Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (April 2026)
39 slides from Alterity Therapeutics's investor presentation, Apr 1, 2026
Slide 1: Corporate Presentation April 2026
For personal use only Corporate Presentation April 2026
Slide 2: Forward looking statements
Forward looking statements For personal use only 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
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 biopharmaceutical Our goal is to slow the course of disease progression company 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 Advancing ATH434, a Potential First-in-Class, Disease-Modifying Therapy for Multiple System Atrophy (MSA) Differentiated, Disease- Oral iron chaperone ATH434 targets excess reactive iron and α-synucleinopathies For personal use only Modifying Approach for
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 Planned 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 * n=8 S. nigra (pc) Putamen (L) n=3 n=8 n = 13 Cerebellum n=8 n = 24 Globus pallidu
Slide 10: 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 11: Treatment approach: Address underlying pathology
Treatment approach: Address 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 aggregation and potential disease oxidative injury modifying therapy Chaperone exc
Slide 12: 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 13: 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 14: ATH434 clinical development program in MSA
For personal use only ATH434 clinical development program in MSA
Slide 15: Diligent approach to de-risk development program
Diligent approach to de-risk development program Natural History Study Phase 2 For personal use only bioMUSE ATH434-201 Randomized double-blind placebo-controlled trial • Observational study in 21 Results: clinically meaningful efficacy on participants with clinically MSA rating scale, measures of o
Slide 16: 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 17: 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 18: 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 Swallowing Falling FDA endorsed Handwriting Orthostatic symptoms clinical endpoint Rated from 0 to 48 higher scores worse to support Cutting food Urinary fu
Slide 19: Populations and key endpoints
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 Biomarker (Prim
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 2.5 (0.8) 2.6 (0.8) 2.3 (0.9) baseline except for
Slide 21: Clinically significant efficacy on modified UMSARS Part I
Clinically significant efficacy on modified UMSARS Part I ATH434-201 Change from baseline to week 52 26 For personal use only Placebo Difference Relative 24 vs. placebo treatment N=22 LS mean (SE) effect Modified UMSARS I 22 ATH434 20 worsening 50 mg - 3.8 (1.6) 48% N=25 18 * 16 P=0.02 ATH434 for 50
Slide 22: Efficacy on Clinical Global Impression of Severity (CGI-S) scale
Efficacy on Clinical Global Impression of Severity (CGI-S) scale ATH434-201 Change from baseline to week 52 For personal use only 1.5 • CGI-S (week 52 - Baseline) • 7-point scale Change in CGI-S 1.0 • higher score indicates a worse outcome worsening * p=0.009 • Assesses total picture over prior 28 d
Slide 23: Orthostatic Hypotension Symptom Assessment (OHSA)
Orthostatic Hypotension Symptom Assessment (OHSA) ATH434-201 Change from baseline to week 52 10 For personal use only Change In OHSA (week S2 BL) worsening 5 p=0.08 p=0.14 0 • Assesses symptoms of low blood pressure when going from sitting to mean (SE) standing (e.g., dizziness / feeling faint / -5
Slide 24: 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 ATH434-201 Change In steps/day -10 -1000 50 mg worsening worsening -20 ATH434-201 p = 0.04 p = 0.13 75 mg -2000 * p = 0.15 p
Slide 25: Adverse Events
Adverse Events 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%) participants Fall 8 (30.8%
Slide 26: Neuroimaging showed target engagement and trends in reduced atrophy
Neuroimaging showed target engagement and trends in reduced atrophy ATH434-201 Reduced Iron Accumulation on MRI Change in Brain Volume* 26 weeks 52 weeks For personal use only 50 mg 75 mg 0.0000 Region Week 26 Week 52 Week 26 Week 52 -0.1000 ¶ Pallidum -0.2000 worsening Z-score Putamen -0.3000 S. ni
Slide 27: 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 28: Phase 2 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 UMSARS I Preserved walking in outpatient setting as and important secondary endp
Slide 29: Proposed Phase 3 trial design
Proposed Phase 3 trial design Patient criteria: Study design: Endpoints: For personal use only ATH434 Primary endpoint: N = ~200 twice daily MSA Rating Scale (UMSARS I) FDA endorsed clinical endpoint • Clinical diagnosis of MSA 1:1 • Ambulatory without assistance • No severe impairment Secondary end
Slide 30: Commercial assessment & corporate overview
For personal use only Commercial assessment & corporate overview
Slide 31: 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 32: Key Objectives for 2026
Key Objectives for 2026 The Foundation is Set • Robust efficacy in Phase 2 study in MSA, a rapidly progressive rare disease with no approved treatment For personal use only • Commercial assessment supports significant opportunity: USD $2.4B potential peak sales • Moving into Phase 3 program led by a
Slide 33: For personal use only
For personal use only ASX: ATH NASDAQ: ATHE
Slide 34: APPENDIX
For personal use only APPENDIX 34
Slide 35: 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 Iron converts native α-SYN into a β-sheet conformation and promotes Directl
Slide 36: Excess labile iron is the key driver of pathology
Excess labile iron is the key driver of pathology causing α‐synuclein aggregation and oxidative injury α-Synuclein aggregation For personal use only α-syn fibrils damage multiple organelles Fe2+ PCBP Fe2+ PCBP monomer oligomers fibrils or normal Fe2+ Fe3+ Fe2+ Fe2+ Fe2+ α-syn fibrils Neuron death im
Slide 37: 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+ DMT1 Labile iron ZIP8 ZIP14 Fe2+ Chaperone Transferrin receptor Fe2+ 3 Fe2+ Fe2+ ROS mechanisms: PCBP Fe2+ Efflux iron from Fe2+ Fe2+ 1 ATH434 Fe2+ Fe2+ Fe2
Slide 38: 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 39: 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 75 mg BID 75mg BID Change over 12 Months The 75 mg dose N=10 N=24 demonstrated comparable efficacy Modified UMSARS I 3.5 (4.7) 5.6 (5.6) to that observed in Clinical gl
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