Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Shareholder Meeting (November 2022)
31 slides from Alterity Therapeutics's shareholder meeting presentation, Nov 11, 2022
Slide 1: Alterity Therapeutics
For personal use only Alterity Therapeutics (NASDAQ:ATHE, ASX:ATH) David Stamler, MD November 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 is dedicated to being different
For personal use only Alterity means the state of Alterity is dedicated to being different creating an alternate future for people living with neurodegenerative Our goal is to modify the 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 • Developing disease modifying therapies • 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 treatm
Slide 5: 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 6: 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 sy
Slide 7: Discovery and Development Portfolio in Neurodegenerative Diseases
Discovery and Development Portfolio in Neurodegenerative Diseases For personal use only Program Indication Current Status Future Plans ATH434 Multiple System Atrophy Phase 2 Ongoing Expand enrollment globally BioMUSE Multiple System Atrophy Ongoing Enrolling up to 20 patients Natural History Study P
Slide 8: The Role of Alpha-Synuclein and Iron in Parkinsonian Diseases
For personal use only The Role of Alpha-Synuclein and Iron in Parkinsonian Diseases 8
Slide 9: Alpha-Synuclein: Critical for Normal Neuron Function
Alpha-Synuclein: Critical for Normal Neuron Function For personal use only 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-Synu
Slide 10: Iron: Critical in Disease Pathogenesis
Iron: Critical in Disease Pathogenesis For personal use only Oxidative Stress • α-Synuclein and iron are strong contributors to MSA pathology • Hallmark of MSA pathology is the accumulation of α-synuclein in glial cells and neuron loss in multiple brain regions • Adverse impact of increased labile i
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=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 12: Our Approach: Dual Mode of Action to Address Underlying Pathology
Our Approach: Dual Mode of Action to Address the Underlying Pathology of Disease For personal use only Redistribute excess iron Reduce α‐synuclein Rescue neurons in multiple brain regions to in the CNS of patients with aggregation and oxidative address underlying Parkinsonian disorders stress pathol
Slide 13: ATH434: Disease Modifying Drug Candidate
For personal use only ATH434: Disease Modifying Drug Candidate 13
Slide 14: ATH434: Potential Use in Multiple Indications
ATH434: Potential Use in Multiple Indications For personal use only R O • Small molecule drug that reduces α-synuclein aggregation R • Iron chaperone which redistributes loosely bound excess iron N • Readily crosses the blood brain barrier R N R • Oral agent for ease of use OH • Potential to treat v
Slide 15: Pharmacologic Actions of ATH434
Pharmacologic Actions of ATH434only For personal use only Reduces Redistributes loosely bound, α‐synuclein excess iron aggregation 15000 *** Fe released (CPM) 10000 *** 60 * 5000 ** 40 Fe (mg/kg) Blocks increase 0 in brain iron 0 1 10 20 20 ATH434 (µM) 0 UL VEH ATH434 Ligand Kd for Fe3+ 400 8-Isopro
Slide 16: ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson's Animal Models
ATH434 Reduces Alpha-Synuclein-related Neuropathology in Parkinson’s Disease Animal Models For personal use only ↓ α-Synuclein Preserves Neurons ** 6 8000 ** Total SNpc neurons hA53T hA53T α-syn 4 Mouse 4000 2 0 Vehicle ATH434 0 W/T Vehicle ATH434 3 6000 Total SNpc neurons *** 2 ** *** α-syn (OD) MP
Slide 17: ATH434 Improves Motor Function in MSA Animal Model
ATH434 Reduces α-Synuclein-related Neuropathology and Improves Motor Function in MSA Animal Model For personal use only α-Synuclein SN neurons Glial inclusions *** ** *** ** ** 4000 *** Total SNpc neurons 0.8 6000 ** Relative to Total Protein 3000 Number of GCI 0.6 Exp. #1 0.4 4000 2000 0.2 1000 0.0
Slide 18: Multiple System Atrophy Clinical Development Program
For personal use only Multiple System Atrophy Clinical Development Program 18
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, uncoordinated movements, and/or impairment of the body’s involuntary (autonomic) nervous system • Blood pressure maintenance, bladder control, impaired balance and/or coordinati
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 Stage at which death can occur Clinically Established MSA Premotor MSA Clinically Probable MSA 0 3 6 9 Years Sources: Fanciulli, Wenning. NEJM 2015;372:249-63 | Wenning et al, M
Slide 21: 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 years) Objectives: Assess safety and pharmacokinetics of ATH434 Pharmacokinetics: Plasma, cerebrospinal fluid (CSF) in two top multiple dose levels Safety: Ad
Slide 22: 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 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
Slide 23: Well-Tolerated with No Serious Adverse Events
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 Placebo
Slide 24: Favorable Safety Profile
Favorable Safety Profile For personal use only No evidence of QT prolongation ΔΔQTcF (msec) • All AEs were mild to moderate in severity • Most common AE reported in ATH434 subjects was headache • Similar AE profile for adults and older adults Concentration (ng/mL) (≥ 65 years) • No significant findi
Slide 25: bioMUSE: Biomarkers of Progression in MSA
bioMUSE: Biomarkers of Progression in MSA 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 • Early-stage MSA patients similar
Slide 26: bioMUSE Natural History Study: Characterizing Early-Stage MSA
bioMUSE Natural History Study: Characterizing Early-Stage MSA For personal use only Advanced MRI methods New MRI Template Iron distribution in MSA Alpha-synuclein Profiles Wearable Sensors 1000000 100000 PD Fluorescence 10000 MSA 1000 100 Time → Iron/voxel Identify “iron signature” Improve precision
Slide 27: Phase 2 Clinical Trial in Early-Stage MSA Patients
Phase 2 Clinical Trial in Early-Stage MSA Patients For personal use only 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 part
Slide 28: Phase 2 Design and Primary Endpoint
Phase 2 Design and Primary Endpoint For personal use only Primary Endpoint: Change in Brain Iron on MRI ATH434 0.30 Iron Content (GPe) High dose 0.25 0.20 0.15 Early MSA ATH434 0.10 y = 0.0017x + 0.1298 R² = 0.6269 (N=60) Low dose 0.05 0.00 0 20 40 60 80 Placebo Unified MSA Rating Scale 12 months tr
Slide 29: 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 30: Alterity: Poised for Progress
Alterity: Poised for Progress For personal use only Milestones • Targeting Orphan disease with no approved treatments Q1 2022: Submit ATH434 European Clinical Trial Application (CTA) • bioMUSE Natural History Study de-risking Phase 2 Q2 2022: Launch ATH434 Phase 2 • Phase 2 trial ongoing with le
Slide 31: For personal use only
For personal use only
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