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Light-Directed Drug Delivery Nanoteknologi for styrt medisinering Anders Høgset, Nanomat-seminar 28. Mai 2008 Disposisjon PCI Biotech AS Målrettet legemiddellevering med nanoteknologi PCI Biotechs teknologi – lysdirigert levering av nanomedisin PCI Biotechs utvikling - samarbeid – støtteordninger 2 PCI Biotech AS • Kommersialisere patentert teknologi for levering av legemidler - fotokjemisk internalisering (PCI) • Ny metode for kreftbehandling – lysdirigert legemiddellevering • Kraftigere virkning i kreftsvulst • Mindre bivirkninger • Teknologien kan forbedre virkningen av mange typer legemidler: • Cellegifter – klinisk studie start 2008 • Makromolekyler (proteiner, siRNA, gener) • Nanomedisiner • PCI Biotech vil tjene penger ved å lisensisere ut teknologien til firmaer som har legemidler PCI kan forbedre. • Upfront-betaling • Milepelsbetaling • Royalties 3 PCI Biotech AS • 6 ansatte (2 hovedkvarter - 4 Radiumhospitalet) • Rekruttering pågår • Arbeider via samarbeidspartnere • Samarbeidsavtale med Radiumhospitalet • Teknologien oppfunnet der • Ca. 15 personer arbeider med PCI teknologien • Datterselskap av Photocure ASA (OSE: PHO) • Andre eiere: Radiumhospitalets Forskningsstiftelse, ansatte • Fisjoneres fra Photocure NÅ • Betydelig finansiering fra offentlige kilder (NFR, EU) • Ca. NOK 22 mill. til nå • Ca. NOK 7 mill. per år i 2008 og 2009 • Planlagt notert på Oslo Børs (Oslo Axess) i juni 2008 • Hente inn NOK 60-100 mill. i ny egenkapital • 4 Aksjetegning pågår. Disposisjon PCI Biotech AS Målrettet legemiddellevering med nanoteknologi PCI Biotechs teknologi – lysdirigert levering av nanomedisin PCI Biotechs utvikling - samarbeid – støtteordninger 5 Drug delivery - general Make drugs reach their body target in an optimal way Market: NOK 450 billion per year Growing 10-15 % per year Increasing need because of more “advanced” drug molecules – Genes – Oligonucleotides – Proteins – Nanomedicines 6 Challenge in cancer therapy Killing cancer cells is not difficult! • Lots of drugs can do this • But, effect not specific side effects Common situation Desired situation How ? - Targeted delivery 7 Drug targets and drug delivery to cells Drug target: • Molecule in the body that interacts with drug • Physical interaction gives therapeutic effect Drug Targeted delivery Drug target Desired effect cell membrane 8 Side effect X - If drug is taken up only into cancer cells it can only have effect there - Normal cells will be spared Nanoparticles to carry drug to target cell Nanoparticle shell - Lipid - Polymer drug drug Protect drugs that are degraded in the body Change route for traveling through the body 9 Antibodies for targeting nanoparticles to specific cells Antibodies: - Can bind to surface features specific for cancer cells - Can be used for delivering drugs specifically to such cells drug drug 20 - 200 nm 10 Other kinds of nanostructures for drug delivery Antibodies with drugs directly attached Binds to surface of target cell 9 nm 11 Nanomedicines on the market Liposomal cytotoxic drugs Protein conjugates • Cytotoxic drug attached to albumin Antibody conjugates 12 • Cytotoxic drugs • Radioisotopes Targeted Disposisjon PCI Biotech AS Målrettet legemiddellevering med nanoteknologi PCI Biotechs teknologi – lysdirigert levering av nanomedisin PCI Biotechs utvikling - samarbeid – støtteordninger 13 Getting drug to right place within the cell Nanoparticles usually taken up by endocytosis Endocytosis Endosomal release Endosome Lysosome 14 Therapeutic effect Photochemical internalisation (PCI) light-induced endosomal release of nanoparticles AmphinexTM Photosensitiser: Light ”Nanomachine” making it possible to exploit the energy in light for targeting drug delivery. Light energy in Chemical energy out Therapeutic effect 1,2 nm 15 Drug delivery Illumination induces rupture of endosomes Before illumination: photosensitiser in endosomes GFP + Hoechst 33342 + Photosensitiser (in endosomes) 16 Pål K. Selbo Illumination induces rupture of endosomes After