Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Cappello US Investor Conference (January 2013)

30 slides from Benitec Biopharma's conference presentation, January 2013

1. Slide 1: Corporate Presentation

   Corporate Presentation January 2013 Copyright © Benitec Biopharma Ltd, 1" www.benitec.com

2. Slide 2: Forward looking statement

   Forward looking statement This"presenta-on"contains"forward"looking"statements"that"involve"risks" and"uncertain-es."" Although"we"believe"that"the"expecta-ons"reflected"in"the"forward" looking"statements"are"reasonable"at"this"-me,"Benitec"Biopharma""can" give"no"assurance"that"these"expecta-ons"wil

3. Slide 3: Benitec Biopharma: Company Profile

   Benitec Biopharma: Company Profile !Unique"patent"protected"long"las-ng"gene"silencing"technology"" !DNA"Directed"RNA"interference"(ddRNAi)"with"poten-al"to"provide"“one" shot"cures”" “Unlike(current(an.retroviral(therapies,((shRNA):based(gene(therapy(may(be( poten.ally(cura.ve,(reversing(the(virus’

4. Slide 4: Benitec Biopharma: Financial Profile

   Benitec Biopharma: Financial Profile !Australian"biotechnology"company" Key!Financials!at"30"June"2012" ASX:BLT! Price"per"share! AUD"0.017"! Market"capitalisa-on! AUD"16.7"million! Issued"equity:"ordinary"shares! 970,628,529! Op-ons"on"issue"! 428,985,202! Cash"balance"! AUD"3.1"million"! Monthly"b

5. Slide 5: Benitec Biopharma: ddRNAi Technology

   Benitec Biopharma: ddRNAi Technology ! ddRNAi!technology!u;lizes!the!power!and! Benitec!technology! specificity!of!RNAi!while!avoiding!many!of! 1" ddRNAi!DNA! construct! the!problems!with!siRNA! 1. DNA"construct"is"delivered"to"the"nucleus"by" EnzymaIc"cleavage"of" hairpin"loop"by"DICER" a"clinically

6. Slide 6: Benitec Biopharma: Pipeline

   Benitec Biopharma: Pipeline Indica;on! Partners/Collaborators! Discovery" Pre`clinical" Clinical" HIV/AIDS" Calimmune" OutVlicensed"" Acquired"from" Hepa--s"C" "" Tacere/Pfizer" University"of"New"South" Non"Small"Cell"Lung"Cancer"*" Wales" Cancer"associated"pain" Stanford"University" Hepa--s"B" Biomi

7. Slide 7: Lead program (TT-034): Novel Hepatitis C Therapeutic

   Lead program (TT-034): Novel Hepatitis C Therapeutic !A"“molecular"monotherapy”"intended"to"treat"and"cure"HCV" infec-on"with"a"single"injec-on" !Developed"in"collabora-on"with"Pfizer" " Developed"on"a"large"pharma"scale"to"very"high"standards" " Ended"with"the"closure"of"the"Sandwich"UK"facility"due

8. Slide 8: Lead program (TT-034): Novel Hepatitis C Therapeutic

   Lead program (TT-034): Novel Hepatitis C Therapeutic TTS034! HCV!Genome! ! TT`034"comprises"three"shRNAs"targe-ng"three"separate,"highly"conserved" regions"in"the"virus"genome" ! Robust:"expression"of"mul-ple"shRNAs"from"a"single"construct"avoids" genera-on"of"escape"mutants"" ! Targeted"against"gen

9. Slide 9: TT-034 - Broad Therapeutic Window

   TT-034 - Broad Therapeutic Window ! Clinically"relevant"doses"of"TT`034"produce"sustained"levels"of"shRNA" without"toxicity"" Quan;;es!of!shRNA/cell!!required! Assessment!of!liver!toxicity! shRNA/cell!in!cynomolgus! for!HCV!Replicon!Inhibi;on! in!cynomolgus!monkeys! monkey!livers!at!day!50! 1400! !

10. Slide 10: TT-034 - Delivery Into Near 100% Cells With a Single Injection

    TT-034 - Delivery Into Near 100% Cells With a Single Injection ! Qualita-ve"ISH"analysis"of"shRNA"expression"in"liver"-ssue"demonstrates" nearly"complete"transduc-on"of"cynomolgus"monkey"hepatocytes" 12! SALINE! 1.25X10!!!vg/kg! shRNAS6! shRNAS19! shRNAS22! Copyright © Benitec Biopharma Ltd, 10" www

11. Slide 11: TT-034 – High Liver Tissue Specificity

    TT-034 – High Liver Tissue Specificity TTS034!Tissue!distribu;on;!!>90%!localized!to!liver! Copies of vector per cell Copyright © Benitec Biopharma Ltd, 11" www.benitec.com

