Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (July 2025)
35 slides from Alterity Therapeutics's investor presentation, Jul 31, 2025
Slide 1: July 2025 Corporate Presentation
July 2025 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 individuals living with neurodegenerative diseases Our goal is to slow the course of disease We strive to create an alternate future and improve patient quality of life Alterity means the state of bein
Slide 4: Investment highlights
Investment highlights 4 Positive Phase 2 data in multiple system atrophy (MSA), a Parkinsonian disorder Demonstrated robust efficacy on functional endpoint endorsed by FDA/EMA Large market potential in neurodegenerative diseases Highly experienced leadership team in movement disorders Oral administr
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: Targeting the pathology in Parkinsonian disorders
Targeting the pathology in Parkinsonian disorders
Slide 7: Alpha-synuclein and iron balance are important for normal CNS function
Alpha - synuclein and iron balance are important 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 neuro
Slide 8: Pathology of Parkinsonian disorders
Pathology of Parkinsonian disorders α - synuclein Aggregation Increased Brain Iron Parkinson’s disease Multiple system atrophy n = 24 n = 9 n = 7 * n = 3 n = 13 n = 8 * 0 10000 20000 nmol iron/g of human brain 30000 Putamen (M) Putamen (L) Globus pallidus (M) Globus pallidus (L) S. nigra (T) n = 11
Slide 9: Role of iron and α-synuclein in disease pathogenesis
Role of iron and α - synuclein in disease pathogenesis Iron converts native ˣ - SYN into a ˤ - sheet conformation and promotes its aggregation either directly or via increasing levels of oxidative stress. The disturbance of its [iron] homeostasis leads to abnormal iron deposition in the brain and ca
Slide 10: Excess reactive iron drives α-synuclein aggregation and oxidative injury
Iron imbalance Mitochondrial dysfunction ROS damage to cellular components. Lipid peroxidation monomer or normal oligomers fibrils Increased ROS α - - syn fibrils damage multiple organelles Neuron death and impaired oligodendrocyte function α - syn fibrils impair myelin production in MSA α - Synucle
Slide 11: Treatment approach: Address underlying pathology
Treatment approach: Address underlying pathology Redistributes excess labile iron in the CNS Potential Disease Modifying Therapy Reduces α - synuclein aggregation and oxidative injury Preserves neurons and oligodendrocyte support cells Stabilises or improves patient function 11
Slide 12: ATH434: Potential disease modifying drug candidate
ATH434: Potential disease modifying drug candidate ATH434 binding to iron Small molecule Penetrates blood - brain barrier and acts intracellularly to address pathology Oral administration Preferred by patients and doctors vs infusions (IV, intrathecal) or injections Iron chaperone Moderate binding a
Slide 13: Accumulated evidence of ATH434 efficacy
Clinical observations Preserve neurons / function α - Synuclein Midbrain iron incl. s. nigra Model Target disease Improved motor performance n/a Monkey MPTP Parkinson’s disease Improved motor performance Monkey MPTP Parkinson’s disease Improved motor performance Mouse A53T Parkinson’s disease Improv
Slide 14: ATH434 clinical development program in MSA
ATH434 clinical development program in MSA
Slide 15: Multiple System Atrophy: Parkinsonian disorder with no approved treatment
Multiple System Atrophy (MSA): Parkinsonian disorder with no approved treatment 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) • Highly debilitating an
Slide 16: Our diligent clinical development approach in MSA
Our diligent clinical development approach to achieve meaningful outcomes in MSA • observational study in individuals with MSA • designed to de - risk clinical development program • optimized patient selection for Phase 2 trials Phase 1 Program Phase 2: ATH434 - 201 ATH434 - 202 Randomized double -
Slide 17: BioMUSE natural history study informs and de-risks treatment studies
BioMUSE natural history study informs and de - risks treatment studies BioMUSE natural history study allowed us to optimize patient selection for our Phase 2 trials • Iron content: Significant increase in iron observed at 12 months in key brain region (substantia nigra) • Brain volume: Significant d
Slide 18: BioMUSE natural history study results
BioMUSE natural history study results bioMUSE Optimized patient selection in Phase 2 trials: Advanced MRI methods: α - synuclein in CSF: Precision biomarker assessment: Structural mapping: Iron content in substantia nigra: Identified ”iron signature” of early MSA Differentiated MSA from Parkinson’s
Slide 19: Phase 2 randomized, double-blind, placebo-controlled trial design
ATH434 - 201 randomized, double - blind, placebo - controlled trial 19 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 en
Slide 20: Importance of the Unified MSA Rating Scale Part I
Importance of the Unified MSA Rating Scale Part I (UMSARS I) UMSARS is the FDA endorsed clinical endpoint to support approval for the treatment of MSA ATH434 - 201 Speech Walking Swallowing Falling Handwriting Orthostatic symptoms Cutting food Urinary function Dressing Bowel function Hygiene Sexual
Slide 21: Populations and key endpoints
Criteria * Population: Change from BL to week 52: Endpoint: ≥ 1 post - baseline MRI (26 weeks) (+) aggregating α - synuclein SAA Imaging Iron content in s. nigra by MRI Primary (Biomarker) ≥ 1 post - baseline UMSARS I (13 weeks) Clinical Change in Modified UMSARS Part I Key secondary (Clinical) 21 *
Slide 22: Baseline characteristics
ATH434 - 201 75 mg twice daily ATH434 - 201 50 mg twice daily Placebo Age (y) N=24 N=25 N=22 63.9 (6.7) 63.1 (6.1) 61.3 (6.6) 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 I1 48.9 (16.8) 47.8 (18.4) 57.
