high throughput screening (hts) at inovacia
DESCRIPTION
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.TRANSCRIPT
iNovacia
right from the start
High-throughput Screening (HTS)
Fragment Based Screening
(FBS)
Markus Thor
Chief Business Officer
www.inovacia.se
iNovacia
iNovacia
right from the start
Screening
& Assay
Development
LAB
Structure-
Based
Optimization
LAB
Compound
Collection
High-Throughput Screening
Fragment-Based Screening
Assay Development
Hit Validation
Medicinal Chemistry
Crystallography
Mechanism of Action Studies
Biophysical toolbox
Target Lead Compounds
Diversity
Novelty
Lead-likeness
~280,000 compounds
iNovacia Laboratories
iNovacia
right from the start
Screening
& Assay
Development
LAB
Structure-
Based
Optimization
LAB
Compound
Collection
High-Throughput Screening
Fragment-Based Screening
Assay Development
Hit Validation & Profiling
Medicinal Chemistry
Crystallography
Mechanism of Action Studies
Biophysical toolbox
Target Lead Compounds
Diversity
Novelty
Lead-likeness
~280,000 compounds
Assay Development & Screening LAB
iNovacia
right from the start
Assay Development & Screening LAB
• 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
384
FRET
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
Functional cell assays 96-384 Luminescence, fluorescence
High-Throughput Screening
iNovacia
right from the start
Assay Development & Screening LAB
• ~280,000 cherry-picked compounds
• High level of diversity (~100 compounds per scaffold)
• Mix of exclusive, semi-exclusive and commercial
• Contains novel scaffolds
• Experimental ADME profiling
• Chemical protocols available
• QC by LC-MS validates integrity
Compound Collection
Cherry-picked
Asinex and others
~200,000
Cherry-picked
Biovitrum~70,000
Exclusive, in iterative
development~10,000
iNovacia
right from the start
Assay Development & Screening LAB
• 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
Due Diligence Compound Collection
Report from top-5 Pharma
iNovacia
right from the start
Assay Development & Screening LAB
• 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.
Fast and Flexible Sample Storage and Retrieval
iNovacia
right from the start
• 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.
S
NO S
N
NH
NH
O
O O
Examples of PAIN substructures
Assay Development & Screening LAB
Filters introduced 2010 for Screening Set
iNovacia
right from the start
Assay Development & Screening LAB
• 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
Fragment-Based Screening
iNovacia
right from the start
Assay Development & Screening LAB
Identity/Purity/Stability/Solubility
DRC and analysis
Counter assays
Clustering of confirmed hits
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)
Surface Plasmon Resonance (SPR)
Mass spectrometry (ESI-MS/MALDI-MS)
Analogs
In-house, commercialy available, small
expansions by parallel chemistry, SAR
analysis
In vitro ADME assays
HSA binding, CYP inhibition, membrane
affinity, metabolic stability, hERG binding,
cytotoxicity
Final prioritization
of hit series
HTS single
point data
Hit Validation & Profiling
Full chemistry
program
iNovacia
right from the start
Screening
& Assay
Development
LAB
Structure-
Based
Optimization
LAB
Compound
Collection
High-Throughput Screening
Fragment-Based Screening
Assay Development
Hit Validation
Medicinal Chemistry
Crystallography
Mechanism of Action Studies
Biophysical toolbox
Target Lead Compounds
Diversity
Novelty
Lead-likeness
~280,000 compounds
iNovacia Laboratories
iNovacia
right from the start
• 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
– Humanized ex vivo and in vivo models within cancer
Structure-Based Optimization LAB
Validated Hits to Competitive Lead Series
iNovacia
right from the start
Typical Project Scopes
CustomerSegment
Characteristics Typical Service
Smaller Biotechs Typically strong in specific disease area biology.
Seek access to drug discovery expertise and technology
General step-wise support in drug discovery ranging from assay development to lead optimization
Larger Biotechsand Mid-sized Pharmas
Fully integrated research in-houseOften lack HTS/FBS capacity
Seek access to additional screening technologies, novel lead series
Full projects ranging from assay development to lead series generation.
Big Pharmas Fully integrated research in-house
Seek chemical diversity/novel lead series, additional capacity, complementing approaches and fresh thinking
Full projects ranging from assay development to lead series generation.
iNovacia
right from the start
Key Success Factors
The Right PEOPLE
The Right ATTITUDE
Excellence in OPERATiONS
Vast Pharma EXPERiENCE
iNovacia
right from the start
The History of iNovacia
1996
Merger of Pharmacia & UpjohnSmall molecule Center of Excellenceformed in Stockholm
Biovitrum spins out from Pharmacia CorporationContinued investments in small molecule R&D
Biovitrum small molecule deals
2002 - 5HT2c deal with GSK2003 - 11beta HSD deal with Amgen
Management buy-out of iNovaciaAsinex Ltd invests in iNovacia
2007
iNovacia: First Big Pharma deal
iNovacia: First deal in the US
2010
Karolinska professors and iNovacia management establish Kancera AB
2001
2006
2008
Kancera acquires iNovacia and is listed on the Nasdaq OMX First North
2011