new_dpac_external_presentation_mar15
TRANSCRIPT
Introduction to
Discovery Partnerships
with Academia (DPAc)
Alternative Discovery & Development
GlaxoSmithKline R&D
A new model for partnering
with academia to discover
innovative medicines
DPAc model is unique
March 2015 Introduction to DPAc
Collaborative Invention
Shared Ownership
Risk Embracing
Staged Pre-Clinical Research
Support
Development Milestones;
- Candidate Clinical NME(s)
- FTIH
- Clinical PoC
- Launch of medicine
Build integrated
partnerships that
can translate
innovative research
into medicines to
benefit patients
A collaborative approach from GSK Giving academic researchers an opportunity to partner with GSK scientists, taking
advantage of our expertise and technical resources
What do we seek?
3
Clear
Therapeutic
Hypothesis
Coherent and
supportable
hypothesis that
modulating a target
will produce a
physiological effect
resulting in
therapeutic benefit
to particular
patients
March 2015 Introduction to DPAc
Defined Target
Specific drug target
identified and some
understanding of type
of pharmacology
desired
(Exclusive)
Enabling
Expertise
Academic partner has
know-how and / or
expertise not (readily)
found elsewhere for
progressing the
target
Tractability
Path to identifying a
drug molecule can
be defined
Target knowledge
suggests that a
drug-like molecule
can be generated
Enabling GSK
Contribution
GSK has
capabilities and
expertise that will
help progress the
project
Key elements of DPAc
Focus on the medicine • Collaborative partnerships focused on drug discovery
• Starts at any point from initiation of early screening, finishes with the medicine
Undertake the best science • Minimal infrastructure: undertake projects independent of location or disease area
• Access to all GSK drug discovery and development capabilities
Share in the investment, share in the reward • Both sides contribute – complementary match of skills where both academic institutions
and GSK can contribute to success
• Research funding synchronized with research goals
• Post-research milestone payments and royalties
• If partnership terminates, academic institution is free to progress
4 March 2015 Introduction to DPAc
Academic researchers who:
• Want to be involved in turning their
innovative research into medicines
• Contribute effort and resources to making
projects work
• Are recognized experts in their fields
• Bring unique capabilities to the collaboration
Who is best suited for DPAc?
5 March 2015 Introduction to DPAc
DPAc partnership
6 March 2015 Introduction to DPAc
• Co-authored and detailed work plan creates
framework to promote rapid project initiation
and execution
• Work together via Joint Research Committee
• Jointly invest time / energy / resources to
progress project at both partner sites
• Strong interactive relationships between
project teams
• Equitable approach to IP
- Academic institution receives commercial
rights if GSK terminates collaboration
Avalon/GSK
Newcos
Start a venture-
capitalist-backed
company, co-founded
with GSK
Pre-DPAc
Funds for promising
concepts that are too early
for full DPAc agreement
Discovery Fast
Track Challenge
Offers a chance to
win a screening
collaboration
with GSK
Multiple ways to collaborate with DPAc
March 2015 Introduction to DPAc
Innovative medicines
to benefit patients Full DPAc
YOU and your
IDEAS
How DPAc projects operate
Collaborative partnerships focus on drug discovery
Start at any point from initiation of early screening to late lead optimization
Consider any disease area
Operate in any geography
Seek complementary match of skills where both academic institution and GSK can
contribute to success
They are not
✗ Licensing or sponsored research agreements
✗ Support for exploratory work
✗ Focused on technology platforms
✗ Broad multi-project collaborations
✗ Open-ended funding streams
8 XX March 2015 An Introduction to DPAc
What capabilities can GSK bring
to DPAc partnerships?
