Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (June 2023)
29 slides from Alterity Therapeutics's investor presentation, Jun 22, 2023
Slide 1: Alterity Therapeutics
Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) David Stamler, MD June 2023 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 different Alterity is dedicated to creating an alternate future for people living Our goal is to modify the with neurodegenerative 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 • 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 devastating disease with no approved treatment • Orphan D
Slide 5: Experienced Leadership Team with Multiple FDA Approvals in Neurology
Experienced Leadership Team with Multiple FDA Approvals in Neurology 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/Teva | Abbott | Prestwic
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 Early Stage Multiple System Atrophy ATH434-202 Advanced Multiple System Atrophy bioMUSE Natural H
Slide 8: The Role of Alpha-Synuclein and Iron in Parkinsonian Disorders
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 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 10: 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 11: Iron: Critical in Disease Pathogenesis
Iron: Critical in Disease Pathogenesis Oxidative Stress α-Synuclein and iron are strong contributors to MSA pathology • Adverse impact of excess loosely bound iron • Promotes α-synuclein aggregation • Root cause of oxidative stress which damages intracellular structures and leads to neuroinflammatio
Slide 12: Approach: Address Underlying Pathology of Disease
Approach: Address Underlying Pathology of Disease Reduce α-synuclein Redistribute excess iron aggregation Rescue neurons in the Central Nervous System and in multiple brain regions Oxidative stress Potential Disease Modifying Therapy for MSA 12
Slide 13: ATH434: Disease Modifying Drug Candidate
ATH434: Disease Modifying Drug Candidate 13
Slide 14: ATH434: Potential Use in Multiple Indications
ATH434: Potential Use in Multiple Indications • Small molecule drug 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 ATH434 • Potential to treat vario
Slide 15: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434only Reduces Redistributes loosely bound α-synuclein excess iron aggregation 15000 *** Fe released (CPM) 10000 *** 60 * 5000 ** Fe (mg/kg) 40 Blocks increase 0 in brain iron 0 1 10 20 20 ATH434 (µM) 0 UL VEH ATH434 Ligand Kd for Fe3+ 400 8-Isoprostane (% UL) α-synuclei
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 ↓ α-Synuclein Preserves Neurons ** 8000 6 ** Total SNpc neurons hA53T hA53T a-syn 4 Mouse 4000 2 0 Vehicle ATH434 0 W/T Vehicle ATH434 3 6000 Total SNpc neurons *** ** *** a-syn (OD) 2 MPTP * 3000 Mouse * 1 **
Slide 17: ATH434 Reduces α-Synuclein Neuropathology and Improves Motor Function in MSA Animal Model
ATH434 Reduces α-Synuclein-related Neuropathology and Improves Motor Function in MSA Animal Model α-Synuclein SN neurons Glial inclusions *** ** *** ** ** 4000 *** Total SNpc neurons 0.8 6000 ** Relative to Total Protein Number of GCI 0.6 3000 Exp. #1 0.4 4000 2000 0.2 1000 0.0 2000 0 Vehicle ATH434
Slide 18: Multiple System Atrophy Clinical Development Program
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 • Clinical impairments include • Motor: Parkinsonism, uncoordinated movements, balance problems/falls • Autonomic dysfunction: Reduced ability to maintain blood pressure, control bladder a
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 • 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 Concentration (ng/mL)
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 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=0.72 10 0 1 0 50 100
Slide 22: 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 23: bioMUSE Natural History Study: Design and De-risk Phase 2
bioMUSE Natural History Study: Design and De-risk Phase 2 New MRI Template Advanced MRI methods 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 Wearable Sensors Urinary Sy
Slide 24: 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 25: 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 0.10 y = 0.0017x + 0.1298 R² = 0.6269 0.05 0.00 0 20 40 60 80 Unified MSA Rating Scale BioMUSE Natural History Study Demonstrates Brain iron correlates with disease sev
Slide 26: 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 27: 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 28: Alterity: Poised for Progress
Alterity: Poised for Progress Milestones • ATH434-201 Phase 2 trial enrolling globally • Targeting Orphan disease with no approved treatments ATH434-201 Phase 2 Trial ü 2H 2022: First Patient In • bioMUSE Natural History Study de-risking Phase 2 ü Q1 2023: Launch in U.S. • Development team with prov
Slide 29: Therapeutics
THERAPEUTICS
Alterity Therapeutics — Investor Presentation (June 2023) on 6ix