rescuing neuronal function[23](index=23&type=chunk) - The compound has potential as a treatment for Multiple System Atrophy (MSA), Parkinson's disease, and Friedreich Ataxia[24](index=24&type=chunk)[25](index=25&type=chunk) [ATH434 Clinical Trials for Multiple System Atrophy (MSA)](index=9&type=section&id=ATH434%20Clinical%20Trials%20for%20Multiple%20System%20Atrophy%20(MSA)) The ATH434-201 Phase 2 trial showed a **48%** slowing of MSA progression, while the ATH434-202 trial also yielded positive interim data - The ATH434-201 Phase 2 trial in early-stage MSA demonstrated a clinically meaningful benefit, achieving statistical significance with a **48%** slowing of clinical progression on the UMSARS I rating scale at the **50** mg dose[18](index=18&type=chunk) - The ATH434-202 trial in more advanced MSA showed positive interim data, with **30%** of participants demonstrating stable or improved clinical outcomes and slower progression compared to a historical untreated group[34](index=34&type=chunk) - **ATH434** has received Orphan Drug Designation (ODD) for the treatment of MSA from both the U.S. FDA and the European Commission, which provides benefits like market exclusivity and fee reductions[26](index=26&type=chunk) [Other Research and Development Progress](index=10&type=section&id=Other%20Research%20and%20Development%20Progress) Pre-clinical data showed ATH434 improved motor performance in Parkinson's models, and the bioMUSE study is advancing MRI as an MSA biomarker - In a study on macaques with experimentally induced Parkinson's disease, **ATH434** treatment improved motor performance and was associated with reduced iron levels in the affected brain area[37](index=37&type=chunk) - A peer-reviewed publication in *Metallomics* characterized **ATH434** as an "iron chaperone" that targets the damaging, reactive form of iron[38](index=38&type=chunk) - The bioMUSE natural history study is utilizing advanced MRI and deep learning to track brain volume changes, establishing it as a potential biomarker for MSA progression[42](index=42&type=chunk)[43](index=43&type=chunk) [Corporate Activity and Subsequent Events](index=11&type=section&id=Corporate%20Activity%20and%20Subsequent%20Events) The company appointed a new Company Secretary and successfully raised approximately **A$42** million post-period to accelerate ATH434 development - Abby Macnish Niven was appointed as Company Secretary on November **18**, **2024**, following her earlier appointment as Chief Financial Officer[44](index=44&type=chunk) - Subsequent to the period end, in February **2025**, the company strengthened its balance sheet by raising approximately **A$42** million via an ATM facility and a two-tranche placement[46](index=46&type=chunk)[48](index=48&type=chunk) [Consolidated Financial Statements](index=14&type=section&id=Consolidated%20financial%20statements) [Consolidated Statement of Profit or Loss and Other Comprehensive Income](index=14&type=section&id=Consolidated%20statement%20of%20profit%20or%20loss%20and%20other%20comprehensive%20income) The Group reported a net loss of **A$7.17** million for H1 FY2025, driven by significant R&D and general/administration expenses Statement of Profit or Loss (Half-year ended 31 December) | Item | 2024 (A$) | 2023 (A$) | | :--- | :--- | :--- | | Interest income | 111,299 | 118,400 | | Other income (R&D tax incentive) | 1,605,925 | 1,900,724 | | General and administration expenses | (2,984,023) | (2,061,250) | | Research and development expenses | (5,717,901) | (6,361,034) | | **Loss for the period** | **(7,173,335)** | **(6,507,183)** | | **Basic loss per share (Cents)** | **(0.14)** | **(0.26)** | [Consolidated Statement of Financial Position](index=15&type=section&id=Consolidated%20statement%20of%20financial%20position) The Group's net assets decreased to **A$7.79** million as of December **31**, **2024**, primarily due to a reduction in cash and cash equivalents Statement of Financial Position (As at) | Item | 31 Dec 2024 (A$) | 30 Jun 2024 (A$) | | :--- | :--- | :--- | | **Current Assets** | | | | Cash and cash equivalents | 4,536,559 | 12,638,885 | | Trade and other receivables | 5,684,107 | 4,041,675 | | **Total Assets** | **10,546,933** | **19,223,743** | | **Total Liabilities** | **2,760,926** | **5,425,686** | | **Net Assets** | **7,786,007** | **13,798,057** | | **Total