1. Pivot Park Screening Centre
Your Partner in Screening & Automation
Dr. Saman Honarnejad
Team Leader Assay Development

3. Pivot Park Screening Centre (PPSC)
What
• PPSC is an independent Contract Research Organization
(CRO) specialized in early drug discovery services
Services
• Biochemical and cell-based assay development
• Medium to (ultra) high-throughput screening (uHTS)
• H2L biological profiling
3
PPSC 25 Oct 2018

4. Medication for a healthier society
• The pharma world is changing: adoption
of open innovation and externalization of
activities
• Starting points for new medicines are
identified at PPSC
• Pivot Park Screening Centre is the centre
of expertise for early drug discovery
PPSC 25 Oct 2018
4

5. Mission and Vision
Mission
With our partners we accelerate the discovery of new
medicines for a healthier society.
Vision
Our long-standing experience in early drug discovery and our
state-of-the-art (ultra) High Throughput Screening
infrastructure provides our partners with the best confirmed
leads. We are valued as a flexible, efficient, transparent and
innovative company.
PPSC 25 Oct 2018
5

6. Screening history in Oss (The Netherlands)
1995 2000 2005 2010 2015
Introduction MTS & HTS
Biochemical and cellular screening
ASPIRE: Integrated in-vitro screening platform
uHTS: capacity & miniaturisation
Closure of research @ Oss
New legal Entity 2012
1st HTS in January 2013
6
PPSC 25 Oct 2018

7. Dutch Life Sciences in Oss
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8. A unique science park for drug discovery in Oss, NL
Pivot Park
CMO’s
Other Services
Product
Development
CRO’s
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9. High Throughput Screening is our core business
PPSC in the drug discovery process
$20 billion
Target
Discovery
Hit
finding
Hit to
lead
Lead
series
Phase
I, II
Phase III &
registration
Sales €
Compound
Value
Years 3 5 7 11 13
$50M
$500M
$2 billion
Pre-clinical
development
$100M
>159
PPSC 25 Oct 2018
9

10. High Throughput Screening is our core business
PPSC in the drug discovery process
$20 billion
Target
Discovery
Hit
finding
Hit to
lead
Lead
series
Phase
I, II
Phase III &
registration
Sales €
Compound
Value
Years 3 5 7 11 13
$50M
$500M
$2 billion
Pre-clinical
development
$100M
>159
PPSC 25 Oct 2018
9

11. General capabilities
• Assay development
• Cell culturing
• Sample handling
• Screening
• Biochemical and cellular assays
• single point/dose responses
• Automation of in-vitro experiments
• lots of different dispensing equipment
• Optimization of automation protocols
• 96, 384, 1536 well
• Automated data processing
• Assay panels
• Kinase/GPCRs/proteases/redox/CYPs
• High content analysis
• Tox testing
• Cytokine analysis
• Cardiomyocytes and neuronal cells
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12. HTS workflow & terminology
300,000+
100
5
Compound Collection
Leads
Confirmed actives
Actives
Confirmed hits
Assay development
Triaging
uHTS
Hit to
lead
PPSC 25 Oct 2018
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13. PPSC is active in many therapeutic areas
Broad target class portfolio
20%
5%
9%
4%
2%
23%
13%
3%
7%
14%
Protease Lipase Kinase
Transferase Ligase Other enzyme
PPI Ion channel Receptor
Other
PPSC 25 Oct 2018
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14. 300,000 drug-like compounds for HTS
• Diversity based libraries
• Purity > 95% at time of purchase
• Circa 50% available at PPSC as solid
compound for quick follow-up
• Freedom to progress hits from libraries
130K historical collection 87K acquired 2012
8K pharma origin 70K BioAscent extention
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15. Flexible access to (shared) libraries
Expansion through
collaborations
Unique library,
Includes 200K
“public library”
Unique PPSC
capability
PPSC
300K compounds
ELF
ESCulab
550K compounds
Pharma
Clients
300K to >1M
compounds
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16. Fully automated dataprocessing
INPUT
SOURCES
ASSAY PLATE
PREPARATION
ASSAY DECISION
MAKING
CALCULATION
VALIDATION
Automated Sample Tracking
(SAMTRACK)
ActivityBase XE Data Mining
Plates
Tests
Results
Source-multiple intermediates-assay plate Raw data
Experiment definition
Screening
quality
control
Data
authori-
zation
Triage
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17. Demonstrated as number of data points
Increasing HTS production
0
2,000,000
4,000,000
6,000,000
8,000,000
10,000,000
12,000,000
14,000,000
2013 2014 2015 2016 2017
Commercial
Shared Risk
ELF
16
Year
Numberofdatapoints
PPSC 25 Oct 2018

