Established December 2004; Shareholders SINTEF Venture AS (Norway( Norway), Verdane Capital (Norway), Karolinska Development AB (Sweden( Sweden), OBS Østersjøstiftelsen stiftelsen (Sweden( Sweden). Mission Development of safer and more efficient drugs against bacterial and fungal infections and cancer; Technology Development of drug candidates from biologically active compounds produced by bacteria using gene manipulation technology, optionally combined with chemical synthesis Strategy - Selected drug candidates will be brought through clinical phase I and II. Successful candidates will be licensed out after phase II, at the latest. The development will be supported by an early focus on marketing. Projects: 2004 - : Development of a new antifungal drug based the Nystatin gene cluster 2008- : Development of a new anticancer drug based on bioprospecting results 1
Bioprospecting for antibiotics in the Trondheim fjord 2
Infections: Death toll Deaths in 2002, in millions Lower respiratory infections 1,6 1,2 0,6 3,9 HIV/AIDS Diarrheal diseases Tuberculosis 1,8 2,8 Malaria Measles Total: 11,9 Source: : World Health Organisation,, 2004 3
6.7 million people worldwide die from cancer each year (WHO, 2005) Africa 4% Asia 12% Europe 19% Latin America & the Carribbean 13% Northern America 23% Oceania 21% The proportion of deaths caused by cancer 4
Markedet for antibiotika Tradisjonelle antibiotika: 24 mrd USD pr år, 7% vekst Anti fungal: 9 mrd USD i 2007 Anti bacterial: 30 mrd USD i 2008 Anti cancer: 10 mrd USD pr krefttype Inntektspotensial for et banebrytende nytt antibiotika: 500 1000 mill USD pr år i 10 år Cubicin (Cubist Pharma): Lansert 2004, salg første 26 mnd 180 mill USD, prognose 2006 200 mill USD, forventet platå 500 mil USD i 2010 Linezolid (Pfizer): 620 mill USD i 2005, forventet platå 1000 mill USD Caspofungin (Merck): 275 mill USD i 2003, 570 mill USD i 2005, forventet platå 1000 mill USD 5
Bioprospektering i Trondheimsfjorden Utført av SINTEF og NTNU 2003-2006 Finansiert av NFR: 8 mill kr Kartlegging av bakterier som kan produsere antibiotika fra biologisk materiale i Trondheimsfjorden Sedimenter i bunnen, svamper på bunnen, organismer i øvre vannlag Innsamling: 2003-2004 Kartlegging: 2005 Testing av utvalgte bakterier: 2006 6
Foreløpige resultater 70% av innsamlet materiale behandlet: ca 12.000 bakterier isolert Ca 7000 antibiotikaproduserende bakterier identifisert 13500 ekstrakter produsert og screenet 33 ekstrakter har sterk effekt mot resistente sopper, et av disse kan være et helt nytt stoff (antibiotika) 99 ekstrakter har sterk effekt mot resistente bakterier 3 ekstrakter har effekt mot leukemi, herav et som kan være et helt nytt stoff (antibiotika) 52 ekstrakter har spesifikk aktivitet mot 6 forskjellige typer kreftceller; Alle disse ekstraktene kan inneholde kandidater til nye antibiotika Betydelige mengder prøver er ikke analysert men nedfrosset Ikke analysert materiale kan innehold tusenvis av nye bakterier 7
Bioprospecting of antibiotics: what s important? Where to look search for unique ecological niches; How to look establishment of cultivation techniques; How to reveal producing potential choice of poduction media and conditions; How to assess activity assay development; How to assess novelty development of analytic techniques; How to reveal mechanism of action use of molecular biology; How to evaluate usefulness preclinical and clinical studies. 8
How do we search for antibiotic producers? Sampling of sediments, sponges and upper water layer in the Trondheim fjord Sample pre-treatment and plating on the selective agar media Selection of actinomycetes and preparation of master plates Replication of master plates to production agar media Preparation of extracts from production media, and testing for antibiotic activity 9
SINTEF Materials and Chemistry: High throughput screening Purification, Identification and characterization Production / development of production processes 10
High throughput screening for antimicrobial activity Strategy: Measurement of growth inhibition of indicator strains with high resistance to antibiotics. Robotic protocols with the possibility of running more than 15.000 bioassays per day are used. More than 250.000 bioassays performed so far (>1.200.000 pipetting operations) Evaluation of antimicrobial activity in 384-well microplates 11
Identification of bioactive components Choice of interesting extracts from strains Repeated fractioning and LC-MS-analyses of extracts followed by bioassays LC-F1 LC-F2 LC-F3 LC-F4 MW = 963.1434 Preliminary identification: - LC (DAD)-MS TOF - LC (DAD)-MS QTOF - Database search Production of larger amounts for: - NMR studies - LC-MS TRAP (Fragmentation Msn) - Bioactivity or application testing -Novel compound? -New organism? 12
Partners Development: Department of Biotechnology, NTNU (Trondheim); Department of Biotechnology, SINTEF Materials and Chemistry (Trondheim); Department of Biomedicine, University of Bergen (Bergen); Gauze Institute of New Antibiotics (Moscow, Russia); ChemDiv (Moscow, Russia; San Diego, USA). Commercialization: (SINTEF) NTNU Technology Transfer AS 13
Fortsettelse Verifikasjon og dokumentasjon av potensielle drug candidates : 2007-2008 10 mill NOK SINTEF, NTNU, Norges forskningsråd (FORNY), Innovasjon Norge, Sør- Trøndelag fylkeskommune, Helse Midt-Norge/St Olavs Hospital Drug development : Første prosjekt: 2008-2011 Anti cancer Drug candidate development 28 mill NOK Biosergen AS/Norges forskningsråd Nye prosjekt: 2009 : Anti bacterial? 14
Fortrinn Trondheimsfjorden? Sterkt faglig team!! Veltilpassede laboratorier!! Internasjonalt nettverk!! Effektive arbeidsprosesser!!! Kommersielt fokus!! Motiverte og kompetente faglige og finansielle partnere!! 15
Ambisjon Trondheim på Biotek verdenskartet i et internasjonalt nettverk: Ikke et eventyr.. men En besluttet kommersiell suksess!! 16