Equity** | **7,786,007** | **13,798,057** | [Consolidated Statement of Changes in Equity](index=16&type=section&id=Consolidated%20statement%20of%20changes%20in%20equity) Total equity decreased by **A$6.01** million to **A$7.79** million, mainly due to the net loss, partially offset by share-based payments and new share issues Movements in Equity (Half-year ended 31 Dec 2024) | Item | Amount (A$) | | :--- | :--- | | Balance at 1 July 2024 | 13,798,057 | | Loss for the period | (7,173,335) | | Issue of ordinary shares | 398,645 | | Share-based payment expenses | 794,717 | | Transaction costs | (32,077) | | **Balance at 31 December 2024** | **7,786,007** | [Consolidated Statement of Cash Flows](index=17&type=section&id=Consolidated%20statement%20of%20cash%20flows) The Group experienced a net cash decrease of **A$8.06** million, primarily from **A$8.36** million in net cash used for operating activities Statement of Cash Flows (Half-year ended 31 December) | Item | 2024 (A$) | 2023 (A$) | | :--- | :--- | :--- | | Net cash (outflow) from operating activities | (8,359,622) | (4,494,940) | | Net cash (outflow) from investing activities | - | (5,722) | | Net cash inflow from financing activities | 298,319 | 1,050,347 | | **Net (decrease) in cash** | **(8,061,303)** | **(3,450,315)** | | Cash at beginning of period | 12,638,885 | 15,773,783 | | **Cash at end of period** | **4,536,559** | **12,320,426** | [Notes to the Consolidated Financial Statements](index=18&type=section&id=Notes%20to%20the%20consolidated%20financial%20statements) [Funding Position and Going Concern](index=27&type=section&id=Funding%20position%20of%20the%20Group) Despite a net loss and operating cash outflow, the company maintains a going concern basis, supported by a post-period **A$40** million capital raise - The Group incurred a recurring loss of **A$7,173,335** and an operating cash outflow of **A$8,359,622** for the half-year ended **31** December **2024**[107](index=107&type=chunk) - Cash and cash equivalents on hand as at **31** December **2024** was **$4,536,559**[108](index=108&type=chunk) - The financial statements are prepared on a going concern basis, justified by a subsequent capital raise of approximately **A$40** million. Of this, **A$12.8** million was received in February **2025**, with the remainder subject to shareholder approval[109](index=109&type=chunk)[110](index=110&type=chunk) [Financial Performance and Position Details](index=19&type=section&id=Financial%20Performance%20and%20Position%20Details) The Group's income is primarily from interest and R&D tax incentives, with major expenses in R&D and G&A, resulting in a basic loss per share of **(0.14)** **cents** Loss Per Share | Metric | 31 Dec 2024 (Cents) | 31 Dec 2023 (Cents) | | :--- | :--- | :--- | | Basic loss per share | (0.14) | (0.26) | | Diluted loss per share | (0.14) | (0.26) | Breakdown of Income (A$) | Source | 31 Dec 2024 | 31 Dec 2023 | | :--- | :--- | :--- | | Interest income | 111,299 | 118,400 | | R&D tax incentive | 1,605,925 | 1,900,724 | - The R&D tax incentive receivable was **A$5,625,211** as of Dec **31**, **2024**, representing the amount the Group expects to recover[80](index=80&type=chunk) [Equity and Share Capital](index=23&type=section&id=Equity%20and%20Share%20Capital) The company issued **75.2** million ordinary shares, raising **A$398,645**, while **1.94** billion options expired and **170** million new options were issued under ESOP Movements in Ordinary Shares (1 Jul 2024 - 31 Dec 2024) | Details | Number of Shares | Amount (A$) | | :--- | :--- | :--- | | Opening balance | 5,245,115,318 | 223,152,985 | | Shares issued during the year | 75,220,800 | 406,193 | | Transaction costs | - | (32,077) | | **Closing balance** | **5,320,336,118** | **223,527,101** | - On August **31**, **2024**, **1,935,759,704** free attaching short-dated options expired[90](index=90&type=chunk) - During the period, **170,000,000** unlisted options were issued under the Employee Stock Option Plan (ESOP)[89](index=89&type=chunk) [Events Occurring After the Reporting Period](index=25&type=section&id=Events%20occurring%20after%20the%20reporting%20period) Post-period, Alterity announced positive ATH434-201 Phase 2 trial results and secured **A$40** million in capital commitments to accelerate development - On January **30**, **2025**, the company