Slide 23: Clinically significant efficacy on modified UMSARS Part I
Achieved clinically significant efficacy on modified UMSARS Part I change from baseline to week 52 ATH434 - 201 26 24 22 20 18 16 12 0 14 worsening 26 Week Modified UMSARS I 52 39 13 p=0.16 for 75 mg p=0.02 for 50 mg Relative treatment effect Difference vs. placebo LS mean (SE ) Placebo N=22 48% - 3
Slide 24: Efficacy on Clinical Global Impression of Severity
Efficacy on Clinical Global Impression of Severity (CGI - S) scale change from baseline to week 52 Clinical Analysis Population 24 1.5 1.0 * p=0.009 0.5 0.0 worsening Change in CGI - S (week 52 - Baseline) ATH434 - 201 50 mg ATH434 - 201 75 mg LS mean (SE) Placebo • CGI - S is a single - item questi
Slide 25: Efficacy on Orthostatic Hypotension Symptom Assessment
Efficacy on Orthostatic Hypotension Symptom Assessment (OHSA) change from baseline to week 52 ATH434 - 201 10 p=0.08 5 - 5 0 worsening Change In OHSA (week S2 BL) p=0.14 ATH434 50 mg ATH434 75 mg Placebo OHSA: component of the orthostatic hypotension questionnaire Assesses severity of six symptoms:
Slide 26: ATH434 preserved activity in outpatient setting
ATH434 - 201 Step count worsening 0 - 1000 - 2000 - 3000 Change In steps/day p = 0.0437* p = 0.1041 Total time walking Change In bouts/day Total standing time Pendant for wearable sensor ATH434 - 201 50 mg ATH434 - 201 75 mg Placebo Change In minutes/day 0 - 10 - 20 - 40 - 30 p = 0.1267 p = 0.1535 w
Slide 27: Adverse Events
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
Slide 28: Neuroimaging Endpoints
Neuroimaging Endpoints ATH434 - 201 Change in Iron Content by MRI Evidence of target engagement • Reduced/stabilized iron content in Pallidum (GP) > Putamen • Reduced iron content in s. nigra at 50 mg dose but not 75 mg (primary endpoint) Compared to placebo: ^p = 0.025, *p = 0.08 Iron content, No o
Slide 29: Trial conclusions
ATH434 - 201 trial conclusions 29 • ATH434 demonstrated clinically significant efficacy in modifying disease progression in MSA Both 50 and 75 mg efficacious on UMSARS I and important secondary endpoints • Demonstrated target engagement with reduced iron accumulation in MSA affected brain regions •
Slide 30: ATH434 open-label study design
ATH434 - 202 - study design 30 Single arm, open - label Design Efficacy and safety of ATH434 Objectives Advanced MSA (n=10) Population ATH434 75 mg BID x 12 months Treatment Iron, volume Brain MRI Biomarkers NfL, Aggregated α - synuclein Fluid Biomarkers UMSARS I, clinical/patient global impressions
Slide 31: ATH434 baseline characteristics compared to double-blind study
ATH434 202 - Baseline characteristics Comparison to 75 mg group in double - blind study 31 ATH434 - 201 | 75mg BID (N=24) ATH434 - 202 | 75 mg BID (N=10) Parameter 63.9 (6.7) 64.5 (7.5) Age (yr) 62.5% 30.0% Gender (% male) 2.3 (0.9) 3.9 (1.8) Duration of motor symptoms (yr) 14.4 (4.4) 19.2 (5.3) Mod
Slide 32: ATH434 key efficacy data at 12 months
ATH434 - 202 - Key efficacy data at 75 mg Comparison to double blind study at 12 mo 32 The 75 mg dose demonstrated comparable efficacy to that observed in the double - blind study ATH434 - 201 | 75mg BID (N=24) ATH434 - 202 | 75 mg BID (N=10) Parameter 5.6 (5.6) 3.5 (4.7) Modified UMSARS I 21% 30% C
Slide 33: Significant commercial opportunity in MSA
Significant commercial opportunity in MSA $US1.1+ Billion Potential U.S. annual peak sales for ATH434 in MSA Substantial unmet need Severely debilitating illnesses with no current treatments are ripe for new entrants targeting underlying pathology of the disease. Unique MoA Inhibition of protein agg
Slide 34: Creating strong momentum in 2025
Creating strong momentum in 2025 5 Strong cash balance: A $40.7M as of 30 June Robust efficacy in Phase 2 double - blind trial Highly experienced development team with multiple FDA approvals in neurology Lead indication MSA is an Orphan Disease with no approved treatment Open label trial and Natural
Slide 35: Thank you
THANK YOU ofiye Alterity THERAPEUTICS
Alterity Therapeutics — Investor Presentation (July 2025) on 6ix