Pyc Therapeutics Limited · ASX:PYC

Pyc Therapeutics — Phylogica — Investor Presentation (March 2014)

32 slides from Pyc Therapeutics's investor presentation, Mar 3, 2014

1. Slide 1: Harnessing Biodiversity for Peptide Therapeutics

   BREAKTHROUGH PEPTIDE THERAPEUTICS For personal use only Harnessing Biodiversity for Peptide Therapeutics 1/03/2014" 1"

2. Slide 2: Corporate Update

   For personal use only Corporate(Update(

3. Slide 3: Corporate overview

   Corporate(overview( ! Opera&ons*in*Perth,*Australia** For personal use only ! Phylomer®*pep&de*libraries*derived*from*most*structurally*diverse*genomes* ! Discovery*Alliance*business*model*for*rapid*revenue*growth* – Already*received*>$5.8M*in*commiEed*revenue*in*less*than*4*years* ! Alliances*with*

4. Slide 4: Phylogica's partnerships span a wide range of areas

   For personal use only Phylogica’s(partnerships(span(a(wide(a(range(of(areas( Cell penetrating peptides Phylogica CNS Delivery Antimicrobials Vaccines 1/03/2014" 4"

5. Slide 5: Recent highlights

   Recent(highlights( ! June,& 2013:* Expanded* Janssen* collabora&on* to* include* downstream* biological* For personal use only valida&on*of*op&mal*hits* ! Nov&2013:*Nego&ated*early*conversion*of*$1.6*Million*Conver&ble*Note.*** ! Jan& 2014:* Successfully* completed* fully* underwriEen* NonSrenouncea

6. Slide 6: Phylogica stock is tightly held

   Phylogica(stock(is(:ghtly(held( Posi:on( Holder(name( Shares( %(of(issued( For personal use only 1* Hockings*Family*Office* 116,1400,00* 20%* 2* Telethon*Ins&tute* 20,605,501* 3.35%* 3* Paul*WaE* 17,197,326* 2.91%* 4* Ci&corp*Nominees*Pty*Ltd* 14,719,673* 2.53%* 5* Andrew*Swii* 14,010,457* 2.43%* 6* J

7. Slide 7: Business Model: focus on discovery alliances

   Business(Model:(focus(on(discovery(alliances( ! For personal use only FeeSforSservice*screening*generates*revenues*to*achieve*Cash*Sustainbility** ! Building*longSterm*value*through*milestones*and*royal&es* ! Increasing*deal*economics*and*share*of*downSstream*value* ! Opportunity*to*subsidise*intern

8. Slide 8: Phylogica owns an entire class of peptide drug

   Phylogica(owns(an(en:re(class(of(pep:de(drug( ! Exclusive*ownership*enables*PYC*to*control*access*to*Phylomer*pep&des.*** For personal use only ! Analogous* to* ownership* of* rights* to* an* oil* field* by* and* oil* explora&on* company* ! This* control* allows* licensing* of* rights* to* access* th

9. Slide 9: Technology Introduction

   For personal use only Technology(Introduc:on(

10. Slide 10: Phylomers: derived from biodiverse microbial proteins

    Phylomers: derived from biodiverse microbial proteins ( ! Worlds*richest*source*of*diverse*natural*secondary*and*ter&ary*structures* For personal use only Microbial*Genomes* Phylomer*Libraries* (High*quality*building*blocks)* 1/03/2014" 10"

11. Slide 11: Uniquely integrated capabilities of Phylomer platform

    Uniquely(integrated(capabili:es(of(Phylomer( plaSorm( For personal use only Phylogica’s unique discovery platform: ! Discover and validate new therapeutic targets found inside cells Citron& (Phenomica) (Citron&Homology&Domain)& ! Develop therapeutic peptide leads against such targets ! Deliver thera