9 March 2015 Introduction to DPAc
• Large-scale protein production
• HTS capacity 2 million compound set
• Medicinal chemistry and computational
molecular design
• Selectivity screening
• PK-PD modelling
• Flexible, high-tech assay platforms
Lead Identification
Late Lead Optimization
Early Lead Optimization
Assay Development
Target Feasibility
• Biopharm discovery platforms
• Biopharm affinity maturation
• Encoded Library Technology*
>10 billion compounds
• Synthetic & analytical chemistry
• Preclinical development:
safety, chemistry, pharmacy
* Design, synthesis and selection of DNA-encoded small molecule
libraries. Clark et. al. Nature Chemical Biology 5, 647-654 (2009)
Candidate Selection •
FTIH Start •
Clinical POC •
Launch •
Lead Identification
Late Lead Optimization
Early Lead Optimization
Assay Development
Target Feasibility
Partnerships focused on drug discovery Planning all the way to the medicine
10 March 2015 Introduction to DPAc
Lead Identification
Late Lead Optimization
Early Lead Optimization
Assay Development
Target Feasibility
Phase I Phase III Phase II Pre-Clinical Early Drug Discovery
Launch &
Royalties
Drug Discovery Initiated •
Screen Initiated •
Lead Identified in vitro •
Lead Identified in vitro •
Typical GSK Activities
Typical Academic Activities
Shared activities between
academia and GSK
11 March 2015 Introduction to DPAc
Screening Chemistry
Chemistry DMPK Safety Pharmacy
Screening Chemistry DMPK
Assay Development
Assay Feasibility Tool Generation
Physiological
Assays
Physiological
Assays in vivo
Models
Physiological
Assays in vitro
and in vivo
Assay
Development
Reagent
Generation
$ Value of GSK Internal Contribution
$ Value of GSK Support to Academic
Early Lead
Optimization Late Lead
Optimization Lead Identification
Tractability Assessment
and Assay Development
6 months 9-12 months 9-12 months 9-12 months
Example activity plan
12
Assay
transfer
Physchem Pharmacy
Compound profiling (selectivity)
DMPK Toxicology
Compound profiling (biological and biochemical)
Medicinal chemistry Synthetic chemistry 1˚ screen &
selectivity
ELT
Automation/
robustness
testing
Reagent production
1° Assay transfer
Reagent
generation
Assay
development
Compound profiling (phenotypic assessment)
Develop in vivo PD assays In vivo models PK/PD
MOA studies
Structural studies Clinical PD assay development
In vivo models efficacy Develop cellular assay
NIH screen
Screen
initiated
Proof of
in vitro biology
Proof of
in vivo biology Candidate
GSK
Academic
Partner
Dr Jonathan
Fallowfield
University of
Edinburgh
Mark
Bamford,
GSK
Seven active DPAc partnerships in Europe
13 Introduction to DPAc
Treating Fibrotic
Liver Disease
Preventing
Multiple
Organ Failure in
Severe Acute
Pancreatitis Mr Damian
Mole,
University of
Edinburgh
John
Liddle,
GSK
Graft versus
Host Disease
(Biopharm)
Prof. Nathan
Karin, Rappaport
Institute, Israel
Jeremy
Griggs,
GSK
Treating a1-
Antitrypsin
Deficiency using
small molecule
stabilisers Prof. David
Lomas,
University of
Cambridge
Andy
Pearce,
GSK
A disease
modifying
approach to the
treatment of
Huntington’s
Disease Prof. Susann
Schweiger,
University of
Dundee
Iain
Uings,
GSK
Prof. Sir Mark
Pepys,
University College
London
Duncan
Holmes,
GSK
Stabilisers of
Transthyretin
as treatment for
Transthyretin
Amyloidosis
Topical Therapy
for Netherton
Syndrome,
Rosacea and
Atopic Dermatitis Prof. Alain
Hovnanian,
Paris
Descartes
University
John
Liddle,
GSK
March 2015
Five active DPAc partnerships in North America
14 Introduction to DPAc March 2015
Z
Treatment of
Cystic Fibrosis
Prof. Christine
Bear
SickKids Hospital
Toronto
Jakob
Busch-
Petersen,
GSK
Treatment of
Alzheimer’s
Disease
Prof. Paul
Lombroso
Yale
University
Dennis
Yamashita,
GSK
Prof. Roger
Cone
Vanderbilt
University
David
Becherer,
GSK
Treatment of
Obesity
Treatment of
Triplet Repeat
Diseases
Prof. Christopher
Pearson
SickKids Hospital
Toronto
Debra
Peattie,
GSK
Prof. Nicholas
Tonks
Cold Spring
Harbor Labs
Jon Collins,
GSK
Treatment of
Obesity
and Type 2
Diabetes
Discovery Fast Track Challenge
• Innovative approach to sourcing new partnership ideas – inviting academic researchers to propose project ideas in a challenge -like format
• Rigorous review and detailed face-to-face feedback and advice to investigators selected as finalists; up to 30 finalists will be selected in 2015
• Partnership with challenge winners (up to 12 in 2015) to perform high-throughput and encoded library screening of their target
