CarTarDis

Cardiovascular Target Discovery

EU FP7 Health call 2013 CarTarDis

www.cartardis.eu

Discovery of novel cardiovascular drug targets

CarTarDis = Cardiovascular Target Discovery Public-private partnership, 13 partners, 8 countries, project budget 8.0M Eur Start 1 Oct 2013 for 4 years

(Coordinator)

CarTarDis

Discovery of novel cardiovascular drug targets

(Coordinator)

CarTarDis

A strong interdisciplinary team of experts in: Cardiovascular disease biology, drug discovery processes, translational medicine, population studies, Omics, imaging, bioinformatics, applied technology

CarTarDis = Cardiovascular Target Discovery

Public-private partnership (4 years) Project budget 8.0M Eur Start 1 Oct 2013 13 partners from 8 countries: research-driven SME’s, universities, research & technology institutes, large pharma

Unique cohort and sample data CarTarDis

A global network of human cohort study data, biobanks and clinical scientists.

Unique translational CVD models CarTarDis

CVD mouse CVD patient

CVD mouse and cellular models used in >200 studies. Intensive phenotyping and molecular analyses.

Unique CVD samples CarTarDis

Unique human biobanks with samples across the cardiovascular disease spectrum.

Unique molecular detection methods CarTarDis

Immunohistochemistry (protein)

In situ hybridisation (miRNA, mRNA)

MS Imaging (lipids, metabolites)

Human/mouse CVD samples

Laser capture microdissection + targeted omics (RNA, proteins)

Histology

Rational framework for target selection

The 5R’s assessment:

• Right Target

• Right Tissue

• Right Safety

• Right Patients

• Right Commercial Potential

CarTarDis

Target identification & selection process CarTarDis

1. Generate a comprehensive candidate target database

• GWAS, literature, proprietary

2. Review all candidate targets

• Automatic scoring

• Expert review

3. Rank targets (following 5R’s)

• 1. Drugability

• 2. Novelty

• 3. Omics/genetics

• 4. Feasibility (within CarTarDis)

• 5. Pathways (expertise within CarTarDis)

4. Select shortlist of candidate targets for validation

Target View: web interface CarTarDis

http://146.107.41.240/db/CarTarDisApp/

GWAS cohort data 302

Other literature 43

Partners research 35

Total: 380

Target View: Details about each target

• Annotations

• Cross references

• Auto-collected data

• Reviewed data from

publications

• Hyperlinks to public

databases (PubMed, GWAS,

proteinatlas, etc)

• Personal comments by

experts

Ordered by ‚Target Name‘

CarTarDis

CarTarDis target reviewing process CarTarDis

• Build and improve database as central knowledge base (month 3)

• Decide on target prioritisation criteria and review procedure (month 6)

• Fill database and apply automated scoring (month 6-12)

• Discussed during various live target review jamborees (months 6, 12)

• Off line expert reviewing in small groups (email, telephone)

• Finish target selection during selection meeting (month 14)

• Prioritise targets for validation activities (month 18)

• Draft target validation plans (month 14-18)

380 candidate targets → 23 pre-selected targets → 11 selected targets

CarTarDis target evaluation dossiers CarTarDis

Knowledge sharing using Google Sites

All

selected

targets

Potential drug target

Links to

target

information

in external

databases

• Target summary - key points of pro’s and con’s of the candidate target

• Target details - description, relevant data, selection scores following 5R’s criteria

• Gap analysis - lacking data

• Validation planning - directing activities in WP1, WP2, WP3

• References - relevant literature

CarTarDis on www CarTarDis

CarTarDis website CarTarDis

www.cartardis.eu