Bio-mining the microbial treasures of the ocean …concarneau.mnhn.fr/sites/concarneau.mnhn.fr/files/upload/... · 2012-10-11 · Lead structure development Isolation Cultivation

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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

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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”:

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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

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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“

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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

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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

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A N T J E L A B E S

TeknologiskInstitut

A N T J E L A B E S

Success?

Kellner 2010

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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

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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)

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