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CEO's presentation Dr David Stamler 21 November 2025 Forward looking statements 2 This presentation may contain some statements that may be considered "Forward - Looking Statements", within the meaning of the US Securiti

Key Takeaway: CEO's presentation Dr David Stamler 21 November 2025 Forward looking statements 2 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

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CEO's presentation Dr David Stamler 21 November 2025
Forward looking statements 2 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 uncertainties as they relate to us, please refer to our 2025 Form 20 - F, filed with US Securities and Exchange Commission, in particular Item 3, Section D, titled "Risk Factors.''
Investment highlights 3 Large market potential in neurodegenerative diseases Highly experienced leadership team in movement disorders Oral administration preferred over competition Positive Phase 2 data in Multiple system atrophy (MSA), an aggressive Parkinsonian disorder Robust efficacy on functional endpoint in double - blind study Patient friendly administration Three FDA approvals in neurology ATH434 has Orphan Drug designation for MSA treatment Potential to treat Parkinson's disease and related disorders
Promising portfolio in neurodegenerative diseases 4 Program: Drug discovery Indication: Discovery Pre - clinical Phase 1 Natural History Positive topline data Positive topline data Phase 2 Phase 3 Collaboration Multiple system atrophy Open label study Parkinson's disease Neurodegenerative diseases Friedreich's ataxia ATH434 - 201 ATH434 - 202 ATH434 ATH434 Multiple system atrophy Natural history study bioMUSE Multiple system atrophy Double blind study
Multiple System Atrophy (MSA): Parkinsonian disorder with no approved treatment 0 Years: 3 6 9 7.5 years median survival after symptom onset Over 50% require wheelchair in 5 years Rapidly progressive Highly debilitating Up to 50,000 patients in U.S. Disease characteristics: Motor: Parkinsonism, uncoordinated movements, balance problems, falls Autonomic dysfunction: blood pressure maintenance, bladder control, bowel function Atrophy and - synuclein accumulation in multiple brain regions Premotor MSA Clinically probable MSA Death can occur Clinically established MSA Urinary dysfunction REM sleep behavior disorder Orthostatic hypotension Parkinsonism Cerebellar features Multidomain autonomic failure Pyramidal signs 5 Sources: Fanciulli, Wenning. NEJM 2015 | Wenning, et al. Mov Disorders 2022 | Coon, et al. Brain 2015 | Multiple System Atrophy: National Institute of Neurological Disorders and Stroke (nih.gov) Recurrent falls Indwelling catheter Frontal executive dysfunction Unintelligible speech Gastrostomy Tracheostomy Bronchopneumonia Uroseptic fever Sudden death
ATH434: Small molecule drug candidate 6 Broad treatment potential Potential to treat many neurodegenerative diseases (e.g., Parkinson's, Frederich Ataxia) Orphan & Fast Track designations US FDA Fast Track Designation and Orphan drug designation in U.S. and EU Blood - brain barrier penetrant Acts intracellularly to address underlying pathology Efficacy in animal models of disease Efficacy shown in animals with experimental Parkinson's disease and MSA Oral administration Preferred by patients and doctors vs infusions (IV, intrathecal) or injections ATH434 binding to labile iron
Targeting the pathology of MSA
8 Key players in MSA pathology Two forms of iron required for cellular function: Energy production and activity of many enzymes Neurotransmitter synthesis (e.g., dopamine) Myelin synthesis - Synuclein protein: Present in all neurons Regulates neurotransmitter release Facilitates neuronal communication Myelination of axons Fe 2+ Fe 3+ Fe 2+ Reactive Fe 3+ Stable Alpha - synuclein and iron balance vital for normal CNS function
Fe 3+ Stable Fe 3+ Fe 2+ Reactive Fe 2+ ATH434 mechanism of action: Iron chaperone ATH434 redistributes excess labile (reactive) iron to reduce neuronal injury Sources: Adapted from Yanatori et al., BBA 2020 and Philpott et al., Frontiers Mol Bio. 2023 | Pall, et al. Metallomics, 2024. Buffering Fe 2+ in labile iron pool PCBP: Poly(rC) - binding proteins 1 Efflux iron from cell (ferroportin) 2 Increase iron storage (ferritin) Fe 3+ Endosome Mitochondria Ferroportin DMT1 ZIP8 ZIP14 Transferrin receptor Labile iron Fe 2+ Fe 2+ Fe 2+ Fe 2+ Fe 2+ Fe Fe 2+ 2+ Fe 2+ Fe 2+ Fe 2+ ATH434 Fe 2+ ATH434 PCBP PCBP 1 Fe 2+ PCBP Ferritin 2 Tf Fe 3+ Fe 3+ Fe 2+ PCBP Fe 2+ Enzyme PCBP ROS Fe 2+ Fe 2+ ATH434 Fe 2+ Fe 2+ 3 9 Redistribution mechanisms: 3
