Alterity Therapeutics Ltd. · ASX:ATH

Alterity Therapeutics — Prana Biotechnology — Investor Presentation (April 2016)

18 slides from Alterity Therapeutics's investor presentation, Apr 22, 2016

  1. Slide 1: Metal Protein Attenuating Compounds (MPACs): A Unique Approach to Unmet Medical Need in CNS Indications

    Metal Protein Attenuating Compounds (MPACs) A Unique Approach to Unmet Medical Need in CNS Indications Birgit Anderegg, Ph.D. a cting VP Business Development

  2. Slide 2: Safe Harbor Statement

    MPACs – A unique approach to unmet medical needs in CNS 2 Safe Harbor S tatement 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 projecti

  3. Slide 3: Pipeline of Proprietary MPACs Positions Prana as Speciality Player in CNS

    MPACs – A unique approach to unmet medical needs in CNS 3 Pipeline of Proprietary MPACs Positions Prana as Speciality Player in CNS (Orphan, non - Orphan) Discovery MedChem Screening IND - enabling Phase I Phase IIa Phase IIb Phase III Approval PBT2 AD PBT2 HD PBT434 PBT519 1,000+ MPACs misc . orpha

  4. Slide 4: Metals are Highly Enriched and Tightly Regulated in the Healthy Brain

    MPACs – A unique approach to unmet medical needs in CNS 4 Metals concentrate in specific brain structures, reflecting metal functions in specialised neuronal activities . Grey : zinc, Red : iron, Green : copper Hare, D.J. et al. Anal. Chem. 2012 Metals are Highly Enriched and Tightly Regulated in th

  5. Slide 5: Metal Dyshomeostasis Provides Link Between AD and HD Pathology

    MPACs – A unique approach to unmet medical needs in CNS 5 Xiao G et al , PNAS (2013); DOI: 10.1073/pnas.1308535110 Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding Metal Dyshomeostasis Provides Link Between AD and HD Pathology Alzheimer’s Huntington’s Aggrega

  6. Slide 6: Numerous CNS Disorders Are Characterised By Altered Metal Homeostasis

    MPACs – A unique approach to unmet medical needs in CNS 6 Loss of effective regulation of brain metals causes: • D ysregulation of metal - responsive pathways involved in protein activation, trafficking and clearance » A ccumulation of misfolded proteins • A berrant interaction of metals with misfol

  7. Slide 7: Metal Hypothesis Clinically Validated Across Independent Trials, Indications

    MPACs – A unique approach to unmet medical needs in CNS 7 Metal Hypothesis Clinically Validated in Across Independent Trials, Indications PBT2 meets the Therapeutic Challenge: x Restores metal homeostasis x Counteracts protein misfolding = Prevents pathophysiological consequences of aberrant protein

  8. Slide 8: Pathways Affected by MPACs' Metal Re-Distribution

    MPACs – A unique approach to unmet medical needs in CNS 8 PATHWAYS AFFECTED BY MPACS’ METAL RE - DISTRIBUTION Further MPAC MoA Aspects of Disease - Relevance

  9. Slide 9: MPACs Compete w/ Toxic Misfolded Proteins, But Not w/ High-Affinity Physiological Ligands

    MPACs – A unique approach to unmet medical needs in CNS 9 10 - 3 10 - 6 10 - 9 10 - 12 10 - 15 10 - 18 10 - 24 Affinity for metal (M) Iron Zinc Copper 10 - 21 High Low EDTA Deferiprone Deferiprone Deferiprone EDTA EDTA Transferrin SOD Metallo - thionene SOD Ctr1 Atox - 1 Cyt - oxidase = metalloprote

  10. Slide 10: MPAC-Driven Metal Re-Distribution Triggers Disease-Relevant Signalling Pathways

    MPACs – A unique approach to unmet medical needs in CNS 10 PBT2:Zn Extracellular Intracellular Calcineurin activity CREB activity CaMKII activity pTau LTP GSK3 β activity LTP Spine morphology MPAC - Driven Metal Re - Distribution Triggers Disease - Relevant S ignalling Pathways

  11. Slide 11: Example 1: PBT2 Activates Pathways of Neuronal Plasticity

    MPACs – A unique approach to unmet medical needs in CNS 11 PBT2 30mg/kg vehicle normal Tg2576 apical CA1 dendrites EXAMPLE 1: PTB2 Activates Pathways of Neuronal Plasticity * p ൑ Ͳ Ǥ Ͳ͵ ** p ൑ Ͳ Ǥ ͲͲͻ Adlard et al Neuron 2008 PBT2 30mg/kg vehicle * s oluble pTau

  12. Slide 12: Example 1: PBT2 Activates Pathways of Neuronal Plasticity

    MPACs – A unique approach to unmet medical needs in CNS 12 PBT2 30mg/kg vehicle normal Tg2576 apical CA1 dendrites EXAMPLE 1: PTB2 Activates Pathways of Neuronal Plasticity * p ൑ Ͳ Ǥ Ͳ͵ ** p ൑ Ͳ Ǥ ͲͲͻ Adlard et al Neuron 2008 PBT2 30mg/kg vehicle * s oluble pTau

  13. Slide 13: MPAC-Driven Metal Re-Distribution Restores Signalling in Parkinsonism

    MPACs – A unique approach to unmet medical needs in CNS 13 Altered brain iron distribution in PD, MSA, DLB and PSP patients . Here, strong labelling of the Lewy bodies in neurons of the SNpc in a PD patient Pathological pathways of Fe dyshomeostasis Iron colocalises with dopamine in the substantia n

  14. Slide 14: Example 2: PBT434 Reduces Neuronal Stressors in Parkinsonism

    MPACs – A unique approach to unmet medical needs in CNS 14 PBT434 inhibits metal - mediated oxidative stress PBT434 delays onset and reduces degree of iron - mediated a S yn aggegation . Met - Ox: non - metal binding PBT434 analogue PBT434 prevents toxicity by nitrosative stress by a metal - binding

  15. Slide 15: Strategic & Tactical Aspects: Market Approval and Market Access

    MPACs – A unique approach to unmet medical needs in CNS 15 STRATEGIC & TACTICAL ASPECTS Market Approval and Market Access

  16. Slide 16: Huntington's disease competitive landscape of therapies in development

    MPACs – A unique approach to unmet medical needs in CNS 16 Company Name Product Names Description Partners Milestones Effect Valeant Xenazine , tetrabenazine Selective inhibitor of vesicular monoamine transporter (VMAT2) Chiesi ; HLu ; Temmler Marketed. Phase IV ongoing Symptomatic Chorea Auspex SD

  17. Slide 17: PBT434 Has Potential in an Exceptionally Broad Array of CNS Orphan Disorders

    MPACs – A unique approach to unmet medical needs in CNS 17 PBT434 Has Potential in an Exceptionally Broad Array of CNS Orphan Disorders tau  - Syn Aggregation disorders caused by respective protein/pathway PSP, FTD, CBD, CTE MSA, PD non - orphan Reduction of protein aggregation, deposition in vivo

  18. Slide 18: First-To-Market, First-in-Class Opportunities Across the Pipeline of Prana MPACs

    MPACs – A unique approach to unmet medical needs in CNS 18 Target Product Profile aims at closing “therapeutic gaps” … x b y addressing unmet medical need in orphan (HD) and non - orphan (PD; AD) indications: x PD, atypical parkinsonian: Motor and/or cognitive benefits x HD, AD: Cognitive benefit, e

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