12. Slide 12: TT-034 is Ready For Clinic

    TT-034 is Ready For Clinic !Benitec"plans"to"conduct"a"phase"I/IIa"study"in"HCV"pa-ents"in"2013" " All"required"safety"and"toxicology"studies"have"been"conducted"with"an"excellent" safety"profile" " Pre`IND"mee-ngs"with"FDA"were"held"in"June"2007"and"January"2010" " GMP"clinical"product"has"been"manu

13. Slide 13: TT-034 is a “Disruptive Technology” in a market that will remain very large

    TT-034 is a “Disruptive Technology” in a market that will remain very large !Even"with"promising"data"showing"high"cure"rates"for"new"drugs," HCV"will"remain"a"“Problem"Not"Solved”."According"to"many"KOLs:" " Significant"numbers"of"pa-ents"will"be"non`responders" " Treatment"-mes"and"side"effects"of"n

14. Slide 14: TT-034 Significant Commercial Opportunity in Western Markets

    TT-034 Significant Commercial Opportunity in Western Markets 40"million"HCV"infected" outside"US"&"EU"" "12"" In"addiIon"there"is" 75"%"of"HCV"cases" a"huge"emerging" HCV"Genotype"1"Prevalence" are"GT1."About" ((million(HCV(subjects(in(US,(JP(&(EU12)( market"outside"US" 10"million"in"US"&" &"EU" "10

15. Slide 15: HBV: Companion Program to HCV

    HBV: Companion Program to HCV !The"HBV"therapeu-c"is"a"copy"of"HCV"" " 3"shRNAs"against"highly"conserved"regions"on"HBV"genome" " Same"delivery"vector"as"HCV" " Iden-cal"regulatory"path" " HCV"toxicology"studies"applicable"to"HBV" !Significant"indica-on"but"limited"anen-on"–"absence"of"new" therapies

16. Slide 16: HBV: Another Large Commercial Opportunity

    HBV: Another Large Commercial Opportunity Worldwide"HBV"is"3"Imes" In"the"top"western"markets"HCV"is"" more"prevalent"than"HCV" 2"Imes"more"prevalent"than"HBV" Chronic"HBV"and"HCV"prevalence"worldwide" HBV"and"HCV"prevalence"in"top"7"markets*" 400" 14" Prevalence"of"chronically"infected" subjects"wo

17. Slide 17: Chemotherapy-Resistant Cancer Therapeutic

    Chemotherapy-Resistant Cancer Therapeutic !Therapeu-c"designed"to"inhibit""βIII"tubulin"expression" !Tubulin"is"a"key"component"of"the"cellular"cytoskeleton"and"the" target"of"Tubulin"Binding"Agents"(TBAs)"like"taxol" !Many"cancers"become"resistant"to"TBAs"and"other"chemotherapy"" arer"ini-al"treatm

18. Slide 18: Chemotherapy-Resistant Cancer Therapeutic

    Chemotherapy-Resistant Cancer Therapeutic !Ini-al"indica-on"is"Non`Small"Cell"Lung"Cancer;"the"overwhelming" cause"of"lung"cancer`related"deaths" " 3"shRNAs"used"in"construct"to"ensure"robust"inhibi-on" !Delivery"using"Jet`PEI;"clinically"validated,"targets"lung"-ssue" !Solid"proof"of"principle"in(v

19. Slide 19: Silencing βIII tubulin restores sensitivity to chemotherapy

    Silencing βIII tubulin restores sensitivity to chemotherapy Triple"shRNA"knocks"down"βIII"tubulin"in"H460" Silencing"βIII"tubulin"restores"NSCLC"cell" NSCLC"cells" lines"sensiIvity"to"cisplaIn" %!knockdown!of!βIII!tubulin!RNA!(qRTSPCR)!! Control" Single" shRNA" Triple"shRNA" construct" Copyright © B

20. Slide 20: Triple shRNA silences βIII tubulin in vivo

    Triple shRNA silences βIII tubulin in vivo Experiment M2-Three: Combined data The"JetPEI/βIII"tubulin"triple"shRNA"silences" Relative Gene Expression βIII"tubulin"in!vivo!in"orthotopic"lung"tumors" 150 Trp Ctrl BIII Expression (mean) Control" BIII 100 βIII"tubulin" 50 triple"shRNA" 0 Trp Ctrl BIII T

21. Slide 21: ddRNAi as a Pain Therapeutic

    ddRNAi as a Pain Therapeutic “Chronic"pain"affects"a"large"propor-on"of"the"worldwide" popula-on."" The"socio`economic"stakes"are"huge."" Clinical"management"of"chronic"pain"relies"mainly"on"opioids"and" NSAIDs."However,"these"pharmacological"treatments"remain" inefficient"for"pa-ents"coping"with"chron