Treatment approach: Address underlying pathology 10 Based on its mechanism of action, ATH434 is a potential disease modifying therapy ATH434 redistributes excess labile iron in the CNS Reduces - synuclein aggregation and oxidative injury Preserves neurons and oligodendrocyte support cells Stabilises or improves patient function
ATH434 clinical development program in MSA
Diligent approach to de - risk development program 12 Observational study in individuals with MSA Designed to de - risk clinical development program Identify biomarkers to improve accuracy of patient selection Phase 2 ATH434 - 201 ATH434 - 202 Randomized double - blind placebo - controlled trial Results : clinically meaningful efficacy on MSA rating scale, measures of orthostatic hypotension, disease severity Natural History Study Open label trial in advanced MSA patients Results: showed improved neurological symptoms in more advanced patients and favorable safety bioMUSE
ATH434 - 201: Randomized, double - blind, placebo - controlled study 13 N=77 Study design: Endpoints: Patient criteria: Clinical diagnosis of MSA Motor symptoms 4 years No severe impairment Elevated brain iron on MRI Elevated plasma NfL Placebo twice daily 50 mg twice daily Key clinical endpoint: modified UMSARS Part 1 75 mg twice daily ATH434 ATH434 - 201 MRI - Magnetic Resonance Imaging; UMSARS - Unified MSA Rating Scale (UMSARS) Scale - measures activities of daily living CGI - S - Clinical Global Impression - Severity scale; OHSA - Orthostatic Hypotension Symptom Assessment Additional secondary endpoints: CGI - S, OHSA, Wearable Sensors, Safety ATH434 12 months treatment Key biomarker endpoint: brain iron content by MRI
Importance of the U nified MSA R ating S cale Part I (UMSARS I) 14 ATH434 - 201 Speech Walking Swallowing Falling Handwriting Orthostatic symptoms Cutting food Urinary function Dressing Bowel function Hygiene Sexual function ^ Validated rating scale to assess MSA disease severity Rates functional impairment in domains affected in MSA Rated from 0 to 48 higher scores worse ^ Modified version of UMSARS I excludes sexual function item UMSARS Part I Items: UMSARS is the FDA endorsed clinical endpoint to support approval for the treatment of MSA
Clinically significant efficacy on modified UMSARS Part I Change from baseline to week 52 15 ATH434 - 201 worsening Modified UMSARS I Relative treatment effect Difference vs. placebo LS mean (SE ) Placebo N=22 48% - 3.8 (1.6) ATH434 50 mg N=25 30% - 2.4 (1.7) ATH434 75 mg N=24 Change Placebo Relative Treatment Effect Change ATH434 Change Placebo 14 16 26 24 22 20 18 * P=0.02 for 50 mg 0 13 26 39 52 P=0.16 for 75 mg Clinical Analysis Population 35% P - value 0.11 - 2.8 (1.7) ATH434 75 mg N=24 Effect of ATH434 75 mg strengthens when correcting for important Baseline differences* * Baseline ortho SBP change as covariate given imbalance of severe OH at baseline
Orthostatic Hypotension Symptom Assessment (OHSA) Change from baseline to week 52 10 5 - 5 0 Change In OHSA (week S2 BL) Assesses symptoms of low blood pressure when going from sitting to standing (e.g., dizziness / feeling faint / lightheadedness) Patient reported outcome p=0.08 worsening mean (SE) p=0.14 ATH434 50 mg ATH434 75 mg Placebo 16 Kaufmann, et al. Clin Auton Res 2012.. ATH434 - 201 Clinical Analysis Population
0 - 50 - 100 worsening 17 ATH434 - 201 Step count worsening 0 - 1000 - 2000 - 3000 Change In steps/day p = 0.04 * p = 0.10 Total time walking Change In bouts/day Total standing time Pendant Wearable movement sensor ATH434 - 201 50 mg ATH434 - 201 75 mg Placebo Change In minutes/day 0 - 10 - 20 - 40 - 30 p = 0.13 p = 0.15 worsening Bouts of walking 0 - 20 - 40 - 80 - 60 Change In minutes/day worsening ATH434 preserved walking in outpatient setting Change from baseline to week 52 Clinical Analysis Population
18 1 - Reporting one or more event 2 - None related to Study Drug ATH434 - 201 Similar rates of AEs in ATH434 and placebo participants No severe or serious AEs related to study drug No hematologic side effects ATH434 - 201 ATH434 - 201 Placebo 75 mg N=26 50 mg N=25 twice daily subjects 1 N=26 N (%) of 25 (96.2%) 21 (84.0%) Any Adverse Event (AE) 24 (92.3%) 7 (26.9%) 10 (40.0%) UTI 14 (53.8%) 8 (30.8%) 7 (28.0%) Fall 8 (30.8%) 4 (15.4%) 6 (24.0%) Covid - 19 1 (3.8%) 5 (19.2%) 1 (4.0%) Fatigue 2 (7.7%) 2 (7.7%) 3 (12.0%) Back pain 1 (3.8%) 6 (23.1%) 3 (12.0%) Severe AEs 2 8 (30.8%) 7 (26.9%) 5 (20.0%) Serious AEs 2 10 (38.5%) Adverse Events
