Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (April 2019)
33 slides from Alterity Therapeutics's investor presentation, April 2019
Slide 1: Investor Presentation
Investor Presentation April 2019 Mr Geoffrey Kempler CEO and Chairman Dr David Stamler Chief Medical Officer & SVP Clinical Development
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: An Alternate Future
A N A LT E R N AT E F U T U R E 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 debilitating diseases. Improving Lives
Slide 4: First-in-class therapies for neurodegenerative diseases
Alterity is developing first-in-class therapies to treat neurodegenerative diseases. Our lead drug candidate, PBT434, has demonstrated pre-clinical evidence as a first-in-class therapy for the treatment of Parkinsonian disorders and is well advanced in its Phase 1 clinical program.
Slide 5: Investment Proposition
INVESTMENT PROPOSITION ▪ Well funded clinical stage drug development company following up to $44M strategic investment led by Life Biosciences LLC allowing accelerated and focused clinical development ▪ Strong and highly experienced board and management team with significant R&D and commercialisatio
Slide 6: Strategic Investment
S T R AT E G I C I N V E S T M E N T ▪ Strategic lead investor in a capital raise up to of approx. A$44.5 million. ▪ The funding will accelerate the Company’s drug development programs. ▪ Life Biosciences is a private US biopharmaceutical company focused on the development of novel therapies, techno
Slide 7: Therapeutic Focus
Therapeutic Focus
Slide 8: Parkinsonian Disorders Represent a Substantial Unmet Medical Need
PARKINSONIAN DISORDERS REPRESENT A SUBSTANTIAL UNMET MEDICAL NEED ▪ Parkinsonism is a general term for a group of symptoms in Parkinson's disease such as slowness of movement, stiffness and tremor ▪ Parkinsonian disorders include idiopathic Parkinson disease (PD) and atypical forms such as progressi
Slide 9: Multiple System Atrophy (MSA)
MULTIPLE SYSTEM ATROPHY (MSA) A form of Atypical Parkinsonism ▪ MSA is a rapidly progressive neurodegenerative disorder leading to severe disability and impairment in quality of life ▪ Sporadic (not inherited), typically presents in 50s to 60s ▪ Orphan disease: Prevalence 5 per 100,000 in the U.S.
Slide 10: Phase 1 Clinical Trial Program Advancing
PHASE 1 CLINICAL TRIAL PROGRAM ADVANCING ▪ Single- and Multiple-Ascending Dose study to be completed Q2’19 ▪ Recruiting healthy adult and elderly volunteers ▪ Primary goal is to evaluate the safety and tolerability of PBT434 ▪ Secondary goals include assessing pharmacokinetic measures to understand
Slide 11: FDA Orphan Designation for MSA
F D A O R P H A N D E S I G N AT I O N F O R M S A ▪ January 2019, US Food and Drug Administration (FDA) granted Orphan Drug Designation for PBT434 for the treatment of MSA. ▪ Orphan Drug designation entitles Alterity to seven years of market exclusivity for the use of PBT434 in the treatment of MSA
Slide 12: Therapeutic Strategy
THERAPEUTIC STRATEGY ▪ Alpha (α)-synuclein is an intracellular protein critical for neurotransmission ▪ α-synuclein accumulates and aggregates in many neurodegenerative diseases and is implicated in pathology PBT434 is an excellent drug candidate ▪ PBT434 blocks α-synuclein accumulation and aggregat
Slide 13: Importance of α-Synuclein as Disease Target
IMPORTANCE OF α-SYNUCLEIN AS DISEASE TARGET ▪ 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 neurotr
Slide 14: Science and Technology
offy. Alterity Science and Technology
Slide 15: α-Synuclein as Target for PBT434
α-SYNUCLEIN AS TARGET FOR PBT434 ▪ α-synuclein fibrillizes readily ▪ Factors regulating its production and conformation are relevant to disease pathogenesis and treatment ▪ Homeostasis of iron is disrupted in PD and from Friedlich, Tanzi, et al. 2007 atypical parkinsonism ▪ α-synuclein is highly con
Slide 16: PBT434 Inhibits α-Synuclein Aggregation by Restoring Intracellular Iron Balance
PBT434 INHIBITS α-SYNUCLEIN AGGREGATION BY RESTORING INTRACELLULAR IRON BALANCE Iron efflux from cultured M17 cells I r o n e f f l u x f r o m c u l t u r e d M 1 7 c e l l s 1 5 0 0 0 ) * * * M PBT434 blocks the aggregation of α-synuclein in vitro P 1 0 0 0 0 ( C d * * * e s a l e r e 5 0 0 0 e F
Slide 17: Alpha-Synuclein Pathology and PBT434 Mechanism of Action
ALPHA-SYNUCLEIN PATHOLOGY AND PBT434 MECHANISM OF ACTION PBT434 reduces α-synuclein accumulation, aggregation and preserves neurons Cell Death ↑ Oxidative Stress Accumulation Fe Fe OH• Fe Fe Fe Fe Fe Fe H2O2 Fe Fe Fe Fe Fe PBT434 exports Fe Fe Fe Fe Fe Fe Fe Fe from cell Fe Fe Fe Fe Fe Cytoplasm Ext
