“Good Practice Models for International University-Industry Collaboration” Malcolm Skingle CBE DSc PhD Director – Academic Liaison Drug Discovery Wednesday 11th January 2012 Building University – Business links symposium British Embassy & British Council meeting
Opening Remarks • Companies must collaborate to innovate & survive • Companies can no longer fund all of the research they require to underpin their R&D operations • No single university has all of the answers ! • Governments compete for inward investment • GSK support collaborative research in almost 30 countries • Leveraging research funding is essential for companies
The Structural Genomics Consortium - an open access public-private partnership
The Structural Genomics Consortium an Open Access Public Private Partnership Board of Directors Wayne Hendrickson, Columbia, Chair
Scientific Committee Kirk Clark, Chair, Novartis
CEO Aled Edwards
SGC-Oxford
SGC-Toronto
SGC-Stockholm
~65 staff
~80 staff
~25 staff
The Structural Genomics Consortium - an open access public-private partnership Mandate to place protein structures of relevance to human health into the public domain, free from restrictions on use.
• Funders nominate the SGC Target List of proteins • •
Phase 1: (2005-07) 455 protein structures solved
Phase 2: (2007-11) Target of 660 structures from the Target List (2400 proteins) plus 8 human integral membrane proteins
Target distribution among SGC Laboratories
SGC-Oxford
SGC-Toronto
SGC-Stockholm
–Dehydrogenases, Reductases & Metabolism –Phosphorylation Dependent Signaling –Transmembrane Receptor Signaling –Diabetes and signalling –Chromatin –Apicomplexan-associated diseases –GTPases, ATPases and small molecule kinases – Nucleotide metabolism and RNA helicases – Amino acid metabolism – Lipid signalling
Shared best practice: Methodology & technology
Protein Kinases (Catalytic Domains) Human kinases (518 in genome)
Kinase Structures in Public Databases
20 15 10 5 0 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06
Unique Kinase Structures
25
Year of first release in pdb
Thirteen SGC Funders •
The Wellcome Trust.
• • • • •
The Canada Foundation for Innovation (CFI), The Canadian Institutes of Health Research (CIHR), Genome Canada, The Ontario Genomics Institute (OGI), The Ontario Ministry of Research and Innovation (MRI),
•
GlaxoSmithKline plc. (GSK), Merck & Co., Inc., Novartis, Pfizer
• • • •
Karolinska Institutet, The Knut and Alice Wallenberg Foundation, The Swedish Foundation for Strategic Research, VINNOVA (The Swedish Governmental Agency for Innovation Systems),
>£50m 4 year programme
Developing Chemical Probes for Epigenetics No structures disclosed
Structures disclosed
Chemistry @ GSK X-ray @ Oxford Public Domain
Assays @ Oxford Chemical Probe
* Sigma make probe available
Data to GSK
Only GSK scientists can view data with compound structures
1–5 Compounds meeting probe criteria for potency and selectivity:
* e.g. Potency <100nM, Selectivity >100, Cellular activity <1uM
A future model for Drug Discovery? Wellcome Trust Epigenetics Collaboration GSK-WT-SGC Partnership
Public Domain
Chemical Tractability
Chemical Probes
Drug Discovery
Chemistry (GSK) Screening (WT-NIH) Structure (SGC)
No restrictions on use or publication
Proprietary Target Validation (Re)Screening Lead optimization Pharmacology DMPK Toxicology Chemical development Clinical development
Enable Academic Target Validation
Open Access
Pharmaceutical Industry
Proprietary
Q: Why place Chemical Probes in the Public Domain? A: Potent and selective small molecules provide complimentary (if not better) target validation to genetic methods as evidenced by their scientific impact Compound
Receptor
Papers
Citations
Years
h-index
g-index
GW1929
PPARγ
317
11063
14
47
100
GW0742
PPARδ
392
7212
10
41
78
GW4064
FXR
250
4482
8
37
61
SR12813
PXR
127
4628
8
33
67
GW9662
PPARγ
528
4513
8
32
50
GW3965
LXR
181
3073
7
29
53
GW7647
PPARα
118
2312
7
22
47
CITCO
CAR
73
711
5
14
24
Data compiled from Google Scholar, October 5, 2007
All compounds were made available by GSK to the Public Domain through commercial suppliers (Sigma-Aldrich and Tocris) h-index: a metric of scientific impact, combining quality and quantity of citations g index: a modification of the h-index with more weight on highly-cited articles
Innovation through Public Private Partnerships • Address large research challenges • Access to ……….. Complementary skills and/or technologies Academic lateral thinking Multi-disciplinary problem solving Co-funding
• •
Critical mass In order to work well……. Confidence & trust between partner(s) Shared risks & rewards
We are looking for innovation wherever it may originate