Alterity Therapeutics Ltd. · ASX:ATH

Alterity Therapeutics — Prana Biotechnology — 34th Annual Cowen Healthcare Conference 2014

20 slides from Alterity Therapeutics's conference presentation, Mar 3, 2014

  1. Slide 1: 34th Annual Cowen Healthcare Conference

    34th Annual Cowen Healthcare Conference March 3 - 5, 2014

  2. Slide 2: Safe Harbour

    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, expectatio

  3. Slide 3: Public Market Overview

    Public Market Overview NASDAQ: PRAN; ASX: PBT (as of 28 February 2014) PBT – AU shares ($ in AUD) Prana – US ADRs ($ in USD) Share Price: $1.26 $11.31 52 - Week Range AUD $0.20 – $1.37 $2.11 - $13.29 Shares on Issue 422.66 million PBT ordinary shares 42.266 million PRAN ADR equivalent PRAN ADR = 10

  4. Slide 4: Metal Hypothesis

    Metal Hypothesis • Copper (Cu), zinc (Zn) and iron (Fe) are crucial to healthy brain function. • Due to aging, genetic factors or disease, distribution and uptake of these metals into neurons may be impaired , resulting in: • impaired neurotransmission; • increased metal mediated amyloid formation (

  5. Slide 5: Metal Hypothesis – Alzheimer's

    Metal Hypothesis – Alzheimer’s • Deposition of plaques formed from β - amyloid (A β ) are the primary pathological feature of the disease. • Amyloid plaques contain high concentrations of Cu and Zn (“metal incarceration”). • In - vitro, A β will bind Cu and Zn which promotes aggregation. • In - vitr

  6. Slide 6: How Does PBT2 work?

    How Does PBT2 work? (i) Anti Abeta (AD) & mHtt (HD) effects: x Inhibits Abeta aggregation 1 x Promotes dissolution of amyloid plaques 1 x Prevents Abeta and mHtt toxicity 2,3 x Reduces mHtt aggregation and toxicity 3 x Promotes Abeta degradation & clearance 4 x Reduces free radical generation 1 (ii)

  7. Slide 7: PBT2 – Phase 2a Trial

    PBT2 – Phase 2 a Trial * • 78 mild AD patients; placebo (n=29), 50mg PBT2 qd (20), 250mg PBT2 qd (29). • Patients recruited in Sweden (8 centers) and Australia (7 centers) • Study was well balanced for demographics and treatment history. • Entry criteria/study design. • ADAS - cog 10 - 25, MMSE 20 -

  8. Slide 8: Executive function is impaired in HD & AD

    Executive function is impaired in HD & AD Sources : Tabrizi SJ et al. Lancet Neurol 2013;12:637 - 49, Dorsey ER et al. JAMA Neurol 2013;310:1520 - 30, Paulsen JS et al. JNNP 2013;84:1233 - 9, Stout JC et al. Cogn Behav Neurol 2007;20:212 - 8, O’Rourke JJ et al. J Clin Exp Neuropsychol 2011;33:567 -

  9. Slide 9: Phase 2a Trial Results in Alzheimer's

    -0.1 -0.05 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 placebo n=28 250mg n=27 50mg n=19 p = 0.042 Phase 2a Trial Results in Alzheimer's* n = 74 • 78 mild AD patients; placebo (29), 50mg PBT2 qd (20), 250mg PBT2 qd (29): • ADAS - cog 10 - 25, MMSE 20 - 26; • 74 patients completed study; • 12 weeks of treatmen

  10. Slide 10: PBT2 Phase 2a Trial Results: CSF biomarkers

    PBT2 - Phase 2a trial Results Changes in CSF biomarkers at 12 weeks A β 42 A β 40

  11. Slide 11: AD – Phase 2b IMAGINE Trial

    • 42 prodromal/early AD patients, aged >55yrs. • Stable acetylcholinesterase inhibitor use. • 11 C - PiB PET SUVR score > 1.7. • MMSE ≥20. • 12 months treatment. • Doses: 250mg PBT2 qd or placebo; randomised 2:1. • Double blind, placebo controlled. • Primary endpoint – change in 11 C - PiB PET neoco

  12. Slide 12: AD - Phase 2b Extension Study

    • Open label extension study • All patients receiving study drug 250mg PBT2 qd • 12 month treatment period • 33 of 40 eligible patients chose to enrol into extension study (83%) • First patient enrolled July 2013 • Follow - up imaging, NTB and biomarker analysis continuing over 12 months • Provides

  13. Slide 13: Preclinical and clinical data supported the study of PBT2 in HD

    Preclinical and clinical data supported the study of PBT2 in HD Mechanism Preclinical study Clinical study • In Huntington disease, copper concentrations are elevated in the brain (basal ganglia) where they could bind mutant huntingtin and promote its aggregation . Sources : Butcher LL and Fox SS. S

  14. Slide 14: Reach2HD Phase 2 study design

    Reach2HD : Phase 2, randomized, double - blind placebo - controlled study 36 randomized to PBT2 250mg once daily Study design 109 individuals with early to mid - stage Huntington disease Study Objectives Primary: To evaluate the tolerability and safety of PBT2 Secondary: To evaluate the effect of PB

  15. Slide 15: PBT2 250mg significantly improved performance in HD

    PBT2 250mg significantly improved performance in HD Phase 2 trial Change in Trail Making Test Part B Improvement Trail Making Test Part B was significant at 12 (p<0.001) and 26 weeks (p=0.042)

  16. Slide 16: PBT2 is a promising therapy for HD

    PBT2 is a promising therapy for HD Tolerability and safety • PBT2 was well tolerated and safe in this trial over 26 weeks in individuals with early to mid - stage Huntington disease. Efficacy • PBT2 250mg daily significantly improved cognition on a key measure of executive function. • Trails Making

  17. Slide 17: Path to Market – HD

    Path to Market – HD • Only one drug approved in HD (tetrabenazine). • FDA approved tetrabenazine on 2 small pivotal trials. • Only works on motor symptoms. • No treatments for cognitive or behavioral symptoms. • Huntington’s is an Orphan Disease - ~30,000 patients in US. • PBT2 – Company preparing t

  18. Slide 18: Multiple potential applications

    Multiple potential applications Phase II trial reported Phase II trial reporting in March 2014 Product Indication Screening Preclinical toxicology Phase I Clinical trial Phase II Clinical trial Catalyst 2014 PBT2 PBT2 PBT434 PBT519 MPAC Library Huntington’s Disease Alzheimer’s Disease Parkinson’s Di

  19. Slide 19: Academic Advisors

    Targeting Metals in Alzheimer’s and Other Neurodegenerative Disease symposium hosted by New York Academy of Sciences in January 2013. Significant body of evidence supporting PBT - 2. Visit: http://www.nyas.org/Publications/Ebriefings/ Detail.aspx?cid=1fc1b1f4 - 1c78 - 46ba - 85a1 - 0763632fa129 Acad

  20. Slide 20: Thank you

    16 Thank you Mr Geoffrey Kempler Chairman and CEO Prana Biotechnology gkempler@pranabio.com SIGNATURES Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized. PRANA BIOTE

Prana Biotechnology — 34th Annual Cowen Healthcare Conference 2014 on 6ix