Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Shareholder Meeting (November 2021)
32 slides from Alterity Therapeutics's shareholder meeting presentation, Nov 12, 2021
Slide 1: Alterity Therapeutics AGM CEO Address 2021
Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) AGM CEO Address 2021 David Stamler, MD 12 November 2021 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 = 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 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 neurodegeneration of Parkinson’s
Slide 5: Recent Progress
Recent Progress 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 for ATH434 in Multiple n
Slide 6: 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 7: Parkinsonian Disorders: A Significant Unmet Need
Parkinsonian Disorders: A Significant Unmet Need 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 atrophy (MSA) and Pro
Slide 8: Discovery and Development Portfolio in Neurodegenerative Diseases
Discovery and Development Portfolio in Neurodegenerative Diseases 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 to initiate Q1 2022 ATH
Slide 9: Alterity's Approach to Treating Parkinsonian Disorders
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 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, unfolded protein enables neur
Slide 11: Iron is Critical in the Pathogenesis of Parkinsonian Disorders
Iron is Critical in the Pathogenesis of Parkinsonian Disorders 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 • ODGs are cells with highest iron content in the CNS
Slide 12: Our Approach: Dual Mode of Action to Address the Underlying Pathology
Our Approach: Dual Mode of Action to Address the Underlying Pathology of Disease Bind and redistribute Rescue neurons in Reduce α-synuclein excess iron in the CNS of multiple brain regions to aggregation and oxidative patients with Parkinsonian address underlying stress disorders pathology Targeting
Slide 13: 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 14: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434 Reduces ATH434 redistributes excess iron α-synuclein αSN+Fe aggregation αSN+Fe+ATH434 αSN Fe (mg/kg) Blocks increase in brain iron Ligand Kd for Fe3+ α-Synuclein 10-5 Stronger binding ATH434 10-10 Inhibits oxidative Ferritin 10-22 stress in vivo Transferrin 10-23 Iron
Slide 15: 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 ** 6 hA53T hA53T -syn 4 Mouse 2 0 Vehicle ATH434 6000 *** *** MPTP * ** 3000 Mouse 0 0 1 3 10 30 80 C ATH434 (mg/kg) Finkelstein, et al. Acta Neuropath Comm. 2017 * P < 0.05, **
Slide 16: Clinical Strategy Supported by Proof of Concept with Iron Binding Drug in Parkinson's Disease
Clinical Strategy Supported by Proof of Concept with Iron Binding Drug in Parkinson’s Disease Reducing excess iron led to improved motor function Brain Iron by MRI Motor Symptom Severity Deferiprone • Designed to treat iron overload • Binds iron with very high affinity • Boxed Warning for hematologi
Slide 17: 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 α-Synuclein SN neurons Glial inclusions Exp. #1 Iron in SN Striatal neurons Motor Function Exp. #2 Finkelstein, et al. Neurology 2019 * P < 0.05, ** P < 0.01, *** P < 0.001 17 Heras-Garvin, et al. Mo
Slide 18: ATH434: Clinical Development Program
ATH434: Clinical Development Program 18
Slide 19: ATH434: Potential Use Across Multiple Indications
ATH434: Potential Use Across Multiple Indications • Small molecule designed to cross the blood brain barrier and inhibit α-synuclein aggregation • Potential to treat various Parkinsonian conditions • Orphan Drug Designation granted by FDA and EU for the treatment of Multiple System Atrophy (MSA) • F
Slide 20: Multiple System Atrophy (MSA) is a Rare, Neurodegenerative Disorder
Multiple System Atrophy (MSA) is a Rare, Neurodegenerative Disorder 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 treatments only address sy
Slide 21: MSA is Highly Debilitating and Rapidly Progressive
MSA is Highly Debilitating and Rapidly Progressive 60% require wheelchair confinement within 5 years Fanciulli, Wenning. NEJM 2015;372:249-63. 21
Slide 22: Excellent Progress with Lead Drug Candidate ATH434
Excellent Progress with Lead Drug Candidate ATH434 Robust efficacy in animal models of disease Evidence of neuroprotection with in PD and MSA animal models Findings corroborated in multiple labs Completed Phase 1 Achieved brain levels comparable to efficacious Orally bioavailable, brain penetrant We
Slide 23: Phase 1 Clinical Trial Design
Phase 1 Clinical Trial Design 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 dose levels Safety: Adve
Slide 24: Phase 1 Achieved Target Drug Concentrations
Phase 1 Achieved Target Drug Concentrations Associated with Efficacy in Animal Models Plasma Profile after Single Dose Administration Plasma and CSF Levels at Steady-State ATH434 in plasma (ng/mL) • Rapid absorption after oral administration • Dose dependent pharmacokinetics • CSF and free plasma le
Slide 25: Favorable Safety Profile
Favorable Safety Profile No evidence of QT prolongation • No clinically significant AEs ΔΔQTcF (msec) • All AEs were mild to moderate in severity • Most common AEs reported in ATH434 subjects was headache • Similar AE profile for adults and older adults (≥ 65 Concentration (ng/mL) years) • No signif
Slide 26: ATH434 Well-Tolerated with No Serious Adverse Events
ATH434 Well-Tolerated with No Serious Adverse Events 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 Placebo 100 mg BID 200
Slide 27: Biomarkers of Progression in MSA (bioMUSE) Natural History Study
Biomarkers of Progression in Multiple System Atrophy (bioMUSE) Natural History Study Design • Observational • Inform and de-risk Phase 2 Objectives • Identify biomarker(s) suitable for endpoint in treatment study • Evaluate the change in biomarkers and clinical manifestations in patients with early
Slide 28: bioMUSE Interim Results
bioMUSE Interim Results MSA (N=9) PD (N=17) Identification of Primary Iron Content by endpoint that encompasses Region of Interest all 3 regions ROI MSA vs PD† PT 0.03* GPe 0.04* GPi 0.18 DN 0.11 † P-value 0.30 Iron Content (GPe) Brain iron Images registered with 0.20 correlates with PD25 MNI templa
Slide 29: ATH434 Phase 2 Clinical Trial Early-Stage MSA Patients
ATH434 Phase 2 Clinical Trial Early-Stage MSA Patients 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 the pharmacokinetics of
Slide 30: 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 31: Alterity: Poised for Progress
Alterity: Poised for Progress Targeting Orphan disease with no approved treatments Development team with proven track record and multiple Milestones FDA approvals Lead drug candidate ATH434 Progressing to Phase 2 1H 2021: Commence Phase 2 • Completed Phase 1 demonstrating well-tolerated Feas
Slide 32: Alterity Therapeutics
offo Alterity ERAPEUTICS
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