Presentation by Wolf Ondracek of CHDR and Promasys for the Science meets Business café of 16 May 2013. This event was held in the BioPartner Accelerator building in Leiden.

1. Science meets Business in
Drug Development

2. CHDR: Unlocking the true potential…
• Established in 1987 as a not-for-profit foundation
• By Leiden University and LUMC
• Prof. Douwe Breimer & Prof. Adam Cohen
• Clinical research organization closely linked to top level universities
• Profits re-invested in biomarker and method development & education
• Contract Research for bio-pharmaceutical industry
• Focus on early phase clinical trials
• Data intensive, small number of subjects
• Proof of pharmacology
• Proof of concept
• Organization
• 160 employees (80 FTE)
• Dynamic & International environment
• Wolf Ondracek, Director Business Development

3. Market positioning: A unique dual focus

4. Research areas
Cardiovascular
System &
Metabolism
Respiratory
System&
Immuno-
inflammation
Central
Nervous
System
Oncology
Food &
Nutraceuticals

5. PK/PD
modeling
First-in-
humans
Research in
Children
Micro-dose
studies
CHDR, among others, offers
substantial experience with:
• First-in-human studies in
healthy volunteers &
patients
• Research in special
populations such as young
& elderly patients
• Research in patients with
hepatic and/or renal
impairment or patients
from different ethnicity
• Thorough QT-studies, and
bioequivalence experiments
Study Types

6. Innovative Tools for ‘Proof-of-
Pharmacological-Concept’ Studies
• Continuous CSF-Sampling
– CNS-drug concentrations
– τ /ß-profiles, etc
• NeuroCart
– multidimensional CNS-pharmacodynamics
– optimized for CNS-drug effects and PK/PD
– applicable in patients
• Neuroimaging
– resting state fMRI
– PET-imaging

7. Innovative Tools for CNS Studies: NeuroCart
• Cognitive and memory testing
• Electroencephalography
• Saccadic and smooth pursuit eye movement
• Adaptive tracking
• Finger tapping
• Body sway
• Visual analogue scales
• Psychometric questionnaires
• Autonomic function tests (pupillometry, heart rate
variability)
• Polysomnography
• Other CNS function tests like Symbol Digit
Substitution Test, Critical Flicker Fusion, Stroop
conflict task, etc

8. Innovative Tools for CNS Studies: NeuroCart
Features NeuroCart
-scope -neurocognitive functions included*, but also all other
drug-responsive domains (neurophysiological,
neuroendocrine, motor, subjective, etc)
-clinical relevance -functional validity for large number of individual
functions: postural stability, eye-hand coordination,
attention, subjective, etc
-interpretability -simple because each test mainly assess single brain
function
-frequent repeatability -up to 10 times/day or more
-learning/carry-over effects -limited/absent
-dose/concentration responsiveness -extensive PK/PD-relations possible
-experience -extensive across large number of different drugs,
accumulated within same CRO (CHDR)

9. Innovative Tools for CNS Studies: NeuroCart

10. • Electrical Stimulation
– Olofsen and Dahan, 2005
• Pneumatic Pressure
– Polianskis, 2001
• Cold Pressor
– Eckhardt et al. 1998 and Jones et al. 1988
• Thermal stimulation
– Medoc
• Hyperalgesia models
– UV-B
– capsaicin
– thermal grill
Innovative Tools for Pain Studies: PainCart

11. Research Collaboration agreements with:
• Leiden University Medical Center, Leiden
• Free University Medical Center, Amsterdam
• Alzheimer Research Center, Amsterdam
• Academic Medical Center, Amsterdam
• Erasmus Medical Center, Rotterdam
Collaborations: National Collaborations

12. • Collaboration agreements with:
• Seoul National University Hospital
• Kyungpook National University Hospital
• Peking Union Medical College
• Showa University Hospital Tokyo
• Melbourne
• Edinburgh
• University of Bucharest
• Data management system (Promasys)
• Used at >30 locations worldwide
• Including in Korea
• Seoul National University Hospital
• Yonsei University Hospital
• Samsung Medical Center
• ASAN Medical Center
• Kyungpook National University Hospital
• Inje University Pusan Paik Hospital
• Teaching Resource Center for Clinical Pharmacology
Collaborations: International Collaborations

13. Collaborations: Our Customers

14. Collaborations: Our Customers

15. Unlocking the true potential