Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Prana Biotechnology — Investor Presentation (January 2018)
23 slides from Alterity Therapeutics's investor presentation, Jan 8, 2018
Slide 1: Treatment of Neurological Disorders
Treatment of Neurological Disorders Dr. David Stamler, MD Chief Medical Officer and SVP, Clinical Development January, 2018 1
Slide 2: Corporate Overview
Corporate Overview • Developing first-in-class therapies to treat orphan and non-orphan neurological diseases. • Lead program, PBT434, is the first of a new generation of small molecules designed to block iron-mediated accumulation and aggregation of alpha-synuclein, an abundant brain protein widely
Slide 3: An International Business
An International Business Established in 1997 in Australia, listed on ASX (PBT) Melbourne, Australia • Headquarters • Discovery and Research team Listed on Nasdaq in 2000 (PRAN) San Francisco, USA • Clinical Development team 3
Slide 4: Investment Highlights
Investment Highlights 4 Novel Drug Candidate: PBT434 • Targets key proteins implicated in the neurodegeneration of Parkinson’s disease and atypical parkinsonism • Prevents accumulation of α-synuclein and tau • Well tolerated in repeated dose toxicology studies Strong Research and Development • Innov
Slide 5: Management Team
Management Team Geoffrey Kempler, Executive Chairman & CEO Founded Prana in November 1997 • Extensive experience in investment and business development • Overseen operations responsible for the implementation of Prana’s strategic plan and technology commercialization of our technology. David Stamler
Slide 6: Investment Thesis
Investment Thesis • Alpha (α)-synuclein is a soluble, intracellular protein critical for neuro transmission • Alpha-synulein accumulates and aggregates in many neurodegenerative diseases, implicated in pathology • PBT434 blocks α-synuclein accumulation and aggregation, preserves neurons and improves
Slide 7: PBT434: Promising Drug Profile
PBT434: Promising Drug Profile • Good CNS penetration based on low molecular weight and lipophilicity • Concentrates in brain 2 to 3 fold higher than plasma • Straightforward synthetic process with demonstrated ability to make kg amounts of GMP material • Benign safety profile in GLP toxicology stud
Slide 8: Importance of α-Synuclein
Importance of α-Synuclein • α-Synuclein is an intracellular protein, abundantly expressed in the brain • Critical for normal function of neurons • Soluble, in highest concentration at presynaptic nerve endings • Key regulatory protein involved in neurotransmission • Enables neurotransmitter release
Slide 9: α-Synuclein is an Important Disease Target
α-Synuclein is an Important Disease Target Strong genetic and pathological link to disease CONFIDENTIAL The Michael J. Fox foundation for Parkinson’s research Alpha-synuclein priority area our investment in alpha-synuclein research The Michael J. fox Foundation has made signigicant investments in re
Slide 10: PBT434 Inhibits α-Synuclein Accumulation and Aggregation
PBT434 Inhibits α-Synuclein Accumulation and Aggregation α-synuclein fibrillizes in vivo; only form of synuclein to fibrillize in vitro • Factors regulating α- synuclein production and conformation are relevant to disease pathogenesis and treatment • Homeostasis of iron is disrupted in PD and atypic
Slide 11: Alpha-synuclein Pathology and PBT434 Mechanism of Action
Alpha-synuclein Pathology and PBT434 Mechanism of Action Iron Chaperone, reducing α-synuclein accumulation, aggregation and preserving neurons HO NH2 Lipid peroxidation Mitochondrial dysfunction DNA Fragmentation Glial activation. Cell Death. Accumulation FE H2O2 OH R O N Fe2+ Cytoplasm Extracellula
Slide 12: PBT434 Target Product Profile
PBT434 Target Product Profile CONFIDENTIAL 12 Mechanism of Action Inhibitor of iron-mediated protein accumulation and aggregation Product Concept By inhibiting accumulation and aggregation of α-synuclein, PBT434 preserves neurons and improves motor and non-motor symptoms of neurodegenerative disease
