Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (April 2025)
35 slides from Alterity Therapeutics's investor presentation, Apr 22, 2025
Slide 1: David Stamler, MD CEO April 2025
David Stamler, MD CEO April 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,
Slide 3: Creating an alternate future for people living with neurodegenerative diseases
Alterity is dedicated to creating an alternate future for people living with neurodegenerative diseases We aim to disrupt the trajectory of illness and improve quality of life Alterity means the state of being different 3 Our goal is to modify the course of disease
Slide 4: Investment Highlights
• Clinical stage biopharmaceutical company developing disease modifying treatments for Parkinson’s disease and related disorders • Positive Phase 2 data in Jan ‘25 in Multiple System Atrophy, a Parkinsonian Disorder without approved therapy • Robust efficacy on key clinical endpoint • Orphan Drug De
Slide 5: Experienced Clinical Leadership Team with Multiple FDA Approvals in Neurology
Experienced Clinical Leadership Team with Multiple FDA Approvals in Neurology Margaret Bradbury, Ph.D. VP, Nonclinical Development Auspex/Teva | Neurocrine | Merck • Auspex - led strategic planning and program management in Huntington Disease chorea from IND through NDA filing • Teva - led non - cli
Slide 6: Targeting Iron-Related Neurodegenerative Diseases
Targeting Iron - Related Neurodegenerative Diseases Parkinson’s Disease Multiple System Atrophy Dementia with Lewy Bodies Parkinsonian Disorders • Iron: Central to pathology of several neurodegenerative diseases • Parkinsonian disorders include • Parkinson’s disease (PD) • Rare diseases with similar
Slide 7: Promising Portfolio in Neurodegenerative Diseases
PARTNER Promising Portfolio in Neurodegenerative Diseases PARTNER PHASE ASSET PARTNER / COLLABORATOR PHASE 2 PHASE 1 NATURAL HISTORY PRE - CLINICAL DISCOVERY INDICATION PROGRAM Topline Data Positive Multiple System Atrophy ATH434 - 201 plete Enrollment Com Multiple System Atrophy Advanced ATH434 - 2
Slide 8: Double Blind Study Achieved Target Measures for Success
Double Blind Study Achieved Target Measures for Success with Exceptional Clinical Efficacy Favorable Safety Profile No Drug Related Serious Adverse Events Clinically Meaningful Improvement on Activities of Daily Living Scale Target Engagement with Stabilization of Iron Content on MRI 8 MSA Phase 2 A
Slide 9: Significant Commercial Opportunity in Treating Multiple System Atrophy
Significant Commercial Opportunity in Treating Multiple System Atrophy Severely debilitating illnesses with no current treatments are ripe for new entrants targeting underlying pathology of the disease. Substantial Unmet Need Motivated by efficacy of treating the underlying disease and not just the
Slide 10: ATH434: Disease Modifying Drug Candidate Targeting Labile Iron and Alpha-Synuclein Aggregation
ATH434: Disease Modifying Drug Candidate Targeting Labile Iron and Alpha - Synuclein Aggregation in Parkinsonian Disorders 10
Slide 11: Alpha-Synuclein and Iron in Health
Alpha - Synuclein and Iron in Health Iron essential for important cellular functions • Red blood cell production, oxygen transport • Energy production and activity of many enzymes • Neurotransmitter synthesis in neurons α - Synuclein protein • Critical for normal function of neurons • Enables nerves
Slide 12: Excess Iron and Misfolding α-Synuclein Contribute to Pathology
Excess Iron and Misfolding α - Synuclein are Important Contributors to Pathology in Parkinsonian Disorders Neuroinflammation Iron Imbalance Stored iron Labile iron • Needed for cellular functions Oxidative Injury Vicious cycle of cellular injury Effect Pathology Driver Alpha - synuclein aggregation