• Promising results may lead to an opportunity for the academic institution and GSK to collaborate via a full DPAc partnership or via supplied chemical probes
15 March 2015 Introduction to DPAc
For Discovery Fast Track Challenge winners
• GSK will provide state-of-the-art capabilities
• Devise optimal screening strategy (e.g. HTS, Encoded Library
Technologies)
• Adapt and scale biological reagents for screening
• Miniaturize assays for HTS (~2M cpds)
• Run screens, analyze output and "qualify" hits
• Principal Investigator (PI) joins team of GSK scientists to execute the screen
and follow up hits – often culminating in tests within PI's lab (e.g., complex
cellular assays)
• GSK may provide up to 3 chemical structures of selected chemical probe(s) to
help further PI’s research and potentially lead to high-impact publications,
subject to GSK’s existing internal and external obligations
• Promising results may lead to a full DPAc collaboration with GSK to create a
novel medicine with the DPAc team
16 March 2015 Introduction to DPAc
2014 North American Discovery Fast Track
Challenge results
17 March 2015 Introduction to DPAc
196 Proposals Submitted
from
105 Participating Institutions
12 Finalists
6 Winners
40% Increase in proposals submitted from 2013
2014 European Discovery Fast Track
Challenge results
18 March 2015 Introduction to DPAc
232 Proposals Submitted
from
131 Institutions
14 Finalists
9 Winners
24 Countries
DPAc and Discovery Fast Track Challenge
collaborations
19 March 2015 Introduction to DPAc
Discovery Fast Track
Challenge 2013
Winner Institutions
• Pennsylvania State University
• Albert Einstein College of Medicine of
Yeshiva University
• Boston University and University of
California, San Francisco
• Harvard Medical School
• University of Pennsylvania
• Université de Sherbrooke
• University of North Carolina at
Chapel Hill (x2)
Discovery Fast Track
Challenge 2014
Winner Institutions
• Mayo Clinic
• Johns Hopkins
• University of Pennsylvania
• University of Texas Southwestern
Medical Center
• University of Iowa
• University of Toronto
• University of Milan
• University of Cambridge (x3)
• National Institute of Health and Medical
Research
• Research Center for Molecular Medicine
• King’s College London
• VU University Medical
DPAc Partnership
Institutions
• University of Edinburgh
• University of Dundee
• University of Nottingham
• University of Cambridge
• University College, London
• Université Paris Descartes
• University of Dundee (University of
Mainz)
• Rappaport Family Institute, Haifa,
Israel
• Fred Hutchinson Cancer Research
Center
• Vanderbilt University
• University of Toronto/Hospital for Sick
Kids
• Yale University
Discovery Fast Track Challenge proposals
yield broad therapeutic coverage
20 March 2015 Introduction to DPAc
Europe 2014 (232 total) North America 2014 (196 total)
Discovery Fast Track Challenge 2015
21 March 2015 Introduction to DPAc
Challenge
Opened
Mar 23
Europe
North America
Registration
Closes
Apr 24
Europe
North America
TTO Approval
Deadline
May 8
Europe
North America
Finalist
Presentations
Jul 14-17
Europe
(Stevenage, UK)
Sept 28-30
North America
(PA, US)
Winners
announced
Jan 2016
Europe
North America
Investigator submits
1 page non-
confidential proposal
TTO approval required
for GSK review
GSK selects finalists,
assigns mentors
Expanded confidential
proposals
Material transfer and
work-plan agreement s
signed
GSK scientist teams
assigned to project,
and work begins
towards screening
1 2 3 4 5
Find more information at gsk.com/discoveryfasttrack
Who we are: dpac.gsk.com
22 March 2015 Introduction to DPAc
Duncan Holmes
European Head
LONDON
Mark Bamford
Chemistry,
LONDON
Iain Uings
Biology, LONDON
& CALIFORNIA
John Liddle
Chemistry,
LONDON
Ann Walker
Chemistry,
LONDON
Stephane Huet
Biology,
PARIS
Jeremy Griggs
Biology,
LONDON
Danuta Mossakowska
Biology,
LONDON
Andy Pearce
Biology,
LONDON
Colin Macphee
Biology,
PHL
Jakob Busch-Petersen
Chemistry,
PHL
Andy Pope
Biology,
PHL
Carolyn Buser-
Doepner
Global Head, PHL
Dan Paone
Chemistry,
PHL
Dedicated team of scientists, each of
whom has proven track record in drug
discovery
Your gateway to GSK’s global
expertise and resources
Jon Collins
Chemistry,
RTP, NC
Katherine Widdowson
Chemistry,
CALIFORNIA
Debra Peattie
Biology,
BOSTON
Dave Parry
Biology,
CALIFORNIA
Mike Bishop
Chemistry,
RTP, NC
Dave Becherer
Biochem ,
RTP, NC
Dennis Yamashita
Chemistry,
BOSTON