Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (November 2023)
31 slides from Alterity Therapeutics's investor presentation, Nov 22, 2023
Slide 1: Alterity Therapeutics
For personal use only Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) David Stamler, MD November 2023 CEO
Slide 2: Forward Looking Statements
For personal use only 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
Slide 3: Alterity: creating an alternate future for neurodegenerative disease
For personal use only Alterity means the state of Alterity is dedicated to being different creating an alternate future for people living with neurodegenerative Our goal is to modify the course of disease diseases. We’re here to disrupt the trajectory of illness and improve quality of life 3
Slide 4: Investment Highlights
Investment Highlights For personal use only • 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 appro
Slide 5: Experienced Leadership Team with Multiple FDA Approvals in Neurology
Experienced Leadership Team with Multiple FDA Approvals in Neurology For personal use only David Stamler, M.D. Kathryn Andrews, CPA Margaret Bradbury, Ph.D. Cynthia Wong, M.P.H. Chief Executive Officer Chief Financial Officer VP, Nonclinical Development Senior Director, Clinical Operations Auspex/Te
Slide 6: Parkinsonian Disorders: A Significant Unmet Need
Parkinsonian Disorders: A Significant Unmet Need • Parkinsonism is a syndrome of motor symptoms that For personal use only PARKINSONIAN DISORDERS includes slowed movement, stiffness and tremor • Parkinson’s disease most common cause • Major source of disability MSA • Parkinsonian disorders include M
Slide 7: Promising Portfolio in Neurodegenerative Diseases
Promising Portfolio in Neurodegenerative Diseases For personal use only ASSET PHASE PARTNER PRE- NATURAL PARTNER / PROGRAM INDICATION DISCOVERY PHASE 1 PHASE 2 CLINICAL HISTORY COLLABORATOR Multiple System Atrophy ATH434-201 Early Stage Multiple System Atrophy ATH434-202 Advanced Multiple System Atr
Slide 8: The Role of Alpha-Synuclein and Iron in Parkinsonian Disorders
For personal use only The Role of Alpha-Synuclein and Iron in Parkinsonian Disorders 8
Slide 9: Alpha-Synuclein: Critical for Normal Neuron Function
Alpha-Synuclein: Critical for Normal Neuron Function For personal use only 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-Synu
Slide 10: Increased Brain Iron in Synuclein-related Diseases
Increased Brain Iron in Synuclein-related Diseases Parkinson’s disease Multiple System Atrophy For personal use only 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 30
Slide 11: Iron: Critical in Disease Pathogenesis
Iron: Critical in Disease Pathogenesis For personal use only 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
Slide 12: Approach: Address Underlying Pathology of Disease
Approach: Address Underlying Pathology of Disease For personal use only Reduce α‐synuclein Redistribute excess iron aggregation Rescue neuronal in the Central Nervous System and function Oxidative stress Potential Disease Modifying Therapy for MSA 12
Slide 13: ATH434: Disease Modifying Drug Candidate
For personal use only ATH434: Disease Modifying Drug Candidate 13
Slide 14: ATH434: Potential Use in Multiple Indications
ATH434: Potential Use in Multiple Indications For personal use only • 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 A
Slide 15: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434only Reduces Redistributes loosely bound For personal use only α‐synuclein excess iron aggregation 15000 *** Fe released (CPM) 10000 *** 60 * 5000 ** 40 Fe (mg/kg) Blocks increase 0 in brain iron 0 1 10 20 20 ATH434 (µM) 0 UL VEH ATH434 Ligand Kd for Fe3+ 400 8-Isopros
Slide 16: ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson's Disease Animal Models
ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson’s Disease Animal Models For personal use only ↓ α-Synuclein Preserves Neurons ** 6 8000 ** Total SNpc neurons hA53T hA53T α-syn 4 Mouse 4000 2 0 Vehicle ATH434 0 W/T Vehicle ATH434 3 6000 Total SNpc neurons *** 2 ** *** α-syn (OD) MP
Slide 17: ATH434 Reduces Neuropathology and Improves Motor Function in MSA Animal Model
ATH434 Reduces Alpha-Synuclein-related Neuropathology and Improves Motor Function in MSA Animal Model For personal use only α-Synuclein SN neurons Glial inclusions *** ** *** ** ** 4000 *** Total SNpc neurons 0.8 6000 ** Relative to Total Protein 3000 Number of GCI 0.6 Exp. #1 0.4 4000 2000 0.2 1000
Slide 18: Multiple System Atrophy Clinical Development Program
For personal use only Multiple System Atrophy Clinical Development Program 18
Slide 19: 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 For personal use only • Clinical impairments include • Motor: Parkinsonism, uncoordinated movements, balance problems/falls • Autonomic dysfunction: Reduced ability to maintain blood press
Slide 20: Phase 1: ATH434 Well-Tolerated with No Serious Adverse Events
Phase 1: ATH434 Well-Tolerated with No Serious Adverse Events No evidence of QT prolongation For personal use only • No SAEs or AEs leading to withdrawal ΔΔQTcF (msec) • All AEs were mild to moderate in severity • Most common AE reported was headache • Similar AE profile for adults and older adults
Slide 21: Phase 1: Achieved Drug Concentrations Associated with Efficacy in Animal Models
Phase 1: Achieved Drug Concentrations Associated with Efficacy in Animal Models Plasma Profile after Single Dose Plasma and CSF Levels at Steady-State For personal use only Administration 250 10000 Plasma (unbound, ng/mL) 50 mg 200 ATH434 in plasma (ng/mL) 100 mg 1000 300 mg 600 mg 150 100 100 50 r2
Slide 22: bioMUSE: Natural History Study in MSA
bioMUSE: Natural History Study in MSA For personal use only 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: I
Slide 23: bioMUSE Natural History Study
bioMUSE Natural History Study Design and De-risk Phase 2 New MRI Template Advanced MRI methods For personal use only Optimize Patient Selection Assess Endpoints with Precision Pilot Clinical Measures Identify “iron signature” Improve precision of iron in early MSA vs. PD quantification by MRI Wearab
Slide 24: ATH434-201: Randomized Phase 2 Clinical Trial in Early-Stage MSA
ATH434-201: Randomized Phase 2 Clinical Trial in Early-Stage MSA For personal use only 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-
Slide 25: ATH434-201 Phase 2 Design and Primary Endpoint
ATH434-201 Phase 2 Design and Primary Endpoint For personal use only 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 seve
Slide 26: Patient Specific Map to Evaluate Primary Endpoint with Precision
Patient Specific “Map” to Evaluate Primary Endpoint with Precision ATH434 targets increased iron in For personal use only patient-specific Region of Interest Iron Distribution Age Distribution of brain iron varies Patient Map Patient’s age among MSA determines the patients Generates patient specific
Slide 27: ATH434-202: Phase 2 Biomarker Trial in MSA
ATH434-202: Phase 2 Biomarker Trial in MSA For personal use only 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 biomark
Slide 28: Significant Commercial Opportunity in Treating Multiple System Atrophy
Significant Commercial Opportunity in Treating Multiple System Atrophy For personal use only 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 targeti
Slide 29: Alterity: Poised for Progress
Alterity: Poised for Progress Clinical Milestones For personal use only • Targeting Orphan disease with no approved treatments ATH434-201 Phase 2 Double-Blind Trial • Two Phase 2 clinical trials ongoing Q1 2023: First Patients Dosed in U.S. and Europe • Double-blind trial enrolling globally Q2 2
Slide 30: Key Milestones
Key Milestones For personal use only 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
Slide 31: For personal use only
offo Alterity THERAPEUTICS or personal use only
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