Phylogica 2015 Biotech Showcase -‐ San Francisco (PYC:ASX) Harnessing biodiversity for peptide therapeutics Disclaimer The purpose of the presenta.on is to provide an update of the business of Phylogica Limited (ASX:PYC) [‘Phylogica’]. These slides have been prepared as a presenta.on aid only and the informa.on they contain may require further explana.on and/or clariﬁca.on. Accordingly, these slides and the informa.on they contain should be read in conjunc.on with past and future announcements made by Phylogica and should not be relied upon as an independent source of informa.on. Please contact Phylogica and/or refer to the Company's website for further informa.on. The views expressed in this presenta.on contain informa.on derived from publicly available sources that have not been independently veriﬁed. No representa.on or warranty is made as to the accuracy, completeness or reliability of the informa.on. Any forward looking statements in this presenta.on have been prepared on the basis of a number of assump.ons which may prove incorrect and the current inten.ons, plans, expecta.ons and beliefs about future events are subject to risks, uncertain.es and other factors, many of which are outside Phylogica’s control. Important factors that could cause actual results to diﬀer materially from assump.ons or expecta.ons expressed or implied in this presenta.on include known and unknown risks. Because actual results could diﬀer materially to assump.ons made and Phylogica’s current inten.ons, plans, expecta.ons and beliefs about the future, you are urged to view all forward looking statements contained in this presenta.on with cau.on. This presenta.on should not be relied on as a recommenda.on or forecast by Phylogica. Nothing in this presenta.on should be construed as either an oﬀer to sell or a solicita.on of an oﬀer to buy or sell shares in any jurisdic.on. 2 About Phylogica !  Owns unique proprietary class of pep.de therapeu.cs (Phylomers®) !  Extensive & mature IP estate with mul.ple granted patents !  World’s ‘Best-‐in-‐Class’ pep.des for delivering biologics drugs inside cells !  Launched proprietary Oncology programme (Product focus) !  ‘Discovery Alliance’ business model for rapid revenue growth –  Generated >$6.5M in discovery alliance income in <5 years 2015 3 Corporate Snapshot Shareholders B. Hockings Sietsma Holdings Bonadido Top 15 % 25 8 4 55 Summary ASX Cash (9/14) Net Burn Market Cap PYC $4.7m $3.2m ~$20m Execu&ve Team Dr Richard Hopkins – CEO Dr Paul WaR -‐ CSO Board of Directors Dr Doug Wilson Dr Richard Hopkins Non-‐Execu\ve Chairman CEO Jeremy Curnock Cook NED Dr Bernard Hockings NED Bruce McHarrie NED 4 Every $1 invested in Phylogica yields $1.76 in research impact Recurring impact of the Australian government’s R&D rebate1 – 100 cents invested at \me zero 19 100 8 4 2 176 44 Original Year 1 R&D investment rebate reinvested in research Year 2 R&D rebate reinvested in research Year 3 R&D rebate reinvested in research Year 4 R&D Year 5 R&D rebate rebate reinvested in research Total research impact of $1 investment Phylogica operates in a highly capital eﬃcient environment 1 The Australian government provides a 43.5% rebate in cash at the end of each ﬁnancial year for research expenditure eligible for the AusIndustry R&D rebate 5 Phylogica: focussed on intracellular delivery of biologics CNS Delivery Vaccines Cell penetrating peptides Intracellular Drug Delivery Cancer Antimicrobials Diﬀeren\a\on Product Focus 6 Technology Update Majority of drug targets are inside cells Intracellular Drug Targets Small Molecule Drugs (10%) Undrugged targets (90%) Biologics? !  