Slide 18: PBT434 Lowers α-Synuclein, Prevents Neuronal Death in Transgenic Model
PBT434 LOWERS α-SYNUCLEIN, PREVENTS NEURONAL DEATH AND IMPROVES MOTOR FUNCTION IN TRANSGENIC ANIMAL MODEL OF PARKINSON’S DISEASE ↓ α-Synuclein aggregation Preserves neurons in S. nigra Foot Clasping * * 6 8 0 0 0 1 0 0 * * s * * n n r o y 4 u - s g e i n n p T s c 4 0 0 0 5 0 3 l a p 5 N C 2 A S h
Slide 19: 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 Brain Iron by MRI Motor Function – UPDRS III Deferiprone Improvement Worsening • Indicated for Treatment of Iron Overload • Black Box for neutropenia and agranucloctyosis • Iron Bi
Slide 20: PBT434 Has Optimal Iron Binding Affinity
PBT434 HAS OPTIMAL IRON BINDING AFFINITY FOR EFFICACY AND SAFETY Agent/Protein Kd for Fe3+ α-Synuclein 10-5 Stronger binding PBT434 10-10 Ferritin 10-22 Transferrin 10-23 Deferiprone 10-36 Davies et al. PLoS ONE. 2011; 6; 1; e15814. doi.org/10.1371/journal.pone.0015814 Aisen P and Listowsky I. Ann R
Slide 21: Link Between Iron and Severity of PD
LINK BETWEEN IRON AND SEVERITY OF PD Iron concentrations increase with disease severity Gotz et al. Ann N.Y. Acad Sci. 2004 Martin, et al. Neurology 2008;70:1411–1417 However, biochemical studies have reported increased iron content in the nigra in PD,2-4 with the changes most marked in severe disea
Slide 22: Brain Iron Increased in Parkinson's Disease and MSA Patients
BRAIN IRON INCREASED IN PARKINSON’S DISEASE PATIENTS AND IN MULTIPLE SYSTEM ATROPHY PATIENTS n=7 * Patients Substantia nigra (T) n=9 Healthy n=8 n=8 Substantia nigra (pc) * Cerebral cortex n=3 n = 11 n = 13 n=8 Cerebellum Caudate nucleus * n = 24 n = 10 0 10000 20000 30000 n=8 * Putamen (M) n = 10 n
Slide 23: PBT434 Reduces Alpha-Synuclein and Lowers Glial Cell Inclusions
PBT434 REDUCES ALPHA-SYNUCLEIN AND LOWERS GLIAL CELL INCLUSIONS Transgenic Mouse Model (PLP)-α-SYN of MSA ↓ α-Synuclein Oligomeric ↓ Glial Cell Pontine Nucleus Inclusions 0 . 4 * * 1 5 0 0 0 * * u a 0 . 3 e I c C n G 1 0 0 0 0 o f P o 0 . 2 t o r e b t i o m 5 0 0 0 0 . 1 a u R N 0 . 0 0 V e h i c l
Slide 24: PBT434 Preserves Neurons and Improves Motor Function
PBT434 PRESERVES NEURONS AND IMPROVES MOTOR FUNCTION Transgenic Mouse Model (PLP)-α-SYN of MSA S. Nigra Neurons at 16 months Pole Test after 4 months treatment 30 mg/kg at 16 months Rotarod after 4 months treatment 30 mg/kg/day at 20 months P = 0 . 0 0 1 * 4 0 8 ** ) s ( s 6 0 0 0 n ) l e ( s r o 3
Slide 25: Brain Iron is also Increased in Tauopathies
Brain Iron is also Increased in Tauopathies
Slide 26: Progressive Supranuclear Palsy (PSP)
PROGRESSIVE SUPRANUCLEAR PALSY (PSP) A form of Atypical Parkinsonism n = 11 Cerebral cortex n = 13 Patients Healthy n = 11 Caudate nucleus n = 14 Brain Iron increased Putamen (T) n = 11 * compared to Healthy n = 13 controls n=7 * Substantia nigra (T) n=8 n=7 Cerebellum n = 12 0 10000 20000 30000 nmo
Slide 27: PBT434 in an Animal Model of Acute Oxidative Stress
PBT434 IN AN ANIMAL MODEL OF ACUTE OXIDATIVE STRESS Total SNpc neurons Pole test 6000 MPTP mouse model 1 2 T o ta l S N p c n e u ro n s • MPTP is a potent inhibitor of complex 1 *** of the mitochondrial electron * *** ( s e c s ) * * transport chain 3000 6 • Significant neuron loss in SNpc and e i
Slide 28: Market Opportunity and Company Information
Market Opportunity and Company Information
Slide 29: Commercial Opportunity
COMMERCIAL OPPORTUNITY 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 disease and not just the symptoms, entrants targeting what may be the actual clinicians intend to offer PT
Slide 30: Corporate Overview
CORPORATE OVERVIEW Capital Structure Management Team Ordinary Shares on issue 860,837,432 Founded Prana Biotechnology in 1997 , Mr Kempler has extensive Geoffrey Kempler experience in investment and business development and has been CEO & Chairman responsible for the implementation of Alterity’s str
Slide 31: Investment Summary
INVESTMENT SUMMARY • Proven track record in taking new drugs through to market. Team responsible for 3 new drugs approved by FDA • Lead drug candidate PBT434 has the potential as a disease modifying treatment and is currently completing a phase 1 clinical trial program • First disease target selecte
Slide 32: Contact
Contact Geoffrey Kempler [email protected] Tel: +61 3 9349 4906
Slide 33: oflte Alterity
oflte Alterity
Alterity Therapeutics — Investor Presentation (April 2019) on 6ix