Slide 13: Increased Brain Iron in Parkinson's Disease and Multiple System Atrophy
Increased Brain Iron in Parkinson’s Disease and Multiple System Atrophy Dexter et al. Brain.1991 Parkinson’s disease Multiple System Atrophy n = 24 n = 13 n = 9 n = 7 * n = 3 n = 8 * 10000 20000 nmol iron/g of human brain 0 30000 Cerebral cortex Caudate nucleus Putamen (M) Putamen (L) Globus pallidu
Slide 14: Treatment Approach: Address Underlying Pathology
Treatment Approach: Address Underlying Pathology Potential Disease Modifying Therapy for MSA Redistribute excess labile iron in the CNS Reduce α - synuclein aggregation and Oxidative injury Rescue brain cells/ neuronal function 14
Slide 15: ATH434: Potential Disease Modifying Therapy
ATH434: Potential Disease Modifying Therapy ATH434 binding to iron • Small molecule drug candidate • Iron chaperone redistributes excess labile iron in CNS • Oral medication • Preferred over infusions and injections • Potential to treat iron - related neurodegenerative diseases • Orphan Drug Designa
Slide 16: Accumulated Evidence of ATH434 Efficacy
Clinical Observations Preserve Neurons/ Function α - Synuclein Midbrain* Iron Model Target Disease Improved motor performance n/a ⭤ or Monkey MPTP Parkinson’s disease Improved motor performance Mouse MPTP Parkinson’s disease Improved motor performance Mouse A53T Parkinson’s disease I
Slide 17: ATH434 Improved Behavior and Function in Monkey Model of Parkinson's Disease
• Monkey closely related to humans in neuroanatomy and behavior • ATH434 improved behavior and function in monkeys with experimental Parkinson’s disease • Improvement in Parkinson’s symptoms in animals with redistributed brain iron • Data validate clinical approach and increase overall confidence in
Slide 18: ATH434 Clinical Development Program in Multiple System Atrophy
ATH434 Clinical Development Program in Multiple System Atrophy 18
Slide 19: Multiple System Atrophy: Parkinsonian Disorder with No Approved Treatment
Multiple System Atrophy (MSA): Parkinsonian Disorder with No Approved Treatment 19 • Rare, highly debilitating, rapidly progressive neurodegenerative disease • Orphan disease: up to 50,000 patients in U.S. • Disease characteristics • Motor: Parkinsonism, uncoordinated movements, balance problems, fa
Slide 20: Our Diligent Approach to MSA Clinical Development Program
Our Diligent Approach to MSA Clinical Development Program to Achieve Meaningful Outcomes Phase 1 Program • ATH434 achieved blood levels that exceed efficacious concentrations in animal models of MSA • Twice - daily dosing • Favorable safety profile bioMUSE Natural History Study • Observational study
Slide 21: BioMUSE Natural History Study Informs and De-Risks Treatment Studies
BioMUSE Natural History Study Informs and De - Risks Treatment Studies Observational Design Optimize selection of patients and endpoints for Phase 2 Objectives Clinically Probable MSA (n=21) Population 12 months Observation Iron, volume, glial pathology MRI Biomarkers NfL, Aggregated α - synuclein F
Slide 22: Positive Phase 2 Results in MSA
Positive Phase 2 Results in MSA 22
Slide 23: ATH434-201 Phase 2 Randomized, Double-blind, Placebo Controlled Trial
ATH434 - 201 Phase 2 Randomized, Double - blind, Placebo Controlled Trial ATH434 75 mg bid ATH434 50 mg bid Placebo 12 months treatment 12 months treatment 12 months treatment MSA (N=60) Clinical diagnosis of MSA Motor symptoms ≤4 yrs No severe impairment • Key Clinical Endpoint: Change in modified
Slide 24: Baseline Characteristics
Baseline Characteristics 24 Mean (SD) Modified Intent - to - Treat (mITT) population NfL: Neurofilament light chain Overall (n = 61) 75mg BID (n = 21) 50mg BID (n = 21) Placebo (n = 19) Parameter 62.8 (6.5) 64.0 (6.3) 62.9 (6.3) 61.5 (7.0) Age (y) 59.0% 57.1% 57.1% 63.2% Gender (% male) 90.2% 95.2%
