Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (September 2026)
51 slides from Alterity Therapeutics's investor presentation, Sep 23, 2026
Slide 1: Corporate Presentation September 2026
For personal use only Corporate Presentation September 2026
Slide 2: Forward looking statements
Forward looking statements This presentation should be read in conjunction with the risk factors disclosed in Alterity Therapeutics Limited’s most recent filings with the Australian Securities Exchange and the United States Securities and Exchange Commission, including the Company’s most recent Annu
Slide 3: Alterity means the state of being different
For personal use only Alterity means the state of being different Alterity is a late clinical stage Our goal is to slow the course biopharmaceutical company of disease progression dedicated to developing treatments for neurodegenerative diseases We strive to create an alternate future and improve pa
Slide 4: Redefining Neurodegenerative Disease Therapy
Redefining Neurodegenerative Disease Therapy A Potential First-in-Class, Disease-Modifying Therapy for Multiple System Atrophy (MSA) Compelling Phase 2 Efficacy on Unmet Need with Significant 1 2 For personal use only FDA-Endorsed Endpoint Commercial Potential – Up to 46% slowing of disease progress
Slide 5: Broad opportunity for ATH434 in neurodegenerative disease
Broad opportunity for ATH434 in neurodegenerative disease Discovery / Natural Program: Phase 1 Phase 2 Phase 3 Collaboration Pre-clinical History For personal use only Multiple system atrophy Planning Double blind study Multiple system atrophy Open label study in advanced MSA Multiple system atrophy
Slide 6: Multiple System Atrophy (MSA): Parkinsonian disorder with no approved treatment
Multiple System Atrophy (MSA): Parkinsonian disorder with no approved treatment Urinary dysfunction Recurrent falls Rapidly progressive Up to 50,000 For personal use only REM sleep behavior disorder Indwelling catheter Orthostatic hypotension Frontal executive dysfunction Highly debilitating patient
Slide 7: Targeting the pathology in Parkinsonian disorders
For personal use only Targeting the pathology in Parkinsonian disorders
Slide 8: Targeting key players in MSA pathology
Targeting key players in MSA pathology Alpha-synuclein and iron balance in health and disease For personal use only In disease: α-Synuclein α-Synuclein protein aggregates in neurons in MSA • Present in all neurons impairing communication and • Enables neuronal communication leading to dysfunction Fe
Slide 9: Pathology of Parkinsonian disorders
Pathology of Parkinsonian disorders Increased Brain Iron in Areas of Pathology For personal use only Parkinson’s disease Parkinson’s disease Multiple System Atrophy Putamen (M) n=8 * n=7 * S. nigra (T) n = 10 n=9 n=8 * Putamen (L) n=8 S. nigra (pc) n=3 n=8 n = 13 Cerebellum n=8 n = 24 Globus pallidu
Slide 10: Excess labile iron is a key driver of pathology
Excess labile iron is a key driver of pathology causing α-synuclein aggregation and oxidative injury α-Synuclein aggregation For personal use only α-syn fibrils toxic to neurons Fe2+ PCBP Fe2+ PCBP monomer oligomers fibrils or normal Fe2+ Fe3+ Fe2+ Fe2+ Fe2+ α-syn fibrils impair Neuron death oligode
Slide 11: ATH434 mechanism of action: Iron chaperone
ATH434 mechanism of action: Iron chaperone ATH434 chaperones excess labile (reactive) iron to reduce neuronal injury For personal use only Fe2+ + Fe 3 DMT1 Labile iron ZIP8 3+ Tf ZIP14 Fe Fe2+ Chaperone mechanisms: Transferrin Fe2+ ROS receptor Fe2+ 3 Fe2+ PCBP Fe2+ Efflux iron from Fe2+ Fe2+ 1 ATH4
Slide 12: ATH434 treatment approach addresses underlying pathology
ATH434 treatment approach addresses underlying pathology Stabilize function or slow decline For personal use only Preserve neurons and oligodendrocyte cell function Based on mechanism of action, ATH434 is a Reduce α-synuclein potential disease aggregation and modifying therapy oxidative injury Chape
Slide 13: ATH434: Small molecule drug candidate
