TI Pharma by fdh56iuoui


									Annual Report 2007
TI Pharma
16                                            26

     5   Preface
         by Daan Crommelin & Willem de Laat

     6   Chapter 1
         Strategic Research Program

 24      Chapter 2
         Education & Training

 30      Chapter 3

 36      Chapter 4
         Annual accounts

 50      Annex
         Partners, Governance, Staff
 Willem de Laat,
managing director

                        Daan Crommelin,
                        scientific director

TI Pharma up and running
Top Institute Pharma (TI Pharma) is dedicated to fostering new, strategic
collaborations between top-quality academic research groups in The
Netherlands and innovative industrial partners, SMEs and other global players
in the Life Sciences. We conduct groundbreaking and cross-disciplinary research
and offer advanced training programs, working to improve the efficiency of the
entire drug discovery and development chain. Such significant investment in
research is a vital contribution to both public health and a sustainable economy,
eventually reducing the time and cost-to-patient of new drugs.

The World Health Organization (WHO), with its Priority            for opportunities to establish new relationships. These
Medicines Report, provided the framework for our                  and other commitments speak to our inherent ability to
research programme. In 2007, the structural and legal             leverage talent from diverse cultures and backgrounds in
foundations were laid. Project agreements were signed             the discovery and development of new, effective and safe
over the course of that year and research was begun. By           medicines.
the end of 2007, 42 of the 44 projects were underway
comprising circa 500 researchers. During this time,               TI Pharma: jointly shaping the future of medicines.
TI Pharma also began important dialogues and joint
initiatives with other top institutes such as the Bio             July, 2008
Molecular Materials (BMM) programme, the Centre for
Translational Molecular Medicine (CTTM) and Green                 Daan Crommelin & Willem de Laat

From the start, TI Pharma has made a strong commitment
to an education and training programme for its Ph.D.
and postdoctoral fellows. Such a programme would
delve deeply into the intricacies of the drug discovery and
development process, including its business aspects.
2007 saw the first fruits of this commitment materialised,
and the entire programme will be operational by the end
of 2008.

In the European arena, TI Pharma will participate in the
Innovative Medicines Initiative (IMI). We strongly believe
that our experience in bringing academia and industry
together will help advance this new European venture.
As time goes on, TI Pharma will remain on the lookout

  Chapter 1
Strategic Research
Human red blood
cells, activated
platelets and
monocyte and
T lymphocyte white
blood cells at a
of x1,200.
    Forty two projects in the TI Pharma                            Therapeutic c   T1 (Auto-)
                                                                                   T            T2 Cardio-   T3            T4            T5
                                                             Enabling          s
                                                                           areas   Immune
                                                                                   Im           vascular
                                                                                                va           Cancer
                                                                                                             Ca            Infectious
                                                                                                                           Inf           Brain
    portfolio have officially started.                       technologies          Diseases
                                                                                   D            Diseases
                                                                                                Diseases                   Diseases
                                                                                                                           Diiseases     Diseases

    These projects form the core of the                      D1
                                                             Therapeutic Target                 Therapeutic Areas based on
                                                             Finding, Validation
    TI Pharma portfolio: high quality science                & Animal Models
                                                                                                Priority Medicines (WHO)
    to address serious diseases confronting                  D2
                                                             Lead Selection and    Enabling
    the modern world. The 42 consortia                       In-Silico Modeling
    combine top groups from 20 universities,                 D3                    are relevant
                                                             Predictive Drug       to research
    medical centers and knowledge institutes,                Disposition and       across the
    as well as 35 companies, the latter                                            Therapeutic
                                                                                                                      Special overall Research
                                                             D4                    Areas                                      Platform
    includes global pharmaceutical companies                 Biomarkers and
    and small/medium sized companies                                                                            Drug Discovery, Development
                                                                                                                       and Utilization
e   (SME’s).                                                 Drug Formulation,
                                                             Delivery and
                                                                                                                      • Efficiency improvement
                                                                                                                       • Early regulatory input

                                                             Prod. Technologies

                                                          The Strategic Research Program of TI Pharma is based upon a matrix
                                                          of Therapeutic Areas and Enabling Technologies.

    TI Pharma project portfolio
    D1-101                                                                system is deregulated. For some toll-like receptors, agonists
    Exploitation of toll-like receptors in drug discovery                 and their mode of action are fairly well understood. These
    This TI Pharma research project is being conducted by                 can, for example, be used to develop tumor and infection
    a consortium consisting of ISA Pharmaceuticals, Leiden                vaccination strategies. For other toll-like receptors, the
    University, Leiden University Medical Center, Maastricht              link to disease is less well understood and the validity of
    University, Numico Research (part of Danone), Organon                 targeting these to realize new therapeutic strategies still
    (part of Schering-Plough), Radboud University Nijmegen,               needs to be verified.
    Radboud University Nijmegen Medical Centre, TNO
    Quality of Life, University Medical Center Utrecht and                D1-105
    Utrecht University.                                                   The GPCR Forum: novel concepts and tools for
    Toll-like receptors are the sentinels of the innate immune            established targets
    system and play a crucial role in host defense against                This research project of TI Pharma is being conducted by a
    infection. It has become clear that the innate and adaptive           consortium consisting of the Leiden / Amsterdam Center
    immune systems are closely linked. Research has also                  for Drug Research, Organon (part of Schering-Plough), the
    shown that toll-like receptors are not just important in              Radboud University Nijmegen, Solvay Pharmaceuticals,
    infectious diseases but in all diseases where the immune              the University Medical Center Groningen, the University

Project                                                           Projec
          Therapeutic Target Finding,
          T                  Finding                                        Predictive Drug Disposition and Toxicology
          Validation and Animal Models                            D3-201    To
                                                                            Towards novel translational safety
D1-101    T
          The TLR Project: Exploitation of                                  b
                                                                            biomarkers for adverse drug toxicity
          Toll-like receptors in Drug Discovery
D1-105    T
          The GPCR Forum: Novel concepts                                    B
                                                                            Biomarkers and Bio-sensoring
          a tools for established targets
          and                                                     D4-102    T CSF proteome / metabolome as primary
                                                                            biomarker compartment for CNS disorders
          Lead selection, In Silico and PK-PD Modeling
D2-101    A integrated strategy for in silico
          An                                                                D
                                                                            Drug Formulation, Delivery and Targeting
          prediction and preclinical evaluation of                D5-106    V
                                                                            Vaccine Delivery: Alternatives for
          the cardiotoxicity of drug candidates                             co
                                                                            conventional multiple injection vaccines
D2-102    M
          Metabolic stability assessment as a new tool
          in the Hit-to-Lead selection process and the                      P
                                                                            Pharmaceutical Production Technologies
          generation of new compound libraries                           H
                                                                  D6-202 Hot medicines: breaking the cold chain
D2-103    N
          New approaches for Ligand-Gated                                   re
                                                                            requirements for polypeptide-based priority
          Ion Channel (LGIC) drug discovery                                 m
D2-104    M
          Mechanism-based PK-PD modeling platform                 D6-203 D
                                                                         Design quality into products

Medical Center Utrecht and the VU University Amsterdam.           This research project of TI Pharma is being conducted by a
The main goal of this project is to explore and exploit           consortium consisting of the Leiden / Amsterdam Center
novel concepts and tools for G protein-coupled receptors          for Drug Research, NOTOX BV, the Radboud University
with the explicit aim of discovering lead compounds with          Nijmegen, Solvay Pharmaceuticals and the University
an entirely new mechanism of action. G protein-coupled            Medical Center Utrecht.
receptors (GPCRs) have been and still are highly successful       In this project methods will be developed for early
drug targets. In fact, forty to fifty percent of drugs            detection of the pro-arrhythmic potential of drug
currently marketed interact with these proteins. Due to           candidates in order to minimize cardiac safety risks. Drug-
their physiological and pathophysiological relevance, these       induced QT prolongation may lead to torsades de pointes,
GPCRs are prime targets of interest for both academia and         a potentially lethal arrhythmia. A number of drugs have
the pharmaceutical industry.                                      been withdrawn from the market or have failed to obtain
                                                                  market authorization due to QT interval prolongation or
D2-101                                                            due to lethal torsades de pointes. Therefore, this unwanted
An integrated strategy for in silico prediction and               side effect must be recognized as early as possible in drug
preclinical evaluation of the cardiotoxicity of drug              discovery, using in vitro high throughput systems.

Project                                                         Projec
          (Auto-)Immune Diseases
          (A                                                    T2-110    Nuclear receptors as targets
T1-103    CXC chemokine receptors: potential
          C                                                               for anti-atherosclerotic therapies
          targets for chronic inflammatory diseases
T1-106    Glucocorticoid-induced insulin-resistance
          G                                                               Cancer
T1-108    Acute and chronic inflammatory
          A                                                     T3-103    Identification of novel kinases
          responses induced by smoking
          r                                                               involved in cancer-relevant processes
T1-201    Transition of systemic inflammation
          T                                                     T3-105    Kinases in cancer
          into multiorgan pathology
          in                                                    T3-106    Novel cancer drugs based on
T1-213    Osteo-arthritis: models, mechanisms
          O                                                               signal transduction pathways
          and markers for patient stratification
          a                                                     T3-107    Nuclear receptors in targeted cancer therapy
T1-214    Immune modulation and tolerance induction,
          Im                                                    T3-108    Predicting drug responses in breast cancer
          prevention and inhibition of inflammatory
          p                                                     T3-112    TNF ligands in cancer
T1-215    Neuromodulation of innate immune responses
          N                                                               Infectious Diseases
                                                                T4-101    Antibodies against Klebsiella
          Cardiovascular Diseases
          C                                                               pneumoniae
T2-105    Drug induced weight alterations
          D                                                     T4-102    Development of an attenuated
T2-108    Metalloproteases and Novel
          M                                                               parasite vaccine for Malaria
          Targets in Endothelial Dysfunction
          T                                                     T4-211    Efficient eradication of
                                                                          (multidrug) resistant bacteria

D2-102                                                          D2-103
Metabolic stability assessment as a new tool in the             New approaches for Ligand-Gated Ion Channel (LGIC)
Hit-to-Lead selection process and the generation of             drug discovery
new lead compound libraries                                     This research project of TI Pharma is being conducted
This research project of TI Pharma is being conducted by        by a consortium consisting of the Netherlands Cancer
a consortium consisting of Organon (part of Schering-           Institute, Organon (part of Schering-Plough), Solvay
Plough), the Radboud University Nijmegen, VU University         Pharmaceuticals and VU University Amsterdam.
Amsterdam and Xendo Drug Development BV.                        The high-resolution crystal structure of the acetylcholine
This project will create innovative and state-of-the-           binding protein (AChBP) domain of the ligand-gated
art biosynthetic and analytical technologies to assess          ion channel family forms the basis of this project and
the metabolic stability and affinity of leads and their         paves the way for structure-based drug design. New in
metabolites towards drug targets. Efficient and high            silico and in vitro screening tools will be developed that
throughput analysis of metabolic stability/profiles and         cover computational chemistry, molecular biology, X-ray
large-scale biosynthesis of metabolites by engineered           analysis, electrophysiology, PET-imaging and behavioral
cytochrome P450 enzymes offers a potential route to an          analysis. This research will fully exploit the possibilities
improved understanding of toxicity and pharmacokinetic          to use AChBP as an in silico and in vitro tool in novel drug
profiles as a function of their chemical structure              discovery.
(Structure Activity Relationship) and will make the
process of lead selection more efficient.

Project                                                           Project
T4-212    A multidisciplinary approach to monitor                 T5-203    A translational pharmacogenomics approach
          a select effective therapy in HIV infection
          and                                                               to improve drug development strategies for
T4-213    P
          Protective human antibodies                                       p
                                                                            psychiatric disorders
          against multi drug resistant S. Aureus                  T5-207    P
                                                                            Parkinson’s and Alzheimer’s disease:
T4-214    D
          Development and application of novel                              fr
                                                                            from dysordered human brain targets
          strategies to induce and monitor                                  to
                                                                            towards novel therapeutics
          humoral and cellular immunity to protect                T5-209    N
                                                                            Novel susceptibility pathways and drug
          hosts from infection by respiratory viruses                       t
                                                                            targets for psychosis
                                                                  T5-210    R
                                                                            Rapid in vivo CNS drug target validation and
          CNS Diseases                                                      t
                                                                            therapeutic potential using RNA interference
T5-105    N
          Nanoscience as a tool for improving
          bioavailability and Blood-Brain Barrier                           E
                                                                            Efficiency analysis Drug Discovery Process
          penetration of CNS drugs                                T6-101    T Mondriaan Project: The Dutch health
T5-107    T neurophysiological role of the
          The                                                               c
                                                                            care landscape as a population laboratory
          endocannabinoid system in support of                    T6-202    T Escher project: Science driven
          smoking cessation, fighting addiction and                         d
                                                                            drug regulation and innovative research
          treating cognitive decline                                        t                         elopment
                                                                            throughout phased drug development
T5-108    V
          Validation of the use of fMRI as an objective
          measure in clinical pain in patients with and
          without psychiatric comorbidities

