Your Expert Partner in Preclinical Drug Development

Are you looking for a contract research organisation to support your preclinical drug development?

We are specialized in solving complex research ques-tions using interdisciplinary cutting-edge techniques.

With a renowned expertise in biotechnology and life-science, we can support and enhance your product development. We have QA/QC programs in place.

Our partners include international pharmaceutical companies as well as enterprises in an early stage.

FOI is your advanced research partner with a unique profile of research groups covering all needs in the early stage drug development.

Areas of in-house research capabilities:• Synthesis of bioactive compounds• Chemometrics and computational chemistry• Protein characterization and assay development• Macromolecular structure determination and

modelling• Analytical capabilities • Invivo infection models for preclinical evalua-

tion of antimicrobial compounds and vaccines • Models for lung effects• Exvivo model for airway contraction• Invitro lung cell model • Model for skin penetration

foi.se/lifescience

Synthesis of bioactive compounds PhD Anna-Karin Tunemalm, anna-karin.tunemalm@foi.se, orSandra Lindberg, sandra.lindberg@foi.se

Do you need organic compounds such as drug candidates, intermediates, metabolites or reference substances for analytical use?

We can offer• General organic synthesis, including develop-

ment of synthetic methods (in a mg – kg scale)• Synthesis of - isotope labelled compounds - highly potent or air sensitive compounds• Structural and quantitative analysis using NMR-

spectroscopy• Invitro/invivo and insilico studies on physical-

chemical properties

Our laboratory is e.g. equipped with • A continuous flow reactor • Two full size glove boxes for synthesis or toxico-

logical, analytical and other testing assignments.• Preparative HPLC for purification of organic

compounds

Selected reading• A new micro-scale method for the conversion of

phosphorus oxyacids to their halogenated analogues, using cyanuric fluoride in solution and on solid sup-port. Wärme R., Juhlin L., Phosphorus Sulfur and Silicon relat. (2010), 185(12), 2402-2408.

• Synthesis of (14C) Sarin. Norlin R., Lindberg G., J. Radiolabel. Compd. Radiopharm, 46 (2003) 599-604.

Chemometrics and computational chemistry PhD Susanne W Lindström, susanne.lindstrom@foi.se

Do you need to understand what factors that have most influence on your experimental results? Are you producing complex data sets with biological or chemi-cal questions? Do you need to understand structure activity/property relationships?

We can support you with• Statistical experimental design, analysis and inter-

pretation• Extracting most important variables in your data

table• Molecular interaction models• Interpretation of biological and chemical diversity• Structure-activity relationships• Classification of complex samples • Visualization

Protein characterization and assay developmentPhD Fredrik Ekström, fredrik.ekstrom@foi.se

Do you need a simple and reliable assay, suitable for high throughput screening of a chemical library or do you wish to study complex or rapid kinetics in order to characterize and optimize your lead-compound? Do you wish to increase the turn-over of your prod-uct development by shifting from a time consuming invivo assay and to a high-throughput invitro assay? Regardless of your need, the Biochemistry group at FOI possesses a flexibility that matches your expecta-tions and complements your organization.

• Development and validation of assays• Characterization and optimization of ligands by

Stopped-Flow- or complex enzyme kinetics• Receptor binding studies using state-of-the-art

techniques such as Time-Resolved Fluorescence Decay Spectrometry

• Recombinant protein expression in bacteria or cell lines

• Characterization of irreversible inhibitors and other highly toxic compounds

• Protein purification from simple or complex matrices

Macromolecular structure determination and modellingPhD Fredrik Ekström, fredrik.ekstrom@foi.se

Do you want to improve your product by structure-assisted design or elucidate the mechanism of action?

• Structure determination using X-ray crystallo-graphy or Small Angle X-ray Scattering (SAXS) with focus on structure determination of ligand-target complexes

• Primary structure determination using Liquid Chromatography-Mass Spectrometry (LC-MS), including characterization of glycosylation sites and modified residues

• Computational chemistry including Structure-Activity Relationships (SAR)

• Protein crystallization under aerobic and anaero-bic conditions

Selected reading• Similar but Different: Thermodynamic and Structural

Characterization of a Pair of Enantiomers Binding to Acetylcholinesterase. Berg L., Niemiec M.S., Weixing Q., Andersson C.D., Wittung-Stafshede P., Ekström F., Linusson A. Angewandte Chemie Int. Edi, 51, (2012) 12716-12720.

