Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (May 2025)
34 slides from Alterity Therapeutics's investor presentation, May 2025
Slide 1: Alterity Therapeutics Corporate Presentation May 2025
David Stamler, MD May 2025 CEO
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 is dedicated to creating an alternate future
Alterity means the state of being Alterity is dedicated to different creating an alternate future for people living Our goal is to modify the course with neurodegenerative of disease diseases We aim to disrupt the trajectory of illness and improve quality of life 3
Slide 4: Investment Highlights
Investment Highlights • Late clinical stage biopharmaceutical company developing disease modifying treatments for Parkinson’s disease and related disorders • Positive Phase 2 data in Multiple System Atrophy, a Parkinsonian Disorder without approved therapy • Robust efficacy on key clinical endpoint
Slide 5: Experienced Clinical Leadership Team with Multiple FDA Approvals in Neurology
Experienced Clinical Leadership Team with Multiple FDA Approvals in Neurology David Stamler, M.D. Margaret Bradbury, Ph.D. Cynthia Wong, M.P.H. Chief Executive Officer VP, Nonclinical Development Senior Director, Clinical Operations Auspex/Teva | Abbott | Prestwick Auspex/Teva | Neurocrine | Merck A
Slide 6: Targeting Iron Related Neurodegenerative Diseases
Targeting Iron Related Neurodegenerative Diseases • Iron imbalance involved in many neurodegenerative diseases Friedreich Ataxia • Parkinsonian disorders • Parkinson’s disease (PD) • Rare diseases with similar motor symptoms Ø Multiple System Atrophy (MSA) – Lead Indication • Dementia with Lewy Bodi
Slide 7: Promising Portfolio in Neurodegenerative Diseases
Promising Portfolio in Neurodegenerative Diseases ASSET PHASE PARTNER PROGRAM INDICATION DISCOVERY PRE- NATURAL PARTNER / PHASE 1 PHASE 2 CLINICAL HISTORY COLLABORATOR ATH434-201 Multiple System Atrophy Positive Topline Data Multiple System Atrophy ATH434-202 Study Complete Advanced ATH434 Parkinson
Slide 8: Targeting Labile Iron and Aggregating α-Synuclein in Parkinsonian Disorders
Targeting Labile Iron and Aggregating α-Synuclein in Parkinsonian Disorders 8
Slide 9: Alpha-Synuclein and Iron in Health
Alpha-Synuclein and Iron in Health α-Synuclein protein • Critical for normal function of neurons • Enables nerves to communicate with each α-Synuclein other via neurotransmitters Iron essential for important cellular functions • Red blood cell production, oxygen transport • Energy production and act
Slide 10: Increased Brain Iron in Parkinson's Disease and Multiple System Atrophy
Increased Brain Iron in Parkinson’s Disease and Multiple System Atrophy Parkinson’s disease Multiple System Atrophy n=7 * Patients Substantia nigra (T) n=8 n=9 Cerebral cortex Healthy n = 11 n=8 * Substantia nigra (pc) n=3 n=8 * Caudate nucleus n = 13 n = 10 Cerebellum n = 24 n=8 * 0 10000 20000 300
Slide 11: Excess Labile Iron and Misfolding α-Synuclein Drive MSA Pathology
Excess Labile Iron and Misfolding α-Synuclein Drive MSA Pathology Oxidative Injury Vicious cycle of Pathology Driver Impact cellular injury Alpha-synuclein aggregation Excess Free radical production labile iron Lipid, mitochondria, DNA damage Stored iron Neuronal death Glial cell impairment / â trop
Slide 12: Treatment Approach: Address Underlying Pathology
Treatment Approach: Address Underlying Pathology Redistribute Reduce α-syn Preserve neurons and Stabilize or excess labile iron aggregation and ODGs improve function in the CNS oxidative injury Potential Disease Modifying Therapy 12
Slide 13: ATH434: Disease Modifying Drug Candidate
ATH434: Disease Modifying Drug Candidate 13
Slide 14: 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 many iron-related neurodegenerative diseases • Orphan Drug Desi
