Upload
lynhu
View
214
Download
0
Embed Size (px)
Citation preview
1
A N T J E L A B E S
Bio-mining the microbial treasures
of the ocean
Early drug discovery and models for
entering pharmaceutical pipelines
Dr. Antje Labes
A N T J E L A B E S
Helmholtz Centre forOcean Research Kiel
Kiel Center for marine natural products
Marine microbial compounds: from habitat to product
2
A N T J E L A B E S
Natural compounds – highly potential
molecules
Newman & Cragg, J. Nat. Prod. 2007, 70, 461-77.
A N T J E L A B E S
„high potentials“ of the ocean
New compounds
70% of earth‘s surfaceLess than 1% of microbial diversity known
New enzymes1967, a small symposium was held in Rhode Island, USA, with the ambitious title “Drugs from the Sea”:
3
A N T J E L A B E S
Current status of the pipeline of
marine natural products
• 4 drugs approved by FDA, 1 registered in the European Union.
• current clinical pipeline includes more than 10 in different clinical
phases
• 4 of these originate from marine microbes
• preclinical pipeline: continues to supply several hundred novel / year
Eribulin mesylate (Halaven)
Trabectin (Yondelis)
Cytarabin
Salinosporamide A
Mayer et al. 2010
A N T J E L A B E S
High added value chain from habitat to
biotechnological product in marine
biotechnology
► Classical value/risk problem?
MarketEntree
ApprovalClinical trialsProcess
developmentLead structuredevelopment
Bioactivityprofiling
Natural compoundchemistry
ExtractsMarine
microbes
Synthesis/Semisyn-
thesis
Approvalcosmetics, food
Supply of producer strainsAccess to unusual habitats
Reliable and large librariesof pure compounds
Large and relevant testpanels Robust and sustainableprocess design
Pharma‘s Interest, venture capital
4
A N T J E L A B E S
Value/risk/scientific topics
Acc. to Douglas et al. 2010
Scientifctopics and
competencesneeded
$
Discovery
Clinical pharmacology
Phase I and Phase II
Phase III, PMS
A N T J E L A B E S
Number of big pharma deals is
decreasing
Adapted from Kessel, 2011“Post-mega-merger pharmaceutical landscape“
5
A N T J E L A B E S
High added value chain from habitat to
biotechnological product in marine
biotechnology
establishment of research platforms
re-thinking financing of early discovery
MarketEntree
ApprovalClinical trialsProcess
developmentLead structuredevelopment
Bioactivityprofiling
Natural compoundchemistry
ExtractsMarine
microbes
Synthesis/Semisyn-
thesis
Approvalcosmetics, food
Supply of producer strainsAccess to unusual habitats
Reliable and large librariesof pure compounds
Large and relevant testpanels Robust and sustainableprocess design
Pharma‘s Interest, venture capital
A N T J E L A B E S
Example: Culture collectionsca. 15.000 marine bacteria
ca. 10.000 marine fungiAccess to diverse marine habitats
6
A N T J E L A B E S
Marine habitat
Strain collections
Modification ofgrowth parameters*
Genomicapproaches○
Strains Novel isolation strategies
Extracts
Compounds
Structures
Pure compounds
library
Bioactivity
Processdevelopment
Lead structuredevelopment
Isolation
Cultivation andextraction
Bioassays
Selection
Strainoptimization
Purification
Structureelucidation
(aus: Imhoff et al., 2011)
A N T J E L A B E S
WP1: Project Management and Coordination
WP4Chemical identification and biochemical
characterisation of active metabolites and substance purification
WP2Genome analysis, identification of biosynthetic genes and regulators
WP6In vitro bioassays for cancer targets, rational lead structure selection and in vivo
efficacy determination in xenograft models
WP7Robust and sustainable process
development
WP8: Intellectual Property protection & and dissemination activities
WP5Strain improvement
Selected fungal strains Selected marine macrobes fromgeographically distinct habitates
Culture based approachMolecular based approach
WP3Isolation and identification of new fungal
strains and optimisation of secondarymetabolite production
P R O F . D R . J O H A N N E S F. I M H O F F
FP7, 265926
8
A N T J E L A B E S
Transfer models for early drug
discovery• Early – proof of concept
– Broad research possiblitities, public funding for basic tasks
– Enhance academic value
– Early onset of SME
– New financing models, e.g. shared portfolios
• Middle – proof opf relevance
– Focussing on few tasks – transition
– Funding cycle oriented with exit-strategy
• Question of IP models
9
A N T J E L A B E S
„Much of nature‘streasure trove of smallmolecules remains to
be explored, particularly from themarine and microbial
environments.“(Newman & Cragg, 2007)