Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (June 2024)
33 slides from Alterity Therapeutics's investor presentation, June 2024
Slide 1: Alterity Therapeutics Corporate Presentation June 2024
David Stamler, MD June 2024 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 for people living with neurodegenerative diseases
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 • Developing disease modifying therapies • ATH434: Novel drug candidate targeting proteins implicated in neurodegeneration of Parkinson’s disease and related disorders • First indication: Multiple System Atrophy (MSA) • Parkinsonian disorder with no approved treatment • Orphan
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: Parkinsonian Disorders: A Significant Unmet Need
Parkinsonian Disorders: A Significant Unmet Need • Parkinsonism is a syndrome of motor symptoms that PARKINSONIAN DISORDERS includes slowed movement, stiffness and tremor • Parkinson’s disease most common cause • Major source of disability MSA • Parkinsonian disorders include Multiple System Atrophy
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 Multiple System Atrophy ATH434-201 Enrollment Complete Early Stage Multiple System Atrophy Enrollment Complete ATH434-202 Advanced A
Slide 8: Significant Commercial Opportunity in Treating Multiple System Atrophy
Significant Commercial Opportunity in Treating 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,
Slide 9: The Role of Alpha-Synuclein and Iron in Parkinsonian Disorders
The Role of Alpha-Synuclein and Iron in Parkinsonian Disorders 9
Slide 10: Alpha-Synuclein: Critical for Normal Neuron Function
Alpha-Synuclein: Critical for Normal Neuron Function Our Strategy • Inhibit misfolding and aggregation of intracellular α-synuclein • Target misfolding α-synuclein by redistributing loosely bound excess iron in areas of pathology • Address underlying pathology of disease α-Synuclein Health Disease •
Slide 11: Iron is Critical in Disease Pathogenesis
Iron is Critical in Disease Pathogenesis Iron and α-Synuclein are important Oxidative Stress contributors to MSA pathology • Adverse impact of excess labile iron • Leads to α-synuclein aggregation à neuronal dysfunction • Oxidative stress with intracellular damage Stored iron • Cell death • Hallmark
Slide 12: Increased Brain Iron in Synuclein-related Diseases
Increased Brain Iron in Synuclein-related Diseases 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 30000 Putamen (M) n = 10
Slide 13: Approach: Address Underlying Pathology of Disease
Approach: Address Underlying Pathology of Disease Reduce α-synuclein Redistribute excess aggregation labile iron Rescue neurons/glia and and neuronal function in the CNS Oxidative stress Potential Disease Modifying Therapy for MSA 13
Slide 14: ATH434: Disease Modifying Drug Candidate
ATH434: Disease Modifying Drug Candidate 14
Slide 15: ATH434: Potential Use in Multiple Indications
ATH434: Potential Use in Multiple Indications • Small molecule drug candidate Ô α-synuclein aggregation • Iron chaperone, redistributes excess labile iron in CNS • Oral agent (tablet) for ease of use • Readily absorbed, shown to reach site of action in man • Potential to treat various Parkinsonian d
Slide 16: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434only Redistributes loosely bound Reduces excess iron α-synuclein 15000 aggregation *** Fe released (CPM) 10000 *** 60 * 5000 ** Fe (mg/kg) 40 Blocks increase 0 0 1 10 20 in brain iron 20 ATH434 (µM) 0 UL VEH ATH434 Ligand Kd for Fe3+ 400 8-Isoprostane (% UL) α-synuclei
Slide 17: ATH434 Reduces Neuropathology and Improves Motor Function in Parkinson's Disease and MSA Animal Models
ATH434 Reduces Neuropathology and Improves Motor Function in Parkinson’s Disease and MSA Animal Models Preserves Improves Motor ↓ Iron ↓ α-Synuclein Neurons Function 12 60 6000 3 * Total SNpc neurons ** *** Time (secs) Parkinson’s *** * * ** Fe (mg/kg) 40 Disease a-syn (OD) 2 3000 6 Mouse Model * 20
Slide 18: Primate Parkinson's Disease Study
Primate Parkinson’s Disease Study ATH434 Improved Behavior/Function and Increased Neuronal Connectivity Behavior/Function Neuronal Connectivity Synaptophysin in Dorsal Striatum 100 24 80 18 (R as % L) Score** 60 12 40 Lowest 6 Iron 20 Levels 0 Improved 0 Baseline Week 12 Veh 3 mg/kg 10 mg/kg Placebo
Slide 19: Primate Study Validates ATH434 Clinical Approach