ATH434: Small molecule drug candidate Preferred by patients and doctors vs Oral administration infusions (IV, intrathecal) or injections For personal use only Blood-brain barrier Acts intracellularly to address underlying penetrant pathology ATH434 binding to labile iron Moderate binding affinity, r
Slide 14: Multiple models of neurodegenerative disease demonstrate ATH434 efficacy
Multiple models of neurodegenerative disease demonstrate ATH434 efficacy Preserve Target Midbrain iron Clinical For personal use only Model α-Synuclein neurons/ Disease (incl. s. nigra) observations function MSA1 PLP-α-syn Improved motor ATH434 consistently performance improved motor Improved motor
Slide 15: ATH434 clinical development program in MSA
For personal use only ATH434 clinical development program in MSA
Slide 16: Diligent approach to de-risk development program
Diligent approach to de-risk development program Phase 2 · Randomized, Double-blind For personal use only ATH434-201 Natural History Study Clinically meaningful efficacy on MSA rating scale, bioMUSE orthostatic hypotension and disease severity Identified biomarkers to • Randomized, double-blind, pla
Slide 17: BioMUSE natural history study results
BioMUSE natural history study results bioMUSE Optimized patient selection in Phase 2 trials Advanced MRI methods α-synuclein SAA in CSF Identified ”iron signature” of early MSA For personal use only Differentiated MSA from Parkinson’s disease (PD) Revised selection criteria in ATH434‐201 and ATH434-
Slide 18: ATH434-201: Randomized, double-blind, placebo-controlled study
ATH434-201: Randomized, double-blind, placebo-controlled study For personal use only ATH434-201 Patient criteria: Study design: Endpoints: ATH434 75 mg twice daily Key clinical endpoint: N = 77 MSA Rating Scale • Clinical diagnosis of MSA 1:1:1 ATH434 50 mg twice daily Additional secondary endpoints
Slide 19: Importance of the Unified MSA Rating Scale Part I (UMSARS I)
Importance of the Unified MSA Rating Scale Part I (UMSARS I) For personal use only ATH434-201 UMSARS Part I Items: Speech Walking UMSARS is the FDA Swallowing Falling endorsed endpoint Handwriting Orthostatic symptoms to support approval Rated from 0 to 48 higher scores worse for the treatment of Cu
Slide 20: Baseline characteristics
Baseline characteristics ATH434-201 Placebo ATH434-201 ATH434-201 50 mg twice daily 75 mg twice daily N=22 N=25 N=24 For personal use only Age (y) 61.3 (6.6) 63.1 (6.1) 63.9 (6.7) Gender (% male) 63.6% 52.0% 62.5% Groups balanced at Duration of motor baseline except for 2.5 (0.8) 2.6 (0.8) 2.3 (0.9)
Slide 21: Clinically Significant Efficacy on 11-Item UMSARS I
Clinically Significant Efficacy on 11-Item UMSARS I ATH434-201 Change from Baseline to Week 52 26 For personal use only Placebo Difference v. Relative 24 placebo treatment N=22 LS mean (SE) effect Modified UMSARS I 22 ATH434 worsening 20 50 mg -3.7 (1.7) 46% N=25 18 * 16 P =0.037 ATH434 for 50 mg 75
Slide 22: Consistent efficacy across multiple domains on 11-item UMSARS
Consistent efficacy across multiple domains on 11-item UMSARS ATH434 treatment demonstrates a similar pattern of efficacy in both dose groups vs. placebo at 52 weeks For personal use only 50 mg BID 75 mg BID ç Improvement ç Improvement mod. total mod. total speech speech UMSARS Part I item UMSARS Pa
Slide 23: Achieved Efficacy on Clinical Global Impression of Severity
Achieved Efficacy on Clinical Global Impression of Severity ATH434-201 Clinician Reported Outcome For personal use only 1.5 CGI-S (Week 52-Baseline) • 7-point scale Change in CGIS 1.0 • higher score indicates a worse outcome Worsening * p=0.006 Assesses total picture over prior 28 days • illness sev
Slide 24: Achieved Efficacy on Swallowing Disturbance Questionnaire
Achieved Efficacy on Swallowing Disturbance Questionnaire ATH434-201 Patient Reported Outcome For personal use only 10 Validated Scale for Detecting Dysphagia (Week 52-Baseline) Change in SDQ 15-item questionnaire that assesses swallowing impairment (choking, Worsening 5 * coughing when drinking liq
Slide 25: Improvement on Orthostatic Hypotension Symptom Assessment (OHSA)
