Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — Investor Presentation (April 2019)
33 slides from Alterity Therapeutics's investor presentation, Apr 10, 2019
Slide 1: Investor Presentation April 2019
Investor Presentation April 2019 Mr Geoffrey Kempler CEO and Chairman Dr David Stamler Chief Medical Officer & SVP Clinical Development
Slide 2: 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, objectives, expectations or
Slide 3: An Alternate Future
AN ALTERNATE FUTURE 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: Alterity is developing 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. RW2
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
STRATEGIC INVESTMENT ▪ 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, technologies and drugs
Slide 7: Therapeutic Focus
Therapeutic Focus
Slide 8: 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 progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and co
Slide 9: Multiple System Atrophy (MSA)
▪ 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. ▪ Patients have a variable combination of ▪ Parkinsonism, whi
Slide 10: 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 how PBT434 is absorbed and metabolized
Slide 11: FDA Orphan Designation for MSA
▪ 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 and qualifies the sponsor of the drug for various
Slide 12: 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 blocks α - synuclein accumulation and aggregation, preserves neurons and improves function in ani
Slide 13: 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 neurotransmitter release by facilitating synaptic
Slide 14: Science and Technology
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 atypical parkinsonism ▪ α - synuclein is highly conserved in vertebrates but onl
Slide 16: PBT434 inhibits α-synuclein aggregation by restoring intracellular iron balance
0 1 10 20 0 5000 10000 15000 PBT434 (M) F e r e l e a s e d ( C P M ) Iron efflux from cultured M17 cells *** *** PBT434 INHIBITS α - SYNUCLEIN AGGREGATION BY RESTORING INTRACELLULAR IRON BALANCE PBT434 blocks the aggregation of α - synuclein in vitro PBT434 treatment preserves ferroportin levels i
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 Fe Fe Native, unfolded protein Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Aggregation of fibrillar protein Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe Fe F
Slide 18: PBT434 lowers α-synuclein and improves motor function in Parkinson's model
PBT434 LOWERS α - SYNUCLEIN, PREVENTS NEURONAL DEATH AND IMPROVES MOTOR FUNCTION IN TRANSGENIC ANIMAL MODEL OF PARKINSON’S DISEASE Preserves neurons in S. nigra T o t a l S N p c n e u r o n s W/T Vehicle PBT434 0 4000 8000 ** Finkelstein et al. Acta Neuropath Comm (2017) 5:53 ↓ α - Synuclein aggreg
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 Devos et al. Antiox. and Redox Signaling. 2014; 21: 195 S. nigra DFP PBO S. nigra Deferiprone • Indicated for Treatment of Iron Overloa
Slide 20: PBT434 has optimal iron binding affinity for efficacy and safety
PBT434 HAS OPTIMAL IRON BINDING AFFINITY FOR EFFICACY AND SAFETY Agent/Protein Kd for Fe 3+ α - Synuclein 10 - 5 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 Rev B
Slide 21: Link between iron and severity of PD
LINK BETWEEN IRON AND SEVERITY OF PD Gotz et al. Ann N.Y. Acad Sci. 2004 However, biochemical studies have reported increased iron content in the nigra in PD, 2 - 4 with the changes most marked in severe disease (PD) 5 Martin, et al. Neurology 2008;70:1411 – 1417 Iron concentrations increase with di
Slide 22: Brain iron increased in Parkinson's disease and MSA patients
BRAIN IRON INCREASED IN PARKINSON’S DISEASE PATIENTS Substantia nigra (T) Substantia nigra (pc) Cerebellum n = 24 n = 13 nmol iron/g of human brain n = 9 n = 7 * n = 3 n = 8 * 0 10000 20000 30000 AND IN MULTIPLE SYSTEM ATROPHY PATIENTS Cerebral cortex Caudate nucleus Putamen (M) Putamen (L) Globus p
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 Treatment: Randomly allocated, 4 months, 30 mg/kg/day or Vehicle (Veh) Data presented are for animals at 16 mo age Vehicle PBT434 0.0 0.1 0.2 0.3 0.4 R a t i o t o P o n
Slide 24: PBT434 preserves neurons and improves motor function
PBT434 PRESERVES NEURONS AND IMPROVES MOTOR FUNCTION Transgenic Mouse Model (PLP) - α - SYN of MSA Treatment: Randomly allocated, 4 months, 30 mg/kg/day or Vehicle Vehicle PBT434 0 2 4 6 8 T i m e t o d e s c e n d t h e P o l e ( s ) * Pole Test after 4 months treatment 30 mg/kg at 16 months Vehi
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 Cerebral cortex Caudate nucleus Putamen (T) Substantia nigra (T) Cerebellum n = 13 n = 11 n = 14 n = 11 n = 13 n = 11 n = 12 n = 7 nmol iron/g of human brain n = 8 n = 7 * 0 10000 20000 30000 * Healthy Patients Dexter et al . Brain
Slide 27: PBT434 in an animal model of acute oxidative stress
PBT434 IN AN ANIMAL MODEL OF ACUTE OXIDATIVE STRESS Total SNpc neurons 0 1 3 10 30 80 C 0 3000 6000 T o t a l S N p c n e u r o n s PBT434 (mg/kg) *** *** * * Pole test 0 1 3 10 30 80 C 0 6 12 T i m e ( s e c s ) PBT434 (mg/kg) ** * For α - synuclein, lipid peroxidation: PBT434 dose 30 mg/kg/d † Tre
Slide 28: Market Opportunity and Company Information
Market Opportunity and Company Information
Slide 29: Commercial Opportunity
29 I 3 STRATEGY PARTNERS CONFIDENTIAL COMMERCIAL OPPORTUNITY *Does not include spontaneous use in PD. Severely debilitating, fatal illnesses with no current treatments are ripe for new entrants targeting what may be the actual cause of the disease. SUBSTANTIAL UNMET NEED Motivated by efficacy in tre
Slide 30: Corporate Overview
Capital Structure Name Position Geoffrey Kempler CEO & Chairman Lawrence Gozlan Non - Executive Director Peter Marks Non - Executive Director Dr David Sinclair Non - Executive Director Tristan Edwards Non - Executive Director Brian Meltzer Non - Executive Director Board Management Team CORPORATE OVE
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 IR@alteritytherapeutics.com Tel: +61 3 9349 4906 RW12
Slide 33: Slide 33
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