18. Unique Selling Points
uHTS
large
libraries
Pharma
experts
ELF
screening
site

19. Screening history Oss (The Netherlands)
1995 2000 2005 2010 2015
Introduction MTS & HTS
Biochemical and cellular screening
ASPIRE: Integrated in-vitro screening platform
uHTS: capacity & miniaturisation
Closure of research @ Oss
New legal Entity 2012
1st HTS in January 2013
HTS 100 March 2018
PPSC 25 Oct 2018
18

20. Product portfolio
Assay development AD-labs
uHTS uHTS-robot
H2L support ASPIRE-system(s)
~1-9 months
~2-3 months
Biweekly - ~12 months
Automation support ASPIRE-system(s)Days/weeks
Activity Project duration Facilities
Compound library uHTS/ASPIRE
PPSC 25 Oct 2018
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21. Automation of in-vitro experiments
The HTS and open access lab
• Efficient, flexible and versatile
• Worry-free open access
• Broad range of life science applications
Automated workflows
High Content Analysis
(Imaging) Multimode readers
FLIPR Tetra
Pipetting robots
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22. High Content Analysis
• Micronucleus Assay
• Nuclear Fragmentation assay
• Cell proliferation
• Phospholipidosis assay
• Cytotoxicity
0
0.05
0.1
0.15
0.2
0.25
Fragmentationindex
Nuclear Fragmentation
HELA cells
3e-5M Staurosporine
DMSO control
Z’= 0.79
S/B= 2.2
0
20
40
60
80
100
120
1.00E-091.00E-081.00E-071.00E-061.00E-051.00E-041.00E-03
%effect
[Staurosporine] M
Nuclear Fragmentation
HELA cells
PPSC 25 Oct 2018
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23. Open access lab
• Open Innovation
• Access for academia and SME’s
• Shared facilities at Pivot Park
• Automation and scale-up of client’s
production
• Promotion for Pivot Park
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24. Grants and shared risk projects
PPSC as partner in collaborations
• European Lead Factory
‒ 30 partners, 7 from EFPIA
‒ 72 HTS programs completed in 5 year
• Cancer Drug Discovery Initiative (CDDI)
‒ Netherlands Cancer Institute and Leiden University
‒ Joint program to develop clinical candidates in oncology
• Center Of Innovative LEad Discovery (COILED)
‒ Radboud Univ Med Center, Radboud University (Chemistry),
Pansynth, BioAxis, Inntrest
‒ Joint program to develop clinical candidates in epigenetics
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25. Drug discovery consortia
CDDI
TKI
COILED
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26. European Lead Factory
Public contribution
(200,000 cpds by May 2018)
PHARMA
contribution
(>300,000 cpds)
- Compound logistics
- uHTS
- Hit triage
- Medicinal Chemistry
Joint
European
Compound
Library
European
Screening
Centre
LIBRARY
DESIGNS
DRUG
TARGETS
The research leading to these results has received support from
the Innovative Medicines Initiative Joint Undertaking under
grant agreement n°115489, resources of which are composed
of financial contribution from the European Union’s Seventh
Framework Programme (FP7/2007-2013) and EFPIA
companies’ in kind contribution.
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27. ELF Partners
Chemistry CROs
EFPIA partners Public Compound Consortium
funded by
European Screening Centre
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28. PPSC performs all public screening
ELF operates at industry scale
Assay ready
for u-HTS
Hit follow-up work
finished
Improved Hit List
delivered
Submitted Target
Proposals
Accepted Target
Programmes
Ultra-HTS
performed
Qualified Hit List
delivered
88 78 72 72 72 35162
52
Completed
6
Withdrawn
45%
Rejected
PPSC 25 Oct 2018
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29. Thank you!
For more information please contact:
Pivot Park Screening Centre
Oss, The Netherlands
+31-412-846050
www.ppscreeningcentre.com
Helma Rutjes, PhD, COO
Helma.rutjes@ppscreeningcentre.com
Ronald ten Berge, PhD, CBO
ronald.tenberge@ppscreeningcentre.com
Saman Honarnejad, PhD, Team Leader
Saman.honarnejad@ppscreeningcentre.com