20
iNovacia right from the start Brief Overview 2011 Markus Thor Chief Business Officer [email protected] www.inovacia.se iNovacia High-Throughput Screening Fragment Based Screening Assay Development Lead Generation

Inovacia drug discovery 2011

Embed Size (px)

DESCRIPTION

iNovacia is an established quality provider of lead generation services including high-throughput screening and fragmen based screening. This is supported by a compound collection (ca 300,000 cmpds) and screening libraries of highest international standards with focus on diversity and novelty.

Citation preview

Page 1: Inovacia drug discovery 2011

iNovacia

right from the start

Brief Overview

2011

Markus Thor

Chief Business Officer

[email protected]

www.inovacia.se

iNovacia

High-Throughput Screening

Fragment Based Screening

Assay Development

Lead Generation

Page 2: Inovacia drug discovery 2011

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

Page 3: Inovacia drug discovery 2011

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

Page 4: Inovacia drug discovery 2011

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.

Page 5: Inovacia drug discovery 2011

iNovacia

right from the start

Key Success Factors

The Right PEOPLE

The Right ATTITUDE

Excellence in OPERATiONS

Vast Pharma EXPERiENCE

Page 6: Inovacia drug discovery 2011

iNovacia

right from the start

The Right People

Dedication

Pride

Experience

Dedicated to delivery

Want to make a difference

Drug hunter’s attitude

Speak their minds

Extensive experience and skills

Know what works, know what doesn’t work

Understand big pharma as well as small biotech

Take pride in quality

Know quality is key to success

Pride in delivering result

Page 7: Inovacia drug discovery 2011

iNovacia

right from the start

The Right Attitude

• Trust and commitment - necessary for efficient sharing and value maximizing

• Integrity

• Big and small treated the same

• Adapting to the customer’s specific needs – still speaking our mind

• Continuously seeking to improve

Key Mission: To Maximize Value for the Customer

Page 8: Inovacia drug discovery 2011

iNovacia

right from the start

Excellence in Operations

Biophysical measurements implemented in assay optimization and hit validation to ensure e.g. assay quality and only compounds acting by right mechanism of action are considered for SAR development

Extensive hit profiling to secure quality in downstream chemistry program

Continuous and systematic approach to minimize false positives

Speed

Flexibility

Quality

Broad and state-of-the art technology base

Broad experience in designing screening and validation assays, including very challenging assays

Modular approach with flexibility in project scope

Efficient working procedures, with all scientist actively involved in the work flow

Efficient screening approach

Page 9: Inovacia drug discovery 2011

iNovacia

right from the start

Vast Pharma Experience

• We have experience from a wide range of targets and technologies

• We have experience ranging from early discovery to clinical stage

• We understand the industry challenges and trends

We Understand the Customer’s Need for

True Innovation, Quality and Speed

Page 10: Inovacia drug discovery 2011

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

Page 11: Inovacia drug discovery 2011

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

Page 12: Inovacia drug discovery 2011

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

Page 13: Inovacia drug discovery 2011

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

Page 14: Inovacia drug discovery 2011

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

Page 15: Inovacia drug discovery 2011

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

Page 16: Inovacia drug discovery 2011

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

Page 17: Inovacia drug discovery 2011

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

Page 18: Inovacia drug discovery 2011

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

Page 19: Inovacia drug discovery 2011

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

Page 20: Inovacia drug discovery 2011

iNovacia

right from the start

Thank You!

Markus Thor

Chief Business Officer

[email protected]

www.inovacia.se