D2-104                                                            a mechanism-based PK-PD model library and a database
Mechanism-based PK-PD modeling platform                           of biological-system-specific information for use in drug
This TI Pharma research project is being conducted by a           discovery and development.
consortium consisting of Eli Lilly, Erasmus MC (University
Medical Center Rotterdam), GlaxoSmithKline, Johnson &             D3-201
Johnson PRD, Leiden University, Nycomed, Organon (part            Towards novel translational safety biomarkers for
of Schering-Plough), Pfizer, the University Medical Center        adverse drug toxicity
Utrecht and the University of Groningen.                          This TI Pharma research project is being conducted by a
Significant progress has been made in the field of                consortium consisting of BioDetection Systems, BioFocus
pharmacokinetic/pharmacodynamic (PK-PD) modeling.                 DPI, Leiden / Amsterdam Center for Drug Research,
In particular, mechanism-based PK-PD models have                  Leiden University, NOTOX BV, Organon (part of Schering-
been developed, with considerably improved properties             Plough), PamGene, Pepscan Presto BV, Radboud University
for extrapolation and prediction. The models are valid for        Nijmegen Medical Centre, Solvay Pharmaceuticals, the
drug effects in stationary biological systems. However,           University of Groningen, Utrecht University and VU
biological systems are often non-stationary. This is              University Amsterdam. Approximately 25% of all human
observed in progressive diseases (e.g. osteoporosis, COPD)        adverse drug reactions (ADRs) are not predicted by either
and in infants and children. The main goal of this                preclinical safety testing or clinical trials. This results in
project is to develop PK-PD modeling concepts for non-            delay or cancellation of potentially effective treatment
stationary biological systems. The ultimate result will be        and economic loss. It has a major social impact (hospital

      admissions, patient discomfort) and additional treatment           The goal of this project is to develop robust procedures for
      to resolve ADRs may be necessary. For hepatotoxicity,              biomarker discovery in rodent and human cerebrospinal
      blood dyscrasias and drug hypersensitivity in particular,          fluid (CSF), and to use this approach to discover, validate
      no adequate translational predictive safety strategies are         and quantify metabolome and proteome biomarkers in CSF
      available. Yet these ADRs are the top three reasons for            so that drug-related exposure and efficacy for neurological
      market withdrawals of drug candidates in development.              (e.g. multiple sclerosis, Alzheimer’s disease) and psychiatric
      The ultimate goal of this project is to use Dutch molecular        diseases (e.g. schizophrenia, depression) can be predicted.
      pharmaco-epidemiologic data to develop novel in vitro
      predictive screening tools and in vivo translational models        D5-106
      and biomarkers to improve ADR hazard identification.               Vaccine delivery: alternatives for conventional
                                                                         multiple injection vaccines
      D4-102                                                             This TI Pharma research project is being conducted by a
      The CSF proteome / metabolome as primary                           consortium consisting of Leiden University, Netherlands
      biomarker compartment for CNS disorders                            Vaccine Institute, OctoPlus NV, Utrecht University and VU
      This research project of TI Pharma is being conducted by           University Medical Center Amsterdam.
      a consortium consisting of the Erasmus MC (University              Poor patient compliance, inadequate delivery and adjuvant
      Medical Center Rotterdam), Leiden University (Leiden/              properties of existing vaccines are limiting factors in
      Amsterdam Center for Drug Research), Organon (part                 vaccination programs for the prevention or treatment of
      of Schering-Plough), the Radboud University Nijmegen,              infectious diseases. The aim of this project is to rationally
      Solvay Pharmaceuticals, TNO and the University of                  design novel improved vaccine delivery strategies based
      Groningen.                                                         on nano- and microparticles for different administration

                                                                                           Post-doc in the
                                                                                           TLR project

   Mary Morgan
D1-101, Utrecht University

routes. The results may lead to new and improved                     T1-103
vaccination strategies that can be used for prevention or            CXC chemokine receptors: potential targets
treatment of infectious diseases, cancer, and autoimmune             for chronic inflammatory diseases
diseases.                                                            This TI Pharma research project is being conducted by a
                                                                     consortium consisting of Numico Research, Organon (part
D6-202                                                               of Schering Plough), Utrecht University and VU University
Hot medicines: breaking the cold chain requirements                  Amsterdam.
for polypeptide-based priority medicines                             Chronic inflammatory diseases affect a considerable
This research project of TI Pharma is being conducted                number of individuals worldwide. In general, life-long
by a consortium consisting of Leiden University                      treatments are taken to alleviate disease symptoms, yet
(Leiden/Amsterdam Center for Drug Research),                         these do not tackle the cause of the disease. Moreover, the
OctoPlus NV, Organon (part of Schering-Plough), Solvay               lack of specific drugs severely limits the beneficial effects
Pharmaceuticals and the University of Groningen.                     of such therapies. The aim of this project is to deliver
Polypeptide medicines are susceptible to thermal                     fully characterized and validated drugable targets for
degradation. Therefore, many of these drug substances                novel therapies for chronic inflammatory diseases such as
are unstable under tropical conditions and require an                inflammatory bowel disease (IBD) and chronic obstructive
expensive cold chain. The aim of this project is to develop          pulmonary disease (COPD). This approach will also open
dry powder formulations that can resist tropical conditions          up new avenues for the treatment of other autoimmune
without refrigeration. Sugars will be used as stabilizers.           diseases such as arthritis.
The focus will be on the WHO priority medicines: oxytocin
and insulin as well as vaccines for hepatitis B and                  T1-106
influenza.                                                           Glucocorticoid-induced insulin resistance
                                                                     This research project of TI Pharma is being conducted by
D6-203                                                               a consortium consisting of the Leiden University Medical
Design quality into products                                         Center, Organon (part of Schering-Plough), the University
This research project of TI Pharma is being conducted by             Medical Center Groningen, the University Medical Center
a consortium consisting of Organon (part of Schering-                Utrecht and the VU University Medical Center.
Plough), Solvay Pharmaceuticals, TNO and the University              This project will study one of the major adverse effects of
of Groningen.                                                        prednisolone in detail: induction of insulin resistance and
In this project, science-based rules will be developed               beta cell dysfunction. The key role of beta cell dysfunction
for the design, production and control of fixed-dose                 in the development of type 2 diabetes has only recently been
combinations of drugs according to the FDA philosophy                fully recognized. This project will identify the most relevant
of Process Analytical Technology. Fixed-dose combination             tissues for the induction of insulin resistance and beta-
products are typically formulated with more than one                 cell dysfunction, describe the key molecular components
active pharmaceutical ingredient. The development of such            and pathways in those tissues and develop a PK/PD model
products is complex owing to the variation of solid-state            that describes the relation between prednisolone levels in
properties that arise as a result of processing. This project        humans and insulin-mediated glucose uptake, hepatic glu-
presents a unique opportunity to combine expertise,                  cose production and glucose-stimulated insulin secretion.
infrastructure and resources from academia and the
pharmaceutical industry.                                             T1-108
                                                                     Acute and chronic inflammatory responses induced by
                                                                     smoking in individuals who are susceptible and non-
                                                                     susceptible for development of COPD: from specific
                                                                     phenotyping towards novel tailor-made therapy

This TI Pharma research project is being conducted by               (University Medical Center Rotterdam), Leiden University
a consortium consisting of GlaxoSmithKline, Nycomed,                Medical Center and TNO Quality of Life.
University Medical Center Groningen, University Medical             Osteoarthritis is the most common joint disorder,
Center Utrecht and University of Groningen.                         especially in the elderly. Little is known about its etiology
COPD is number three on the WHO list of major global                and pathophysiology, and no treatments are available.
diseases and is the only disease with increasing mortality.         In its Priority Medicines Report, the WHO calls for
The pathogenesis of cigarette smoke-induced COPD is                 additional research. Yet which patients will develop rapidly
obscure and therefore more insight is needed in the design          progressing osteoarthritis and why this happens is not
of effective anti-inflammatory agents. The main goal of             known. The current project will investigate the role of
this project is to develop new biological markers in blood,         synovium and fat tissue in osteoarthritis development and
sputum and exhaled breath to characterize the induction             progression. The ultimate goal is to optimize the efficiency
and progression of local and systemic inflammation in               of clinical trials for osteoarthritis by improving patient
COPD in relation to the underlying genetic make-up. This            stratification, understanding disease mechanisms and
will open up new avenues in design and will facilitate the          predicting disease outcome.
implementation of novel diagnostics as well as the selective
application and monitoring of therapeutics for different            T1-214
types of disease.                                                   Immune modulation and tolerance induction
                                                                    prevention and inhibition of inflammatory diseases
T1-201                                                              This TI Pharma research project is being conducted by
Transition of systemic inflammation into multiorgan                 a consortium consisting of IQ Therapeutics, Numico
pathology                                                           Research, the University Medical Center Utrecht, Utrecht
This TI Pharma research project is being conducted by a             University, Vaxinostics and VU University Medical Center.
consortium consisting of AstraZeneca, GlaxoSmithKline,              The prevalence of inflammatory diseases like allergies
Maastricht University, Numico Research (part of Danone),            and autoimmune diseases is increasing in the Western
Nycomed, the University Hospital Maastricht, the                    world. These diseases are often associated with a
University Medical Center Groningen and the University              disturbed immune balance and a lack of immunological
Medical Center Utrecht.                                             tolerance. Consequently, there is wide spread interest in
COPD is the only major global disease with increasing               the discovery and development of safe treatments that
mortality. The pathogenesis of extrapulmonary COPD                  can modulate immune disorders and compensate for the
manifestations (crucial determinants of its severity) is            lack of tolerance. Understanding the immune system and
poorly defined and there are no evidence-based strategies           selecting appropriate immune modulators is crucial for
for their diagnosis and treatment. The main goal of                 generating safe and effective therapeutic and/or preventive
this research project is to define new avenues for the              treatment strategies, which is the main objective of the
development of new diagnostics and therapeutics for                 underlying project. In addition, the identified components
COPD. This will be realized by combining novel insights in          might be particularly interesting as adjuvants for vaccines.
the interaction between genetic and environmental factors
and by modulating these factors with the help of new                T1-215
therapeutic, nutriceutic and lifestyle strategies.                  Neuromodulation of innate immune responses
                                                                    This TI Pharma research project is being conducted by a
T1-213                                                              consortium consisting of Academic Medical Center (AMC)
Osteoarthritis: models, mechanisms and markers for                  Amsterdam, GlaxoSmithKline R&D UK and the University
patient stratification                                              Medical Center Groningen.
This TI Pharma research project is being conducted                  Inflammatory bowel disease, rheumatoid arthritis, irritable
by a consortium consisting of Centocor, Erasmus MC                  bowel syndrome and postoperative ileus are examples of

disabling inflammatory diseases for which no efficient               University Medical Center Utrecht and the University of
therapy is available. The annual costs associated with               Groningen.
these diseases are enormous. The results of this project             High cholesterol, diabetes and obesity are some of the
may provide several targets to modulate the inflammatory             most important risk factors for heart attack and stroke.
response. Several cholinergic receptor agonists are already          Some therapeutic agents, especially neuroleptics, cause
available for human use but for entirely different clinical          either severe obesity or weight loss as an unexplained
entities (neurological diseases). The major drawback of              side effect. Deducing the mechanisms of these side effects
these agents is their neurological side effects. This project        might prove to be an innovative approach for identifying
will provide more insight into the identity of the receptor          novel central and peripheral targets for the treatment of
and intracellular pathways involved, thereby enabling the            obesity, dyslipidemia, and diabetes and for supporting
selection of more specific agonists.                                 the design of the next generation of antipsychotics with
                                                                     reduced side effects. By bringing together experts from the
T2-105                                                               fields of neuroscience and diabetes with experts from the
Investigation of drug-induced weight alterations to                  field of proteomics and metabolomics and by using both
identify novel therapeutic strategies for the treatment              in vivo and in vitro animal testing and clinical studies, this
of obesity, dyslipidemia and diabetes                                translational project will be able to focus on unravelling
This TI Pharma research project is being conducted by                the peripheral and central mechanisms on which these
a consortium consisting of Leiden University Medical                 drugs act and may lead to concepts for new therapies.
Center, the Netherlands Institute for Neurosciences, PRA
International, Solvay Pharmaceuticals, TNO Quality
of Life, the University Medical Center Groningen, the

                Maikel Wijtmans
                D1-105, VU University

Post-doc on the GPCR forum

PhD student
on the Vaccine

           Suzanne Bal
       D5-106, LACDR Leiden

    T2-108                                                                T2-110
    Metalloproteases and novel targets in endothelial                     Nuclear receptors as targets for anti-atherosclerotic
    dysfunction                                                           therapies
    This research project of TI Pharma is being conducted by              This TI Pharma research project is being conducted by a
    a consortium consisting of the Academic Medical Center                consortium consisting of Academic Medical Center (AMC)
    (AMC) Amsterdam, Leiden University Medical Center,                    Amsterdam, Leiden University, Organon (part of Schering-
    Maastricht University, Solvay Pharmaceuticals and                     Plough), Radboud University Nijmegen and the University
    VU University Medical Center.                                         Medical Center Groningen.
    This project aims to beneficially modulate basic                      Atherosclerotic cardiovascular disease (CVD) is the
    mechanisms underlying different aspects of endothelial                leading cause of mortality worldwide. Current therapeutic
    dysfunction, and will try to identify new relevant targets            regimens are primarily based on the use of statins and
    and mechanisms. The research may make a significant                   aimed at decreasing plasma cholesterol. Despite their
    scientific and therapeutic contribution to this major                 proven effectiveness and widespread use, the incidence
    medical field. Endothelial dysfunction is one of the                  of CVD remains high, implying that there is an urgent
    earliest indicators, but also a key causal factor, of vascular        need for additional therapeutic strategies. Recent work
    disease. This often progresses into overt cardiovascular,             has provided evidence that several nuclear receptors
    cerebrovascular and peripheral vasculopathies, with                   (e.g. LXRs, FXR, and LRH-1) play important roles in
    functional and structural end-organ damage of the heart,              controlling cholesterol and triglyceride metabolism,
    kidney, brain, and other organs.                                      macrophage functioning and vessel wall biology. These

are, therefore, potential therapeutic targets for treatment        in this study, is one of the four major metastatic forms of
and prevention of CVD.                                             cancer and is the second leading cause of cancer death.
                                                                   Cancer is caused by mutations in genes that encode
T3-103                                                             critical components of cell regulation, particularly signal
Identification of novel kinases involved in cancer-                transduction pathways. The aim of this project is to
relevant processes                                                 discover and develop new therapeutic drugs against (novel)
This research project of TI Pharma is being conducted by a         targets in signaling pathways commonly mutated in
consortium consisting of Erasmus MC (University Medical            cancer. The main focus will be on two pathways, namely
Center Rotterdam), Pepscan Presto BV, the University               the Wnt and the receptor tyrosine kinase (RTK) pathways.
Medical Center Groningen and Utrecht University. The
main goal of the project is to generate an inventory of the        T3-107
kinases active in specific forms of cancer, to help select         Nuclear receptors in targeted cancer therapy:
cancer types on which clinical lead compounds should be            improved methods for candidate selection
used and to identify kinome alterations within the patient         This research project of TI Pharma is being conducted by a
population that correlate with clinical outcome. Kinase            consortium consisting of Erasmus MC (University Medical
profiling is a highly novel technology for looking at the          Center Rotterdam), the Leiden/Amsterdam Center for Drug
cancerous process. The identification of cancer specific           Research, the Netherlands Cancer Institute and Organon
kinases using kinase substrate arrays should generate              (part of Schering-Plough).
novel avenues for the therapeutic treatment of disease.            Breast and prostate cancers are treated with anti-hormone
                                                                   therapy targeting the estrogen and androgen receptor,
T3-105                                                             respectively. Despite initial success, anti-hormone
Kinases in cancer                                                  resistance is developing which involves increased kinase
This research project of TI Pharma is being conducted by           activity. This project aims to generate an innovative
a consortium consisting of Organon (part of Schering-              rationale to develop a new generation of high-affinity,
Plough), the Netherlands Cancer Institute and the                  high-specificity hormone receptor antagonists that enable
University Medical Center Utrecht. Kinases are generally           patient-tailored therapy to overcome acquired anti-
believed to be among the best targets for cancer drug              hormone drug resistance.
discovery, yet only a few of the more than 550 kinases
are currently targeted in cancer therapy. In this project          T3-108
new innovative cell-based systems will be used to identify         Predicting drug responses in breast cancer
completely new classes of kinases involved in cancer.              This research project of TI Pharma is being conducted
A major aim of this project is to identify truly validated         by a consortium consisting of Agendia BV, Erasmus
drug targets by using animal models for cancer that very           MC (University Medical Center Rotterdam) and the
closely mimic human disease.                                       Netherlands Cancer Institute.
                                                                   The main goal of this project is to identify gene profiles
T3-106                                                             that predict responses to hormonal therapies in breast
Novel cancer drugs based on signal transduction                    cancer. Breast cancer is by far the most frequently
pathways                                                           occurring cancer in women worldwide, with approximately
This TI Pharma research project is being conducted by              one million new cases annually. Scientists at Erasmus
a consortium consisting of Agamyxis, Biofocus DPI,                 MC and the Netherlands Cancer Institute have developed
Hubrecht Laboratory and the University Medical Center              the world’s first clinically useful DNA microarray tests
Utrecht.                                                           for breast cancer. Agendia, a Dutch microarray diagnostic
This project focuses on cancer, which is still one of the          company, has developed one of these tests into the first
most deadly diseases. Colon cancer, strongly represented           commercially available microarray-based diagnostic test