Slide 13: PBT434 Lowers α-Synuclein, Prevents Neuronal Death and Improves Motor Function
PBT434 Lowers α-Synuclein, Prevents Neuronal Death and Improves Motor Function Transgenic Animal Model (hA53T) of Parkinson’s Disease CONFIDENTIAL 13 Preserves neurons in S. nigra T o t a l S N p c n e u r o n s W / T V e h i c le P B T 4 3 4 0 4 0 0 0 8 0 0 0 * * Finkelstein et al. Acta Neuropath C
Slide 14: Strategy Supported by Proof of Concept with Deferiprone
Strategy Supported by Proof of Concept with Deferiprone 6 month placebo controlled data in Parkinson’s disease patients CONFIDENTIAL 14 S. nigra Brain Iron by MRI Motor Function – UPDRS III Devos et al. Antiox. and Redox Signaling. 2014; 21: 195 DFP PBO DFP PBO S. nigra Improvement Deferiprone • Ind
Slide 15: Link Between Iron and Severity of PD
Link Between Iron and Severity of PD The relevance of iron in the pathogenesis of parkinson’s disease gotz et al ann NY Acad Sci. 2004 The nigral increase in iron levels identified biochemically in the postmortem brain from parkinsonian patients appears to be confirmed and is related to the severity
Slide 16: Brain Iron Increased in Parkinson's Disease Patients
Brain Iron Increased in Parkinson’s Disease Patients Substantia nigra (T) Substantia nigra (pc) Cerebellum Patients controls and in multiple system atrophy patients cerebral cortex caudate nucleus putamen (M) Putamen (L) Globus pallidus (M) Globus pallidus (L) Substantia nigra (T) Cerebellum Special
Slide 17: Multiple System Atrophy
Multiple System Atrophy • Progressive neurodegenerative disorder leading to severe disability and impairment in quality of life • Sporadic, typically presents in 50s to 60s • Orphan Indication: Prevalence ~5 per 100,000 in the U.S. • Characterized by a variable combination of • Parkinsonism, which r
Slide 18: PBT434 Lowers α-Synuclein, Prevents Neuronal Death in MSA Model
PBT434 Lowers α-Synuclein, Prevents Neuronal Death and Improves Function Transgenic Animal Model of MSA [(PLP)-α-SYN] of Multiple System Atrophy Rotarod Test Neurons in S. nigra Preliminary Data Treatment • Randomly allocated • 7-12 months of age • 30 mg/kg/day (via feed) Assessments done in blinded
Slide 19: Structure and Function of Tau
Structure and Function of Tau PBT434 Prevents Abnormal Tau Accumulation • Tau is an intracellular protein expressed in neurons and glial support cells • Natively unfolded, highly soluble protein • Primary role is to regulate and stabilize microtubules inside cells, which is critical to normal cellul
Slide 20: Brain Iron is also Increased in Tauopathies
Brain Iron is also Increased in Tauopathies E.g.: Progressive Supranuclear Palsy Cerebral cortex n=11 n=13 Caudate nucleus n=11 n=14 Putamen (t) n=11 n=13 substantia nigra (t) n=7 n=8 Cerebellum n=7 n=12 patents controls0 10000 20000 30000 nmol iron/g dry weight of human brain Dexter et al . Brain.
Slide 21: PBT434 Lowers Tau Accumulation and Cognitive Function
PBT434 Lowers Tau accumulation and Cognitive Function Transgenic Animal Model of Tauopathy (rTg4510) Tau accumulation in hippocampus Performance in Y-maze Treatment • Randomly allocated • Started at 10.5 months • Low: 1 mg/kg/day x 3-4 mo • High: 30 mg/kg/day x 1.5 mo CONFIDENTIAL 21
Slide 22: PBT434 has Potential for Wide Application in Neurodegenerative Diseases
PBT434 has Potential for Wide application in Neurodegenerative diseases α-Synuclein and Tau proteins Share Pathogenic Features Parameter α-Synuclein Tau Localization Intracellular Intracellular Native form Soluble Soluble Physiologic function Facilitates synaptic function Microtubule assembly and st
Slide 23: Development Milestones
Development Milestones•GMP Manufacturing 1Q ‘18•Phase 1 (SAD/MAD) start mid ‘18•Initiate LT Toxicology 2H ‘18•New IND 2H ‘19•Phase 2 start 1H ’20 CONFIDENTIAL 23 SIGNATURES Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on
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