Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Shareholder Meeting (November 2020)
27 slides from Alterity Therapeutics's shareholder meeting presentation, Nov 18, 2020
Slide 1: Annual General Meeting
For personal use only Annual General Meeting Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) David Stamler, MD Chief Medical Officer November 2020 CONFIDENTIAL 1
Slide 2: Forward Looking Statements
Forward Looking Statements For personal use only 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: Our Purpose
Our Purpose For personal use only We exist to create an alternate future for people living with neurodegenerative diseases. An alternate, healthier life. We’re here to disrupt the trajectory for people with these diseases. CONFIDENTIAL 3
Slide 4: Year in Review
Year in Review For personal use only Allowance of US patent for next ATH434 crosses blood brain barrier in generation compounds to treat humans; clinically tested doses achieved neurodegenerative diseases concentrations in the brain Raises $35M in placement to European Commission approves Orphan int
Slide 5: Parkinsonian Disorders − A Significant Unmet Need
Parkinsonian Disorders − A Significant Unmet Need For personal use only Parkinsonism is a syndrome of motor symptoms that includes slowness of movement, stiffness and tremor Major source of disability Parkinsonian disorders also include MSA atypical variants such as Multiple system atrophy (MS
Slide 6: Leadership of FDA Approvals in Neurology
Leadership of 3 FDA Approvals in Neurology For personal use only David Stamler, M.D. Chief Medical Officer FDA Advisory Committee Votes Unanimously to Recommend Approval of Tetrabenazine for Chorea Associated With Huntington • 3 FDA Approvals in Neurology Disease • Led FDA Advisory Committee and app
Slide 7: Excellent Progress with Lead Drug Candidate ATH434
Excellent Progress with Lead Drug Candidate ATH434 For personal use only Robust efficacy in animal Completed Phase 1 Qualitative research with models of disease Orally bioavailable, brain penetrant U.S. neurologists completed Evidence of neuroprotection with ATH434: safe and well tolerat
Slide 8: Clinical Development
For personal use only Clinical Development 8
Slide 9: Clinical Pharmacokinetics of ATH434
Phase 1 Completed Clinical Pharmacokinetics of ATH434 Plasma Profile after Single Dose Administration CSF Levels at Steady-State For personal use only 250 10000 Plasma (unbound, ng/mL) 50 mg 200 PBT434 in plasma (ng/mL) 100 mg 1000 300 mg 600 mg 150 100 100 50 r2=0.72 10 0 0 50 100 150 200 250 1 0 1
Slide 10: Adverse Event Summary
Adverse Event Summary Placebo 50 mg 100 mg 300 mg 600 mg For personal use only Single Ascending 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 11: Excellent Safety Profile
Excellent Safety Profile • No clinically significant AEs For personal use only • All AEs with ATH434 were mild to moderate in severity • Most common AEs reported in ATH434 subjects was headache • Similar AE profile for adults and older adults (≥ 65 years) • No significant findings observed in vital
Slide 12: bioMUSE Natural History Study
bioMUSE Natural History Study • Design: Observational (no treatment) For personal use only • Objective: De-risk Phase 2 study • Identify biomarker(s) suitable for endpoint in treatment study • Evaluate the change in biomarkers and clinical manifestations in patients with early MSA to track disease p
Slide 13: Phase 2 Study Design
Phase 2 Study Design • Design: Randomized, double-blind, placebo controlled For personal use only • Objectives • Assess target engagement and preliminary efficacy of ATH434 • Evaluate safety and tolerability of ATH434 • Population: Early MSA patients (parkinsonian variant) with motor symptoms ≤ 3 ye
Slide 14: Clinical Development Timeline