for breast cancer prognosis: MammaPrint. These three                 T4-102
parties will now work together to develop microarray tests           Development of an attenuated parasite vaccine for
to predict which patients will respond to various types of           malaria
hormonal therapy in breast cancer.                                   This TI Pharma research project is being conducted by a
                                                                     consortium consisting of Leiden University Medical Center,
T3-112                                                               the Radboud University Nijmegen Medical Centre and
TNF ligands in cancer                                                Sanaria Inc.
This research project of TI Pharma is being conducted                The long-term goal of the study is to develop a highly
by a consortium consisting of the Academic Medical                   protective malaria vaccine that will save the lives of
Center Amsterdam, the Netherlands Cancer Institute,                  millions of people in developing countries. The mission
Organon (part of Schering-Plough), Pepscan Presto BV, the            of Sanaria Inc. is to develop, produce, and commercialize
University Medical Center Groningen, the University of               a malaria vaccine based on live, radiation-attenuated
Groningen and the VU Medical Center Amsterdam.                       sporozoites (RAS). The technology platform developed
Receptors belonging to the Tumor Necrosis Factor                     by Sanaria Inc. is based upon studies showing that
(TNF) receptor family are potential targets for therapy.             RAS immunization confers long-lasting, high levels
Activation of the TNF-Related Apoptosis-Inducing Ligand              of protection in human subjects exposed to the major
(TRAIL) receptors induces controlled cell death in cancer            human malaria parasite. Radboud University Nijmegen
cells, whereas activation of other receptors stimulates              Medical Centre and Sanaria have been collaborating
proliferation and survival. The project’s goal is to develop         on the production of sporozoites in mosquitoes. Recent
strategies to target these receptors providing the scientific        collaborative efforts of research groups at Leiden University
basis for novel cancer therapies.                                    Medical Center and Radboud University Nijmegen Medical
                                                                     Centre have resulted in the generation of murine malaria
T4-101                                                               parasites attenuated by the introduction of targeted gene
Antibodies against Klebsiella pneumoniae                             deletions. These genetically-attenuated sporozoites (GAS)
This TI Pharma research project is being conducted by                were able to induce protective immunity in mice at levels
a consortium consisting of the Erasmus MC (University                comparable to radiation-attenuated sporozoites and provide
Medical Center Rotterdam), IQ Corporation and Utrecht                a degree of cross-species protection. This finding broadens
University. The project involves the development of a non-           current prospects for human malaria vaccine development
antibiotic treatment strategy for K. pneumoniae infections           and will be explored in this program.
using human monoclonal antibodies. A set of in vitro
assays is used to predict the in vivo efficacy of potential          T4-211
leads at an early stage of drug discovery. There is an urgent                                         ug)
                                                                     Efficient eradication of (multidrug) resistant bacteria
medical need for new treatments for K. pneumoniae                                                              g
                                                                     This research project of TI Pharma is being conducted by a
infections due to the increased resistance to all commonly           consortium consisting of Leiden University Medical Center,
used antibiotics. The fight against antibiotic resistance            Prosensa, PROXY Laboratories BV and the the University of
and its development is listed as the number 1 problem to             Groningen.
be tackled in the Priority Medicines program. Infections             Efficient eradication of multidrug resistant bacteria
resulting from antibacterial resistance pose an enormous             will initially focus on two multidrug resistant strains of
threat to global public health.                                      bacteria: Pseudomonas aeruginosa (the primary cause of
                                                                     severe lung infection in cystic fibrosis) and Acetinobacter
                                                                     baumannii (an emerging problematic multidrug resistant
                                                                     pathogen). As only two completely new antibiotics have
                                                                     been approved by the FDA in recent decades, there is
                                                                     a clear general need for new innovative antimicrobial

                                                                                            Post-doc on
Keren Borensztajn
  T1-215, Amsterdam
    Medical Centre
                                                                                            of innate immune

 therapies. In this project, proprietary sensitizers will be        problems. Improved knowledge of drug dosage by means
 combined with existing cheap and abandoned antibiotics.            of precise measurements of drug levels will help to reduce
 Preliminary experiments indicate that these combinations           these problems. Currently, extracellular concentrations of
 overcome resistance and result in effective elimination of         antiretroviral drugs can be measured accurately, but these
 the previously multidrug resistant strains.                        correlate poorly with the intracellular concentrations due
                                                                    to bioprocesses such as active drug transport and metabol-
 T4-212                                                             ism. The understanding of the intracellular pharmacology
 A multidisciplinary approach to monitor and select                 of antiretroviral drugs is largely hampered by the lack of
 effective therapy in HIV infection                                 proper analytical tools. In particular, more sensitive tools
 This TI Pharma research project is being conducted                 for monitoring intracellular drug metabolism and pharma-
 by a consortium consisting of the Erasmus MC,                      cokinetics (DMPK) of treatment regimens as a whole are
 GlaxoSmithKline, TNO and the Radboud University                    being investigated and will be exploited.
 Nijmegen Medical Centre.
 Current treatment during HIV infection consists of com-
 binations of antiviral drugs (HAART) directed against
 virus-specific enzymes, notably reverse transcriptase
 (RT) and protease. Despite major successes in reducing
 morbidity and mortality, toxic side effects and the devel-
 opment of viral resistance remain serious HAART-related

Post-doc on Development
of an attenuated parasite
vaccine for malaria

                                                                                  Shahid Kahn
                                                                              T4-102, Leiden University
                                                                                   Medical Center

T4-213                                                                 MRSA, with the ultimate aim of providing new strategies
Protective human antibodies against multidrug                          to combat life-threatening staphylococcal infections.
resistant Staphylococcus aureus
This research project of TI Pharma is being conducted by               T4-214
a consortium consisting of Biomade Technology, Erasmus                 Development and application of novel strategies to
MC (University Medical Center Rotterdam), IQ Corporation               induce and monitor humoral and cellular immunity to
and the University Medical Center Groningen.                           protect hosts from infection by respiratory viruses
The main goal of this project is to develop human                      This research project of TI Pharma is being conducted by a
antibodies against multidrug resistant Staphylococcus                  consortium consisting of Erasmus MC (University Medical
aureus bacteria. Staphylococcus aureus is an opportunistic,            Center Rotterdam), Leiden University, the Netherlands
but dangerous, community and hospital-acquired pathogen                Vaccine Institute, Nobilon International BV, OctoPlus NV,
that employs a great variety of cell wall-associated and               Solvay Pharmaceuticals, the University Medical Center
secreted virulence factors to subvert its human host. This             Groningen, University Medical Center Rotterdam, Utrecht
gram-positive bacterium represents an increasing human                 University, ViroClinics BV and Virosome Biologicals BV.
health threat, especially for frail individuals, because of its        The aim of the project is to develop novel strategies to
amazing capacity to develop resistance to antibiotics. The             induce and monitor the humoral and cellular immunity
objective of this proposal is to develop protective human              that protects the host from respiratory virus infections.
antibodies for antimicrobial therapy against multidrug                 Respiratory viruses are the cause of a large burden of
resistant and highly virulent S. aureus strains, including             disease in humans and although effective vaccines exist

to protect against seasonal influenza, no vaccines are             medical need, such as addictive behaviors and cognitive
currently available for other important human respiratory          disorders. The combination of technologies, ranging from
viral diseases such as avian influenza, pandemic influenza         in vitro approaches to behavioral models matched between
and respiratory syncytial virus (RSV) infection.                   animals and humans, might lead to an integrated systems
Nanoscience as a tool for improving bioavailability                T5-108
and blood-brain barrier penetration of CNS drugs                   Validation of the use of fMRI as an objective measure
This research project of TI Pharma is being conducted by           in clinical pain in patients with and without psychiatric
a consortium consisting of the Leiden/Amsterdam Center             disorders
for Drug Research, the Radboud University Nijmegen,                This TI Pharma research project is being conducted by
the Radboud University Nijmegen Medical Centre,                    a consortium consisting of Organon (part of Schering-
Solvay Pharmaceuticals, the University Medical Center              Plough), PRA International and the University Medical
Groningen, the University of Groningen and Utrecht                 Center Groningen.
University.                                                        The project aims to validate the use of innovative non-
In this project novel nanosize formulation strategies will         invasive technology in early clinical trials in order to
be developed for improving oral availability and increasing        facilitate the development of novel analgesic medicines.
brain penetration of new CNS-active drugs based upon               To date, subjective measures are mainly available for use
a multi-disciplinary approach, combining distinct                  as early predictors of success or failure of novel analgesic
disciplines such as pharmaceutical technology, chemistry,          drugs. This project aims to identify and validate objective
cell biology, ADME, pharmacology, and diagnostics                  measures for use in early clinical trials. In addition to
(PET-imaging) in one research team. The objective of               fMRI imaging parameters for pain, parameters related to
this project is to determine the influence and interplay           personality traits and psychiatric co-morbidities (anxiety
of absorption, transporters, metabolizing enzymes and              and depression) will also be identified in order to discern
targeting on drug deposition, translate from in vitro to in        these phenomena from the actual pain sensation. Global
vivo and from animals to humans and hence accurately               objectives of the project are the development of innovative
define the optimal approach/ process for development               fMRI methodology and expertise for use in future Phase
of new drugs with higher bioavailability and controlled            IIa pain studies and gaining a better understanding of the
targeting into the brain in CNS diseases.                          neuronal networks involved in pain and related psychiatric
                                                                   processes, which are valuable for the identification of new
T5-107                                                             drug targets.
The neurophysiological role of the endocannabinoid
system in support of smoking cessation, fighting                   T5-203
addiction and treating cognitive decline                           A translational pharmacogenomics approach to
This research project of TI Pharma is being conducted              improve drug development strategies for psychiatric
by a consortium consisting of the Academic Medical                 disorders
Center (AMC) Amsterdam, Centre for Human Drug                      This research project of TI Pharma is being conducted by
Research, Organon (part of Schering-Plough), Solvay                a consortium consisting of Organon (part of Schering-
Pharmaceuticals, the University Medical Center Utrecht,            Plough), University Medical Center Utrecht, VU University
the University of Amsterdam, the University of Groningen           Amsterdam and VU University Medical Center.
and VU University Medical Center.                                  This project aims to improve the efficacy of antidepressants
This project addresses the role of the brain endocanna-            and shorten the costly drug development trajectory. It
binoid system in the regulation of brain functions                 focuses on the preclinical prediction of drug efficacy,
implicated in psychopathological syndromes with high               specificity and the long-term effects of pharmacotherapy.

     Moreover, it involves the identification and validation of             of Parkinson’s disease and Alzheimer’s disease. These are
     biomarkers to allow for classification of patient types and            essential steps in the strategy towards a rational design
     response to treatments (across a spectrum of psychiatric               of new drugs that induce neural repair and/or prevent
     disorders, i.e. anxiety, depression and schizophrenia).                nervous degeneration. All findings will be verified directly
                                                                            in post-mortem human brain material of Parkinson
     T5-207                                                                 and Alzheimer patients and in a large collection of CSF
     Parkinson’s disease and Alzheimer’s disease: from                      from the Netherlands Brain Bank and the VU University
     disordered human brain targets to novel therapeutics                   Medical Center.
     This TI Pharma research project is conducted by a
     consortium consisting of DNage BV, Erasmus MC                          T5-209
     (University Medical Center Rotterdam), Leiden                          Novel susceptibility pathways and drug targets
     University Medical Center, the Netherlands Institute for               for psychosis
     Neuroscience, Solvay Pharmaceuticals, the University                   This TI Pharma research project is being conducted by a
     Medical Center Utrecht, Utrecht University, VU University              consortium consisting of the Leiden/Amsterdam Center
     Amsterdam and VU University Medical Center.                            for Drug Research, Lundbeck, and Radboud University
     Parkinson and Alzheimer are neurodegenerative diseases                 Nijmegen
     with a considerable socio-economic burden. The immediate               The primary objective of this project is the identification
     objectives of this project are identification and validation of        of novel targets for drugs attenuating the susceptibility
     potential drug targets, provision of novel cell and animal             for psychosis and thus enhancing the ‘resilience’ of brain
     models as well as clinically validated biomarkers directly             and body. The focus of the research is on genetically
     relevant for development of early diagnosis and treatment              programmed abnormalities in brain network wiring that

    Joanna Korecka
 T5-207, Netherlands Institute                                                                  PhD student
for Neurosciences, Amsterdam
                                                                                                on Parkinson’s
                                                                                                and Alzheimer’s
                                                                                                diseases                :

are fundamental for the development of psychosis, and                The Dutch healthcare landscape with its highly-structured
provide the unique possibility of exploitation of expertise          general practitioner information systems, national hospital
and profile in psychiatric (neurodevelopmental) disorders            morbidity and pharmacy registrations, and the health
and stress biology. Psychosis is a challenging scientific            statistics database, currently allows for ongoing access
problem that obviously has clinical significance in for              to longitudinal data about clinical and laboratory tests,
example severe depression and schizophrenia, and draws               medical drug prescriptions, primary and secondary care
heavily on society. An improved understanding of the                 diagnosis and disease outcomes for Dutch citizens. The
causal factors precipitating this disorder will therefore            Mondriaan Project aims to provide a grid to integrate
serve the common good of our society, benefiting not only            and enrich existing and new health data platforms in
the patients themselves (development of a good therapy),             order to fuel pharmaceutical research in the Netherlands
but also their family members.                                       and to enable the Netherlands to play an internationally
                                                                     competitive role in drug innovation.
Rapid in vivo CNS drug target validation and                         T6-202
therapeutic potential using RNA interference                         The Escher project: Science-driven drug regulation
This TI Pharma research project is being conducted by a              and innovative research throughout phased drug
consortium consisting of Academic Medical Center (AMC)               development
Amsterdam, Leiden University, Organon (part of Schering-             This TI Pharma research project is being conducted by a
Plough), Prosensa and the University Medical Center                  consortium consisting of Amgen, Erasmus MC (University
Utrecht.                                                             Medical Center Rotterdam), GlaxoSmithKline, Merck &
CNS disorders are complex, poorly understood and                     Co., Organon (part of Schering-Plough), the University
debilitating diseases. The unmet medical need for new                Medical Center Groningen, the University Medical Center
CNS drugs is extremely high. Genetic and functional                  Utrecht, the University of Groningen, Utrecht University
genomics studies have identified novel drug targets with             and WINAp.
considerable therapeutic potential that will be validated            This project encompasses a series of synergistic research
in this project. One of the major hurdles facing the                 activities that address three questions.
pharmaceutical industry is the time-consuming process                What kind of regulatory barriers preventing the launch of
of CNS drug target validation in vivo, which is needed to            medicinal products on the market can be identified, are
confirm clinical relevance. RNA-based technology (e.g.               there scientifically sound alternatives, and how can these
RNAi and exon skipping) is an alternative for the selective          contribute to science-based regulatory reform?
and rapid validation of novel targets in animals and it can          What are the foundations of current research designs for
also be used in a clinical setting. This project will shorten        testing the efficacy and safety of new drugs, are there
the time-consuming process of target validation by using             scientifically sound alternative models (in terms of design,
RNA-based technology in vivo.                                        statistical analysis and outcomes definition) and how
                                                                     can these contribute to efficiency in drug development?
T6-101                                                               What can we learn from the accumulated regulatory and
The Mondriaan project: The Dutch health care                         drug development data, is scientifically valid information
landscape as a population laboratory                                 management feasible, and how can these data contribute
This TI Pharma research project is being conducted by a              to an improved understanding of the interface between
consortium consisting of GlaxoSmithKline, University                 drug development, regulatory affairs and clinical use of
Medical Center Utrecht and Utrecht University.                       medicines?
The Netherlands has an outstanding international
reputation in the use of routine medical data for
pharmaco-epidemiologic and health economic research.

