Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (March 2022)
32 slides from Alterity Therapeutics's investor presentation, Mar 7, 2022
Slide 1: Alterity Therapeutics
For personal use only Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) David Stamler, MD March 2022 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 means the state of being different
For personal use only 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 For personal use only Novel approach to treat the underlying pathology of disease Strong and highly experienced management team with significant R&D experience including 3 drug approvals by US FDA ATH434 is a novel drug candidate targeting key proteins implicated in neurodegene
Slide 5: Recent Progress
Recent Progress For personal use only Presentation of advanced EMA endorses clinical strategy for quantitative MRI as potential Phase 2 study in early MSA novel biomarker in early MSA patients Two new US patents expand portfolio US FDA provides development of next generation compounds for pathway fo
Slide 6: 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 7: Parkinsonian Disorders: A Significant Unmet Need
Parkinsonian Disorders: A Significant Unmet Need For personal use only PARKINSONIAN DISORDERS Parkinsonism is a syndrome of motor symptoms that includes slowed movement, stiffness and tremor • A major source of disability MSA Parkinsonian disorders also include atypical forms such as Multiple system
Slide 8: Discovery and Development Portfolio in Neurodegenerative Diseases
Discovery and Development Portfolio in Neurodegenerative Diseases For personal use only Program Indication Current Status Future Plans bioMUSE Multiple System Atrophy Ongoing Enrolling up to 20 patients Natural History Study Partner: ATH434 Multiple System Atrophy Phase 1 Complete Phase 2 expected t
Slide 9: Alterity's Approach to Treating Parkinsonian Disorders
For personal use only Alterity’s Approach to Treating Parkinsonian Disorders 9
Slide 10: Alpha-Synuclein: A Major Focus for Treating Parkinsonian Disorders
Alpha-Synuclein: A Major Focus for Treating Parkinsonian Disorders For personal use only Health Disease Structure of α-Synuclein • α-Synuclein is an intracellular protein critical for normal Our Strategy function of neurons • Inhibit oligomerization and aggregation of intracellular • Native, unfolde
Slide 11: Iron is Critical in the Pathogenesis of Parkinsonian Disorders
Iron is Critical in the Pathogenesis of Parkinsonian Disorders For personal use only Oxidative Stress α-Synuclein and iron are strong contributors to the pathogenesis of MSA Prominent pathology in Oligodendroglial cells (ODG) • ODGs are vital support cells for neurons • Cells with highest iron conte
Slide 12: Our Approach: Dual Mode of Action to Address the Underlying Pathology of Disease
Our Approach: Dual Mode of Action to Address the Underlying Pathology of Disease For personal use only Bind and redistribute Rescue neurons in Reduce α-synuclein excess iron in the CNS of multiple brain regions to patients with Parkinsonian aggregation and oxidative address underlying disorders stre
Slide 13: Increased Brain Iron in Synuclein-related Diseases
Increased Brain Iron in Synuclein-related Diseases For personal use only 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 30
Slide 14: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434 For personal use only 1 . 5 ´ 1 0 5 Reduces ATH434 redistributes excess iron α-synuclein 1 ´ 1 0 5 αSN+Fe U aggregation F R 5 ´ 1 0 4 15000 αSN+Fe+ATH434 αSN *** 0 Fe released (CPM) 0 1 0 2 0 3 0 4 0 5 0 T i m e ( H r ) 10000 *** 60 * 5000 ** Fe (mg/kg) 40 Blocks incr
Slide 15: ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson's Disease Animal Models
ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson’s Disease For personal use only 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 MP
Slide 16: ATH434 Reduces Neuropathology and Improves Motor Function in Animal Model of MSA
ATH434 Reduces α-Synuclein-related Neuropathology and Improves Motor Function in Animal Model of MSA For personal use only 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
Slide 17: ATH434: Clinical Development Program
For personal use only ATH434: Clinical Development Program 17
Slide 18: ATH434: Potential Use Across Multiple Indications
ATH434: Potential Use Across Multiple Indications For personal use only • Small molecule designed to cross the blood brain barrier and inhibit α-synuclein aggregation • Potential to treat various Parkinsonian disorders • Orphan Drug Designation granted by FDA and EU for the treatment of Multiple Sys
