Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (September 2025)
38 slides from Alterity Therapeutics's investor presentation, September 2025
Slide 1: Corporate Presentation September 2025
Corporate Presentation September 2025
Slide 2: Forward looking statements
Forward looking statements 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, objec
Slide 3: Alterity means the state of being different
Alterity means the state of being different Alterity is a late clinical stage biopharmaceutical Our goal is to slow the course of disease company dedicated to developing treatments for neurodegenerative diseases We strive to create an alternate future and improve patient quality of life 3
Slide 4: Investment highlights
Investment highlights Positive Phase 2 data in Large market potential Oral administration Highly experienced Multiple system atrophy, in neurodegenerative preferred over leadership team in a Parkinsonian disorder diseases competition movement disorders Robust efficacy on Potential to treat Parkinson
Slide 5: Promising portfolio in neurodegenerative diseases
Promising portfolio in neurodegenerative diseases Program: Indication: Discovery Pre-clinical Phase 1 Natural History Phase 2 Phase 3 Collaboration Multiple system atrophy ATH434-201 Positive topline data Double blind study Multiple system atrophy ATH434-202 Positive topline data Open label study Mu
Slide 6: Targeting the pathology in Parkinsonian disorders
Targeting the pathology in Parkinsonian disorders
Slide 7: Alpha-synuclein and iron balance vital for normal CNS function
Alpha-synuclein and iron balance vital for normal CNS function α-Synuclein protein: • Present in all neurons • Regulates neurotransmitter release • Facilitates neuronal communication Myelination Two forms of iron required for cellular function: of axons Fe3+ Fe2+ • Energy production and activity of
Slide 8: Pathology of Parkinsonian disorders
Pathology of Parkinsonian disorders α-synuclein Aggregation Increased Brain Iron Parkinson’s disease n=7 * S. nigra (T) n=9 Healthy n=8 * Control S. nigra (pc) n=3 n = 13 Cerebellum n = 24 0 10000 20000 30000 nmol iron/g of human brain PET imaging of Multiple system atrophy Parkinson’s α-synuclein P
Slide 9: Role of iron and α-synuclein in disease pathogenesis
Role of iron and α-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 neuroto
Slide 10: Excess labile iron is the key driver of pathology
Excess labile iron is the key driver of pathology causing oxidative damage and α-Synuclein aggregation Fe2+ Lipid peroxidation ROS PCBP Fe2+ PCBP Increased Mitochondrial dysfunction ROS ROS damage to cellular components. Fe2+ Fe3+ Fe2+ Fe2+ Fe2+ Fe2+ α-Synuclein aggregation Iron Excess Neuron death
Slide 11: ATH434 mechanism of action: iron chaperone
ATH434 mechanism of action: iron chaperone ATH434 redistributes excess labile (reactive) iron to reduce neuronal injury Fe2+ + Fe 3 DMT1 Labile iron ZIP8 3+ Tf ZIP14 Fe Fe2+ Redistribution mechanisms: Transferrin Fe2+ ROS receptor Fe2+ 3 Fe2+ PCBP Fe2+ Efflux iron from Fe2+ Fe2+ 1 ATH434 Fe2+ Fe2+ F
Slide 12: Treatment approach: address underlying pathology
Treatment approach: address underlying pathology Redistributes excess labile iron in the CNS Based on Reduces α-synuclein mechanism of aggregation and oxidative action, ATH434 is a injury potential disease modifying therapy Preserves neurons and oligodendrocyte support cells Stabilises or improves p
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 Blood-brain barrier Acts intracellularly to address underlying penetrant pathology ATH434 binding to labile iron Moderate binding affinity, redistributes Iron chap
Slide 14: Accumulated evidence of ATH434 efficacy
Accumulated evidence of ATH434 efficacy Target disease Model Midbrain iron α-Synuclein Preserve Clinical incl. s. nigra neurons / observations function Improved motor Parkinson’s disease Monkey MPTP n/a performance ATH434 consistently improved motor Improved motor Parkinson’s disease Mouse MPTP perf
Slide 15: ATH434 clinical development program in MSA
ATH434 clinical development program in MSA
Slide 16: Multiple System Atrophy: Parkinsonian disorder with no approved treatment
Multiple System Atrophy (MSA): Parkinsonian disorder with no approved treatment Urinary dysfunction Recurrent falls Highly debilitating Up to 50,000 REM sleep behavior disorder Indwelling catheter Orthostatic hypotension Frontal executive dysfunction and rapidly progressive patients in U.S. Parkinso
Slide 17: Diligent approach to de-risk development program
Diligent approach to de-risk development program Natural History Study Phase 2 bioMUSE ATH434-201 Randomized double-blind placebo-controlled trial • Observational study Results: clinically meaningful efficacy on in individuals with MSA MSA rating scale, measures of orthostatic hypotension, disease s
Slide 18: BioMUSE natural history study informs and de-risks clinical development
BioMUSE natural history study informs and bioMUSE de-risks clinical development program 12 months of N=21 observation BioMUSE natural history study Patient criteria: Objectives: allowed us to Clinically Probable MSA Optimize patient selection optimize patient Biomarkers: and endpoints selection in o
