Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (June 2021)
26 slides from Alterity Therapeutics's investor presentation, Jun 17, 2021
Slide 1: Alterity Therapeutics
For personal use only Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) June 2021 David Stamler, MD CEO
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. 3
Slide 4: Recent Progress
Recent Progress For personal use only Oral presentation demonstrating the neuroprotective effect of ATH434 in animal Potential application of PBT2 for model of MSA antibiotic resistance in superbugs Cardiovascular data which strengthens Commence enrolling Multiple System 7th International Congress f
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 Atypical forms of Parkinsonism include Multiple system atrophy MSA (MSA) and Progressive supr
Slide 6: Leadership of FDA Approvals in Neurology
Leadership of 3 FDA Approvals in Neurology For personal use only David Stamler, M.D. • 3 FDA Approvals in Neurology FDA Advisory Committee Votes Unanimously to Recommend Approval of Tetrabenazine for Chorea Associated With Huntington Disease • Led FDA Advisory Committee and approval of Dec 7, 2007 X
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: Commercial Opportunity: Multiple System Atrophy
Commercial Opportunity Multiple System Atrophy For personal use only Independent Analysis 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 9: 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 10: Development Strategy Overview
Development Strategy Overview For personal use only • Disrupt the underlying pathology of α-synuclein related diseases • Atypical parkinsonism (i.e., MSA) • Parkinson’s disease • Inhibit accumulation and aggregation of intracellular α-synuclein • Target “labile iron” which is increased in areas of p
Slide 11: 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 = 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 12: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434 For personal use only ATH434 restores intracellular iron balance ATH434 blocks increase in brain iron Ligand Kd for Fe3+ α-Synuclein 10-5 Stronger binding ATH434 10-10 Fe (mg/kg) Ferritin 10-22 ATH434 Transferrin 10-23 Iron trafficking proteins > ATH434 > α-synuclein
Slide 13: ATH434 Reduces Alpha-Synuclein Neuropathology in Parkinson's Animal Models
ATH434 Reduces Alpha-Synuclein-related Neuropathology and Improves Motor Function in Parkinson’s Disease Animal Models For personal use only ↓ α-Synuclein Preserves nigral neurons Improves motor function ** 100 6 P<0.001 hA53T hA53T -syn 4 Mouse 50 2 0 0 Vehicle ATH434 VEH ATH434 VEH ATH434 ATH434 D
Slide 14: Strategy Supported by Proof of Concept with Iron Binding Drug
Strategy Supported by Proof of Concept with Iron Binding Drug For personal use only 6-month placebo-controlled data from study of Deferiprone in Parkinson’s disease Brain Iron by MRI Motor Symptom Severity Deferiprone • Approved for treating iron overload • Binds iron with very high affinity • Boxed
Slide 15: ATH434 Improves Motor Function in Animal Model of MSA
ATH434 Reduces Alpha-Synuclein-related Neuropathology and Improves Motor Function in Animal Model of MSA For personal use only α-Synuclein Neurons Glial inclusions Motor Function (pole test) 4 months treatment with ATH434 or vehicle 15 Finkelstein, et al. Neurology 2019; 92 (15 Suppl.) Transgenic Mo
Slide 16: Clinical Development
For personal use only Clinical Development 16
Slide 17: Clinical Pharmacokinetics of ATH434
Phase 1 Completed Clinical Pharmacokinetics of ATH434 For personal use only 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 • Single doses up to 600 mg • CSF
Slide 18: Adverse Event Summary
Adverse Event Summary 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 Placebo 100 mg BID 200 mg BID 25
Slide 19: Excellent Safety Profile
Excellent Safety Profile For personal use only • No clinically significant AEs • 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 years) • No significant findings observed in vital signs, clini
Slide 20: bioMUSE Natural History Study
bioMUSE Natural History Study For personal use only • Design: Observational (no treatment) • Objective: De-risk Phase 2 study • Identify biomarker(s) suitable for endpoint in treatment study • Evaluate the change in biomarkers and clinical scales in patients with early MSA to track disease progressi
Slide 21: bioMUSE – Preliminary Brain Iron Data
bioMUSE – Preliminary Brain Iron Data For personal use only QSM MSA (n=7) QSM PD (n=17) • Preliminary MRI QSM data shows increased iron in bioMUSE patients • Higher iron content than Parkinson’s disease in Globus pallidus and Putamen Globus Pallidus(e) 0.30 0.25 0.20 QSM 0.15 R² = 0.6269 0.10 0.05 0
Slide 22: Phase 2 Design
Phase 2 Design For personal use only • Design: Randomized, double-blind, placebo controlled • Objectives: • Assess efficacy, safety and tolerability of ATH434 in subjects with MSA • Assess target engagement based on imaging and fluid biomarkers of disease progression • Evaluate the pharmacokinetics
Slide 23: Clinical Development Timeline
Clinical Development Timeline ATH434 in Multiple System Atrophy For personal use only 2021 2022 Natural History Study in early MSA Phase 2 Optimization E.g., Data to inform P2 Phase 2 Study in early MSA 2H ’20 1H ’21 2H ’21 1H ’22 2H ’22 European Phase 2 First patient Last patient Top line National
Slide 24: Competitive Landscape
Competitive Landscape For personal use only DEVELOPMENT PHASE/ ESTIMATED AGENT (COMPANY) INDICATION MOA TARGET COMPLETION MEASURES/ENDPOINT FORMULATION RG7935/PRX002 Parkinson’s Alpha-synuclein Phase 2 / Apr ’20 52 wk change UPDRS IV Infusion every 4wks (Roche/Prothena) Disease Antibody MEDI1341 Par
Slide 25: 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 • Completed Phase 1 with excellent safety profile • Achieved CS
Slide 26: For personal use only
For personal use only
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