A scanning electron
microscope image of
HIV. The glycoprotein
complex on its surface
enables the virus to
attach to and fuse with
target cells to initiate the
infectious cycle.
  Chapter 2
& Training
A new generation of researchers
Apart from funding and promoting high-quality                    a database, a catalog of courses in life sciences in the
translational research by teaming up academia and                Netherlands. Although we have a great number of
industry, TI Pharma aims to create a new generation              excellent PhD training courses, the valorization aspect
of researchers by providing a high level Education &             of the courses leaves room for improvement”.
Training Program. This is based on the existing course           Consequently, TI Pharma is now running courses
system in the Dutch academic research schools. In this           in business and entrepreneurship for PhD students
existing program, gaps were identified in the courses            that contribute to a successful participation in and
that offer an integrated insight into the drug design and        contribution to pharmaceutical industrial activities,
development process.                                             as well as courses for postdocs in which the drug
Scientific director Daan Crommelin: “We have built               development process is simulated.

Jeroen Nijwening took the course         and concepts needed to write                 science and in particular that of my
Business & Entrepreneurial Skills.       business plans and investment                field, molecular carcinogenesis. So
This course is designed to provide       proposals. ”As a typical biologist           at first I felt a little sceptical about
participants with the basic tools        I am actually only interested in             attending a business course. Well,
                                                                                      I learned a lot. The course was not
                                                                                      only very versatile but also quite
                                                                                      intensive, since my knowledge
                           “I learned a lot”                                          about the different subjects was
                                                                                      quite poor. All the ins and outs of
                                                                                      biopharmaceutical business were
                                                                                      touched upon in several days. From
                                                                                      finance to intellectual property
                                                                                      and from pharmaco-economics
                                                                                      to examples of successfully
                                                                                      created biotech companies.
                                                                                      The ‘learning experience’ n only
                                                                                               ning             not
                                                                                      consisted of lectures, but also
                                                                                      the hands-on experience gained
                                                                                      when preparing case studies.
                                                                                      I would recommend the BES
                                                                                      course to other PhD students.”

                  Jeroen Nijwening
                                                                                      Jeroen Nijwening,
                  T3-105, The Netherlands
                      Cancer Institute                                                PhD student, NKI/AvL,
                                                                                      The Netherlands Cancer Institute
                                                                                      (project T3-105 Kinases in cancer)

Andrea Hawe followed the Drug           in an academic setting, and at the   which she experienced the whole
Development Simulation course.          same time being in contact with      drug development trajectory.
She comes from Munich, Germany,         industry. She particularly enjoys    “We were competing in teams
where she completed her PhD             the frequent and stimulating         and all participants had a role that
thesis in the field of pharmaceutical   exchange of information and          differed from their actual jobs
technology, focusing on protein         ideas between the researchers        and expertise. Experiencing the
formulation, which was an excellent     at different locations.              complete development process
preparation for the research            In the Drug Development              – from concept to market – in five
project she is working on for           Simulation course Andrea very        intensive days of training, made
TI Pharma. Andrea likes working         much liked the interactive way in    me see the process from a much
                                                                             wider perspective. We were forced
                                                                             to take decisions very fast but in
                                                                             a carefully considered manner,
                                                                             something I now experience to be
                                            Andrea Hawe                      very useful in my present research
                                        D6-202, Leiden/Amsterdam             project. At a seminar I recently
                                         Centre for Drug Research
                                                                             attended I also found out that I
                                                                             have gained a thorough knowledge
                                                                             of the development trajectory
                                                                             and this enables me to put new
                                                                             information into perspective.”
                                                                             The social side of the course also
                                                                             appealed to Andrea. Working
                                                                             in a team you get to know each
                                                                             other really well. “We had a lot
                                                                             of fun during the long, intensive
                                                                             days of training and at the end of
                                                                             the day in the bar discussing the
                                                                             developments within our team.”

                                                                             Andrea Hawe,
                                                                             Post-doctoral fellow, Leiden/
                                                                             Amsterdam Centre for
                                                                             Drug Research LACDR
                                                                             (project D6-202 Hot Medicines:
                                                                             breaking the cold chain
          “Very useful experience”                                           requirements for polypeptide
                                                                             based priority medicines)

Helicopter view
Leon Delbressine, of the Organon       ethical and regulatory aspects          the process and its intricacies
Global Learning Center (part of        are important in this complex           and the different roles of the key
Schering-Plough), is the founding      process. You need a helicopter          players are the ingredients of
father of the Drug Development         view in cross-functional thinking       a successful product launch.
Simulation course that TI Pharma       and in real life at least 15 years of   The course, developed within
offers all its post-docs.              development experience to be            Organon (part of Schering-
“During 5 intensive days, 18           able to act adequately and take         Plough), was successfully rolled
participants, divided over 3 teams,    the right decision at the right time.   out almost 10 years ago.
experience the complete drug           “Our aim is to help researchers,        I am proud that TI Pharma fellows
development process, from finding      who have just started their             are now able to participate.
a compound to the marketing of a       career, realize and understand the      It has been very rewarding
new drug.” In real life this process   complexity and the necessity to         for me to receive the positive
takes 10 to 15 years. Factors such     cooperate, synchronize and think        feedback from both researchers
as safety, efficacy, marketability,    ahead. Mutual understanding of
                                       a                                       and their employers.”

 “Human assets are the most important assets”

Leon Delbressine

Lymphoid cells
are derived from
stem cells of the
lymphoid lineage.
  Chapter 3
Impression of the Workshop
Neglected Diseases

     TI Pharma’s objectives include providing
     a strong impetus to the development
     of drugs that are important to the
     well being of society and addressing
     many of the illnesses of the Priority
     Medicines project of the World Health
     Organization. Neglected diseases are
     common, fatal or disabling, and no
     suitable therapy exists to treat patients
     suffering from these inflictions. They
     affect populations that are large but
     have little or no purchasing power. In
     recent years, Product Development
     Partnerships (PDP’s) have become
     the primary drivers at the international
     level of developing new medicines,
     vaccines and diagnostics.

     On January 17, 2007 over 70
     participants from industry and
     academic communities gathered in
     the Naturalis museum in Leiden to
     discuss different options for partnering.
     This meeting was chaired by Richard
     Laing (WHO Geneva and TI Pharma
     International Scientific Review
     Committee) and Daan Crommelin,
     scientific director of TI Pharma. Besides
     listening to lectures from distinguished
     experts in the field of neglected
     diseases, in the afternoon participants
     attended face-to-face meetings to
     exchange information and become
     acquainted with each other. Rob
     Ridley, director of the WHO Tropical
     Diseases Program closed this inspiring
     event, where many new contacts were
     established and new ideas seeded.

TI Pharma Workshop Tailor-Made
Drug Treatment for Children

     The use of unlicensed and off-label medicine
     for children is widespread and has become
     an increasing point of concern in recent
     years. Approximately 70 percent of the
     drugs prescribed to children are unlicensed
     or are used in an off-label manner, with
     percentages of up to 90 percent for
     newborns. Dosing of drugs for children
     is often empirical and/or extrapolated
     from adults despite profound differences
     in responses between children and
     adults and between children of different
     ages. Furthermore, many drugs are not
     currently available in formulations suitable
     for administration to children. Defining
     effective and safe dosing regimens for
     children requires detailed information
     about the pharmacokinetics (PK) and
     pharmacodynamics (PD), but properly
     designed studies to obtain such information
     are difficult to perform. However, there are
     promising developments. Thanks to growing
     insights in PK-PD relationship and the
     availability of new formulation technologies,
     it is now possible to improve the quality
     of medication in children. On October 19,
     2007, scientists from industry and academia
     gathered in Leiden to discuss and exchange
     ideas and to identify priorities for further
     research and development. Key aspects
     were the infrastructure for clinical trials in
     children, pediatric formulation issues, and
     the design of dosage forms specifically
     for children. The setting up of a European
     Research Network on Population PK-PD
     modeling in children and on Novel Drug
     Formulations for Children was brought a
     step closer on this day.

  Chapter 4
accounts 2007

     An alveolar macrophage
     in a lung alveolus with red
     blood cells in capillaries in
     the interalveolar septum.
     Magnification of x3840.

Directors’ report
In 2007 we made important progress. After 1 signed project agreement in 2006,
39 project agreements were signed in 2007, involving 21 academic partners
and 36 industrial partners. The projects are in line with the Strategic Research
Program, which covers 5 therapeutic areas based on WHO’s Priority Medicines
report and 6 enabling technologies relevant to research across the therapeutic
areas. Two more projects were signed in January 2008. Of the 42 signed projects,
36 were up and running at the end of 2007. These involve approximately 250
researchers and technical staff, which is 50% of the total expected staff. We made
substantial investments in research equipment in 2007; 35% of the budgeted
investments have been purchased. As most projects were up and running in the
fourth quarter of 2007, the period up until October 2007 is seen as the start-up
period. The positive result over 2007 amounts to     1,255,479 and has been added
to the reserve for future research. Future losses will be offset with this reserve.

The cash position on December 31, 2007 was       11,459,102. This is directly
available for the foundation. The solvability ratio is 0.05. For the duration of the
Strategic Research Program the costs are covered in the following proportion:
government 50%, industrial partners 25% and academic partners 25%.
The contributions to cover the costs up until 2007 amounted to        3,495,301
by industrial partners,   2,797,951 by academic partners and        6,319,443 of
subsidy from the Ministry of Health, Welfare and Sport (VWS). The received
advance payments amount to        2,042,606 from industrial partners and
  9,780,557 of subsidy from the Ministry of Health, Welfare and Sport (VWS).

Based on the current status of the portfolio, a small part of the budget has
yet to be committed. We will use the remaining budget to start up projects
at a later stage and to expand current projects which are successful, for
example to include first clinical validation studies. The education and training
program for researchers will be started at the beginning of 2008.

Since Top Institute Pharma is more than just a funding partner for each project we
will monitor the progress realized on the basis of milestones and team updates.

D.J.A. Crommelin
W.N.G.M. de Laat

1.    Foundation annual accounts 2007
1.1   Foundation balance sheet as at
      December 31st, 2007
      (Including proposed appropriation of the result)

      (   )                                     2007          2006
      A   t
      Intangible Fixed Assets                  47,876        76,627

      Tangible Fixed Assets
      Scientific equipment                  1,723,541       560,121
      Other tangible fixed assets             317,792
                                                 ,          397,202
                                            2 041 333
                                            2,041,333       957 323
      Financial Fixed Assets
      Capitalized start-up costs            4,233,983     2,876,925
      Long-term loan                             ,
                                                3,750          ,
                                            4 237 733
                                            4,237,733     2 885 675
      Current Assets
      Accounts receivable                     721,705       588,162
      Other receivables                     4,889,162        79,909
      Cash                                   ,   ,
                                           11,459,102      ,   ,
                                           17,069,969     6,241,125
      Total Assets                         23 396 911
                                           23,396,911    10 160 750


      Reserve for future research            ,   ,
                                            1,255,479            0
                                            1 255 479
                                            1,255,479            0

      Current Liabilities
      Advance payments received            11,823,163     8,562,500
      Trade creditors                       2,748,696       901,967
      Taxation and social security             21,094        14,708
      Other creditors and accruals          7,548,479       681,575
                                           22,141,432    10,160,750
      Total Liabilities                    23 396 911
                                           23,396,911    10 160 750

1.2   Foundation profit and loss account for the period
      as from January 1st, 2007 until December 31st, 2007

      (   )
      (eur)                                           2007         2006
      E    d it
      Direct research expenses                  -10,302,843           0
      Personnel expenses                         -1,292,536     -985,078
      Depreciation fixed assets                    -132,352      -26,830
      Depreciation start-up costs                  -282,266           0
      Accommodation expenses                        -82,073      -75,495
      Recruitment & communication expenses         -431,698      -87,073
      Education and training expenses               -89,505           0
      Start-up expenses, consultancy & advice      -311,801   -1,590,967
      General and administrative expenses              ,
                                                   -210,020         ,
      Total Expenses                             13 135 094
                                                -13,135,094    2 922 057

      Project Income
      Contribution industrial partners            3,495,301           0
      Contribution academic partners              2,797,951           0
      Subsidy Ministry of
      Health, Welfare and Sport (VWS)              , ,
                                                  6,319,443           0
                                                 12 612 695
                                                 12,612,695           0

      Financial Income                                 ,
                                                    138,553         ,

      Total Income                                ,   ,
                                                12,751,248         ,

      Gross Result                                -383.846    -2,876,925

      Capitalization start-up costs                , ,
                                                  1,639,325     ,   ,

      Net Result                                 1,255,479             -

2.    Notes to the foundation annual accounts
2.1   Summary of significant accounting principles

      General Accounting Principles
      The annual accounts have been based on generally
      accepted accounting principles in the Netherlands, which
      defer from the principles as stated in the terms of the
      government subsidy.