Primate Study Validates ATH434 Clinical Approach • Monkey closer to humans in neuroanatomy and behavior • ATH434 treatment improved behavior/function in monkeys with experimentally induced Parkinson’s disease • Dose dependent increase in synaptophysin, marker of functional connection between neurons
Slide 20: 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 Mouse MPTP â â á performance Improved motor Parkinson’s disease Mouse A53T â â á performance Improved motor Parkinson’s disease
Slide 21: Multiple System Atrophy Clinical Development Program
Multiple System Atrophy Clinical Development Program 21
Slide 22: Completed Phase 1: Favorable Safety Profile
Completed Phase 1: Favorable Safety Profile ATH434 Levels at Steady-State 250 • Achieved drug concentrations associated Plasma (unbound, ng/mL) 200 with efficacy in animal models 150 CSF, plasma 1.5 hours post -dose CSF, plasma 11 hours post dose • Favorable safety profile 100 50 r2=0.72 • All Adver
Slide 23: Multiple System Atrophy (MSA): Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disease
Multiple System Atrophy (MSA): Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disease • Parkinsonian disorder with no approved treatment • Orphan disease • Disease characteristics • Motor: Parkinsonism, uncoordinated movements, balance problems/falls • Autonomic dysfunction: blo
Slide 24: Clinical Studies in MSA: Natural History Study
Clinical Studies in MSA: Natural History Study Study bioMUSE Design Observational Objectives Characterize early-stage MSA Population Clinically Probable MSA Sample Size N = 21 enrolled Observation period 12 months Brain MRI Biomarkers Iron, volume, glial pathology Fluid Biomarkers NfL, Aggregated α-
Slide 25: BioMUSE Natural History Study Learnings to Date
BioMUSE Natural History Study Learnings to Date Advanced MRI methods α-synuclein in CSF 1000000 100000 PD Fluorescence Optimize Patient 10000 Revised selection criteria in Selection MSA ATH434-201 and ATH434-202 1000 protocols to exclude PD patients 100 Time → Differentiate MSA from PD 0 Iron conten
Slide 26: BioMUSE: Longitudinal MRI Data
BioMUSE: Longitudinal MRI Data Iron Content in Volume in Substantia Nigra MSA Regions* 0.06 ** 0 % Change from baseline Change from baseline ** 0.04 -2 0.02 ** 0.00 -4 -0.02 -6 6M 12M ** p < 0.01 6M 12M Iron significantly increased at 12 months in the substantia nigra Volume significantly decreased
Slide 27: BioMUSE Summary
BioMUSE Summary • Observational Study in MSA • Goals: improve patient selection and choose endpoints for Phase 2 • Iron content: Significant increase in iron observed at 12 months in one brain region (s. nigra) • Brain volume: Significant decrease in volume observed over 12 months in all four MSA re
Slide 28: Clinical Studies in MSA: Phase 2
Clinical Studies in MSA: Phase 2 Study bioMUSE – Natural History ATH434-202 – Phase 2 ATH434-201 – Phase 2 Design Observational Single arm, open-label Randomized, double-blind Objectives Characterize early-stage MSA Efficacy and safety of ATH434 Efficacy and safety of ATH434 Population Clinically Pr
Slide 29: ATH434-202 Key Study Endpoints
ATH434-202 Key Study Endpoints Based on bioMUSE Findings Change in MSA Volume Index by MRI at 12 months Primary Endpoint • Based on the significant decrease in volume in relevant brain regions in MSA Change in Iron content in the substantia nigra by MRI at 12 months Secondary Endpoint • Based on the
Slide 30: Brain iron correlates with disease severity
ATH434-201 Phase 2 Design Brain iron correlates with disease severity 0.30 Iron Content (GPe) 0.25 0.20 0.15 R² = 0.63 0.10 0.05 0.00 0 20 40 60 80 Unified MSA Rating Scale BioMUSE Natural History Study 30 Source: Claassen, et al. Mov Disorders 2021
Slide 31: Key Milestones
Key Milestones ATH434-202 ATH434-201 Preliminary Phase 2 Trial 6 mo Data Topline Data BioMUSE ATH434-201 Data Phase 2 Trial Study Complete ATH434 MoA data Scientific Meeting Presentations Jan 24 Feb 24 Mar 24 Apr 24 May 24 Jun 24 Jul 24 Aug 24 Sep 24 Oct 24 Nov 24 Dec 24 Jan 25 Feb 25 31
Slide 32: Alterity: Poised for Progress
Alterity: Poised for Progress • Targeting Orphan disease with no approved Catalysts treatments • Two Phase 2 clinical trials ongoing MSA Natural History Study • Global double-blind trial enrollment completed ü H1 2024: Present new biomarker data • Biomarker trial enrollment completed ATH434-201 Phas
Slide 33: ASX:ATH | NASDAQ:ATHE
ofifo Alterity THERAPEUTICS ASX:ATH | NASDAQ:ATHE
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