• Solution Structure poly(ethylene) Glycol-Conjugated Hemoglobin Revealed by Small-Angle X-Ray Scat-tering: Implications for a New Oxygen Therapeutic. Svergun D I, Ekström F, Vandegriff K D, Malavalli A, Baker D A, Nils-son C, and Winslow R M. Biophysi-cal Journal, 94 (2008) 173-181.

Crystal structure of a lead compound identified by a high throughput screening of a chemical library

Analytical capabilitiesPhD Crister Åstot, crister.astot@foi.se, or PhD Tove Johansson Mali’n, tove.johansson.malin@foi.se

Do you need support to analyze your drug candi-date? Are there metabolites yet to be discovered? The analytical chemical laboratory at FOI offers sophis-ticated analytical instrumentation and experienced scientists. We can develop and validate analytical methods to meet your highest demands. A broad range of instrumental techniques are available for quantitative and qualitative analysis of bioactive substances, including small molecules, peptides and protein complexes

ActivitiesSmall molecules:• Quantitive and qualitative analysis of diverse

biomedical samples • Structure determination• In vitro drug metabolism studies• Chemical stability studies

Peptides/proteins: • Protein identifica-

tion and characteri-zation

• Determination of disulphide bridge positions

• Analysis of pegylated proteins

• Glycosylation and deamidation studies

Analytical techniquesThe facility includes techniques of high sensitivity and selectivity:• LC-MS/MS (liquid chromatography tandem

mass spectrometry, Xevo-TQ and QTof)• GC-MS (gas chromatography mass spectrom-

etry)• NMR (Nuclear Magnetic Resonance)• LC-ICP-MS (Inductively Coupled Plasma Mass

Spectrometry)

Selected reading• Novel glutathione conjugates of phenyl isocyanate

identified by ultra-performance liquid chromatogra-phy/electrospray ionization mass spectrometry and nuclear magnetic resonance. Johansson Mali’n T, Lindberg S, Åstot C. J Mass Spectrom,(2014), In press.

• A concept study on identification and attribution profiling of chemical threat agents using LC-MS ap-plied to Amanita toxins in food. Jansson D, Fredriks-son S-Å, Herrman A, Nilsson C. For Sci Int, 221 (2012) 44-49.

• De Novo Sequencing of RCB-1 to -3: Peptide Bio-markers from the Castor Bean Plant Ricinus com-munis. Ovenden S P B, Fredriksson S-Å, Bagas C K, Bergström T, Thomson S A, Nilsson C and Bourne D J. Anal. Chem., 81 (10) (2009) 3986–3996.

Sangart Inc. contracts complex analytical chemistry investigations on polymers and proteins by NMR and LCMS techniques to FOI. The analytical capabili-ties of the laboratory in Umeå, the competency and professionalism of the staff and the elaborate reports have been an asset to our organization.

Nils U. Olsson, Ph.D. Vice President of Quality. Sangart, Inc. San Diego, CA, USA

In vivo infection models for preclinical evaluation of antimicrobial compounds and vaccinesPhD Laila Noppa, laila.noppa@foi.se, orPhD Emelie Näslund Salomonsson, emelie.salomonsson@foi.se, or MSc Elin Nilsson, elin.nilsson@foi.se

Are you developing new pharmaceutical drugs? We offer help with preclinical testing of your early drug candidates in our invivo infection models.

The rapidly emerging threat of multi-resistant pathogens highlights the great demand for research developing novel strategies and drugs to combat infections. A critical step in evaluations of poten-tial antimicrobial compounds is the availability of relevant invivo infection models.

If you are involved in research and development of novel antimicrobials, FOI has designated facilities for animal infections which are equipped with an invivoimaging instrument.

Features of our invivo infection models include: • Determination of invivo stability of candidate

drug compounds in small animals • Early toxicity evaluations• Trauma associated infections – incision and burn

wounds • Lung infection models • Gastrointestinal infection models

The research group at FOI is internationally recognised in the field of molecular infection and has also experi-ence from contract research from biotech companies and institutes to evaluattion of vaccines and antimicro-bial compounds. FOI has carried out several studies on new antimicro-bial compounds under development by Innate Pharma-ceuticals. FOI’s recognised competence and expertise in the area of bacterial infections and together with their infrastructure and quality of documentation of results are major strengths in providing support in develop-ment of new antimicrobial drugs. We are very positive regarding the plans to establish techniques for direct visualisation of bacteria in real time during infection. This will provide new powerful tools in studies of bacte-rial infections and evaluation of new drug candidates.