Slide 25: Importance of the Unified MSA Rating Scale Part I (UMSARS I)
rt I Items • Walking • Falling • Orthostatic symptoms • Urinary Function • Bowel Function • [Sexual Function] UMSARS Pa • Speech • Swallowing • Handwriting • Cutting food • Dressing • Hygiene Importance of the U nified MSA R ating S cale Part I (UMSARS I) • Validated rating scale to assess MSA disea
Slide 26: Clinically Significant Efficacy on Key Clinical Endpoint
0 13 39 52 26 Week 12 14 16 20 18 22 24 26 Modified UMSARS I Placebo (n=22) ATH434 50 mg BID (n=25) ATH434 75 mg BID (n=24) P =0.07 for 75 mg P =0.02 for 50 mg Worsening Clinically Significant Efficacy on Key Clinical Endpoint Modified UMSARS Part I Relative Treatment Effect* vs Placebo at 52 weeks
Slide 27: ATH434 Demonstrated Efficacy on Important Secondary Clinical Endpoints
ATH434 Demonstrated Efficacy on Important Secondary Clinical Endpoints - 5 0 5 10 Change in OHSA (W52 - BL) Placebo ATH434 50 mg BID ATH434 75 mg BID P =0.08 P =0.14 Orthostatic Hypotension Symptom Assessment CGI - S is a single - item questionnaire that assesses total picture of subject over the pr
Slide 28: ATH434 Preserved Activity in Outpatient Setting
ATH434 Preserved Activity in Outpatient Setting Change from Baseline to Week 52 - 3000 - 2000 - 1000 0 Step Count Change in steps/day P =0.0437 P =0.1041 * - 40 - 30 - 20 - 10 0 Total Time Walking Change in Minutes/day Placebo ATH434 50 mg BID ATH434 75 mg BID P =0.1267 P =0.1535 - 100 - 50 0 Bouts
Slide 29: Adverse Events
Adverse Events 29 75mg BID (n=26) 50mg BID (n=25) Placebo BID (n=26) Number (%) of Subjects 1 25 (96.2%) 21 (84.0%) 24 (92.3%) Any Adverse Event (AE) AE by Severity 8 (30.8%) 10 (40.0%) 10 (38.5%) Mild 11 (42.3%) 8 (32.0%) 6 (23.1%) Moderate 6 (23.1%) 3 (12.0%) 8 (30.8%) Severe 7 (26.9%) 5 (20.0%) 1
Slide 30: ATH434 Reduced Iron Accumulation Compared to Placebo
ATH434 Reduced Iron Accumulation Compared to Placebo 75 mg BID 50 mg BID Region Week 52 Week 26 Week 52 Week 26 Substantia nigra ^ Putamen * Pallidum By - subject analysis Reduced Increased Compared to placebo: Reduced Iron content, No observable difference, ^ P = 0.025, * P = 0.08 G
Slide 31: ATH434 Demonstrated Trends in Reduced Brain Atrophy
- 0.5000 - 0.4000 - 0.3000 - 0.2000 - 0.1000 0.0000 - 0.6000 Placebo ATH434 50 mg BID ATH434 75 mg BID ^ Composite z - score of the putamen, globus pallidus, cerebellum and brainstem regions vs. healthy age - matched population ATH434 Demonstrated Trends in Reduced Brain Atrophy Change from Baseline
Slide 32: Summary of Positive Phase 2 Trial Results
Summary of Positive Phase 2 Trial Results • ATH434 demonstrates clinically significant efficacy in modifying disease progression • Robust efficacy on the UMSARS Activities of Daily living scale at both dose levels • Evidence for efficacy on several additional clinical outcomes • Baseline differences
Slide 33: ATH434-202 Interim Data Support MSA Program
ATH434 - 202 Interim Data Support MSA Program Advanced MSA Single arm, open - label Design Efficacy and safety of ATH434 Objectives Advanced MSA (n=10) Population 12 months Treatment Iron, volume, glial pathology Brain MRI Biomarkers NfL ^ , Aggregated α - synuclein Fluid Biomarkers ADLs (UMSARS I),
Slide 34: Creating Strong Momentum in 2025
Creating Strong Momentum in 2025 • Robust efficacy observed in Phase 2 double - blind trial • Open label and Natural history studies support ATH434 clinical development approach • Lead indication of MSA is an Orphan disease with no approved treatment • Highly experienced development team with multip
Slide 35: Alterity Therapeutics
THERAPEUTICS offo Alterity ASX:ATH | NASDAQ:ATHE
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