Slide 1: ATH434-201 Phase 2 Topline Results
ATH434 - 201 Phase 2 Topline Results January 30, 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: Achieved Our Target Measures for Success
Achieved Our Target Measures for Success Favorable Safety Profile / No Drug Related Serious Adverse Events 3 Strong Clinical Results with Statistical Significance Reached on UMSARS I Rating Scale Drug Effect on Biomarker Endpoint with Reduction in Iron Content MSA Phase 2 ATH434 - 201
Slide 4: Positive ATH434 Phase 2 Trial Results
Positive ATH434 Phase 2 Trial Results Exceptionally strong clinical results overall Robust efficacy on UMSARS I rating scale Reduced or stable brain iron concentrations on MRI Maintained brain volume compared to placebo Evidence of clinical benefit on several secondary endpoints 4
Slide 5: ATH434 Clinical Development Program in Multiple System Atrophy
ATH434 Clinical Development Program in Multiple System Atrophy 5
Slide 6: Multiple System Atrophy: Rare, Rapidly Progressive and Highly Debilitating Neurodegenerative Disease
Multiple System Atrophy (MSA): Rare, Rapidly Progressive and Highly Debilitating Neurodegenerative Disease 6 • Parkinsonian disorder with no approved treatment • Orphan disease: up to 50,000 patients in U.S. • Disease characteristics • Motor: Parkinsonism, uncoordinated movements, balance problems a
Slide 7: ATH434: Potential Disease Modifying Therapy
ATH434: Potential Disease Modifying Therapy ATH434 binding to iron • Small molecule drug candidate • Decreases pathologic protein aggregation (α - synuclein) in CNS • Iron chaperone: redistributes excess labile iron in CNS • Oral medication • Preferred over infusions and injections • Potential to tr
Slide 8: ATH434-201 Trial Design in Early-Stage MSA
ATH434 - 201 Trial Design in Early - Stage MSA ATH434 - 201 – Phase 2 Study Randomized, double - blind, placebo controlled Design Efficacy, safety and pharmacokinetics of ATH434 Objectives Early - stage MSA Population N = 77 Sample Size 12 months Treatment Activities of daily living (UMSARS), global
Slide 9: ATH434 Phase 2 Double-Blind Design
ATH434 - 201 Phase 2 Double - Blind Design ATH434 75 mg bid ATH434 50 mg bid Placebo 12 months treatment 12 months treatment 12 months treatment 9 Early MSA • Key Clinical Endpoint: Change in modified UMSARS Part I (activities of daily living) • Key Biomarker Endpoint: Change in brain iron concentra
Slide 10: Unified MSA Rating Scale (UMSARS) Key Clinical Outcome
U nified MSA R ating S cale (UMSARS) Key Clinical Outcome • Validated rating scale developed specifically for MSA • Part I assesses functional impairment in areas affected in MSA • Part I, symptom inventory of 12 items • Modified version of scale used in our trial excludes the sexual function domain
Slide 11: Key Eligibility Criteria
Key Eligibility Criteria Inclusion Criteria • Clinical evidence of parkinsonism • Evidence of autonomic impairment • Ambulatory without assistance • Elevated iron on brain MRI Exclusion Criteria • Motor symptoms for > 4 years • Significant swallowing impairment (choking > 1x per week) • Frequent fal
Slide 12: ATH434-201 Phase 2 Topline Results
ATH434 - 201 Phase 2 Topline Results 12
Slide 13: Baseline Characteristics Consistent with Early-Stage MSA Patient Profile
Baseline Characteristics Consistent with Early - Stage MSA Patient Profile 13 Mean (SD) Efficacy analyses performed on the 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 (
Slide 14: Outstanding Clinical Outcomes
Outstanding Clinical Outcomes 14
Slide 15: ATH434 Exceptional Results on Key Clinical Endpoint
0 13 39 52 26 Week 30 28 26 24 22 20 18 16 14 12 10 Score Placebo (n=19) Low Dose (n=21) High Dose (n=21) * p=0.05 for 75 mg * p=0.03 for 50 mg Clinical progression v. placebo at 52 weeks • Low dose: 48% slowing (p=0.03) • High dose: 29% slowing (p=0.2) Both ATH434 dose levels demonstrated clinicall
Slide 16: Evidence of Efficacy on Other Clinical Endpoints
Evidence of Efficacy on Other Clinical Endpoints Clinical global impression of severity (7 - point scale, lower score = improvement) Clinician assessment of the total picture of the participant over prior 28 days • Mean change at 50 mg: - 0.81 (p=0.009) • Mean change at 75 mg: - 0.18 (p=NS) Parkinso
Slide 17: Positive Impact on Brain Iron & Volume
Positive Impact on Brain Iron & Volume 17
Slide 18: Brain Iron and Volume Assessments are Unique Aspects of the Phase 2 Trial
Brain Iron and Volume Assessments are Unique Aspects of the Phase 2 Trial 18 Brain Iron Content • MRI is an unconventional outcome measure that was designed specifically for the ATH434 - 201 trial to evaluate target engagement • Led to the primary endpoint: change in iron content as measured by brai
Slide 19: ATH434 Reduced Iron Accumulation Compared to Placebo
ATH434 Reduced Iron Accumulation Compared to Placebo Brain Iron by MRI 75 mg BID 50 mg BID Region Week 52 Week 26 Week 52 Week 26 Substantia nigra ^ Putamen * Pallidum Compared to placebo Reduced Iron content, No observable difference ^ P = 0.025, uncorrected * P = 0.08, uncorrected
Slide 20: Clear Trends Showing ATH434 is Reducing or Stabilizing Iron Content in MSA Brain Regions
Clear Trends Showing ATH434 is Reducing or Stabilizing Iron Content in MSA Brain Regions • Achieved objective of demonstrating target engagement of iron in the brain • Preliminary analysis is positive with reductions in iron content in key brain regions affected by MSA • Significant reduction in iro
Slide 21: ATH434 Demonstrated Trends in Reduced Brain Atrophy
- 0.6000 - 0.5000 - 0.4000 - 0.3000 - 0.2000 - 0.1000 0.0000 MSA Atrophy Index Placebo ATH434 50 mg BID ATH434 75 mg BID 26 weeks 52 weeks ATH434 Demonstrated Trends in Reduced Brain Atrophy Change from Baseline in Brain Volume Source 21
Slide 22: Well-Tolerated Safety Profile with No Serious Adverse Events Related to Study Drug
Well - Tolerated Safety Profile with No Serious Adverse Events (SAEs) Related to Study Drug Safety population: enrolled participants who received at least one dose of treatment • 50 mg dose (n=26) • 75 mg dose (n=25) • Placebo (n=26) Safety Results: • ATH434 was well - tolerated with similar adverse
Slide 23: Alterity Therapeutics
THERAPEUTICS a 23
Slide 24: Positive ATH434 Phase 2 Trial Results
Positive ATH434 Phase 2 Trial Results Exceptionally strong clinical results overall Robust efficacy on UMSARS I rating scale Reduced or stable brain iron concentrations on MRI Maintained brain volume compared to placebo Evidence of clinical benefit on several secondary endpoints 24
Slide 25: Daniel Claassen, M.D., M.S., Coordinating Investigator
Professor of Neurology Vanderbilt University Medical Center Research focus: Neuroimaging/Therapeutics Coordinating Investigator of the ATH434 - 201 Clinical Trial Daniel Claassen, M.D., M.S. 25
Slide 26: Alterity Therapeutics
fifo Alterity THERAPEUTICS ASX:ATH | NASDAQ:ATHE