Sune Rosell, CEO Innate Pharmaceuticals, Sweden

Selected reading• Reintroduction of two deleted virulence loci restores

full virulence to the live vaccine strain (LVS) of Fran-cisellatularensis. Salomonsson E, Kuoppa K, Forslund AL, Zingmark C, Golovliov I, Sjöstedt A, Noppa L, Forsberg Å. Infect Immun, 77 (2009) 3424-3431.

• Role of Yersinia murine toxin in survival of Yersiniapestis in the midgut of the flea vector. Hinnebusch BJ, Rudolph AE, Cherepanov P, Dixon JE, Schwan TG, Forsberg Å. Science, 296 (2002) 733-735.

Models for lung effectsProf Anders Bucht, anders.bucht@foi.se, or Bo Koch, bo.koch@foi.se

Are you developing new pharmaceutical drugs? FOI can offer you help with preclinical testing of your early drug candidates in our models for:• Acute and chronic asthma• Industrial chemicals

Evaluate following invivo effects:• Lung mechanics/respiration• Inflammatory cells and mediators• Histopathological changes• Emphysema formation

Ex vivo model for airway contraction Lina Thors, lina.thors@foi.se

We can offer precision-cut lung slices (PCLS) for airway contraction measurements.

In vitro lung cell model Barbro Ekstrand-Hammarström, barbro.ekstrand-hammarstrom@foi.se

We have the ability to evaluate the cellular effects in both primary lung cells and epithelial cell lines. Using our lung cell systems, we can evaluate the following end-points after exposure to your sub-stances:• Toxicity• Oxidative stress• Pro-inflammatory responses

Control airway Exposure to metacholine for 10 min

Epithelial cell exposed to nanoparticlesViability assay

Model for skin penetration Bo Koch, bo.koch@foi.se

Many drugs are designed to be applied on the skin. We use human or animal skin to study• Penetration of active substances• Effect of different formulations• Toxicological evaluation• Effects of decontamination

Selected reading• A mouse model for in vivo tracking of the major

house dust mite allergen Der p 2 after inhalation. Linda Johansson, Linda Svensson, Ulrika Bergström, Gunilla Jacobsson-Ekman, Elias Arnér, Marianne van Hage, Anders Bucht, Guro Gafvelin. FEBS J. (2005) 272:3449-3460.

• Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury. Sofia Jonasson, Bo Koch, Anders Bucht. Toxicology. (2013) 303:34-42.

• Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B. Barbro Ekstrand-Hammarström, Christine Akfur, Per-Ola Andersson, Christian Lejon, Lars Österlund, Anders Bucht. Nanotoxicology. (2012) 6(6):623-34.

• Skin decontamination of organophosphorus com-pounds with RSDL. Bo Koch, Lina Thors, Mona Koch, Lars Hägglund, Anders Bucht. 11th Interna-tional Symposium on Protection against Chemi-cal and Biological Warfare Agents, June 3-5 2013, Stockholm, Sweden.

Contact informationFor general information, contact

Head of CBRN Defence and Security Mats Strömqvist, mats.stromqvist@foi.se

FOI, Swedish Defence Research AgencyCBRN Defence and Security

SE-901 82 UmeåSWEDEN

Phone: +46 (0)90 10 66 00Visiting address: Cementvägen 20, Umeå, Sweden

www.foi.se

What is FOI?

FOI (The Swedish Defence Research Agency) is one of Europe’s leading research institutes in the defence and security area. The agency is mainly financed on contracts’ basis and is responsible to the Ministry of Defence. The core business is research, method and technology develop-ment and studies.

CBRN Defence and SecurityFOI’s CBRN Defence and Security Division house many of the country’s leading experts on chemical, biological, radioactive and nuclear (CBRN) issues and are working on projects relevant to the performance of our defence forces and to the civilian crisis management system.FOI is every day accumulating new knowledge relating to the emission and dispersion of chemicals and microbio-logical agents, to ionizing radiation and to radioactive materials. Dissemination may occur in air, to the ground or in water. Important areas of work include environmen-tal issues, radiation protection and chemical hazards. The division has a solid research base in fields such as analytical chemistry, organic chemistry, toxicology, microbiology, medicine, physics, environmental chemistry and geology. The analytical laboratory is part of interna-tional networks consisting of the world’s leading labora-tories, giving us access to a unique spectrum of expertise. We provide support for our customers also in the field of threat and risk assessment.