Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (April 2024)
32 slides from Alterity Therapeutics's investor presentation, April 2024
Slide 1: Alterity Therapeutics Corporate Presentation April 2024
David Stamler, MD April 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
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), a 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 ATH434-202 Advanced ATH434 Parkinson’s Di
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: Critical in Disease Pathogenesis
Iron: Critical in Disease Pathogenesis α-Synuclein and iron are strong contributors to Oxidative Stress the pathology of MSA • Adverse impact of excess loosely bound iron • Promotes α-synuclein aggregation • Root cause of oxidative stress which damages intracellular structures and leads to neuroinfl
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 iron aggregation Rescue neuronal in the Central Nervous System and function 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 that reduces α-synuclein aggregation • Iron chaperone, redistributes loosely bound excess iron in brain • Oral agent (tablet) for ease of use • Readily absorbed, shown to reach site of action in man • Potential to treat va
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 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: Monkey Parkinson's Disease Study
Monkey Parkinson’s Disease Study Disease Onset Baseline Daily oral doses Train, habituate Placebo vs ATH434 3 mg/kg vs ATH434 10 mg/kg Week 0 4 8 12 12 - 14 Motor Assessment Motor Assessment Motor Assessment Measure Brain Iron Source: Bradbury, et al, “Effects of ATH434, a Clinical-Phase Small Molec
Slide 19: ATH434 Improved Behavior/Function and Increased Neuronal Connectivity
Monkey 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 20: Monkey Study Validates ATH434 Clinical Approach
Monkey Study Validates ATH434 Clinical Approach Established Model of Parkinson’s Disease • Monkey closer to humans in neuroanatomy and behavior • ATH434 treatment improved behavior/function in monkeys with experimentally induced Parkinson’s disease • ATH434 increased marker of functional connections
Slide 21: Accumulated Evidence of ATH434 Efficacy
Accumulated Evidence of ATH434 Efficacy Target Disease Model Brain Iron Neurons/ Clinical α-Synuclein Author Connectivity Observations Improved motor Parkinson’s disease Mouse MPTP â â á performance Finkelstein Improved motor Parkinson’s disease Mouse A53T â â á performance Finkelstein Improved moto
Slide 22: Multiple System Atrophy Clinical Development Program
Multiple System Atrophy Clinical Development Program 22
Slide 23: MSA is a Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disorder
Multiple System Atrophy (MSA) is a Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disorder • Clinical impairments include • Motor: Parkinsonism, uncoordinated movements, balance problems/falls • Autonomic dysfunction: Reduced ability to maintain blood pressure, control bladder a
Slide 24: Completed Phase 1 with Favorable Safety Profile
Completed Phase 1 with 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 A
Slide 25: bioMUSE: Natural History Study in MSA
bioMUSE: Natural History Study in MSA Design • Observational • Design and de-risk Phase 2 Objectives • Identify biomarker endpoints for treatment study • Early-stage MSA patients similar to Phase 2 population Population • ~20 participants Observation • 12 months Period • MRI: Iron (QSM/R2*), glial p
Slide 26: bioMUSE Natural History Study
bioMUSE Natural History Study Design and De-risk Phase 2 Advanced MRI methods New MRI Template Optimize Patient Selection Assess Endpoints with Precision Pilot Clinical Measures 0 Iron content [ppb] 300 Improve precision of MRI assessments Identify “iron signature” in early MSA vs. PD Wearable Senso
Slide 27: ATH434-201: Randomized Phase 2 Clinical Trial in Early-Stage MSA
ATH434-201: Randomized Phase 2 Clinical Trial in Early-Stage MSA Design • Randomized, double-blind, placebo controlled • Assess efficacy and safety of ATH434 in participants with MSA Objectives • Assess target engagement based on imaging and fluid biomarkers Population • Early-stage MSA: ambulatory
Slide 28: ATH434-201 Phase 2 Design and Primary Endpoint
ATH434-201 Phase 2 Design and Primary Endpoint Primary Endpoint: Change in Brain Iron on MRI 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 Demonstrates Brain iron correlates with disease severity in MSA Source: Cl
Slide 29: ATH434-202: Phase 2 Biomarker Trial in MSA
ATH434-202: Phase 2 Biomarker Trial in MSA Design • Single arm, open-label • Assess target engagement based on imaging and fluid biomarkers Objectives • Assess efficacy and safety of ATH434 in participants with MSA Population • Clinically Established (advanced) MSA with biomarker evidence of disease
Slide 30: Key Development Milestones
Key Development Milestones Enrollment Complete ATH434-201 Phase 2 Trial Data with ATH434 in Monkey Model Study Complete of Parkinson’s ATH434-201 Disease Phase 2 Trial bioMUSE Data Preliminary Data from ATH434-202 Open Label Biomarker Trial Oct Nov Dec Jan Feb Mar Apr May Jun July Aug Sep Oct Nov De
Slide 31: Alterity: Poised for Progress
Alterity: Poised for Progress • Targeting Orphan disease with no approved treatments Upcoming Catalysts • Two Phase 2 clinical trials ongoing • Global double-blind trial enrollment completed ATH434-201 Phase 2 Double-Blind Trial • Biomarker trial enrolling in U.S. ü Nov 2023: Enrollment Complete • N
Slide 32: ASX:ATH | NASDAQ:ATHE
ofifo Alterity THERAPEUTICS ASX:ATH | NASDAQ:ATHE
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