Slide 19: Multiple System Atrophy (MSA) is a Rare, Neurodegenerative Disorder
Multiple System Atrophy (MSA) is a Rare, Neurodegenerative Disorder For personal use only Characterized by Parkinsonism, autonomic instability and/or cerebellar impairments Affects the body's involuntary (autonomic) functions, including blood pressure, bladder control and bowel function Current trea
Slide 20: MSA is Highly Debilitating and Rapidly Progressive
MSA is Highly Debilitating and Rapidly Progressive For personal use only 60% require wheelchair confinement within 5 years Fanciulli, Wenning. NEJM 2015;372:249-63. 20
Slide 21: Excellent Progress with Lead Drug Candidate ATH434
Excellent Progress with Lead Drug Candidate ATH434 For personal use only Robust efficacy in animal models of disease Evidence of neuroprotection in PD and MSA animal models Findings corroborated in multiple labs Completed Phase 1 Achieved brain levels comparable to efficacious Orally bioavailable, b
Slide 22: Phase 1 Clinical Trial Design
Phase 1 Clinical Trial Design For personal use only Design: Randomized, double blind, placebo-controlled, healthy adult and older adults (≥65 yo) Objectives: Assess safety and pharmacokinetics of ATH434 after single and multiple oral doses Plasma PK in each cohort, CSF sampled in two top multiple do
Slide 23: Phase 1 Achieved Target Drug Concentrations Associated with Efficacy
Phase 1 Achieved Target Drug Concentrations Associated with Efficacy in Animal Models For personal use only Plasma Profile after Single Dose Administration Plasma and CSF Levels at Steady-State 250 10000 Plasma (unbound, ng/mL) 50 mg 200 ATH434 in plasma (ng/mL) 100 mg 1000 300 mg 600 mg 150 100 100
Slide 24: Favorable Safety Profile
Favorable Safety Profile For personal use only No evidence of QT prolongation ΔΔQTcF (msec) • No clinically significant AEs • All AEs were mild to moderate in severity • Most common AE reported in ATH434 subjects was headache Concentration (ng/mL) • Similar AE profile for adults and older adults (≥
Slide 25: ATH434 Well-Tolerated with No Serious Adverse Events
ATH434 Well-Tolerated with No Serious Adverse Events For personal use only Placebo 50 mg 100 mg 300 mg 600 mg Single Doses (N=8) (N=6) (N=6) (N=6) (N=6) Patients with ≥ 1 AE 3 (38%) 0 0 1 (17%) 1 (17%) Patients with AEs leading to 0 0 0 0 0 Withdrawal Patients with Serious AEs 0 0 0 0 0 250 mg BID P
Slide 26: Biomarkers of Progression in Multiple System Atrophy (bioMUSE) Natural History Study
Biomarkers of Progression in Multiple System Atrophy (bioMUSE) Natural History Study For personal use only Design • Observational • Inform and de-risk Phase 2 Objectives • Identify biomarker endpoint(s) for treatment study • Evaluate the change in biomarkers and clinical manifestations in early MSA
Slide 27: bioMUSE Interim Results: Increased Brain Iron in MSA and PD
bioMUSE Interim Results: Increased Brain Iron in MSA and PD For personal use only Multiple System Atrophy MSA (N=9) PD (N=17) Basal ganglia MSA patients Iron Content by have higher iron Region of Interest in basal ganglia ROI MSA vs PD† PT 0.03* GPe 0.04* m AtrophyParkinson disease GPi 0.18 S. nigra
Slide 28: Phase 2 Primary Endpoint: Change in Brain Iron by MRI
Phase 2 Primary Endpoint: Change in Brain Iron by MRI For personal use only BioMUSE images registered with PD25 MNI template 0.30 Iron Content (GPe) 0.25 PT 0.20 CN 0.15 GPe 0.10 y = 0.0017x + 0.1298 0.05 R² = 0.6269 GPi 0.00 SN 0 20 40 60 80 RN Unified MSA Rating Scale DN Brain iron correlates with
Slide 29: ATH434 Phase 2 Clinical Trial in Early-Stage MSA Patients
ATH434 Phase 2 Clinical Trial Early-Stage MSA Patients For personal use only Design • Randomized, double-blind, placebo controlled • Assess efficacy and safety of ATH434 in subjects with MSA Objectives • Assess target engagement based on imaging and fluid biomarkers of disease severity • Evaluate th
Slide 30: 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 31: Alterity: Poised for Progress
Alterity: Poised for Progress For personal use only Milestones ü Targeting Orphan disease with no approved treatments ü Development team with proven track record and multiple • Q1 2022: Submit ATH434 European FDA approvals Clinical Trial Application (CTA) ü Lead drug candidate ATH434 Progressing to
Slide 32: For personal use only
For personal use only
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