      TI Pharma initially received a subsidy commitment from
      the Dutch Ministry of Health, Welfare and Sport (VWS)
      for a period of four years (until December 2010, the
      initial course of the strategic program). If this subsidy
      is not consumed before the end of 2010, TI Pharma will
      receive the remainder in order to complete its Strategic
      Research Program.

      Unless otherwise stated, all assets and liabilities are
      stated at the amounts they were acquired or incurred.

      The Foundation was founded on July 11th, 2006.
      Prior to that date, activities started under an Escrow
      Agreement between the Dutch State, prof. dr. D.J.A.
      Crommelin, dr. V.J. Nickolson and mr. F.J. Oranje,
      notary, which is dated December 29th, 2005.

      Foundation’s objective
      The foundation’s objective is to secure a leading position
      in pharmaceutical research and in the training of
      researchers in areas which strengthen the competitive
      position of the Dutch pharmaceutical industry and
      research, by formulating and implementing a strategic
      research and training program, and by means of any
      other activity which is either connected with the above
      objective or promotes same in the widest sense.

Related parties
The following organizations are involved in TI Pharma projects:

Academic Partners                                                 Industrial Partners
University of Amsterdam
U i    it
       it f A t d                                                 Agamyxis
Academic Medical Center Amsterdam                                 Agendia
VU University Amsterdam                                           Amgen
VU University Medical Center                                      AstraZeneca
University of Groningen                                           BioDetection Systems
University Medical Center Groningen                               Biofocus DPI
Leiden University                                                 Biomade Technology Groningen
Leiden University Medical Center                                  Centocor
Maastricht University                                             Danone
University Hospital Maastricht (azM)                              Pharming / DNage B.V.
Radboud University Nijmegen                                       Eli Lilly
Radboud University Nijmegen Medical Center                        Galapagos
Utrecht University                                                GlaxoSmithKline
University Medical Center Utrecht                                 IQ Corporation
Centre for Human Drug Research (CHDR)                             ISA Pharmaceuticals
Erasmus MC                                                        Johnson & Johnson PRD
Hubrecht Institute                                                H. Lundbeck A/S
Netherlands Institute for Neuroscience (NIN)                      Merck & Co. Inc.
Netherlands Vaccine Institute                                     Nobilon International B.V.
Netherlands Organization for Applied                              NOTOX B.V.
Scientific Research (TNO)                                         Nycomed
The Netherlands Cancer Institute                                  Octoplus N.V.
                                                                  - part of Schering-Plough
                                                                  Pepscan Presto B.V.
                                                                  PRA International
                                                                  Prosensa B.V.
                                                                  PROXY Laboratories B.V.
                                                                  Sanaria Inc.
                                                                  Solvay Pharmaceuticals
                                                                  Virosome Biologicals B.V.
                                                                  Xendo Drug Development B.V.

From the total of 57 academic and industrial partners,                Category                             Assigned useful life
24 have signed a partner agreement with an annual                     Scientific equipment                Duration of research project
contribution of at least   250,000 per year.
                                                                      Other tangible fixed assets
Projects                                                              Office automation                    3 years
Before the 31st of December 2007 40 projects had been                 Office equipment and furniture       4 years
signed. The projects T1-214 (Immune modulation                        Office reconstruction                5 years
and tolerance induction, prevention and inhibition of
inflammatory diseases) and T6-202 (The Escher project)
were both signed on the 31st of January 2008.                         Financial fixed assets
                                                                      Financial fixed assets are stated at historical cost less
Translation of foreign currencies                                     accumulated depreciation. Depreciation is calculated using
Transactions in foreign currencies are translated into                the straight-line method based on the duration of the
the local currency at the exchange rate at the date of the            Strategic Research Program. The depreciation term is 4
transaction. At the balance sheet date, assets and liabilities        years starting October 2007.
denominated in foreign currencies are translated at the
year-end rates of exchange. Positions for which forward               Equity
contracts have been closed will be valued according to                The result over the year 2007 is    1,255,479 positive. This
the negotiated forward rate. The resulting net trans-                 result is caused by the fact that the annual investments
lation gains or losses are recognized in the profit and loss          in scientific research equipment are directly subsidized as
account.                                                              part of the Subsidy of the Ministry of VWS. In the profit
                                                                      and loss account only the annual depreciation is charged as
Intangible fixed assets                                               cost. The positive result is added to the “reserve for future
Intangible fixed assets are stated at historical cost less            research” as part of equity. Future losses will be offset with
accumulated depreciation. Depreciation is calculated                  this reserve.
using the straight-line method based on estimated useful
lives without taking into account residual values. The                Government subsidies and contributions from
depreciation term is 3 years.                                         TI Pharma partners
                                                                      Government subsidies and partner contributions are
Tangible fixed assets                                                 recognized as income in the financial year the expected
Tangible fixed assets are stated at historical cost less              project costs are realized. For the duration of the Strategic
accumulated depreciation. Depreciation is calculated using            Research Program the costs are covered in the following
the straight-line method based on estimated useful lives              proportion:
without taking into account residual values.
The depreciation terms can be specified as follows:                   Government                    50%
                                                                      Industrial partners           25%
                                                                      Academic partners             25%

2.2   Notes to the foundation balance sheet

      Intangible Fixed Assets
      The intangible fixed assets consist of the following:
      (eur)                              Book Value       (Dis) Investments         Depreciation            Book Value
                                    January 1st, 2007                   2007                 2007 December 31st 2007
      License fee
      Promise Suit                             76,627                       -               28,751                47,876
      Total Intangible
      Fixed Assets                            76,627                        -              28,751                47,876

      Tangible Fixed Assets
      The tangible fixed assets consist of the following:
      (eur)                              Book Value       (Dis) Investments        Depreciation             Book Value
                                    January 1st, 2007                   2007                2007     December 31st 2007
      Scientific equipment
      ACE dual                                73,800                    3,200              16,500                 60,500
      Nano HPLC Chipcube                      326,055                       -              65,211               260,844
      IVIS Lumina series                      114,807                       -              22,961                 91,846
      Ultimate 3000                                 -               150,000                30,000               120,000
      Nikon pfs microscope                          -               250,403                12,732                237,671
      LCMS it tof                                   -               233,737                39,691               194,046
      Biacore T100                                  -               261,000                32,625               228,375
      Eclipse 3 FFF                                 -               100,000                 9,615                 90,385
      Customized Lifespec-pS
      in T Geo                                      -               101,859                 9,794                 92,065
      Other                                    45,459               362,571                60,221               347,809
                                              560,121             1,462,770               299,350              1,723,541

      Other tangible fixed assets
      Computer equipment                       70,491                   3,979              26,693                 47,777
      Office reconstruction                   195,099                   4,201              40,460               158,840
      Office equipment and
      furniture                               131,612                16,011                36,448                111,175
                                              397,202                24,191               103,601                317,792
      Total Tangible
      Fixed Assets                           957,323              1,486,961               402,951             2,041,333

      Capitalized start-up costs
      As the Strategic Research Program mainly started in the           is calculated using the straight-line method. The
      4th quarter of 2007 all overhead costs until September            depreciation term is 4 years (duration of the Strategic
      2007 are considered to be start-up expenses, which are            Research Program) and started in October 2007.
      capitalized and will be depreciated. Depreciation

(eur)                              Book Value      (Dis) Investments                Depreciation            Book Value
                           January 1st, 2007                         2007                   2007     December 31st 2007
Start-up costs                       2,876,925                 1,639,324                 282,266                 4,233,983
Total start-up costs                 2,876,925                 1,639,324                 282,266                 4,233,983

Long-term loan
The long-term loan is the long-term portion of a non-interest bearing loan, which
will be fully paid back in September 2009.

Accounts receivable
Accounts receivable are stated at nominal value.

Other receivables
The other receivables consist of the following:
(eur)                                                  2007                 2006
Accounts receivable personnel                              -            13,858
Short term portion of non interest bearing loan        5,000                5,000
Interest                                              42,001            28,432
Receivable project contributions                   4,382,175                    -
Value added tax                                      331,603                    -
Other                                                128,383            32,619
                                                   4,889,162            79,909

The receivable project contributions split in 1,187,489 in cash and         3,194,685 in kind. Before May 16th
  863,849 in cash was received and      2,709,775 in kind was reconciled with received project invoices.

The cash balance consists of the bank accounts with Fortis Bank The Hague. Cash is directly available for
the foundation. Cash contains       591,797 which is the amount of the escrow account which is currently at
the account of notary Oranje.

Advance payments received
The advance payments received consist of the following:
(   )
(eur)                                                                                      2007         2006
Ad            t              t b id b th Mi i t         f H lth
Advance payments on government subsidy by the Ministry of Health,
Welfare and Sport (VWS)                                                               16,100,000    6,100,000
Income of Subsidy by the Ministry of Health, Welfare and Sport (VWS)                  -6,319,443            -
        payments on cash contributions by Industrial TI Pharma p
Advance p y                             y                      partners                ,   ,
                                                                                      2,042,606     ,   ,
                                                                                     11 823 163    8,562,500
                                                                                                   8 562 500

Taxation and social security
The taxation and social security consist of tax on wages and social security to be paid.

      Other creditors and accruals
      The other creditors and accruals consist of the following:
      (   )
      (eur)                                                2007          2006
      Value dd d t
      V l added tax                                            -     240 337
      Holiday allowances and holidays                     31,606        18,674
      Pension premiums                                         -        28,078
      Payable project costs                         7,471,667                -
      Other                                                ,
                                                         45,206         ,
                                                    7 548 479
                                                    7,548,479        681 575
                                                                     681 575
      Of the payable project costs    6,188,664 was paid or reconciled before May 16th.

2.3   Notes to the foundation profit and loss account

      Direct research expenses
      The direct research expenses consist of the following:
      (   )                                                2007          2006
      Research staff
      R      h t ff                                 9 382 050
                                                    9,382,050                -
      Research materials                                 621,443             -
      Depreciation investment research
       q p                                               299,350
                                                            ,                -
                                                  10 302 843                 -
      Of the total of 40 signed projects, 36 projects were up and running by the end of 2007.

      Personnel expenses
      The personnel expenses consist of the following:
      (   )
      (eur)                                                2007          2006
      Wages                                              506 255
                                                         506,255      178 835
      Social security costs                               49,118        20,179
      Pensions and Health Insurance                         ,
                                                          45,865          ,
                                                         601 238     212 872

      Other personnel expenses
      Temporary staff and employment agency              48,240         57,649
      Recruitment of office staff                         44,335        72,965
      Charged management fee                             561,396      578,179
      Other                                                 ,
                                                          37,327          ,
                                                         691,298     772,206
                                                    1 292 536
                                                    1,292,536        985 078
                                                                     985 078

      The management team, which consists of a Managing                 headcount year-end 2007 is 11 persons and the average
      Director and a Scientific Director, was contracted from           number of personnel employed on a full-time contract
      N.V. Organon and Utrecht University respectively. The             during the year was 9.7 fte. Research staff will be employed
      Managing Director started on January 1st, 2006. The               by TI Pharma partners and participants and will not be on
      Scientific Director started on December 1st, 2005. The            the payroll of TI Pharma.

Consultancy and advice
The costs for consultancy and advice consist of the following:
(   )
(eur)                                             2007             2006
St t
Start-up expenses                                  998
                                               146 998
                                               146,998          382
                                                              1 382 232
Legal advice                                    57,966            78,412
Audit fee                                       34,700            31,800
International Scientific Review Committee       17,393            30,737
Other consultancy and advice                      ,
                                                54,744              ,
                                              311 801
                                              311,801        1 590 967

General and administrative expenses
General and administrative expenses consist of the following:
(   )                                             2007             2006
M ti       d       i
Meetings and symposia expenses                  10 448
                                                10,448            18 180
Travel costs                                    31,692            33,636
IT and telecom costs                            88,202            50,268
Sponsoring                                      25,399                 -
Office expenses                                   ,
                                                54,279              ,
                                              210 020
                                              210,020            156 614

Project income
(   )
(eur)                                             2007             2006
Contribution industrial t
C t ib ti i d t i l partners                 3 495 301
                                             3,495,301                 -
Contribution academic partners               2,797,951                 -
Subsidy Ministry of
      ,              p (      )
Health, Welfare and Sport (VWS)               , ,
                                             6,319,443                 -
                                            12 612 695                 -
The contribution of companies is    2,793,786 in cash and     701,515 in kind. The contribution of knowledge
institutes is fully in kind. The Subsidy of the Ministry of Health, Welfare and Sport (VWS) is based on
TI Pharma share of the total costs per project until 2007 raised by a share to cover for overhead costs.

(   )
(eur)                                                                                     2007
Subsidy Ministry f Health, Welfare d Sport        d in   j t     t t ( 1 81)
S b id Mi i t of H lth W lf and S t (VWS) as agreed i project contracts (~1.81)        5 725 090
      y        y          ,
Subsidy Ministry of Health, Welfare and Sport (
                                         p (VWS) coverage overhead costs ( 0.19)
                                                )      g                 (~    )           ,
Subsidy Ministry f Health, Welfare and S
     d                lth
S b id Mi i t of H l h W lf  lf            t
                                     d Sport (VWS)                                    6 319 443

Financial income
The financial income consists of the following:
(   )
(eur)                                                7
                                                  2007                6
Interest income
I t    ti                                      142,487
                                               142 487            45,591
                                                                  45 591
Interest expense                                  , 4
                                                -3,934                 9
                                              138 553
                                              138,553                  2
                                                                  45 132
Commitments not shown on the balance sheet
From contracts concerning the operational lease of assets a commitment of       11,700 resulted at the end of the
year. This commitment will amount to        9,360 after 12 months. No commitment will remain after 48 months.
Commitments from office rent amount to        90,618 at the end of the year, which will expire within 12 months.

3.    Information supplementing the annual accounts
3.1   Allocation of the annual result
      Future results will be charged to the cumulative reserves of Foundation
      TI Pharma, which will be used to execute the objectives of the Foundation.

3.2   Events occurring after balance date
      There have been no events after December 31st 2007 which will affect
      the financial position of the Foundation at the reporting date.