12. Slide 12: Majority of Therapeutic Targets are Intracellular

    Majority(of(Therapeu:c(Targets(are(Intracellular( ! Cellular*distribu&on*of*therapeu&c*targets*considered*‘druggable’** For personal use only ! (1,700S3,000*targets)* • Small*Molecules*(10%)* • An&bodies* • Scaffolds* • Pep&des* • Small*Molecules* Undrugged*(70%)* Phylomers( Phylomers( Phylomers( 1/0

13. Slide 13: Cell penetrating Phylomers (CPPs): gaining access to intracellular targets

    Cell(penetra:ng(Phylomers((CPP’s):(( gaining(access(to(intracellular(targets( For personal use only Phylomers(can(expand(the(druggable(landscape(by(>10Afold!!( 1/03/2014" 14&

14. Slide 14: Discovery of Phylomer-Derived Functional Penetrating Peptides (FPPs)

    For personal use only Discovery(of(PhylomerAderived(( Func:onal(Penetra:ng(Pep:des( (FPPs)(

15. Slide 15: The Problem: Drugs are trapped in endosomes

    The(Problem:(Drugs(are(trapped(in(endosomes( Drug( For personal use only Budding( Drug( Drug(contacts(cell( endosome( membrane( Contact(triggers( forma:on(of(endosomes( Cell(Membrane( Endosome( Drug( 99.9%(of(drug( trapped(in(endosome( Cell( Membrane( 1/03/2014" 16"

16. Slide 16: Solution: PYC's Endosomal Escape Trap

    For personal use only Solu:on:(PYC’s(Endosomal(Escape(Trap( Tag( Drug( Drug( Untagged(Drug( Escaped(Drug( * ! Phylogica’s*endosome*escape*trap*for*capture*of*CPPs*which*efficiently*deliver* biologics*cargoes*into*cells*and*out*of*endosome* ( 1/03/2014" 17"

17. Slide 17: Nature's Modular Solution to Cell Penetration

    Nature’s(Modular(Solu:on(to(Cell(Penetra:on( ! The* modular* structure* of* Bacterial* Toxins* provides* a* template* for* improving* For personal use only efficiency*of*cell*penetra&on*and*cargo*delivery* ! Modularity*enable*Phylomers*to*‘PlugSnSPlay’*with*exis&ng*therapies* ! Phylomer*CPPs*are*custo

18. Slide 18: Workflow for FPP Discovery Collaboration

    For personal use only Workflow(for(FPP(Discovery(Collabora:on( Build Phylomer libraries fused to biologics Cargo Screen for Phylomer FPPs using ‘Endosomal Escape Trap’ in mammalian cells Validate hits using microscopy and FACS Confirm functional delivery using therapeutic drugs Split GFP Toxins PPIs

19. Slide 19: Phylomer-mediated delivery of Janssen RBD cargo to mammalian cells

    PhylomerAmediated(delivery(of(Janssen(RBD(cargo( to(mammalian(cells( For personal use only ! Increased*binding/uptake*of*FITCSlabeled*PYC_RBD*fusions*at*2µM* RBD( TAT_RBD( RBD_Phylomer(1( RBD_Phylomer(2( 1/03/2014" 21"

20. Slide 20: Functional validation of cytoplasmic release of Phylomers

    Func:onal(valida:on(of( For personal use only cytoplasmic(release(of(Phylomers( discovered(using((the(Endosome( Escape(Trap:( ( ( S*Developing*a*split*GFP*complementa&on*assay* S*Developing*an*assay*for*delivery*of*an*RIP*toxin*

21. Slide 21: Split-GFP complementation assay to validate endosomal escape of FPPs

    (SplitAGFP(complementa:on(assay(to(validate( &be&expressed&as&independent&protein&fragments&that&com endosomal(escape(of(FPPs(( /reversible&fashion&and&form&a&stable&complex&that&restore rescence&of&GFP2/4.& For personal use only Kent K., Soc. 20 dia’s&engineered&Split&GFP&system&uses&two&fragments:

22. Slide 22: Split-GFP complementation assay to validate endosomal escape

    (SplitAGFP(complementa:on(assay(to(validate( endosomal(escape(of(penetra:ng(Phylomers( For personal use only CPP–(POI)– S11* GFP*1S10* Live(Cell(Microscopy( 1/03/2014" 24"