Improvement on Orthostatic Hypotension Symptom Assessment (OHSA) ATH434-201 Patient Reported Outcome 10 For personal use only Change In OHSA (week S2‒ BL) worsening 5 0 Assesses symptoms of low blood pressure when going from sitting to standing (e.g., dizziness / feeling -5 faint / lightheadedness)
Slide 26: ATH434 preserved walking in outpatient setting
ATH434 preserved walking in outpatient setting ATH434-201 Change from baseline to Week 52 Step count Total time walking Placebo 0 0 For personal use only Change in minutes/day Change in Steps/day -10 ATH434-201 -1000 50 mg Worsening Worsening -20 ATH434-201 -2000 75 mg * p=0.1049 p=0.1506 P=0.0436 P
Slide 27: Favorable safety profile for ATH434
Favorable safety profile for ATH434 ATH434-201 Placebo ATH434-201 ATH434-201 For personal use only twice daily 50 mg 75 mg N (%) of subjects 1 N=26 N=25 N=26 • Similar rates of Any Adverse Event (AE) 24 (92.3%) 21 (84.0%) 25 (96.2%) AEs in ATH434 and placebo UTI 14 (53.8%) 10 (40.0%) 7 (26.9%) parti
Slide 28: Neuroimaging
For personal use only Neuroimaging
Slide 29: Measuring Iron Content with MRI (QSM)
Measuring Iron Content with MRI (QSM) Regional increases in iron in MSA Patient Substantia Nigra Putamen / Globus Pallidus For personal use only Midbrain axial view Basal ganglia axial view QSM: Quantitative Susceptibility Mapping І QSM overlay: warm colors = higher magnetic susceptibility (iron con
Slide 30: Iron Deposition on MRI in Placebo: Change Baseline to Week
Iron Deposition on MRI in Placebo: Change Baseline → Week 52 For personal use only ATH434-201 Mean ± 95% CI 30
Slide 31: Iron Deposition on MRI: ATH434 vs. Placebo
Iron Deposition on MRI: ATH434 vs. Placebo For personal use only ATH434-201 MMRM with sex, age, baseline CSF NfL, and baseline iron as covariates 31
Slide 32: ATH434 decouples iron accumulation from clinical worsening
ATH434 decouples iron accumulation from clinical worsening Correlation Between Change in Iron and Change in UMSARS I Score at Week 52 For personal use only Controlling for Sex, Age, Baseline CSF NfL, Baseline QSM 32
Slide 33: Summary: ATH434 Interrupts the Pathologic Process in MSA
Summary: ATH434 Interrupts the Pathologic Process in MSA For personal use only Iron builds up in the basal In placebo-treated patients, In ATH434-treated patients, ganglia of MSA patients, change in iron strongly change in iron weakly most prominently in the correlates with change in correlates with
Slide 34: ATH434 showed trends in preserving brain volume in MSA
ATH434 showed trends in preserving brain volume in MSA Regions of Interest Change in Brain Volume* 26 weeks 52 weeks For personal use only 0.0000 -0.1000 Subject 1 -0.2000 worsening Z-score -0.3000 -0.4000 -0.5000 -0.6000 Subject 2 Placebo ATH434-201 ATH434-201 50 mg BID 75 mg BID * MSA Atrophy Inde
Slide 35: Carefully designed Phase program demonstrates potential for ATH434 in MSA
Carefully designed Phase 2 program demonstrates potential for ATH434 in MSA ATH434 demonstrated clinically significant efficacy in slowing disease progression in MSA For personal use only Both dose levels efficacious on 11-Item Preserved walking in outpatient setting as UMSARS and important secondar
Slide 36: Successful End-of-Phase meeting with FDA alignment on Phase 3 design
Successful End-of-Phase 2 meeting with FDA alignment on on key elements of the Phase 3 design Primary endpoint: Selection and scoring of the 11-Item UMSARS Part I For personal use only Population: ~200 patients with clinical and biomarker evidence of MSA Dosing regimen: 50 mg dose administered twice
Slide 37: FDA alignment on Phase 3 trial design
FDA alignment on Phase 3 trial design Expect to initiate trial activities by YE 2026 Patient criteria: Study design: Efficacy Endpoints: For personal use only ATH434 Primary endpoint N = ~200 Selection and scoring of 50 mg twice daily the 11-Item UMSARS Part I • Clinical diagnosis of MSA 1:1* • Ambu
Slide 38: Commercial assessment & corporate overview
For personal use only Commercial assessment & corporate overview