3.3   Independent auditor’s report

      Report on the annual accounts                                      preparation and fair presentation of the annual accounts
      We have audited the accompanying annual accounts of the            in order to design audit procedures that are appropriate in
      Foundation Top Institute Pharma, Leiden, which comprise            the circumstances, but not for the purpose of expressing an
      the balance sheet as at December 31st, 2007, the profit            opinion on the effectiveness of the entity’s internal control.
      and loss account for the year then ended and the notes.            An audit also includes evaluating the appropriateness
                                                                         of accounting policies used and the reasonableness of
      Management’s responsibility                                        accounting estimates made by management, as well as
      Management of the Foundation is responsible for the                evaluating the overall presentation of the annual accounts.
      preparation and fair presentation of the annual accounts,
      both in accordance with accounting principles generally            We believe that the audit evidence we have obtained is
      accepted in the Netherlands. This responsibility includes:         sufficient and appropriate to provide a basis for our
      designing, implementing and maintaining internal control           audit opinion.
      relevant to the preparation and fair presentation of the
      annual accounts that are free from material misstatement,          Opinion
      whether due to fraud or error; selecting and applying              In our opinion, the annual accounts give a true and
      appropriate accounting policies; and making accounting             fair view of the financial position of the Foundation
      estimates that are reasonable in the circumstances.                Top Institute Pharma as at December 31st, 2007, and of
                                                                         its result for the year then ended in accordance with
      Auditor’s responsibility                                           Part 9 of Book 2 of the Netherlands Civil Code.
      Our responsibility is to express an opinion on the annual
      accounts based on our audit. We conducted our audit in             Report on other legal and regulatory requirements
      accordance with Dutch law. This law requires that we               Pursuant to the legal requirement under 2:393 sub 5
      comply with ethical requirements and plan and perform              part e of the Netherlands Civil Code, we report, to the
      the audit to obtain reasonable assurance whether the               extent of our competence, that the Directors’ report
      annual accounts are free from material misstatement.               is consistent with the annual accounts as required
                                                                         by 2:391 sub 4 of the Netherlands Civil Code.
      An audit involves performing procedures to obtain audit
      evidence about the amounts and disclosures in the annual           Rotterdam, May 22nd, 2008
      accounts. The procedures selected depend on the auditor’s
      judgment, including the assessment of the risks of material        for Ernst & Young Accountants
      misstatement of the annual accounts, whether due to
      fraud or error. In making those risk assessments, the              sgd W.R.L. Koolhof
      auditor considers internal control relevant to the entity’s


             Arteriole in the human
             cerebellum containing
             red blood cells at a
             magnification of x400.

Partners and related parties of TI Pharma
About Agamyxis                                       cancer. Agendia also offers its expertise to        About BioDetection Systems
Agamyxis is focused on the preclinical testing       pharma companies focusing on the develop-           BioDetection Systems BV (BDS) is an SME that
of drug candidates that inhibit Notch pathway        ment of highly effective personalized drugs in      develops, markets and applies novel effect-
activation/-secretase for the treatment of           the area of oncology. www.agendia.com               based detection methods to monitor clinical,
intestinal neoplastic disease and Barrett’s                                                              environmental and food-chain samples.
esophagus. Notch receptors are large trans-          About Amgen                                         The methods used are extremely sensitive
membrane proteins that regulate a number of          Amgen discovers, develops and delivers              and specific, but also integrative, being able to
cellular properties important in cancer. Once        innovative human therapeutics. A bio-               detect cocktails of chemicals rather than single
activated, Notch receptors are cleaved by            technology pioneer since 1980, Amgen was            compounds. BDS is highly interested in novel
the-secretase protease complex to release a          one of the first companies to realize the new       screening tools and approaches developed in
cytoplasmic domain fragment that translocates        science’s promise by bringing safe, effective       the program. Being the coordinating party of a
to the nucleus to induce expression of genes         medicines from lab, to manufacturing plant,         large initiative in the Netherlands that involves
involved in cell growth, differentiation, and cell   to patient. Amgen therapeutics have changed         metagenomics research (i.e., the Ecogenomics
survival. Our research has shown that in animal      the practice of medicine, helping millions of       Consortium of the Netherlands Genomics
models, pharmacological blocking of intestinal       people around the world in the fight against        Initiative), BDS is increasingly focusing on
Notch signaling by-secretase inhibitors results      cancer, kidney disease, rheumatoid arthritis,       developing screening methods that can be
in the conversion of proliferative adenoma           and other serious illnesses. With a deep and        used in metagenomics approaches to identify
cells into post-mitotic goblet cells, implying       broad pipeline of potential new medicines,          novel natural products.
that-secretase inhibitors could be used in           Amgen remains committed to advancing                The current project will be very important
the treatment of intestinal adenomas and             science to dramatically improve people´s lives.     to further develop BDS´ activities in this
adenocarcinomas. Many-secretase inhibitors of        To learn more about our pioneering science          area. BDS will actively pursue dissemination/
diverse chemical origins have been developed         and our vital medicines, visit www.amgen.nl.        valorization of (HTS) assays and screening
for the treatment of Alzheimer’s disease.                                                                activities developed in the project.
Agamyxis intends to analyze these compounds          About AstraZeneca                                   More information about BioDetection
as potential treatments for intestinal neoplasia     Health and quality of life are vital for            Systems BV can be found at
and Barrett’s esophagus. Agamyxis is located         everybody. Being ill curtails our freedom           www.biodetectionsystems.com.
in the Hubrecht Institute in Utrecht, the            and can even be life threatening. Thankfully
Netherlands, adjacent to the laboratories            much can be done nowadays to positively             About Biomade Technology Groningen
of Prof. Dr. J.C. Clevers, the Chief Scientific      influence health and the quality of life, and to    Biomade Technology is an independent
Officer of Agamyxis.                                 cure diseases. The innovative pharmaceutical        multidisciplinary research organization
Website: www.agamyxis.com.                           industry makes this possible, together with         founded in 2000 that converts scientific
                                                     physicians, pharmacists, scientists, health         knowledge into applications which
About Agendia                                        insurers, government agencies, patient              contribute to an improved quality of life.
Agendia, located in Amsterdam, the                   organizations and all other parties in the          In this process we have developed a set of
Netherlands, is a world leader in gene               healthcare sector. At AstraZeneca our daily         coherent proprietary technologies centered
expression analysis-based diagnostics,               mission is to make the biggest possible             on protein-based bio-nanotechnology. We are
with three products on the market. The               difference for patient health. All our activities   applying them to a variety of issues such as
company focuses on the development and               are aimed at deploying advanced technologies        vaccines, therapeutic peptides and proteins,
commercialization of diagnostic tests using          and scientific insights for the development of      artificial membrane systems and cell growth
tumour gene expression profiling. Agendia            new, even better and safer medicinal products.      matrices for tissue and organ engineering.
was the first company to commercialize such a        We focus on the following therapeutic               Investors have recognized the power and
prognostic test - MammaPrint® - that predicts        areas: cardiovascular, gastroenterology,            validity of our method, resulting in the recent
the risk of breast cancer recurrence. Its second     oncology, psychiatry, respiratory, anesthesia       launch of Mucosis B.V., a Biomade spin-
microarray product, CupPrint®, is a diagnostic       and infectious diseases. In the Netherlands,        out company currently focused on taking a
test to identify the origin of a metastasis in       our staff are involved in medical and clinical      mucosal vaccine into clinical trials. For further
a cancer type called “Cancer of Unknown              research, the marketing and selling of              information, visit www.biomade.nl.
Primary”. Agendia recently also presented            medicinal products, providing services to the
its new colon cancer prognosis profile,              healthcare sector and educating physicians          About Centocor
ColoPrint®, which is currently undergoing            and patients. Visit www.astrazeneca.nl for          Centocor is harnessing the power of world-
further validation. Agendia maintains close          general information about our organization,         leading research and biomanufacturing to
ties with several leading academic centers to        medical information and contact details.            deliver innovative biomedicines that transform
develop state-of-the-art diagnostic tests for                                                            patients’ lives. Centocor has already brought

innovation to the treatment of Crohn’s disease,      in Indianapolis (USA). In the Netherlands we                               perates fac
                                                                                                        employs 460 people and operates facilities in
rheumatoid arthritis, ankylosing spondylitis,        employ over 140 people who are working                                           eadquarters
                                                                                                        seven countries, with global headquarters in
psoriatic arthritis, ulcerative colitis, pediatric   in sales, marketing and clinical research.                                           n
                                                                                                        Mechelen, Belgium. More information about
Crohn’s disease and psoriasis. The world             Eli Lilly and Company now enters its 134th         Galapagos and BioFocus DPI can be found at
leader in monoclonal antibody production             year of delivering answers to some of the          www.glpg.com and www.biofocusdpi.com.
and technology, Centocor has brought critical        world’s toughest healthcare questions. We
biologic therapies to patients suffering from        are proud of our reputation of innovation and      About GlaxoSmithKline
debilitating immune disorders.                       our rich portfolio of best-in-class, first-in-     GlaxoSmithKline – one of the world’s leading
                                                     class pharmaceutical products. Investments         research-based pharmaceutical and healthcare
About Centre for Human                               up to 20% of the net sales ($3 billion a year)     companies – is committed to improving the
Drug Research (CHDR)                                 are invested in research and development.          quality of human life by enabling people to do
CHDR is a full service contract research             This research focuses on psychiatry (such as       more, feel better, and live longer. For company
organization (CRO). We provide a complete            depression, schizophrenia, attention-deficit       information, visit GlaxoSmithKline at
spectrum of clinical pharmacology services to        hyperactivity disorder), endocrinology (such       www.gsk.com.
the (bio)pharmaceutical industry. Our added          as diabetes and osteoporosis) and oncology.
value covers the validation and optimization of      We are committed to providing answers that         About Hubrecht Institute
clinical research methods and the development        matter - through medicines and information         The Hubrecht Institute is a research institute
of new biomarkers. This synergy of clinical,         - for some of the world’s most urgent medical      of the Royal Netherlands Academy of Arts and
research and consultancy services results in a       needs.                                             Sciences (KNAW, www.knaw.nl). It conducts
unique CRO that operates at a high scientific                                                           research in the field of developmental
level. For more information, please visit our        About Erasmus MC                                   biology and stem cells. Integrated with this
website: www.chdr.nl.                                Erasmus MC (University Medical Center              fundamental research, the institute carries out
                                                     Rotterdam) is among the top research               strategic biomedical and genomic research.
About DNage B.V.                                     institutes in the Netherlands. Research            The research program is unique as it focuses
DNage is a subsidiary of Pharming Group NV, a        activities range from fundamental biomedical       on the full developmental biology of animals,
biotech company focusing on the development          research, patient-related research and             from fertilization to the adult organism.
of innovative products for the treatment             epidemiology to public health, healthcare
of genetic disorders and ageing diseases.            policy and management. As the largest              About IQ Corporation
Pharming’s Market Authorization Application          university medical center in the Netherlands,      IQ Corporation is a life sciences company
for lead product Rhucin® for treatment of            with 1,800 students of medicine, 1,500 staff       based in the Netherlands. Its mission is to
acute attacks of hereditary angioedema is            members and more than 10,000 employees,            contribute to human healthcare through the
under review with the EMEA. The advanced             Erasmus MC provides advanced medical               development and worldwide commercialization
technologies of Pharming include innovative          care to 3 million people living in the south-      of products for diagnostic and therapeutic
platforms for the production of protein              western part of the Netherlands. For further       applications. The company’s therapeutics
therapeutics, technology and processes for the       information, visit: www.erasmusmc.nl.              division (IQ Therapeutics) is applying its
purification and formulation of these products,                                                         Cloning the Human Response™ technology
as well as technologies in the field of tissue       About BioFocus DPI                                 for its own pipeline and third parties’ to
repair via its collaboration with NovaThera and      BioFocus DPI is a division of Galapagos.           generate and develop fully human antibodies
DNA repair via DNage. Additional information         Galapagos (Euronext Brussels, GLPG; Euronext       from immunized or vaccinated donors for
is available on: www.pharming.com and                Amsterdam, GLPGA; London AiM: GLPG) is             the prevention and treatment of infectious
www.dnage.nl.                                        a drug discovery company with preclinical          diseases. Lead product is anti-LF, a fully human
                                                     programs in bone and joint diseases and bone       antibody directed against Anthrax’s lethal
About Eli Lilly                                      metastasis. Its division BioFocus DPI offers a     toxin. The company’s diagnostic products
Eli Lilly and Company is a leading, innovation-      full suite of target-to-drug discovery products    division (IQ Products) has developed a range of
driven corporation committed to developing           and services to pharmaceutical and biotech         products for flow cytometry and for perinatal
a growing portfolio of best-in-class and first-      companies, encompassing target discovery           and transplantation-related diagnosis, which
in-class pharmaceutical products that help           and validation, screening and drug discovery       are sold in more than 50 countries. For more
people live longer, healthier and more active        through to delivery of pre-clinical candidates.    information, please visit www.iqcorporation.nl.
lives. Worldwide we employ over 42,000               BioFocus DPI also provides adenoviral
employees and our products are marketed in           reagents for rapid identification and validation   About IQ Therapeutics
143 countries. Integrity, respect and excellence     of novel drug targets, compound libraries for      IQ Therapeutics BV is an antibody technology
have been Lilly’s core values in the company’s       drug screening as well as chemogenomics            company based in Groningen, The
history. Eli Lilly Nederland BV started over 30      and ADMET database products to select              Netherlands. Its mission is to contribute to
years ago, as an affiliate of Lilly’s headquarters   targets and compounds. Galapagos currently         human healthcare through the development