illumination: photosensitiser in cytosol 17 GFP + Hoechst 33342 + Photosensitiser (cytosolic release) after microscopy light exposure Pål K. Selbo Photochemical internalisation (PCI) Targeting drug delivery by illumination Patented Photosensitiser AmphinexTM + light Drug activated only in illuminated region (e.g. tumour) 18 PCI enhances antibody mediated drug delivery in animal model (Selbo et al., in preparation) Melanoma antibody carrying toxin (immunotoxin – ITX) % Tumors < 800 mm 3 100 80 PCI + ITX 60 PCI + ITX 40 ITX alone ITX alone 20 Untreated 0 0 10 20 30 40 50 60 70 80 90 100 110 Time after treatment (days) 19 PCI in nanoparticle-based gene therapy (Ndoye et al., 2006) • Gene that makes cancer cells commit suicide • Gene delivered by targeted (polymer) nanoparticle. 20 Disposisjon PCI Biotech AS Målrettet legemiddellevering med nanoteknologi PCI Biotechs teknologi – lysdirigert levering av nanomedisin PCI Biotechs utvikling - samarbeid – støtteordninger 21 History of PCI Biotech Patent granted on Amphinex for PCI Biotech PCI Biotech signed agreement with Radium Hospital Research Foundation Core PCI technology developed at the Radium Hospital patented 1995 Efficient cancer gene therapy induced by the PCI technology In vivo proof of concept for macromolecules 2000 2002 2004 PCI Biotech Formed 2006 2008 Demerger from Photocure In vivo proof of concept for certain oncology compounds PCI technology enhances effect of anti-cancer drug 22 PCI Biotech acquired patent application for combination of siRNA and the PCI technology Start of first clinical study Top management recruited PCI Biotech and the Norwegian Radium Hospital (NRH) • PCI technology was invented at NRH (Kristian Berg) • NRH Research Foundation (RF) owns about 7 % of shares in PCI Biotech • PCI Biotech has a ”general” research agreement with NRH • Possibilities for contract research • Right to use results within FIELD • Right to aquire inventions (right of first refusal) within FIELD. • Clinicians followed development of technology • Collaboration with RF/NRH has generally run smoothly with established routines and negligible bureaucracy 23 PCI Biotech – relasjoner Photocure EU-prosjekt: Nanoteknologi NFR Radium forskningsstifelse Radiumhospitalet, forskning Senter for forskningsdrevet innovasjon: Stamceller Oslo Cancer Cluster 24 PCI Biotech Synthetica AS Akademiske samarbeidspartnere: England, Nederland, Frankrike, Tyskland, Italia Belgia Radiumhospitalet, klinikk Folkehelseinstituttet Kommersielle samarbeidspart. /lisenstakere PCI Biotech goals PCI Biotech in 2012 • Completed 6 clinical Proof of Concept studies with cytotoxic compounds • 2 licence deals for Amphinex in combination cytotoxic compounds • 1 licence deal for Amphinex in the macromolecule/nanomedicine space • Initiated development of a next generation photosensitiser 25 PCI Biotech – kommersialisering og offentlig støtte Ennå ca. 3 år før PCI Biotech vil begynne å få inntekter Privat kapital innhentes for å nå dit • NOK 60 mill. garantert i nåværende emisjon Offentlige støtte har vært (og er) helt essensielt for utviklingen av selskapet • Nødvendig for å drive forskningen fram til dagens stadium • Viktig overfor investorer – Kvalitetsstempel – Mindre risiko • Pådriver for samarbeidsprosjekter – Økt kompetanse også hos samarbeidspartnere • Viktig for videreutvikling av teknologien og selskapet – Teknologi med mange anvendelsesområder – Viktig å identifisere, dokumentere og kommersialisere slike bruksområder innenfor patentlevetid – Samarbeidsprosjekter 26 PCI Biotech and nanomedicine • Important area for the future – PCI technology very well suited for use in nanomedicine – Clinical study with cytotoxic substance will be important also for nanomedicines • EU project MEDITRANS - Targeted delivery of nanomedicines – Start jan. 2007 – Integrated project, 29 partners ( NOK 100 mill. from EU) • Nanomedicines in cancer and inflammatory diseases • Nanoparticles in delivery of siRNA and genes • Develop nanoparticles for light induced drug delivery. 27 Takk for oppmeksomheten 28