Slide 15: Accumulated Evidence of ATH434 Efficacy
Accumulated Evidence of ATH434 Efficacy Midbrain* Preserve Neurons/ Target Disease Model Iron α-Synuclein Function Clinical Observations Improved motor Parkinson’s disease Monkey MPTP 1 or â n/a á performance Improved motor Parkinson’s disease Mouse MPTP â â á performance Improved motor Parkinson’s
Slide 16: ATH434 Improved Behavior and Function in Monkey Model of Parkinson's Disease
ATH434 Improved Behavior and Function in Monkey Model of Parkinson’s Disease All ATH434-treated Monkeys Improved (n=5) Placebo: 2 of 3 had Stable or Worsening Scores • Monkey closely related to humans in neuroanatomy and behavior ,0 • ATH434 improved behavior and function in +/ monkeys with experime
Slide 17: ATH434 Clinical Development Program in Multiple System Atrophy
ATH434 Clinical Development Program in Multiple System Atrophy 17
Slide 18: Multiple System Atrophy (MSA): Parkinsonian Disorder with No Approved Treatment
Multiple System Atrophy (MSA): Parkinsonian Disorder with No Approved Treatment • 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, falls
Slide 19: Our Diligent Approach to MSA Clinical Development Program
Our Diligent Approach to MSA Clinical Development Program to Achieve Meaningful Outcomes bioMUSE Natural Phase 1 Program Phase 2 Program History Study • ATH434 achieved blood • Observational study in • Double-blind trial in MSA levels that exceed individuals with MSA demonstrated clinically efficaci
Slide 20: BioMUSE Natural History Study Informs and De-Risks Treatment Studies
BioMUSE Natural History Study Informs and De-Risks Treatment Studies Optimize Patient Selection in P2 Design Observational !"""""" Optimize selection of patients Revised selection Objectives !""""" !" and endpoints for Phase 2 criteria in Phase 2 !"""" #A% protocols to exclude !""" PD patients Popul
Slide 21: Positive Phase 2 Results in MSA
Positive Phase 2 Results in MSA 21
Slide 22: ATH434-201 Phase 2 Randomized, Double-blind, Placebo Controlled Trial
ATH434-201 Phase 2 Randomized, Double-blind, Placebo Controlled Trial ATH434 12 months treatment 75 mg bid • Key Clinical Endpoint: MSA Modified UMSARS Part I (N=60) (activities of daily living) 1:1:1 ATH434 12 months treatment Clinical diagnosis of MSA Motor symptoms ≤4 yrs 50 mg bid • Key Biomarke
Slide 23: Baseline Characteristics
Baseline Characteristics Placebo 50mg BID 75mg BID Parameter (N = 22) (N=25) (N=24) Age (yr) 61.3 (6.6) 63.1 (6.1) 63.9 (6.7) Gender (% male) 63.6% 52.0% 62.5% Duration of motor symptoms (yr) 2.5 (0.8) 2.6 (0.8) 2.3 (0.9) Modified UMSARS I1 16.9 (3.9) 15.2 (5.4) 14.4 (4.4) Motor score of Parkinson P
Slide 24: Importance of the Unified MSA Rating Scale Part I (UMSARS I)
Importance of the Unified MSA Rating Scale Part I (UMSARS I) • Validated rating scale to assess MSA disease severity UMSARS Part I Items • Rates functional impairment in areas affected in MSA • Speech • Walking • Symptom inventory of 12 items • Swallowing • Falling • Modified version used excludes s
Slide 25: Clinically Significant Efficacy on UMSARS I
Clinically Significant Efficacy on UMSARS I Change from Baseline to Week 52 "A !"#$B&D()*+II- "# ./(01(2P4()*+I.- Relative '()*+,'-.L-+!+-M(12 5.(01(2P4()*+I6- Difference Dose Treatment "" vs. Placebo Effect* Worsening "& 50 mg - 3.8 (1.6) 48% 75 mg - 2.4 (1.7) 30% !B LS mean (SE) 7 * ChangeATH434 –
Slide 26: Efficacy Shown on Important Secondary Endpoints
Efficacy Shown on Important Secondary Endpoints Change from Baseline to Week 52 Clinical Global Orthostatic Hypotension Impression of Severity Symptom Assessment $"# A# BC'()G+I(+B-.L+01#2+3+45S BC'()*H,(H-.L0H1O"3H!H45S !"#AB&D $"! Worsening Worsening L E)*HIH-.L-01-2P4 " !!"#""$ E)*HIH-5.-01-2P4 !