    worldwide commercialization
         wide    mercializ
and worldwid commercializatio of its Instant         About Leiden University                            partnerships with private-sector firms and
Immunity™ fully human monoclonal antibodies          The first university in the Netherlands.           other European research institutes.
for therapeutic applications. The company is         Founded on 8 February 1575. University
applying its Cloning the Human Response™             motto: Praesidium Libertatis, Bastion of           About Merck
technology for its own pipeline and third            Freedom; - Leiden is a Research University         Merck & Co. Inc. is a global research-driven
parties’ to generate and develop fully human         which chooses for talent, 12 Honours Classes.      pharmaceutical company dedicated to putting
antibodies from immunized or vaccinated              Pre-University College Leiden collaborates         patients first. Established in 1891, Merck
donors for the prevention and treatment of           with other leading universities in the League of   currently discovers, develops, manufactures
infectious diseases. For more information,           European Research Universities; - 51 bachelor’s    and markets vaccines and medicines to
please visit www.iqtherapeutics.nl.                  programs, 98 master’s programs; - 17,616           address unmet medical needs. The Company
                                                     students, 4,500 staff members; - Budget: 425       devotes extensive efforts to increase access
About ISA Pharmaceuticals                            million euro; - www.leidenuniv.nl.                 to medicines through far-reaching programs
ISA Pharmaceuticals B.V. is a biotechnology                                                             that not only donate Merck medicines but
company dedicated to fighting cancer and             About Leiden University Medical Center             help deliver them to the people who need
infectious diseases by providing novel ways          Leiden University Medical Center (LUMC) is         them. Merck also publishes unbiased health
to activate and employ the patient’s immune          strongly committed to the advancement of           information as a not-for-profit service. For
system. ISA Pharmaceuticals B.V. is developing       healthcare, through research and innovation.       more information, visit www.merck.com.
a pipeline of therapeutic vaccines based on its      In particular, the focus is on translational
proprietary long peptide technology platform         research, with the overall aim to accelerate       About the Netherlands Vaccine Institute
(SLP® Technology) in combination with                findings from the laboratory to clinical           The Netherlands Vaccine Institute, as one of
immune stimulating agents (adjuvants). Its lead      application, and to the market. LUMC has           the few institutes in the world, buys, produces
product is a therapeutic HPV vaccine which           a reputation as a pioneering institute, both       and develops vaccines under the authority of
is currently in clinical trials against vulvar and   nationally and internationally. For more           the government. The NVI protects the Dutch
cervical cancer. A number of other therapeutic       information, visit www.lumc.nl.                    population against infectious diseases by
vaccines are currently under development.                                                               supplying vaccines under normal as well as
                                                     About Lundbeck                                     extraordinary circumstances. To achieve this,
About Johnson & Johnson PRD                          H. Lundbeck A/S is an international                NVI has expert knowledge about all aspects of
Johnson & Johnson Pharmaceutical Research            pharmaceutical company engaged in the              the vaccine value chain, ranging from top class
& Development (J&JPRD) is one of the fastest-        research and development, production,              research & development and clinical trials to
growing global pharmaceutical research &             marketing and sale of drugs for the treatment      high standard pharmaceutical production and
development (R&D) companies and part of              of psychiatric and neurological disorders.         distribution.
the world’s most comprehensive and broadly           In 2007, the company’s revenue was DKK
based healthcare company, Johnson &                  11 billion (approximately EUR 1.5 billion or       About Nobilon
Johnson. With more than 3,500 employees,             USD 2.0 billion). The number of employees          Nobilon International BV, since 2007 part of
our R&D reach extends to more than 70                is approximately 5,300 globally. For further       Schering-Plough, was founded in 2003. It has
countries worldwide. Our primary facilities          information, please visit www.lundbeck.com.        production and R&D facilities in Boxmeer
include headquarters in Raritan, New Jersey                                                             and Oss, the Netherlands. The biotechnology
and facilities in La Jolla, California; Beerse,      About Maastricht University                        company is dedicated to the development,
Belgium; High Wycombe, United Kingdom;               Since its foundation in 1976, Maastricht           production and marketing of human vaccines
Schaffhausen, Switzerland; Spring House,             University (UM) has left its mark on higher        against infectious diseases, building on
Pennsylvania; Titusville, New Jersey; Toledo,        education in both the Netherlands and Europe       existing expertise within sister companies
Spain; and Val de Reuil, France. Our pledge is       as a whole. Building on its unique system of       Intervet and Organon. Nobilon focuses on
to bring to market high-value, cost-effective        Problem-Based Learning, the university has         respiratory and traveller’s diseases. One of
products that treat disease and significantly        evolved into a European research university        its core expertises is large-scale cell culture
improve the health and lifestyles of people          with a strong international outlook. Today,        production of viruses, including influenza.
worldwide. To this end, we are focused on            UM is one of Europe’s most international           Nobilon currently employs approximately 75
building a robust and innovative product             universities. UM aims to solve the problems        staff in production and R&D. www.nobilon.com
portfolio that comprises a strategic mix of          affecting tomorrow’s society, such as the
novel targets and fast followers, in-house and       effects of an ageing population, how to            About NOTOX B.V.
in-licensed compounds, and focus on areas of         promote a healthy lifestyle, and the way in        Our objective is to contribute to better human
traditional therapeutic strength and new and         which the media impact people’s behavior.          health, environmental safety and industrial
unmet medical need. www.jnj.com                      Teaching and research are closely intertwined,     progress by accelerating the development
                                                     and are multidisciplinary by nature. Many          process of our customer’s products. We
                                                     university departments have forged close           support our customers by providing quality-

driven contract research services. Our              About OctoPlus N.V.                                About Pfizer
added-value results from dedicated staff            OctoPlus N.V. (Euronext: OCTO) is a                Pfizer is the world’s largest research-based
working together with our customer’s project        biopharmaceutical company creating improved        biomedical and pharmaceutical company. Our
team and enhancing the processes by clear           pharmaceutical products that are based on          corporate headquarters are located in New
communication and scientific interpretation         OctoPlus’ drug delivery technologies and           York, with major research and development
of results. Our staff creates the company’s         have fewer side effects, improved patient          locations in the United States and England.
value and this is augmented by continuous           convenience and a better tolerability than         In 2006, Pfizer earned $48.4 billion in revenues
education, exciting career options and              existing products. The company currently           and invested $7.6 billion in research and
personal development. By these means the            has 5 products in preclinical and clinical         development. For more information visit
NOTOX team remains dedicated and its                development. In addition, OctoPlus is a            www.pfizer.com.
objectives clear. Crystal clear! For further        leading provider of drug formulation and
information, visit www.notox.nl.                    clinical scale manufacturing services, with        About PRA International
                                                    a focus on difficult-to-formulate active           PRA International is a full-service partner for
About Numico Research                               pharmaceutical ingredients in injectable           Early Development Studies. Since 1984, PRA
Numico Research is the innovative life sciences     formulations. For further information about        has conducted Phase I and IIa studies for
organization of Numico, now part of Danone.         OctoPlus, visit our website www.octoplus.nl.       almost every major pharmaceutical company
Numico focuses on specialized nutrition with                                                           in Europe, the United States and Japan, as
leading positions in Baby Food and Medical          About PamGene                                      well as for many renowned biotech companies.
Nutrition, and brings products to the market        PamGene’s novel multi-protein-protein              Our experience includes studies in healthy
under the brand names Nutricia, Milupa, Cow         interaction technology delivers innovative         volunteers as well as special populations or
& Gate, Mellin and Dumex, amongst others.           solutions for cancer biomarker discovery,          those with specific medical conditions such
Numico Research performs research into              drug development and disease diagnosis.            as diabetes mellitus, asthma, respiratory and
the complex interaction between nutritional         The company’s Kinase and Nuclear Hormone           cardiovascular diseases, and HIV. Since 2000,
ingredients, biological processes and disease       Receptor research products are sold                PRA has also conducted studies involving
mechanisms. New insights are translated into        worldwide to pharma, biotech and academic          vaccines for some of the world’s deadliest
nutritional concepts with health claims that are    customers. As well as pre-clinical applications,   viruses/bacteria, including yellow fever,
substantiated by demonstrating the efficacy         PamGene’s products are also used for               cholera, smallpox, influenza, West Nile virus
and safety in carefully designed clinical trials.   development of new drug activity-based             and Japanese encephalitis. Through our clinical
                                                    companion diagnostics, aimed at helping            and laboratory facilities in the Netherlands
About Nycomed                                       doctors make a more personalized choice of         and the United States, PRA can perform all
Nycomed is a pharmaceutical company that            cancer therapy. Such a scenario will benefit       aspects of Phase I and IIa trials, including:
provides medicines for hospitals, specialists       patients, pharmaceutical companies and health      - First-in-human studies; - Single and multiple
and general practitioners, as well as over-the-     insurance providers alike.                         dose safety and tolerability studies; - Proof of
counter medicines in selected markets. The                                                             concept studies ; - Interaction studies; - Mass
company is active within a range of therapeutic     About Pepscan Presto B.V.                          balance/ADME studies; - Single and multiple
areas, including cardiology, gastroenterology,      Pepscan Presto B.V. is a biotechnology             dose bioavailability studies; - Microdosing
osteoporosis, respiratory, pain and tissue          company located in Lelystad, the Netherlands.      studies; - Vaccine studies; - Studies with
management. New products are sourced both           The company focuses on peptide-based               biotechnology-derived therapeutic products.
from own research and from external partners.       analysis of protein function. Pepscan Prestop      We specialize in the more complex, first-
Operating throughout Europe and in fast-            offers a wide range of products and services       in-human studies and studies with delicate
growing markets such as Latin America, Russia/      based on its unique experience with a              pharmacokinetic or pharmacodynamic
CIS and the Asia-Pacific region, Nycomed has        combination of biology, proteomics and             objectives, using extensive methodologies
a presence in about 50 markets worldwide.           peptide chemistry. Among these are peptide         that we have developed. In addition, the
Privately owned, the combined group had             microarrays, protein interaction site mapping      Netherlands provides an advantageous
annual sales of approximately      3.4 billion      and protease substrate profiling services and      regulatory environment. For further
and an EBITDA of      933.4 million (2006           custom peptide. Currently, Pepscan Presto          information visit www.PRAinternational.com.
results). For more information visit www.           markets protein kinase analysis microarray
nycomed.com. Nycomed in the Netherlands is          technology (PepChip™ Kinase) and several           About Prosensa B.V.
located in Hoofddorp where it employs over          novel peptide microarray solutions in the          Prosensa is a Dutch biopharmaceutical
120 people.                                         area of activity-based protein profiling will be   company dedicated to the development of
                                                    released in the future. For further information,   RNA-based therapeutics targeting diseases
                                                    visit www.pepscan.nl.                              with unmet medical needs, in particular
                                                                                                       neuromuscular disorders. Prosensa’s drug
                                                                                                       development is based upon a unique and

proprietary technology platform involving         About Radboud University Nijmegen                  About Schering-Plough
‘exon skipping’, enabling correction of           Medical Centre                                     Schering-Plough acquired Organon in 2007.
mutated RNA. This ability to modulate genes       Radboud University Nijmegen Medical                Schering-Plough is an innovation-driven,
selectively through RNA-based therapeutics        Centre (www.umcn.nl) is a leading academic         science-centered global healthcare company.
could provide a new way to treat a wide           center with expertise in medical science and       Through its own biopharmaceutical research
range of human diseases. The company              healthcare. Expertise plays an essential part      and collaborations with partners, Schering-
has a leadership position in fundamental          in our organization and connects research,         Plough creates therapies that help save and
patents, technology, and know-how relating        education and patient care. Our more than          improve lives around the world. The company
to RNA-based approaches and exon skipping.        8,500 staff and 3,000 students are committed       applies its research-and-development platform
Prosensa’s lead compounds for DMD are             and ambitious, helping to shape the future of      to human prescription and consumer products
currently in clinical phase I/II development      healthcare and medical science. Driven             as well as to animal health products. Schering-
and the company has received orphan drug          by knowledge, empowered by people.                 Plough’s vision is to “Earn Trust, Every Day”
designation both in Europe and the US. For                                                           with the doctors, patients, customers and
more information on Prosensa, please visit        About Royal Netherlands Association for            other stakeholders served by its colleagues
www.prosensa.nl.                                  the Advancement of Pharmacy (KNMP)                 around the world. The company is based in
                                                  Its scientific institute WINAp participated        Kenilworth, N.J., and its website is
About PROXY Laboratories B.V.                     in the TI Pharma research program. KNMP            www.schering-plough.com.
PROXY Laboratories is an independent Quality      (Koninklijke Nederlandse Maatschappij ter
Control laboratory, holding GMP, GLP and          bevordering der Pharmacie) is the professional     About Solvay Pharmaceuticals
GDP licenses, offering QC testing services to     association and the sector organization of         Solvay Pharmaceuticals is a research-driven
the international life sciences industry. Our     Dutch pharmacists. Founded in 1842, the            group of companies that constitute the global
services, whether routine or tailor-made, cover   KNMP has over 4,800 members. The KNMP              pharmaceutical business of the
the whole range of physical, (bio)chemical and    aims to achieve an optimal provision of drugs      Solvay Group. The company seeks to fulfill
microbiological QC testing: from compendial       and encourages the scientific practice of          carefully selected unmet medical needs
testing of pharmaceutical raw materials,          pharmacy. The KNMP promotes the profession         in the therapeutic areas of neuroscience,
excipients and utilities to testing of finished   and the social interests of its members in         cardio-metabolic diseases, influenza vaccines,
drug products, including batch certification      particular, and those of pharmacists in general.   gastroenterology, and men’s and women’s
by our Qualified Person. In addition, PROXY       KNMP website: www.knmp.nl.                         health. Its 2007 sales were   2.6 billion
carries out ICH-compliant stability studies and                                                      and it employs more than 9,000 people
several types of validation studies. Examples     About Sanaria Inc.                                 worldwide. For more information, visit
of the latter are: validation of products,        Sanaria Inc. was founded in 2003. The              www.solvaypharmaceuticals.com. Solvay
processes, (analytical) methods, and cleaning     company’s mission is to develop and                Pharmaceuticals is active in the Netherlands
procedures. PROXY’s premises are located          commercialize a vaccine protective against         and employs about 1,300 people.
in the Bio Science Park in Leiden where its       malaria caused by the pathogen Plasmodium
modern state-of-the-art laboratories and          falciparum. This parasite is responsible for       About the Academic Medical Center (AMC)
GXP infrastructure enable PROXY to develop        more than 95% of the worldwide burden of           Amsterdam
numerous analytical methods using modern LC-      malaria-associated severe illness and death,       The University Medical Centers (UMCs) of
MS and GC-MS instruments. These methods           and is the malaria parasite exhibiting the         the Netherlands combine university patient
are related to impurity profiling of small        most significant levels of drug-resistance.        care with medical, biomedical and healthcare
molecule drug products to the determination       Sanaria’s vaccine is based on an approach to       research and the education and training
of process-related impurities in formulation      immunization that has already proven highly        of doctors, medical researchers and other
buffers of biotechnological products.             protective in humans. The company therefore        healthcare workers. The Academic Medical
Moreover, its microbiology laboratory including   exploits a technology platform that starts         Center (AMC) in Amsterdam is one of the eight
class B clean room facilities enables PROXY to    from an immunogen already known to be              organizations resulting from the merger of the
analyze sterile finished products and fill and    effective. Sanaria’s corporate headquarters,       Netherlands’ university hospitals and medical
finish clinical trial material.                   administrative, research, development, and         faculties. With some 60,000 employees working
                                                  manufacturing operations are located in            to advance medical knowledge and improve
                                                  Rockville, Maryland. The company’s website is      patient care, the UMCs are the largest care and
                                                  www.sanaria.com.                                   knowledge institutions in the Netherlands.

