Only the mediocre are always at their best Seuls les ... · Knapp et al. And redundant World Pre...
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Only the mediocre are always at their best Seuls les médiocres sont toujours à leur meilleur Jean Giraudoux
Transcript of Only the mediocre are always at their best Seuls les ... · Knapp et al. And redundant World Pre...
Only the mediocre are always at their best
Seuls les médiocres sont toujours à leur meilleur
Jean Giraudoux
We are risk-averse
90% of global research still focuses on 10% of human genes
Knapp et al
And redundant
World Pre 2000
# of Publications
World in 2012
# of Publications
Pro
tein
kin
ase r
anke
d a
s o
f 1999
Canada in 2012
# of Publications
www.thesgc.org [email protected]
And they are just as redundant
MarketRegist.Phase
IIIPhase
IIPhase
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100 63 39 25 14 8 3.5 2 <2
Does it work?
Patenthypothesis generated
$500-700 M 5-7 years
STOPPhase II
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In summary
• Despite massive investments we are not delivering enough “novel” medicines
• We don’t understand Human Biology– Most (90+%) early activity is destined for failure
• No organisation has all capabilities
• Current model requires early IP– Secrecy prevents critical mass being reached– Useless duplication– Sub-optimal use of public (and industrial) resources
A public-private partnership that supports the discovery of new medicines through open source researchwww.thesgc.org
www.thesgc.org [email protected]
Open source early-stage drug discovery model
Public-PrivatePartnership
Public Domain Commercial
Reagents & Basic Knowledge
• No patent• No restriction • Open access to
tools and data.
Discovery and Exploration
• Publications
Drug Discovery and Development
Facilitated by access to increased amount of information in the public domain
CREATIVE COMMONS PROPRIETARY
Weigelt J. EMBO Reports 10:941-5 (2009)
Epigenetic Chemical Probes Programme
(+)JQ1UNC0638
www.thesgc.org
High quality, reproduciblePotent: in vitro IC50 /KD< 100nM
Selective: 30 fold over other sub-familiesCell Permeable: activity IC50 <1 µM
Publicly Available (No Patents) No restriction on use.
GSK informs SGC about Mitsubishi compound
July 2009
Oxford and Harvard start collaboration
Jan 2010
Co -publication of JQ1 probe (SGC; cancer) andI-BET probe (GSK; inflammation)
Dec 2010
Open – speed from lab to patients
Booming interest in Academia and Industry
Pfizer BET probe announced
Oct 2011 Mar 2012
GSK carries out first in
man (for open access -
discovered indication!)
JQ1 distributed to 100+ labs
Jan 2011
Brd4 linked toAML (Nature)MM (Cell)
July 2011
6 Months 11 Months 1 Month 6 Months 3 Months2 Years and 2 months
1992 1998
Glivec Tk First
6yrs
Open spurs commercializationBromodomain inhibitors in >15 clinical trials
• NUT midline carcinoma, Mult. Myeloma, small cell lung cancer, colorectal cancer, neuroblastoma and MYCN-amplified solid tumours
GSK
GSK525762[NCT01587703]
• Haematological malignancies: Acute Myeloid Leukaemia (AML), Acute Lymphoblastic Leukaemia (ALL), DLBCL and Mult. Myeloma
Oncoethix
OTX015[NCT01713582]
• Dyslipidemia; Atherosclerosis; Acute Coronary Syndrome; Cardiovascular Disease
Resverlogix
RVX-208/RVX000222[6 trials]
• Progressive LymphomaConstellation
CPI-0610[NCT01949883]
• NUT midline carcinomaTensha
TEN-010[NCT01987362]
• Advanced Cancer, Breast Cancer, Non-Small Cell Lung Cancer, Acute Myeloid Leukemia, Multiple Myeloma
AbbVieABBV-075
[NCT02391480]
• NeoplasmsBayer
BAY1238097[NCT02369029]
www.thesgc.org
THE NEXT STEPS: ASSAYS FROM PATIENT CELLS
Patient Derived Cell Assays – The Case
• Disease models - cell lines and animal - often poorly predictdisease
• The ultimate model should be tissue/cells from the humandisease
• Access to patient cells and tissue has been the key ininflammation; to define and validate new drug targets inrelevant cells and context, e.g. for:- Anti-TNF and- Anti-IL17 therapies
• We are now building a scalable new organization to recapitulatesuch successes
• This partnership, started formally March 1st 2015 and comprisesUniversities, Hospitals, Pharmaceutical Companies, Biotechs andDisease Foundations who work in open source mode
The “agree not to patent” hospital network
• Glioblastoma stem cells
• Colon cancer stem cells
• Key Scientists/Clinicians:
o Michael Taylor, Peter Dirks
o Catharine O’Brien
• Inflammation
• Key Scientists/Clinicians:
o Marc Feldmann
o Jagdeep Nanchahal
o Paul Bowness
• ALS
• Parkinson’s
• Key Scientists/Clinicians
o Ted Fon
o Guy RouleauMontreal Neurological Inst.
• Systemic Autoimmune Diseases
• Key Scientists/Clinicians:
o Lars Klareskog
o Ingrid Lundberg
o Per-Johan Jakobsson
And…
UHN
St. Mike’s
CAMH
Inflammatory Diseases• Clinical research in Fibrosis, AS & FOP
• Well characterized and managed patient cohorts
• Team of 5-6 staff members, 3 already recruited
• Rapid implementation: High quality staffavailable from previously NovoNordisk fundedgroup + existing laboratories, includingequipment
Paul
Mar
cJagdeep
Currently Available Cells and Assays:
Th1 and Th17 responses in ex vivo cultures from AS and other
inflammatory arthritis patients (e.g. psoriatic arthritis)
• Read-outs: e.g. IFN-gamma and IL17 production
Myofibroblasts and control matched fibroblasts from patients with
fibrotic diseases in 3D collagen matrices
• Read-outs: e.g. force of contraction, alpha-smooth muscle actin
mRNA and protein
Fiona Lynn
First Results – CBP/p300 inhibition
CBP30 inhibits IL-17A and IFNg but not IL17F secretion by Th17 cells isolated from healthy donors (HC) and patients with Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PS), no toxic effects observed.
Paul Bowness et al
Biomap, DiscoveRx
www.thesgc.org
NEXT…OPEN SOURCE CLINICAL POC TRIALS?
STOPPhase II
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Why do we need many companies pursuing same ideas in secret if most fail?
• Started in June 2004; led from Canada
• Funded by Ontario, Genome Canada, Sao Paulo, Wellcome Trust, 10 leading pharmacompanies, Gates, philanthropy, EC
• +250-strong team in Oxford, Toronto, Stockholm, Frankfurt, Chapel Hill & Campinas
• Open Access Policy:
SGC at a glance
- Promptly place results, reagents and know-how in the public domain
- SGC scientists never file patents
Global Impact:novel human protein structures
Since 20.Apr. 2004: +1600 structures
~15% Global Output
Global Impact:International
Networkwww.thesgc.org
More than 550 collaborations established since 2004
Austria
Australia
Belarus
Belgium
Brazil
Canada
Denmark
France
Germany
Hungary
Italy
Ireland
Japan
Singapore
Sweden
Switzerland
UK
United Arab Emirates
US… and many more
Openness facilitates
High Quality & Reproducible
Science
847 peer-reviewed articles
(20% in High-Impact Journals)
>2 articles per week
(~1 in high-impact journal/ month)
Co-authored with more than
160 institutions from 47 countries
Selected SGC papers (Jan-Jun 2014)