Slide 27: ATH434 Preserved Activity in Outpatient Setting
ATH434 Preserved Activity in Outpatient Setting Change from Baseline to Week 52 !"#ABCD()" WD"H;BW-<#B=H;>-)I # # @;HA#BD C*H)I#B-)B?-)("#./MH1 !%# CWa5S5BbPB<IBcde C*H)I#B-)B."#A./MH1 Worsening Worsening !%### CWa5S5BTbB<IBcde !$# !2P48fgT !2P48bSb !2P4P5ST !$### !"# 9 !2P48P58 !&# !"### cD(".BDhB=
Slide 28: Adverse Events
Adverse Events Placebo BID 50mg BID 75mg BID Number (%) of Subjects (n=26) (n=25) (n=26) Any Adverse Event (AE)1 24 (92.3%) 21 (84.0%) 25 (96.2%) UTI 14 (53.8%) 10 (40.0%) 7 (26.9%) Fall 8 (30.8%) 7 (28.0%) 8 (30.8%) Covid-19 1 (3.8%) 6 (24.0%) 4 (15.4%) Fatigue 2 (7.7%) 1 (4.0%) 5 (19.2%) Back pain
Slide 29: Neuroimaging Endpoints
Neuroimaging Endpoints Change in Iron Content by MRI Change from Baseline in Brain Volume1 50 mg 75 mg 0.0000 Week 26 Week 52 Region Week 26 Week 52 Week 26 Week 52 S. nigra ↔ â ↔ ↔ -0.1000 Putamen â^ â ↔ ↔ Worsening GP â â* â â -0.2000 Z-score Compared to placebo: â Iron content, ↔ No observable di
Slide 30: Summary of Positive Phase 2 Trial Results
Summary of Positive Phase 2 Trial Results • ATH434 demonstrated clinically significant efficacy in modifying disease progression in MSA • Both 50 and 75 mg efficacious on UMSARS I and important secondary endpoints • Baseline differences in disease severity likely explain different response in 50 mg
Slide 31: ATH434-202 Interim Data Support MSA Program
ATH434-202 Interim Data Support MSA Program Advanced MSA Design Single arm, open-label • Clinical response observed in progressive, unremitting disease Objectives Efficacy and safety of ATH434 • 30% had stable or improved overall neurological symptoms Population Advanced MSA (n=10) • Objective bioma
Slide 32: Significant Commercial Opportunity in Multiple System Atrophy
Significant Commercial Opportunity in Multiple System Atrophy Substantial Unmet Need Strong Intent to Prescribe Severely debilitating illnesses Motivated by efficacy of treating with no current treatments are the underlying disease and not ripe for new entrants targeting just the symptoms, clinician
Slide 33: Creating Strong Momentum in 2025
Creating Strong Momentum in 2025 • Robust efficacy in Phase 2 double-blind trial Milestones • Open label and Natural history studies support ATH434-201 Topline Data üQ1 25 ATH434 clinical development approach ATH434-202 Study complete üQ1 25 • Lead indication MSA is Orphan disease with Data presenta
Slide 34: ASX:ATH | NASDAQ:ATHE
ofifo Alterity THERAPEUTICS ASX:ATH | NASDAQ:ATHE
Alterity Therapeutics — Investor Presentation (May 2025) on 6ix