About the Netherlands Cancer Institute               patient-orientated clinical and non-clinical         About the University of Groningen
Improving cancer treatment depends heavily           research. The interaction between these              The University of Groningen enjoys an
on a better scientific understanding of the          groups stimulates the development of                 international reputation as a leading research
function and development of normal cells and         new clinical and research opportunities.             university. The university is utilizing its
tumor cells. Through fundamental and clinical        Patients go to the UMCG for basic care as            academic heritage to generate innovation,
research we hope to contribute to better             well as highly specialist top clinical and top       with the help of cutting-edge facilities. In a
cancer treatment. Discoveries made in the            reference care, such as organ transplants,           work environment that rewards quality and
laboratory are rapidly introduced into the clinic    complex neurosurgery, neonatology, clinical          achievement, the university offers balanced
through our translational research program           genetics, In Vitro Fertilization (IVF), pediatric    study and research paths that vary in intensity
that is driven by close collaboration between        oncology, renal dialysis and traumatology. All       to encourage everyone to draw on their
our scientists and clinicians. The Netherlands       medical specialties are represented, as well as      individual talents. For further information,
Cancer Institute - Antoni van Leeuwenhoek            education programs for all medical disciplines.      visit: www.rug.nl.
Hospital (NKI-AVL) aims to be a national             The eight Dutch university medical centers, of
and international center of excellence in            which the UMCG is one, have been appointed           About TNO: Netherlands Organisation
cancer research. For futher information,             to render top reference care. This means they        of Applied Scientific Research
visit www.nki.nl.                                    specialize in disorders which are rare, hard to      TNO is a prominent, independent
                                                     diagnose and difficult to treat. However, not        knowledge company whose expertise
About the Netherlands Institute for                  every disease can be cured. That is why the          and research contributes significantly to
Neuroscience (NIN)                                   UMCG also devotes much attention to chronic          the competitiveness of businesses and
The Netherlands Institute for Neuroscience           diseases, pain relief, and palliative care.          organizations, to the economy and to the
(NIN) carries out fundamental neuroscience                                                                quality of life as a whole. Versatility and
research with special emphasis on the                About the University Medical                         capacity to integrate this knowledge makes
brain and the visual system. The research            Center Utrecht                                       TNO unique. TNO employs some 4,300
is multidisciplinary and comprises various           The University Medical Center Utrecht was            professionals. It has five core areas: TNO
levels of biological complexity: - genetic           founded in 1999, as the result of the merger         Quality of Life, TNO Defense, Security and
and molecular approaches; - cellular                 of the University Hospital, the Wilhelmina           Safety, TNO Science and Industry, TNO
approaches and network function;                     Children’s Hospital and the Medical Faculty          Built Environment and Geosciences, TNO
- system approaches. The research is                 of Utrecht University. With a tradition that         Information and Communication Technology.
aimed at fundamental mechanisms, the                 stretches back for more than 180 years, it has       For further information, visit www.tno.nl.
development of normal functioning, the               an outstanding reputation in research, patient
cause of disorders, and the development              care, and education and training. UMC Utrecht        About University Hospital Maastricht (azM)
of diagnostic and therapeutic strategies.            employs a total of 9,238 people, disposes            The main tasks of the University Hospital
                                                     of 1,042 beds, has 350,000 outpatient visits         Maastricht are patient care, education and
About the Radboud University Nijmegen                and 26,244 admissions a year. For further            research, all of which are closely interrelated.
The Radboud University Nijmegen enjoys an            information, visit: www.umcutrecht.nl/               In addition to standard patient care, top
international reputation as a leading research       overumcutrecht/missie_en_strategie.                  referral and advanced clinical care play an
university. Radboud University’s research                                                                 important role at the University Hospital
contributes explicitly and conscientiously           About the University of Amsterdam                    Maastricht. Advanced clinical and top referral
to expanding the limits of knowledge in the          / The Swammerdam Institute                           care require fine-tuning and close cooperation
interests of society as a whole. Not only do         for Life Sciences (SILS)                             with the fundamental research and clinical
research results contribute to international         The University of Amsterdam has bundled its          research at University Hospital Maastricht.
scientific debate and the increase of                life sciences research in a special institute: the   Key research areas are cardiovascular
knowledge, they are also important for               Swammerdam Institute for Life Sciences (SILS).       diseases, oncology, chronic diseases and
national and regional development. For               This institute’s mission is: ‘Understanding          mental healthcare and neurosciences.
further information, visit www.ru.nl/english.        the Fundamentals of Life at the Cellular,            The University Hospital Maastricht is
                                                     Molecular and Systems Level for Food and             located in the center of the Euregion
About the University Medical                         Health’. SILS focuses its research on four           Meuse-Rhine. Intensifying collaboration
Center Groningen (UMCG)                              themes: ‘The Living Cell’, ‘Plants and Health’,      in the Euregion is one of the main goals
Good healthcare is dependent on medical-             ‘Inside and Beyond the Brain’ and ‘Life Science      of the University Hospital Maastricht.
scientific research of a qualitatively high level.   Technologies’. For more information, please          The University Hospital Maastricht (www.
Along with patient care and education, this          visit: www.science.uva.nl/sils.                      azm.nl and www.summum.mumc.nl) has 715
type of research is one of the three core tasks                                                           hospital beds, over 4,700 employees and 4,000
of the UMCG. Our research is characterized                                                                students. It is part of the ‘Dutch Federation
by its combination of fundamental and                                                                     of University Medical Centers’, the NFU

(www.nfu.nl). The NFU is a cooperative             help the transition of academic research           • movement (MOVE is an inter-faculty
venture involving the eight university             from bench to bedside. The company                 joint venture between VU University
medical centers (UMCs) in the Netherlands,         continues to collaborate with Erasmus MC           Medical Center, the Faculty of Human
with the primary aim of promoting                  and is a member of ViroVentures, enabling          Movement Sciences and the Academic
the UMCs’ common interests.                        the latest technologies to be applied in the       Center for Dentistry Amsterdam).
                                                   fight against virus infections. The company        VU University Medical Center
About Utrecht University                           is based in Rotterdam, the Netherlands             holds a top 3 position in the Dutch
Utrecht University is one of Europe’s              and its website is www.viroclinics.com.            scientific research rankings.
leading research universities recognized
internationally for its high-quality approach      About Virosome Biologicals B.V.                    About WINAp
to both research and teaching. Founded             Virosome Biologicals B.V. is a wholly owned        WINAp (Wetenschappelijk Instituut
in 1636, Utrecht University has always             subsidiary of Norwood Immunology Limited           Nederlandse Apothekers) is part of KNMP.
focused strongly on research. Thanks to its        (NIM), having been acquired in November            WINAp supports pharmacists to fulfill
solid basis in discipline-based scholarship,       2006. NIM is a group focused on technologies       their mission: to help people to get the
it is at the forefront of developments in          and therapies to activate and manipulate           best possible benefits from the use of
interdisciplinary knowledge in fields ranging      the immune system, through two platforms:          medicines. Important issues are patient
from biochemistry and biophysics to human          use of temporary sex steroid suppression to        safety and the prevention of medication
rights and cultural studies. Utrecht University    effect rejuvenation of the thymus and bone         errors, correct dispensing and administration
holds the 42nd position in the Shanghai            marrow, with resulting enhancement of T            of medicines of guaranteed quality,
rankings of the world’s top universities. With     cell function and immune responsiveness;           and the support of patients to use their
this position Utrecht is ranked number one         and the development of adjuvanted                  medicines towards optimal clinical and
in the Netherlands and seventh in Europe.          virosomes for vaccines and as a delivery           humanistic outcomes. In these areas, WINAp
For further information, visit: www.uu.nl.         mechanism for SiRNA. NIM is quoted on              develops professional standards based on
                                                   the London AIM Exchange (AIM: NIM).                scientific evidence, and instruments for
About Vaxinostics                                                                                     pharmacists to meet these standards.
As a university-related company Vaxinostics is     About VU University Amsterdam
specialized in clinical development in the field   VU University Amsterdam brings with its            About Xendo Drug Development B.V.
of vaccines, immune modulation and infectious      excellent educational and research programs        Xendo is a fully independent and integrated
disease, and performs clinical-epidemiological     together talents in a wide range of disciplines    service provider for the life sciences,
studies in healthy volunteers of all ages. As      from many different countries. For VU              pharmaceutical and healthcare fields. As
a contract research organization Vaxinostics       University Amsterdam academic endeavor is          a multi-disciplinary organization, we are
works for industrial and governmental              more valuable when it makes a contribution         active in the areas of drug development,
organizations. As a small company, Vaxinostics     to our world. For further information, visit:      manufacturing of clinical trial material and
is flexible to comply with various types           www.vuamsterdam.com//home/index.cfm.               pharmaceutical operations. Our focus is on
of clinical studies while maintaining high                                                            the development and compliance of products,
standards of Good Clinical Practice. The main      About VU University Medical Center                 processes and facilities. Xendo’s underlying
office is located in Beurs-World Trade Center      The Scientific research and patient care of VU     ambition is to enhance the quality and safety
in Rotterdam. A second office in Nijmegen          University Medical Center are based on five        of medicine and to shorten their development
is in preparation, thus increasing capacity.       pivotal points, each one including patient care,   time to market. For general information
Please visit www.vaxinostics.com or www.           training, educational programs and research.       please visit our website: www.xendo.com.
vaccinonderzoek.nl for more information.           The lines of scientific research within each
                                                   of the pivotal points are brought together
About ViroClinics                                  in a multidisciplinary research institute.
ViroClinics is a contract research organization    The pivotal points and associated research
specializing in viruses that cause diseases of     institutes in VU University Medical Center are:
significant impact to public health. It provides   • cancer and immunology (Cancer Center
an array of services to the biopharmaceutical      Amsterdam - VU University Medical Center
industry including diagnostic services,            Institute for Cancer and Immunology)
contract research and general consultancy          • brain (Research Institute for Clinical
to accelerate the development of vaccines,         and Experimental Neurosciences)
antivirals and in vitro diagnostics. ViroClinics   • vital functions (Institute for
was founded in 2000 by the Department of           Cardiovascular Research)
Virology at the Erasmus University Medical         •extramural and transmural (Institute
Center in Rotterdam, the Netherlands, to           for Research in Extramural Medicine)

Members of the Executive Board:             (Utrecht University, the Netherlands).    the University of Southern California.
Representing large                          Professor Ruitenberg has supervised       Prof. Lesko has published more
industrial partners:                        more than 35 PhD students and he          than 135 papers in peer-reviewed
• Dr. A.W.M. Rijnders, Senior Vice          is author or co-author of more than       journals and is a popular national
 President Research, Organon,               500 (inter)national publications.         and international speaker.
 (currently part of Schering-Plough)       • Dr. Richard Laing                       • Prof. Rainer Metternich
• Prof. L. Turski, Head of Global Drug      Richard Laing was a professor of          Rainer Metternich is currently
 Discovery, Solvay Pharmaceuticals          International Public Health at Boston     Vice President Basic Research and
                                            University School of Public Health        Site Head, Merck & Co, West Point,
Representing small- and medium-             before joining WHO in mid-2003 as         Pennsylvania, USA. Metternich is an
sized industrial partners:                  a medical officer. At WHO, Laing is       honorary professor at the Technical
• Dr. Joost van Bree, Chief                 responsible for editing the Essential     University of Berlin, Germany. His
 Executive Officer, Pepscan                 Drugs Monitor and for coordinating        career to date includes positions
 (since November 2007)                      training and research related to          in pharmaceutical research in both
• Dr. J.M. Holthuis, Founder                promoting rational use of drugs           academia and industry. Metternich
 and Chief Executive Officer,               in the community. Most recently he        has published numerous scientific
 OctoPlus (until November 2007)             was one of the authors of the Priority    articles and filed several patents.
• Dr. R. Lageveen, Chief Executive          Medicines for Europe and the World       • Prof. Alexander Florence
 Officer, IQ Corporation                    report.                                   Alexander Florence recently retired
                                           • Prof. Povl Krogsgard-Larsen              from the Deanship of The School
Representing academic partners              Povl Krogsgard-Larsen is professor        of Pharmacy, University of London,
• Prof. L.F.M.H. de Leij, Head              of Medicinal Chemistry at the             a position he held since 1989.
 of department of Medical                   Danish University of Pharmaceutical       Previously he was Professor of
 Biology and Dean, University               Sciences. Prior to his current            Pharmaceutics (1975-1988) at the
 Medical Center Groningen                   position at the Danish University,        University of Strathclyde in Glasgow.
• Prof. R. Leurs, professor of Medicinal    professor Krogsgard-Larsen held           He has published over 270 papers.
 Chemistry, VU University,                  various academic positions including     • Prof. Trevor Jones
 Amsterdam                                  rector at The Royal Danish School         Trevor Jones is a Director of Allergan
• Prof. F.G.M. Russel, professor            of Pharmacy. He presently chairs          Inc (USA) and Senior R&D Advisor
 of Pharmacology and Toxicology,            the board of the Drug Research            to Esteve SA (Spain) and Servier
 Radboud University Nijmegen                Academy. Professor Krogsgard has          (France). From 1987-1994, he was a
 Medical Center/NCMLS                       published several books and               main board director of The
                                            numerous articles and organized           Wellcome Foundation, where he
Members of the International                and co-organized various                  was responsible for R&D including
Scientific Review Committee                 international symposia.                   the development of AZT, Zovirax,
• Prof. Joost Ruitenberg (Chair)           • Prof. Lawrence Lesko                     Malarone and other medicines.
 Joost Ruitenberg is professor              Lawrence Lesko has been the               In 2005, he was the winner of the
 of International Public Health             Director of the Office of Clinical        SCRIP Life Time Achievement
 at the Institute of Innovation             Pharmacology in the Center for Drug       award for his contribution to the
 and Transdisciplinary Research             Evaluation and Research at the Food       pharmaceutical sciences and
 (VU University Amsterdam,                  and Drug Administration since 1995.       industry.
 the Netherlands), as well as               In addition to this, he has been
 emeritus professor of Immunology           appointed as an Adjunct Professor
 at the Faculty of Veterinary Medicine      at the University of Florida and at

TI Pharma Staff in June 2008
From left to right Hanneke Heeres, Hans Schuitmaker, Jorg Janssen, Daan Crommelin,
Willem de Laat, Lilian Loos, Désirée Elderhorst, Karin Huiberts, Martijn Holleman,
Hélène Engelkamp, Denis Groot, Myrthe Krook, Louise Lammers, Sander Hendriks

TI Pharma Management and Staff
Victor Nickolson                       Managing Director
(Willem de Laat as per January 2008)
Daan Crommelin                         Scientific Director
Jorg Janssen                           Strategy & Business Development
Louise Lammers-Johnson                 Program Manager
Hans Schuitmaker                       Program Manager
Wiegert Smallegange                    Controller
(Denis Groot as per 1-2-2008)
Karin Huiberts                         Human Resources Manager
Hanneke Heeres                         Communications Manager
Hélène Engelkamp                       Office Manager
(as per January 2008)
Martijn Holleman                                              rdinator
                                       Program Information Coordinator
Désirée Elderhorst                     Coordinator Education & Training
(as per March 2008),
Sander Hendriks                        Communications Assistant
(as per February 2008)
Myrthe Krook                           Assistant Controller
Lilian Loos                            Assistant Office Support


     Published by TI Pharma
     Text Media-Advice, TI Pharma
     Design Van Horen Zeggen, www.vanhorenzeggen.com
     Photographs Marc de Haan, Corbis, Frank Zwinkels
     Printing Station Drukwerk

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