Slide 19: 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 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 P
Slide 20: ATH434-201 randomized, double-blind, placebo-controlled trial
ATH434-201 randomized, double-blind, placebo-controlled trial ATH434-201 Patient criteria: Study design: Endpoints: ATH434 75 mg twice daily Key clinical endpoint: N=77 modified UMSARS Part 1 • Clinical diagnosis of MSA ATH434 50 mg twice daily Additional secondary endpoints: • Motor symptoms ≤4 yea
Slide 21: Importance of the Unified MSA Rating Scale Part I (UMSARS I)
Importance of the Unified MSA Rating Scale Part I (UMSARS I) 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 function approval for th
Slide 22: Populations and key endpoints
Populations and key endpoints ATH434-201 6 no post baseline UMSARS I Clinical analysis 71 population 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: Criteria* ≥ 1 post-baseline MRI (2
Slide 23: 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 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 symptoms (y) severe o
Slide 24: Clinically significant efficacy on modified UMSARS Part I
Clinically significant efficacy on modified UMSARS Part I ATH434-201 Change from baseline to week 52 %# Placebo Difference Relative %" vs. placebo treatment N=22 LS mean (SE) effect Modified UMSARS I %% ATH434-201 worsening 50 mg - 3.8 (1.6) 48% %& N=25 !$ ! ATH434-201 !# "#$%$& 75 mg - 2.4 (1.7) 30
Slide 25: 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 1.5 • CGI-S (week 52 - Baseline) • 7-point scale, ranging from 1 to 7 Change in CGI-S 1.0 • higher score indicates a worse outcome worsening * p=0.009 • Assesses total picture over prior 28 da
Slide 26: Orthostatic Hypotension Symptom Assessment (OHSA)
Orthostatic Hypotension Symptom Assessment (OHSA) ATH434-201 change from baseline to week 52 10 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 lightheadedness) Place
Slide 27: 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 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 = 0.10 -30 -3000 -40
Slide 28: Adverse Events
Adverse Events ATH434-201 Placebo ATH434-201 ATH434-201 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%) 7 (28.0%) 8 (30.8%)
Slide 29: Neuroimaging Endpoints
Neuroimaging Endpoints ATH434-201 Change in Iron Content by MRI Change in Brain Volume* 26 weeks 52 weeks 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. nigra -0.4000 Compared to placebo: Iron content, No observable differenc
Slide 30: ATH434-202: Baseline characteristics
ATH434-202: Baseline characteristics ATH434-202 Design Single arm, open-label Population Advanced MSA (n=10) Treatment ATH434 75 mg BID x 12 months Brain MRI Biomarkers Iron, volume Clinical Measures UMSARS I, clinical/patient global impressions of change Key objective was to assess efficacy ATH434-
Slide 31: 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 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 global impression of cha
Slide 32: ATH434 Phase 2 summary
ATH434 Phase 2 summary Double-blind trial: ATH434 demonstrated Open-label trial: Similar clinically significant efficacy in slowing efficacy in advanced MSA as disease progression in MSA observed in double-blind study • Both dose levels efficacious on UMSARS I and important secondary • Data consiste
Slide 33: Commercial assessment & corporate overview
Commercial assessment & corporate overview
Slide 34: Determining the market opportunity for ATH434 in MSA
Determining the market opportunity for ATH434 in MSA STAGE 1 STAGE 2 STAGE 3 STAGE 4 Utilize best Develop target Understand the Quantify revenue practices marketing product profile market size, growth potential research techniques based on aggregate and any new to ensure data clinical data dynamics
Slide 35: Approach to Commercial Assessment
Approach to Commercial Assessment Conducted by independent marketing research and forecasting group Opportunity Analysis Exploratory Research Quantitative Research and Forecast • Conduct secondary market • Conduct ~30-minute online • Develop forecast assumptions research Assess unmet needs survey am
Slide 36: Key attributes of ATH434 drive significant commercial opportunity in MSA
Key attributes of ATH434 drive significant commercial opportunity in MSA Slowing disease progression is Over 70% of neurologists Severely debilitating illness Importance of inhibiting key driver of physician interest were “extremely likely” or with no approved treatment α‐synuclein aggregation to “v
Slide 37: Creating strong momentum in 2025
Creating strong momentum in 2025 1 2 3 4 5 Robust efficacy in Open label trial Lead indication Highly experienced Cash Balance: Phase 2 double- and Natural History MSA is an Orphan development A $40.7M as of 30 June blind trial study support Disease with no team with multiple A $20M raised in Sept.
Slide 38: ASX: ATH NASDAQ: ATHE
ASX: ATH ofiye Alterity NASDAQ: ATHE THERAPEUTICS
Alterity Therapeutics — Investor Presentation (September 2025) on 6ix