PYC addressing unmet need to deliver biologic drugs inside cells! Cell Penetra\ng Phylomer (CPPs): delivering biologics cargoes inside cells Poten\al to expand the druggable landscape by >10-‐fold!! 9 The Problem: Biologics drugs are trapped within endosomes Drug Drug contacts cell membrane Drug Budding endosome Contact triggers forma\on of endosomes Cell Membrane Endosome Drug Cell Membrane 99.9% of drug trapped in endosome The Solu\on: PYC’s Endosomal Escape Trap Bio\n Tag Enzyma.c ajachment Streptavin Avitag Phylomer Trapped Phylomer + Cargo Phylomer Escaped Phylomer + Cargo Phylomer Release and Capture (Streptavidin Beads) !  Phylogica’s endosome escape trap for capture of novel cell penetra.ng Phylomers Valida\on of ‘Best in Class’ Phylomers for intracellular drug delivery 12 Phylomers are best-‐in-‐class for func\onal delivery of biologics cargoes into cells Biologics cargo !  New assay reveals more efficient Phylomer-derived CPPs defined as ‘FPPs’ !  Best in class delivery against conventional CPPs including TAT (gold standard) 13 Applica\ons for Phylogica’s ‘Best-‐in-‐Class’ Drug Deliver Solu\on 14 Mul\ple commercialis\on opportuni\es ‘Value Adding’ Improve delivery of exis.ng drugs Cell Penetra.ng Phylomers ‘Phylomer TherapeuIcs’ Fully integrated drug delivery/ discovery plalorm Plalorm Products 15 MYC: A classic cancer target Breast – 80% !  MYC: Ampliﬁed in many common cancers Prostate – 85% Colorectal – 70% Gynecological – 90% !  Eﬀects of MYC Inhibi.on –  MYC considered undruggable with small molecules –  Models conﬁrm an.-‐tumour eﬀects of MYC inhibi.on –  Par.al inac.va.on of MYC ac.vity suﬃcient to: •  Induce senescence/apoptosis •  Reduce drug resistance •  Increase sensi.vity to chemotherapy !  OmoMyc: Most potent Myc inhibitor in vivo –  90 amino acid miniprotein derived from Myc –  Inhibits both N-‐myc and c-‐myc –  Eradicates established lung cancer in K-‐Ras mouse model1 –  Use as model for proof-‐of-‐concept of eﬃcient intracellular delivery of Myc inhibitors 1(Soucek et al.(2013) Genes Dev. 27: 504-513) 16 Delivering a dominant nega\ve MYC inhibitor protein: The ‘Omomyc’ model !  Potent func.onal ac.vity at submicromolar concentra.ons (280-‐560nM) –  Decreased prolifera.on –  IC50 best-‐in-‐class for this transcrip.on factor target. MDA-MB-468 72h Viability - 0.56µM MDA-MB-468 72h Viability - 0.28µM 17 46 _O m yc 0 yc 17 46 _O m yc m yc 0 50 m 50 * O *** % Viability 100 O % Viability 100 17 ‘Value Adding’: Approaching key potency thresholds Drug Amount 10 µM Compe\tors Increasing Drug Potency Standard CPP_Cargoes 1 µM Phylomer CPPs_Cargoes <1µM = key potency threshold 0.1 µM Phylomer CPPs_Toxins 18 Phylogica’s Oncology Programme Targe\ng Breast Cancer 19 Phylogica’s Proprietary Oncology Program !  Phylomer screens against 4 validated and clinically relevant oncology targets Program Indica\on Discovery Func\onal Valida\on In vitro cMyc, nMyc Breast Cancer Stat 5a Breast Cancer YB1 Breast Cancer Preclinical In vivo 20 Upcoming commercial milestones !  Discovery Partnerships –  New discovery alliances –  Cosmeceu.cal out-‐license (Biolink) !  Oncology programme –  Early 2015: In vitro data –early-‐stage partnering opportunity. –  Late 2015: In vivo data -‐ Licensing opportunity 21 Expanding the intracellular landscape for novel biotherapeu\cs with Phylomers Cell Penetra\ng Phylomers Extracellular (20% of drug targets) Abs, SMs, pep.des Biologics Cargoes (eg. Phylomer) Intracellular targets (80% of drug targets) -‐ Small Molecules: 10% -‐ Phylomers: 70% Membrane Membrane Cytoplasm Nucleus DNA 22 Summary !  World leaders in pep.de-‐based intracellular drug delivery !  Combined with Phylogica’s powerful Drug Discovery technology to develop fully-‐integrated drug development plalorm !  Transi.oning from plalorm to product focussed company !  Well posi.oned for mul.ple commercialisa.on opportuni.es 23 Dr. Richard Hopkins Chief Execu\ve Oﬃcer Tel: +61 8 9489 7777 Fax: +61 8 9489 7700 Mobile: +61 405 656 868 [email protected] Contact Details Dr. Paul WaR Chief Scien\ﬁc Oﬃcer Tel: +61 8 9489 7777 Fax: +61 8 9489 7700 Mobile: +61 421 550 213 [email protected] www.phylogica.com 24