iNovacia offers high quality high-throughput screening services supported by a compound collection and screening libraries of highest international standards. iNovacia has a broad experience with all major target families and assay types.
1. iNovacia
High-throughput
Screening (HTS)
Fragment Based Screening
(FBS)
Markus Thor
Chief Business Officer right from the start
markus.thor@inovacia.se
www.inovacia.se
iNovacia
2. iNovacia Laboratories
Diversity
Novelty
Lead-likeness
~280,000 compounds
Compound
Collection
Screening Structure-
& Assay Based
Target Lead Compounds
Development Optimization
LAB LAB
High-Throughput Screening Medicinal Chemistry
Fragment-Based Screening Crystallography
Assay Development Mechanism of Action Studies
Hit Validation Biophysical toolbox right from the start
iNovacia
3. Assay Development & Screening LAB
Diversity
Novelty
Lead-likeness
~280,000 compounds
Compound
Collection
Screening Structure-
& Assay Based
Target Lead Compounds
Development Optimization
LAB LAB
High-Throughput Screening Medicinal Chemistry
Fragment-Based Screening Crystallography
Assay Development Mechanism of Action Studies
Hit Validation & Profiling Biophysical toolbox right from the start
iNovacia
4. Assay Development & Screening LAB
High-Throughput Screening
• Successfully developed and used a large number of high-throughput
screening assays
• Successfull delivery of qualified chemical series in over 30 screening
projects
• Quality and speed in all steps e.g. use of acoustic dispensing to avoid
artifacts
Targets Format Examples of Technologies
Nuclear receptors 384 FRET
384 Reporter Gene Assay
Kinases 384 HTRF
Proteases 384 FRET
Metabolic enzymes 96-384 SPA, HTRF, Isotopic
GPCRs 384 Ca-kinetics
384 cAMP, Isotopic
Ion channels 384 Cellux: voltage/ion sens. probe right from the start
Functional cell assays 96-384 Luminescence, fluorescence
iNovacia
5. Assay Development & Screening LAB
Compound Collection
• ~280,000 cherry-picked compounds
• High level of diversity (~100 compounds per scaffold)
• Mix of exclusive, semi-exclusive and commercial
Cherry-
picked
• Contains novel scaffolds Cherry-
Biovitrum
~70,000
picked
• Experimental ADME profiling Asinex and
others
~200,000
• Chemical protocols available
• QC by LC-MS validates integrity Exclusive, in
iterative
development
~10,000
right from the start
iNovacia
6. Assay Development & Screening LAB
Due Diligence Compound Collection
Report from top-5 Pharma
• 95 % of the compounds passed their stringent drug likeness
criteria
• 79 % where unique compared to their extensive compound
collection
• <1,5 % published with biological data
• 35 % are not, or have not been, commercially available
right from the start
iNovacia
7. Assay Development & Screening LAB
Fast and Flexible Sample Storage and Retrieval
• Storage under N2, at +4 C, dark and dry. No measurable
degradation since 2006.
• Compound handling under inert atmosphere.
• ~280,000 compounds in 1.4 ml microtubes
• 10 mM dry DMSO stock solutions
• All microtubes individually traceable
• Fast cherry-picking
• Ability to pick and plate during an HTS campaign to verify and
validate.
right from the start
iNovacia
8. Assay Development & Screening LAB
Filters introduced 2010 for Screening Set
• The publication of new substructure filters for removal of Pan Assay Interference
Compounds (PAINS) promted us to apply these filters and remove all PAINS from
the iNovacia screening set. These compounds are not recognized by the filters
commonly used to identify reactive compounds.
(J. B. Baell and G. A. Holloway, J. Med. Chem., 2010, 53, 2719-2740.)
• Redox active compounds identified by an in-house assay have been removed.
Interestingly, we see a correlation between redox activity and PAINS. In a recent
HTS, 79 hits were identified as being PAINS and 53 of those (67%) were also
identified as redox active.
• A few substructures that are not identified by the two filters above, but still
appear as frequent hitters or suffer from lack of chemical stability have been
removed.