22. Slide 22: Benitec’s Pain Therapeutic

    Benitec’s Pain Therapeutic !Molecular"target"is"Protein"Kinase"C"γ"(PKCγ)"in"spinal"neurons" !PKCγ"is"involved"in"transmission"of"both"neuropathic"and" nocicep-ve"pain" !Silencing"of"PKCγ"using"shRNA"has"been"demonstrated"to"abrogate" neuropathic"pain"long"term"AND"overcome"morphine"tolerance"in( vi

23. Slide 23: Intractable Pain in Cancer Patients

    Intractable Pain in Cancer Patients !Ini-al"indica-on"is"intractable"pain" in"late"stage"cancer"pa-ents" Brain" " Significant"unmet"need" " No"opioid`like"side"effects"(opiate"haze," Intrathecal"injecIon" Spinal"Cord" of"ddRNAi"construct" cons-pa-on,"nausea,"tolerance)" " Easier"regulatory"pathway"" !

24. Slide 24: Oculopharyngeal Muscular Dystrophy (OPMD)

    Oculopharyngeal Muscular Dystrophy (OPMD) !Gene-c"orphan"disease"with"6,000"cases"in"western"countries" !Severe"swallowing"difficul-es,"oren"leading"to"choking"and"death" !No"effec-ve"treatment" !Cause:"a"muta-on"in"the"Poly(A)"Binding"Protein"Nuclear"1"gene" (PABPN1)" Copyright © Benitec Biopharma Ltd

25. Slide 25: Oculopharyngeal Muscular Dystrophy (OPMD)

    Ȍ pAAV-H1-shRNA-G-spc512-eGFP 5’ITR H1 sh-G spc512 eGFP pA 3’ITR Oculopharyngeal Muscular Dystrophy pAAV-Tri-shRNA(short) Ȍ 5’ITR U61 sh-A U69 sh-F H1 sh-G 3’ITR (OPMD) pAAV-Tri-shRNA(long) 5’ITR Ȍ U61 sh-A U69 sh-F H1 sh-G Stuffer 3’ITR pAAV-U61-shRNA-Luc-spc512-eGFP Ȍ5’ITR U61 Sh-Luc spc512 eGFP p

26. Slide 26: Wet Age-related Macular Degeneration (wet AMD)

    Wet Age-related Macular Degeneration (wet AMD) ! Leading"cause"of"vision"loss"in"elderly" ! Over"2"million"pa-ents"in"US" " $2"Bn"market" ! Current"treatments"stabilize"disease"but"require" monthly"injec-ons"into"the"eye" " All"approved"drugs"target"Vascular"Endothelial" Growth"Factor"A"(VEGF`A)" !

27. Slide 27: Wet Age-related Macular Degeneration (wet AMD)

    Wet Age-related Macular Degeneration (wet AMD) !shMiR"–"Next"Genera-on"Technology" " ddRNAi"in"miRNA"backbone;"shMiR"–"Next"genera-on"Benitec"technology" " Cell`specific"promoters"for"controlled"expression" " Modified"vehicle"engineered"for"eye"–""permits"delivery"of"shMiR"through"all"cell" layers"of"

28. Slide 28: Multi-pronged strategy for revenue generation

    Multi-pronged strategy for revenue generation Plahorm!and!knowShow! ! Strong!patent!posi;on!and!unique!development!knowShow!in!ddRNAi!therapeu;cs! " A"con-nually"evolving"technology"platorm"applicable"to"numerous"diseases"" ! Discovery!collabora;ons! ! Internal!product!pipeline! " Most"pharma’s"use"

29. Slide 29: Strong Management and Board

    Strong Management and Board Management" Board" ! CEO:!Peter!French,!PhD,!MBA,!MSc! Chairman:!! " Fermiscan,"Cryosite,"Probiomics."Past" ! Peter!Francis,!LLB,!Grad!Dip.! President"Australia"Society"for"Cell"Biology"" " Partner"at"Francis"Abourizk"Lightowlers"" ! CSO:!Michael!Graham,!PhD! Directors:!!

30. Slide 30: Summary and upcoming events

    Summary and upcoming events Summary" Upcoming"milestones" !Product`focused"biotech" !First`in`man"phase"I/IIa"trial"in" company" Hepa--s"C"in"2013" !Unique"proprietary"long"term" !Out`Iicensing"agreements"for" gene"silencing"platorm"–"new" other"disease"areas" therapeu-c"modality" !Significant"milest

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