Introduction to Discovery Partnerships with Academia (DPAc)

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


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?


DPAc partnership


• 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


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?


• 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



Assay Development

Target Feasibility

Partnerships focused on drug discovery Planning all the way to the medicine


Lead Identification



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


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

http://karin.md.technion.ac.il/Karin/UploadFiles/pgallery/6674088454.jpg

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

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&ved=0CAcQjRw&url=http://en.wikipedia.org/wiki/Cold_Spring_Harbor_Laboratory&ei=YJ7GVLzuJYLSaLCbgvgG&bvm=bv.84349003,d.d2s&psig=AFQjCNFlN8xlGv85BLW3H-BZQrY2gTLVrg&ust=1422389208486949

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


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


2014 North American Discovery Fast Track

Challenge results


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


232 Proposals Submitted

from

131 Institutions

14 Finalists

9 Winners

24 Countries

DPAc and Discovery Fast Track Challenge

collaborations


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


Europe 2014 (232 total) North America 2014 (196 total)

Discovery Fast Track Challenge 2015


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


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

http://www.dpac.gsk.com/

Science

Introduction to Discovery Partnerships with Academia (DPAc)