O
O N S HN
S N right from the start
O N O
H
Examples of PAIN substructures iNovacia
9. Assay Development & Screening LAB
Fragment-Based Screening
• Scientists at iNovacia pioneers in developing fragment-based
screening
• Long experience and world-class competencies in NMR screening
• Fragment libraries for primary screening
– Primary screening by NMR: 900+ fragments containing 9-20 heavy
atoms. Carefully designed with large numbers of readily available
analogues from both commercial sources and the in-house iNovacia
compound collection
– Primary screening by biochemical assay at high compound
concentration: 20,000 ”larger fragments” with MWs 200 - 350
right from the start
iNovacia
10. Assay Development & Screening LAB
Hit Validation & Profiling
Identity/Purity/Stability/Solubility
DRC and analysis
HTS single
Counter assays
Clustering of confirmed hits point data
Chemistry evaluation of hit series
Tractability
Library expansion
Emerging SAR
IP space
Biophysical assays
Dynamic Light Scattering (DLS)
Nuclear Magnetic Resonance (NMR)
Microcalorimetry (DSC/ITC) Final prioritization
Surface Plasmon Resonance (SPR) of hit series
Mass spectrometry (ESI-MS/MALDI-MS) Full chemistry
Analogs
In-house, commercialy available, small program
expansions by parallel chemistry, SAR
analysis
In vitro ADME assays
HSA binding, CYP inhibition, membrane
affinity, metabolic stability, hERG binding, right from the start
cytotoxicity
iNovacia
11. iNovacia Laboratories
Diversity
Novelty
Lead-likeness
~280,000 compounds
Compound
Collection
Screening Structure-
& Assay Based
Target Lead Compounds
Development Optimization
LAB LAB
High-Throughput Screening Medicinal Chemistry
Fragment-Based Screening Crystallography
Assay Development Mechanism of Action Studies
Hit Validation Biophysical toolbox right from the start
iNovacia
12. Structure-Based Optimization LAB
Validated Hits to Competitive Lead Series
• Efficient chemical expansion and increasing the odds
– Through early SAR generation (in-house analogs, parallel chemistry
and/or x-ray crystallography)
– Through high quality chemical starting points
– Through high quality pharmacological profiling
• Highly integrated work flow
– Medicinal chemistry
– Pharmacology
– Crystallography (in collaboration with Sprint Biosciences)
– ADME
– Automatic data capture and ELN
right from the start
– Humanized ex vivo and in vivo models within cancer
iNovacia
13. Typical Project Scopes
Customer Characteristics Typical Service
Segment
Smaller Biotechs Typically strong in specific disease General step-wise support in drug
area biology. discovery ranging from assay
development to lead optimization
Seek access to drug discovery
expertise and technology
Larger Biotechs Fully integrated research in-house Full projects ranging from assay
and Often lack HTS/FBS capacity development to lead series generation.
Mid-sized Pharmas
Seek access to additional screening
technologies, novel
lead series
Big Pharmas Fully integrated research in-house Full projects ranging from assay
development to lead series generation.
Seek chemical diversity/novel lead
series, additional capacity,
complementing approaches and fresh
thinking
right from the start
iNovacia
14. Key Success Factors
The Right PEOPLE
The Right ATTITUDE
Excellence in OPERATiONS
Vast Pharma EXPERiENCE
right from the start
iNovacia
15. The History of iNovacia
1996
Merger of Pharmacia & Upjohn
Small molecule Center of Excellence
formed in Stockholm 2001
Biovitrum spins out from
Pharmacia Corporation
Biovitrum small molecule deals Continued investments in
small molecule R&D
2002 - 5HT2c deal with GSK
2003 - 11beta HSD deal with Amgen 2006
Management buy-out of iNovacia
Asinex Ltd invests in iNovacia
2007
iNovacia: First Big Pharma deal
2008
iNovacia: First deal in the US
2010
2011
Karolinska professors and iNovacia
Kancera acquires iNovacia and
management establish Kancera AB
is listed on the Nasdaq OMX First North
right from the start
iNovacia