Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (January 2026)
37 slides from Alterity Therapeutics's investor presentation, Jan 13, 2026
Slide 1: January 2026 Corporate Presentation
January 2026 Corporate Presentation
Slide 2: Forward looking statements
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,
Slide 3: Alterity is a late clinical stage biopharmaceutical company
Alterity is a late clinical stage biopharmaceutical company dedicated to developing treatments for neurodegenerative diseases Our goal is to slow the course of disease progression We strive to create an alternate future and improve patient quality of life Alterity means the state of being different
Slide 4: Investment highlights
Investment highlights 4 Positive Phase 2 data in Multiple system atrophy, a Parkinsonian disorder Large market potential in neurodegenerative diseases Highly experienced leadership team in movement disorders Oral administration preferred over competition Robust efficacy on functional endpoint in dou
Slide 5: Promising portfolio in neurodegenerative diseases
Promising portfolio in neurodegenerative diseases 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 Fri
Slide 6: Multiple System Atrophy: Parkinsonian disorder with no approved treatment
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, un
Slide 7: Targeting the pathology in Parkinsonian disorders
Targeting the pathology in Parkinsonian disorders
Slide 8: Alpha-synuclein and iron balance vital for normal CNS function
Alpha - synuclein and iron balance vital for normal CNS function Two forms of iron required for cellular function: • Energy production and activity of many enzymes • Neurotransmitter synthesis (e.g., dopamine) • Myelin synthesis α - Synuclein protein: • Present in all neurons • Regulates neurotransm
Slide 9: Pathology of Parkinsonian disorders
Pathology of Parkinsonian disorders α - synuclein Aggregation PET imaging of α - synuclein pathology (18F - C05 - 05) Parkinson’s disease n = 24 n = 13 n = 9 n = 7 * n = 3 n = 8 * 0 30000 S. nigra (T) S. nigra (pc) Cerebellum 10000 20000 nmol iron/g of human brain Multiple system atrophy n = 8 n = 8
Slide 10: Role of iron and alpha-synuclein in disease pathogenesis
Iron converts native α - SYN into a β - sheet conformation and promotes its aggregation either directly or via increasing levels of oxidative stress. The disturbance of iron homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of free radicals and oxidat
Slide 11: 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 Iron imbalance Excess labile iron Fe 2+ Fe 2+ Fe 2+ Fe 2+ Fe 2+ Fe 3+ PCBP Fe 2+ Neuron death and impaired oligodendrocyte function monomer or normal oligomers fibrils α - syn fibrils damage mult
Slide 12: ATH434 mechanism of action: Iron chaperone
Fe 3+ Stable Fe 3+ 2+ Fe Reactive Fe 2+ ATH434 mechanism of action: Iron chaperone ATH434 chaperones excess labile (reactive) iron to reduce neuronal injury Sources: Adapted from Yanatori et al., BBA 2020 and Philpott et al., Frontiers Mol Bio. 2023 | Buffering Fe 2+ in labile iron pool PCBP: Poly(r
Slide 13: Treatment approach: Address underlying pathology
Treatment approach: Address underlying pathology Based on mechanism of action, ATH434 is a potential disease modifying therapy Chaperones excess labile iron in the CNS Reduces α - synuclein aggregation and oxidative injury Preserves neurons and oligodendrocyte cell function Stabilizes or improves pa
Slide 14: ATH434: Small molecule drug candidate
ATH434: Small molecule drug candidate 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 intr
Slide 15: Accumulated evidence of ATH434 efficacy
Accumulated evidence of ATH434 efficacy 15 Sources: Bradbury et al, Am Acad. Neurol 2024; Finkelstein, Acta Neuropath Comm 2017; Beauchamp et al, Neurotherapeutics 2022; 1 Heras - Garvin et al, Mov Disord. 2021; 2 Finkelstein et al, J Park Dis 2022 Clinical observations Preserve neurons / function α
Slide 16: ATH434 clinical development program in MSA
ATH434 clinical development program in MSA
Slide 17: Diligent approach to de-risk development program
Diligent approach to de - risk development program 17 • 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 tri
Slide 18: BioMUSE natural history study informs and de-risks clinical development
BioMUSE natural history study informs and de - risks clinical development program N=21 Patient criteria: Clinically Probable MSA Biomarkers: • MRI: iron, volume, glial pathology • Fluid: NfL, aggregated α - synuclein • Digital: Wearable movement sensors Clinical: UMSARS 1, autonomic function, motor