Slide 39: Independent commercial assessment in MSA
Independent commercial assessment in MSA Target product profile based on positive Phase 2 data For personal use only Over 70% of neurologists Severely debilitating illness Importance of inhibiting Slowing disease progression is were “extremely likely” or with no approved treatment α‐synuclein aggreg
Slide 40: Positioned for Success
Positioned for Success For personal use only REGULATORY PHASE 3 READINESS MILESTONES BUILDING VALUE ACTIVITIES • FDA alignment on Phase 3 study • Clinical site identification and • New U.S. composition of matter design qualification patent granted for ATH434 with • Type C alignment on clinical • Man
Slide 41: For personal use only
For personal use only ASX: ATH NASDAQ: ATHE
Slide 42: APPENDIX
For personal use only APPENDIX 42
Slide 43: Inadequately chaperoned cellular iron drives MSA pathology
Inadequately chaperoned cellular iron drives MSA pathology Promotes α-synuclein cross linking1 Christine Kaindlstorfer, Kurt A Jellinger, Sabine Eschlbök, Nadia Stefanova, Günter Weiss, Gregor K Wenning For personal use only Journal of Alzheimer’s Disease (2018) DOI 10.3233/JAD-170601 Iron converts
Slide 44: Animal data supporting Phase dose selection
Animal data supporting Phase 2 dose selection PLP-α-syn MSA Mouse model MPTP Mouse model For personal use only 6000 6000 Total SNpc neurons Total SNpc neurons *** *** *** *** 5000 * ** *** 4000 3000 3000 2000 0 Veh 3 10 30 WT 0 1 3 10 30 80 C ATH434 (mg/kg) ATH434 (mg/kg) Exposure at 3 mg/kg ~ to 50
Slide 45: ATH434 affinity for Fe2+ and Fe3+ relative to endogenous iron binding proteins
ATH434 affinity for Fe2+ and Fe3+ relative to endogenous iron binding proteins Fe2+ Fe3+ µM constant µM constant For personal use only ATH434 4.6a 10-5.33 0. 0003b 10-9.6 PCBPs 0.9c 10-6.04 5.8c 10-5.24 Glutathione ~8d 10-5.10 Transferrin 10-23 e a: Pall et al 2024 | b: Finkelstein et al 2017, consi
Slide 46: Iron is a key driver of the MSA Pathology
Iron is a key driver of the MSA Pathology ATH434 chaperones excess iron to reduce neuronal injury For personal use only MSA Pathology Cycle Reactive iron Disrupted Generates free radicals Control of Promotes α-synuclein aggregation CNS Iron Overwhelms Oxidative stress natural iron Key disease Disrup
Slide 47: Correlation Between Change in Iron and Change in UMSARS I Score at Week 52
Correlation Between Change in Iron and Change in UMSARS I Score at Week 52 ATH434 decouples iron accumulation from clinical worsening For personal use only Controlling for Sex, Age, Baseline CSF NfL, Baseline QSM 47
Slide 48: ATH434-201: Populations and key endpoints
ATH434-201: Populations and key endpoints ATH434-201 6 no post baseline UMSARS I Clinical analysis 71 population For personal use only 77 Randomized Imaging analysis 61 population 5 neg. CSF α-syn SAA 10 d/c before week 26 1 completed week 26 w/o MRI Endpoint Change from BL to week 52 Population Bio
Slide 49: ATH434-202: Open label study in advanced MSA
ATH434-202: Open label study in advanced MSA ATH434-202 Design Single arm, open-label For personal use only Objective Assess safety and efficacy in advanced MSA Population Advanced MSA (n=10) Treatment ATH434 75 mg BID x 12 months Brain MRI Biomarkers Volume, Iron The study indicates the potential o
Slide 50: ATH434-202: Open label study in advanced MSA
ATH434-202: Open label study in advanced MSA For personal use only ATH434-202 ATH434-202 ATH434-201 Parameter 75 mg BID 75mg BID N=10 N=24 Key objective was to assess efficacy Age (yr) 64.5 (7.5) 63.9 (6.7) and safety of Duration of motor symptoms (yr) 3.9 (1.8) 2.3 (0.9) ATH434 75 mg dose Modified
Slide 51: ATH434-202: Key data at 75 mg dose
ATH434-202: Key data at 75 mg dose ATH434-202 Comparison to double blind study at 12 mo For personal use only ATH434-202 ATH434-201 Change over 12 Months 75 mg BID 75mg BID The 75 mg dose N=10 N=24 demonstrated 3.5 (4.7) 5.6 (5.6) comparable efficacy Modified UMSARS I to that observed in Clinical gl
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