Download Nanoteknologi for styrt medisinering

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
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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
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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
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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
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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
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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
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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
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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
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Other kinds of nanostructures for drug
delivery
Antibodies with drugs directly attached
Binds to
surface of
target cell
9 nm
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Nanomedicines on the market
Liposomal cytotoxic drugs
Protein conjugates
•
Cytotoxic drug attached to albumin
Antibody conjugates
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•
Cytotoxic drugs
•
Radioisotopes
Targeted
Disposisjon
PCI Biotech AS
Målrettet legemiddellevering med nanoteknologi
PCI Biotechs teknologi – lysdirigert levering av nanomedisin
PCI Biotechs utvikling - samarbeid – støtteordninger
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Getting drug to right place within
the cell
Nanoparticles usually taken up by endocytosis
Endocytosis
Endosomal release
Endosome
Lysosome
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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
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Drug
delivery
Illumination induces rupture of
endosomes
Before illumination:
photosensitiser in
endosomes
GFP + Hoechst 33342 + Photosensitiser (in endosomes)
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Pål K. Selbo
Illumination induces rupture of
endosomes
After illumination:
photosensitiser in
cytosol
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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)
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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
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Untreated
0
0
10
20
30
40
50
60
70
80
90 100 110
Time after treatment (days)
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PCI in nanoparticle-based gene therapy
(Ndoye et al., 2006)
• Gene that makes cancer cells commit suicide
• Gene delivered by targeted (polymer) nanoparticle.
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Disposisjon
PCI Biotech AS
Målrettet legemiddellevering med nanoteknologi
PCI Biotechs teknologi – lysdirigert levering av nanomedisin
PCI Biotechs utvikling - samarbeid – støtteordninger
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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
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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
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PCI Biotech – relasjoner
Photocure
EU-prosjekt:
Nanoteknologi
NFR
Radium
forskningsstifelse
Radiumhospitalet,
forskning
Senter for
forskningsdrevet
innovasjon:
Stamceller
Oslo Cancer
Cluster
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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
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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
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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.
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Takk for oppmeksomheten
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