Slide 19: BioMUSE natural history study results
BioMUSE natural history study results bioMUSE Identified ”iron signature” of early MSA Differentiated MSA from Parkinson’s disease (PD) Revised selection criteria in ATH434-201 and ATH434 - 202 protocols to exclude PD patients Improved precision of volume measurements Novel strategies for measuring
Slide 20: Randomized, double-blind, placebo-controlled study design
ATH434 - 201: Randomized, double - blind, placebo - controlled study 20 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 e
Slide 21: Importance of the Unified MSA Rating Scale Part I
Importance of the U nified MSA R ating S cale Part I (UMSARS I) 21 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 im
Slide 22: Populations and key endpoints
Populations and key endpoints 22 All patients in Imaging and Clinical analysis populations were randomized and treated Imaging analysis population Clinical analysis population 71 61 6 no post baseline UMSARS I 5 neg. CSF α - syn SAA 10 d/c before week 26 1 completed week 26 w/o MRI Population Change
Slide 23: Baseline characteristics
ATH434 - 201 ATH434 - 201 Placebo 75 mg twice daily 50 mg twice daily N=24 N=25 N=22 63.9 (6.7) 63.1 (6.1) 61.3 (6.6) Age (y) 62.5% 52.0% 63.6% Gender (% male) 2.3 (0.9) 2.6 (0.8) 2.5 (0.8) Duration of motor symptoms (y) 14.4 (4.4) 15.2 (5.4) 16.9 (3.9) Modified UMSARS I 48.9 (16.8) 47.8 (18.4) 57.6
Slide 24: Clinically significant efficacy on modified UMSARS Part I
Clinically significant efficacy on modified UMSARS Part I Change from baseline to week 52 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 Relative Treatment Effect
Slide 25: Efficacy on Clinical Global Impression of Severity scale
Efficacy on Clinical Global Impression of Severity (CGI - S) scale Change from baseline to week 52 Clinical Analysis Population 25 1.5 1.0 * p=0.009 0.5 0.0 worsening Change in CGI - S (week 52 - Baseline) ATH434 - 201 50 mg Placebo • CGI - S • 7 - point scale, ranging from 1 to 7 • higher score ind
Slide 26: Orthostatic Hypotension Symptom Assessment
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
Slide 27: ATH434 preserved walking in outpatient setting
0 - 50 - 100 worsening 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 - 3
Slide 28: Adverse Events
28 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 75 mg N=26 ATH434 - 201 50 mg N=25 Placebo twice daily N=26 N (%) of su
Slide 29: Neuroimaging Endpoints
Neuroimaging Endpoints 29 * MSA Atrophy Index: composite z - score of putamen, GP, cerebellum and brainstem vs. healthy age - matched population Change in Iron Content by MRI ATH434 demonstrated target engagement on reducing iron on MRI • Reduced/stabilized iron content in Pallidum (GP) > Putamen •
Slide 30: ATH434-202: Open label study in advanced MSA
ATH434 - 202: Open label study in advanced MSA 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 ATH434 - 202 75mg BID 75 mg BID Parameter N=24 N=10 63.9 (6.7) 64.5 (7.5) Age (yr) 2.3 (0.9) 3.9 (1.8) Duration of
Slide 31: ATH434-202: Key data at 75 mg dose
ATH434 - 201 ATH434 - 202 75mg BID 75 mg BID Change over 12 Months N=24 N=10 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 d
Slide 32: ATH434 Phase summary
ATH434 Phase 2 summary Double - blind trial: ATH434 demonstrated clinically significant efficacy in slowing disease progression in MSA • Both dose levels efficacious on UMSARS I and important secondary endpoints • Efficacy signal at 75 mg strengthens when accounting for baseline differences in sever
Slide 33: Commercial assessment & corporate overview
Commercial assessment & corporate overview
Slide 34: Approach to commercial assessment
Approach to commercial assessment Conducted by independent marketing research and forecasting group • 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 an
Slide 35: Key attributes of ATH434 drive significant commercial opportunity in MSA
Key attributes of ATH434 drive significant commercial opportunity in MSA 35 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 i
Slide 36: Key Objectives for 2026
Key Objectives for 2026 36 Finalize Regulatory Strategy • Align with the U.S. FDA on pivotal Phase 3 clinical trial protocol • Conduct meetings related to non - clinical data and chemistry/manufacturing • End of Phase 2 meeting mid - year Build for Scalable Growth • Expand intellectual property prot
Slide 37: Alterity Therapeutics
ASX: ATH ofiys Alterity NASDAQ: ATHE THERAPEUTICS
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