23. Slide 23: Microscopy confirms FPP-mediated split GFP complementation

    Microscopy(confirms(FPPAmediated(split(GFP( complementa:on( use only RBD_S11( FPP3_RBD_S11( FPP3_RBD_S11( personalLow*Receptor* GFP* GFP*(100X)* GFP* DAPI* High*Receptor* For GFP* GFP* GFP* DAPI* 1/03/2014" 25"

24. Slide 24: Cell-specific and concentration-dependent GFP complementation

    CellAspecific(and(concentra:onAdependent(GFPA complementa:on((%(fluorescent(cells)( For personal use only Differen&al*>*PYCSCG3:* 24.9Sfold** High(receptorAexpressing(cells:( 50 transfec&on*efficiency:*70.3%* 10µM protein 40 3µM protein 24.3Sfold** % green viable cells (Q3) single cell population 30 20 1

25. Slide 25: Alternative cargoes: FPP fusion to a toxin

    Alterna:ve(cargoes:(FPP(fusion(to(a(toxin( For personal use only ! Bouganin*Toxin*(26*kDa)* – Type*I*RIP*Toxin* – Derived*from*Bougainvillea* – Only*func&onal*in*cytoplasm*of*cell* FPP* RBD* Bougainin*Toxin* 1/03/2014" 28"

26. Slide 26: FPP-RBD-Bouganin fusions show decreased viability and increased apoptosis

    FPPARBDABouganin(fusions(show(decreased(viability(and( increased(apoptosis(in(targetAexpressing(cells(( For personal use only EGFR % viability - Fluorescence (48hrs) PYC-FPP-3 150 Bouganin RBD Fluorescent counts Bouganin-RBD 100 Bouganin-RBD-PYC-FPP-3 50 0 -1 0 1 2 3 4 [log toxin] (nM) • FPP*fusion*

27. Slide 27: The Future: Functional Assays to Measure Intracellular Delivery

    The(Future:(Func&onal*Assays*to*Measure*Intracellular* Delivery*Against*Different*Target*Classes* For personal use only 1/03/2014" 32"

28. Slide 28: Key Outcomes

    Key(Outcomes( ! Successfully*validated*novel*endosomal*escape*trap* For personal use only ! Iden&fied* panel* of* Func&onal* Penetra&ng* Phylomers* capable* of* delivering*a*range*of*therapeu&c*cargoes*inside*cells* ! High*func&onal*hit*rate*for*discover*of*novel*FPPs*(~14%)* ! Phylogica’s( empirical

29. Slide 29: Phylogica Differentiation, Deals and Growth Strategy

    For personal use only Phylogica(Differen:a:on,(Deals( and(Growth(Strategy(

30. Slide 30: Three overlapping strategic phases

    (Three(overlapping(strategic(phases( ! Partnering:* generate* nearSterm* revenue* from* discovery* alliances* to* achieve* cash*sustainability* For personal use only ! Technological&leadership:*enhance*pla`orm*through*valueSadding*upgrades* ! Development:* InShouse* drug* development:* build* value*

31. Slide 31: Anticipated commercial milestones

    An:cipated(commercial(milestones( ! Further*Pharma*deals*around*areas*of*exper&se*such*as:* For personal use only - Efficient* delivery* of* biologics* by* PhylomerSderived* cell* penetra&ng* pep&des* - Phenotypic* screening* for* discovery* and* valida&on* of* new* targets* (Phenomica)* - Discovery*o

32. Slide 32: Contact Details

    Dr.(Richard(Hopkins( Contact(Details( Dr.(Paul(Wak( Chief(Execu:ve(Officer( Chief(Scien:fic(Officer( Tel:*+61*8*9489*7777* Tel:*+61*8*9489*7777* For personal use only Fax:*+61*8*9489*7700* Fax:*+61*8*9489*7700* Mobile:*+61*405*656*868* Mobile:*+61*421*550*213* richardh@phylogica.com( paulw@phylogica.com(

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