Panel2: Working with the Current Regimepearl.s.huang@gsk.com22Nov2013National Academy of SciencesWashington, D.C.

Investing in innovation

230 September 2013GSK at a glance

£3.5bnR&D investment in 2012

Increasing trust through open science

“At GSK we recognize that great science happens outside as well as inside our walls. In fact, we see collaborations with other researchers as an important component of our R&D activities, complementing our in-house efforts and advancing scientific understanding in key areas and facilitating the rapid discovery and development of new medicines for patients.”

From trustinscience.gsk.com

DDW Open Innovation Approach

4

Investment in DDW to act as a catalyst and stimulate research outside of GSK

22nd October 2013D34DDW

1. Providing access to our

know-how and resources via

the open lab

2. Sharing our data with the

research community – “open

source”

3. Being more flexible with

our IP

Three key elements

K. Guy, R. Gilbertson (St. Jude CRH)• Neurosphere models of rare pediatric cancers

The Kinome Test Set: > 100 collaborations

V. Lemmon, J. Bixby (U. of Miami)• High content imaging in primary rat neurons

6 nM GW779439X

Examples

External funding enabled by GSK PKIS

Category Investigator Focus Source

<$0.1M Adrienne Flanagan, UCL Chordoma Sarcoma UK

John de Groot, MD Anderson Glioblastoma TxSACT

Andrew Tobin, U of Leicester Malaria MRC

$0.1-1.0 M Milica Radisic, U of TorontoBeating cardiacorganoids

CIHR

Steve Pollard , UCL Neuroblastoma CRUK

Nanosyn Kinase screening Nanosyn/SGCCIHR: Canadian Institute for Health Research

TxSACT: Texas Screening Alliance for Cancer Therapeutics CRUK: Cancer Research UK

Category Investigator Focus Source

<$0.1MBin Teh(Natl. U of Singapore)

Bile duct cancer Public

>$1.0MMultiparty (U of Campinas, Brazil)

Kinome PPP Public

Pending applications:

Funded applications:

The DPAc Model and Organization Are Unique

Collaborative Invention

Shared Ownership

Risk Embracing

Research Milestones

Candidate Clinical NMEs

POCs and C2MD

A discovery team with the remit to build a rolling pipeline of 13

candidate medicines, with an academic partner at the center of each project.

A collaborative approach from GSK

Build integrated partnerships that can translate

innovative research into medicines that benefit patients.

GSK has capabilities and expertise which will help

progress the project to the next milestone.

A path to identification of a drug molecule can be defined.

Target knowledge suggests that a drug-like molecule can

be generated.

Academic partner has know-how and/or expertise essential to

progressing the target which is not (readily) found elsewhere.

Specific drug target identified, and some understanding

of type of pharmacology desired.

What Are We Looking For?

A coherent and supportable hypothesis that modulation of

target will produce a physiological effect which will be of

therapeutic benefit to particular patients.

Requirement

for GSK

contribution

Tractability

(Exclusive)

enabling

expertise

Target

defined

Clear

therapeutic

hypothesis

Academic researchers who:

• Want to be involved in turning their innovative research

into medicines

• Will contribute their own effort and resources to making

projects work

• Have recognised expertise in their chosen field

• Bring something unique to the collaboration

Who is best suited for DPAc ?