announced positive topline results from its **ATH434-201** Phase **2** clinical trial, demonstrating a **48%** slowing of clinical progression on the UMSARS I scale[98](index=98&type=chunk) - On February **10**, **2025**, the company announced it had received binding commitments for a capital raising of **A$40** million via a two-tranche placement at **A$0.011** per share[100](index=100&type=chunk) - Tranche One of the placement was completed on February **17**, **2025**, raising **A$12.8** million. Tranche Two, to raise **A$27.2** million, is subject to shareholder approval expected in late March **2025**[100](index=100&type=chunk)[101](index=101&type=chunk) [Declarations and Reports](index=28&type=section&id=Declarations%20and%20Reports) [Directors' Declaration](index=28&type=section&id=Directors'%20declaration) The directors declare the financial statements provide a true and fair view and affirm the company's ability to meet its debts on a going concern basis - The directors affirm that the financial statements give a true and fair view of the consolidated entity's financial position and performance and are in accordance with the Corporations Act **2001**[111](index=111&type=chunk) - The directors state there are reasonable grounds to believe that Alterity Therapeutics Limited will be able to pay its debts as and when they become due and payable[111](index=111&type=chunk) [Independent Auditor's Review Report](index=30&type=section&id=Independent%20auditor's%20report%20to%20the%20members) PwC's review found no matters indicating non-compliance with accounting standards or the Corporations Act **2001** for the half-year financial report - The auditor, PricewaterhouseCoopers, concluded that based on their review, they have not become aware of any matter that makes them believe the financial report does not comply with the Corporations Act **2001**, including giving a true and fair view and complying with AASB **134**[117](index=117&type=chunk)[121](index=121&type=chunk) - The review was conducted in accordance with ASRE **2410**, which is substantially less in scope than an audit, and consequently, the auditor does not express an audit opinion[123](index=123&type=chunk)

Core Insights - Alterity Therapeutics has announced the completion of the last patient visit in the ATH434-201 Phase 2 trial for early-stage Multiple System Atrophy (MSA), with topline data expected in early 2025 [1][2] Company Overview - Alterity Therapeutics is a biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, particularly targeting MSA and other Parkinsonian disorders [1][6] - The lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins associated with neurodegeneration, showing promise in preclinical studies [4][6] Clinical Trial Details - The ATH434-201 Phase 2 trial is a randomized, double-blind, placebo-controlled study involving 77 adults, assessing the efficacy and safety of ATH434 over a 12-month treatment period [3][4] - The trial aims to evaluate neuroimaging and protein biomarkers, including brain iron and α-synuclein, to demonstrate drug activity and clinical efficacy [3][4] Disease Context - Multiple System Atrophy (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. [5][6] - Currently, there are no approved drugs that can slow the progression of MSA, highlighting the potential significance of ATH434 as a treatment option [5][6]

Core Viewpoint - Alterity Therapeutics has appointed Abby Macnish Niven as Company Secretary following her role as Chief Financial Officer, effective November 18, 2024, succeeding Phillip Hains [1][2]. Group 1: Management Changes - Abby Macnish Niven was appointed as CFO on September 30, 2024, and has extensive experience in private wealth management with firms such as ANZ, UBS, and Ord Minett [3]. - Ms. Macnish Niven will be responsible for communications between the Company and ASX as per ASX Listing Rule 12.6 [4]. Group 2: Company Overview - Alterity Therapeutics is a clinical stage biotechnology company focused on developing treatments for neurodegenerative diseases, with its lead asset ATH434 currently evaluated in two Phase 2 clinical trials for Multiple System Atrophy [5]. - The Company is based in Melbourne, Australia, and San Francisco, California, and has a drug discovery platform aimed at creating patentable compounds for neurological diseases [5].