Clinical Development Timeline For personal use only 2020 2021 2022 Natural History Study in early MSA Phase 2 Optimization E.g., Data to inform P2 Phase 2 Study in early MSA ATH434 Multiple System 1H ’20 2H ’20 2H ’21 1H ’22 2H ’22 U.S. FDA European First patient Last patient Top line Atrophy Regula
Slide 15: Commercial
For personal use only Commercial CONFIDENTIAL 15
Slide 16: Commercial Opportunity – Multiple System Atrophy
Commercial Opportunity – Multiple System Atrophy Independent Analysis For personal use only STRONG INTENT TO SUBSTANTIAL UNMET NEED PRESCRIBE Severely debilitating, fatal illnesses with Motivated by efficacy in treating the no current treatments are ripe for new underlying disease and not just the e
Slide 17: Deal Landscape
Deal Landscape For personal use only Target / Therapeutic Neuro including AD & PD AD Neuro including PD area AD, PD AD, PD Development phase Preclinical Phase 1 Phase 1 Preclinical Preclinical Royalties High-single to low Sub-teens to Double-digit Undisclosed Undisclosed (% on net sales) double-digi
Slide 18: Scientific Background
For personal use only Scientific Background CONFIDENTIAL 18
Slide 19: Our Target is Alpha-Synuclein
Our Target is Alpha-Synuclein A Major Focus of Treating Parkinsonian Disorders For personal use only Structure of α-synuclein • α-synuclein is an intracellular protein, abundantly “We conclude that alpha-synuclein remains one of the expressed in nerve terminals most compelling therapeutic targets fo
Slide 20: Disease Background and Strategy Overview
Disease Background and Strategy Overview For personal use only • Lead indication: Multiple System Atrophy (MSA) • Severely debilitating and rapidly progressive disease • No approved therapy for treatment of MSA • Characterized by Parkinsonism, autonomic instability and/or cerebellar impairments • Pa
Slide 21: 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 = 9 Healthy n=8 n=8 * Cerebral cortex Substantia nigra (pc) n = 11 n=3 n = 13 n=8 * Cerebellum Caudate nucleus n = 24 n = 10 0 10000 20000 30000
Slide 22: Iron is Critical in the Pathogenesis of MSA
Iron is Critical in the Pathogenesis of MSA Oxidative Stress ATH434 restores intracellular iron balance For personal use only 15000 *** Fe released (CPM) 10000 *** 5000 R O Neuroinflammation Iron Dyshomeostasis R N 0 R N R 0 1 10 20 • Abundant evidence that labile iron is central in the OH ATH434 (µ
Slide 23: ATH434 Reduces Alpha-Synuclein-related Neuropathology
ATH434 Reduces Alpha-Synuclein-related Neuropathology Preserves Neurons and Improves Function in PD and MSA Animal Models For personal use only ↓ α-Synuclein Preserves nigral neurons Improves motor function ** 100 6 8000 ** Total SNpc neurons Parkinson’s P<0.001 % Clasping hA53T α-syn 4 disease 50 4
Slide 24: Strategy Supported by Proof of Concept in Parkinson's
Strategy Supported by Proof of Concept in Parkinson’s 6 month placebo-controlled data from study of Deferiprone – a drug for treating iron overload Brain Iron by MRI Motor Symptom Severity For personal use only Deferiprone • Binds iron with very high affinity • Boxed Warning for hematological toxici
Slide 25: Competitive Landscape
Competitive Landscape DEVELOPMENT PHASE/ ESTIMATED For personal use only AGENT (COMPANY) INDICATION MOA TARGET COMPLETION MEASURES/ENDPOINT FORMULATION BIIB054 Parkinson’s Alpha-synuclein Phase 2 / 2H ’20 Safety, PK and PD IV Infusion every 4wks (Biogen) Disease Antibody RG7935/PRX002 Parkinson’s Al
Slide 26: Investment Summary
Investment Summary For personal use only Targeting Orphan disease with no approved treatments • ATH434 has potential U.S. peak sales up to US$ 725 million Development team with proven track record at FDA Lead drug candidate ATH434 • Commenced natural history study to inform Phase 2 study • Com
Slide 27: For personal use only
For personal use only
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