Managing the relationship

• A co-authored and detailed work plan creates a framework to

promote rapid project initiation and execution

• Working together – Joint Research Committee

• Joint investment of time/energy/resource to progress the

project at both partner sites

• Strong interactive relationships between project team

• Equitable approach to IP

– Academic will receive commercial rights if GSK terminates the collaboration

How these new projects operate

Collaborative partnerships focussed on drug discovery

Starts at any point from initiation of early screening to late lead optimisation

Considers any disease area

Operates in any geography

Looks for a complementary match of skills where GSK can make a positive

contribution to success

This isn’t

✗Support for exploratory work

✗Focus on technology platforms

✗Broad multi-project collaborations

✗An open ended funding stream

Screening

Chemistry

Value of GSK

contribution$

Typical GSK activities

Assay Feasibility

Tool GenerationAssay Development

Screening

Chemistry

DMPK

Chemistry

DMPK

Safety

Pharmacy

$ $$ $$$ $$$

Assay

Dev

Target

Feasibility

Lead

ID

Early

LO

Late

LO

Pre-

ClinicalFTIH PhIIa PhIIb PhIII

Launch

Lead

Identification

Late Lead

OptimizationEarly Lead

Optimization

Assay

Development

Target

Feasibility

Drug Discovery

Initiated

Screen

Initiated

Lead Identified

In Vitro

Candidate

Selection

Lead Identified

In Vivo

Reagent Generation

Value research

support & reward

Physiological AssaysAssay Development

Typical academic activities

Physiological Assays

In Vitro and In VivoPhysiological Assays

In Vivo Models

$ $ $ $ $$+ downstream milestones

and royalties

Shared Activities Between Academia and GSK

We Have Established Nine Rewarding Partnerships

Developing treatments

for Recessive Dystrophic

Epidermolysis Bullosa and

other genetic diseases

Professor

Irwin McLean,

University of

Dundee

Mark

Bamford,

GSK

Preventing Multiple

Organ Failure in Severe

Acute Pancreatitis

Mr Damian

Mole,

University of

Edinburgh

John

Liddle,

GSK

Stabilisers of Transthyretin

as a treatment for

Transthyretin Amyloidosis

Professor Sir

Mark Pepys,

University

College of

London

Duncan

Holmes,

GSK

A disease modifying

approach to the

treatment of

Huntington’s Disease

Professor

Susann

Schweiger,

University of

Dundee

Iain

Uings,

GSK

Treating a1-Antitrypsin

Deficiency using small

molecule stabilisers

Professor

David

Lomas,

University of

Cambridge

Andy

Brewster,

GSK

Topical Therapy for

Netherton Syndrome,

Rosacea and Atopic

Dermatitis

Professor

Alain

Hovnanian, Paris

Descartes

University

John

Liddle,

GSK

We Have Established Nine Rewarding Partnerships

Progression through “Research Events”

already met in several projects

Professor

Roger

Cone

Dennis

Lee,

GSK

Prevention of DUX4-

mediated muscle atrophy

for treatment of

facioscapulohumeral

muscular dystrophy Professor

Stephen

Tapscott

Jon

Collins,

GSK

Modulators of MC4R for

treatment of obesity

Dual potentiator-

correctors of F508del

CFTR For Cystic Fibrosis

Professor

Christine

Bear

Jakob Busch-

Petersen,

GSK

Discovery Fast Track Competition

• For the first time, GSK will open access to its internal screening

capability—and industrialize a novel discovery concept posed by U.S.

and Canadian academic institutions

• Promising results may lead to an opportunity for the academic

institution and GSK to collaborate via the Discovery Partnerships for

Academia (DPAc) team

• The researcher provides a novel drug development concept that may include

assay protocols, tools, reagents and models

• GSK contributes an established capability to scale up and industrialize

assays and data analysis

How Does Discovery Fast Track Work?

70 institutions participated and 47% were new to DPAc

17

Surprisingly, all but one of the winners are on the East Coast…

We received 142 applications from 70 institutions

Graphical depiction of states participating in the US (blue)

Applications from 26 US States and 4 Canadian Provinces

10,589 hits to the website

14 of the Top 25 US Research

Universities applied,

of those four winners were

selected

Winners represented a range of therapeutic areas

18

Distribution of all proposals matched well with TA funded research in academia

Distribution of all proposals matched well

with TA funded research in academia

• Finalists and winners crossed a variety

of therapeutic areas

We Have Selected Eight Fast Track Winners

The selected scientists will collaborate

with GSK to rapidly screen and identify

novel compounds to test their promising

hypotheses.

Professor

Myles

Akabas

Patrick

Eidam,

GSK

A novel approach for

an anti-microbial

agent class of

antibiotic for gram

negative bacteria Professor

Sarah

Ades

Dennis

Lee,

GSK

A novel approach for

new treatments for

malaria

New compounds

for new

treatments of

LeishmaniasisProfessor

Lauren

Brown

Debra

Peattie,

GSK

Professor

Scott

Schaus

A novel approach for

the design of

antibiotics to

overcome clinical

resistance Professor

Rahul

Kohli

Katherine

Widdowson

GSK

Professor

Jim

McKerrow

We Have Selected Eight Fast Track Winners

The winning projects show clear

opportunities to deal with important

unmet medical needs.

Professor

Deborah

O’Brien

Jon

Collins,

GSK

A novel approach for

new treatments for

iron overload diseases

Professor

Richard

Leduc

Jakob Busch-

Peteresen,

GSK

A novel approach to

regulation of male

fertility

A novel approach for

new treatments for

metastatic epithelial

cancers

Professor

John

Sondek

Andy

Pope,

GSK

Winner wishes to

remain anonymous

Winner chooses to

remain anonymous

Dennis YamashitaGSK

DPAc: Who we are

Duncan Holmes European Head

LHR

Jon CollinsChemistry , RTP

David ParryBiology,, SAN

Pearl HuangBiologist and Global Head. PHL

Mark BamfordChemistry, LHR

Iain UingsBiologist, LHR and SAN

John LiddleChemistry, LHR

Andy PopeChemistry, PHL

Dennis LeeChemistry , PHL

Jakob Busch-Petersen

Chemistry , PHL

Ann WalkerChemist. LHR

Dennis YamashitaChemistry, BOS

Jeremy GriggsBiology, LHR

Katherine WiddowsonChemistry, SAN

Debra PeattieBiology,, BOS

Patrick EidamChemistry , Esprit

Stephane HuetBiology, CDG

Danuta MossakowskaBiology, LHR

A dedicated team of scientists,

each of whom have a proven track

record in drug discovery

Your gateway to GSK’s global

expertise and resources

Andy BrewsterRespiratory Chemistry, LHR

? ?

Thank you