ATH434 - 202: Open label study in advanced MSA 19 Key objective was to assess efficacy and safety of ATH434 75 mg dose for comparison to 75 mg dose in 201 double - blind study ATH434 - 201 75mg BID N=24 ATH434 - 202 75 mg BID N=10 Parameter 63.9 (6.7) 64.5 (7.5) Age (yr) 2.3 (0.9) 3.9 (1.8) Duration of motor symptoms (yr) 14.4 (4.4) 19.2 (5.3) Modified UMSARS I 1 48.9 (16.8) 57.5 (20.4) Motor score of Parkinson Plus Scale2 32.3 (9.0) 42.1 (14.1) Plasma NfL (pg/mL) 15.0 (12.2) 16.7 (14.8) OH Symptom Assessment 29.2% 40.0% Severe Orthostatic Hypotension Mean (SD) 1 MSA affected areas by MSA - atrophy index. Trujillo, P. et al Annals of Clin and Trans Neuro, 2025 Single arm, open - label Design Advanced MSA (n=10) Population ATH434 75 mg BID x 12 months Treatment Iron, volume Brain MRI Biomarkers UMSARS I, clinical/patient global impressions of change Clinical Measures ATH434 - 202
ATH434 - 201 75mg BID N=24 ATH434 - 202 75 mg BID N=10 Change over 12 Months 5.6 (5.6) 3.5 (4.7) Modified UMSARS I 21% 30% Clinical global impression of change (% stable) 26.4% 30% Patient global impression of change (% stable) - 0.42 (0.29) - 0.44 (0.14) Brain volume 1 Mean (SD) ATH434 - 202: Key data at 75 mg dose Comparison to double blind study at 12 mo 20 No serious AEs related to study drug AEs consistent with underlying disease 1 In MSA affected areas by MSA - atrophy index. Trujillo, P. et al. Annals of Clin and Trans Neuro, 2025 ATH434 - 202 The 75 mg dose demonstrated comparable efficacy to that observed in the double - blind study
Approach to commercial assessment Conducted by independent marketing research and forecasting group 21 Conduct secondary market research Assess unmet needs and competitive landscape Develop target product profile based on Phase 2 clinical data Qualitative research Conduct In - depth interviews and Focus groups with general neurologists, movement disorder neurologists and autonomic specialists to identify decision - making behavior and key drivers and barriers to adoption leveraging the target product profile Develop physician screener and discussion guide for Quantitative Research Exploratory Research Conduct ~30 - minute online survey among 100 neurologists (~50% general, ~50% specialists) to determine their awareness, interest, market demand and likelihood of product adoption Assess the Target Product Profile to better understand its viability, differentiation opportunities and potential barriers to adoption Rigorous methods used to ensure data quality and integrity Quantitative Research Develop forecast assumptions based on qualitative and quantitative findings. Build a financial valuation of ATH434 in treatment of MSA Opportunity Analysis and Forecast
Commercial opportunity in MSA Key attributes of ATH434 drive significant value 22 USD $2.4 Billion Potential worldwide annual peak sales for ATH434 in MSA Severely debilitating illness with no approved treatment ripe for new entrants Critical need for a tolerable, disease modifying therapy Importance of inhibiting -synuclein aggregation to address the underlying pathology of disease Over 70% of neurologists were "extremely likely" or "very likely' to prescribe ATH434 based on its profile Slowing disease progression is key driver of physician interest Stabilizing orthostatic hypotension ^ , one of the most challenging symptoms in MSA, strongly positions ATH434 ^Orthostatic hypertension is the drop in blood pressure on standing; Global peak sales number in U.S. Dollars; Independent market research survey conducted in 2025. Peak sales estimate based on U.S. prevalence of ~19,000
1 2 3 4 2025: Strengthening the Foundation for the Future 23 Phase 3 Trial Planning Ongoing with FDA End - of - Phase 2 expected in mid - 2026 ATH434 - 201 Positive Topline Data ATH434 - 202 Positive Topline Data Data presentations and publications: x Annals of Clinical and Translational Neurology: Publication on MSA Atrophy Index x American Academy of Neurology (Platform Presentation) x American Autonomic Society (Oral Presentation) x American Neurological Association x International Congress of Parkinson's Disease & Movement Disorders (Platform presentation) x International MSA Congress (Oral Presentation) x MSA Trust Symposium (Oral Presentation) Key Data Readouts, FDA Interactions & Medical Community Engagement FDA Fast Track Designation in MSA 5 Robust efficacy in Phase 2 double - blind trial on key FDA endpoint Accomplished team with multiple FDA approvals in neurology Lead indication MSA is an Orphan Disease with no approved treatment Open label trial confirms ATH434's safety and efficacy profile Cash Balance: A $54.5M as of 30 September
ASX: ATH NASDAQ: ATHE
Last updated: Nov 21, 2025