Engineering Academic Collaborations Malcolm Skingle CBE PhD

IoB Launch Event, QML

8th October 2015

Talk Plan

• GSK Global Collaborations programme

- Scale

- Process for initiating new collaborations

• Innovation examples involving engineering:

- Bioelectronics

- Working with equipment manufacturers

- Working with other funding agencies & sectors

• Concluding remarks

Who we are

Pharmaceuticals

Develop and make medicines

to treat a range of conditions

including respiratory diseases

and HIV/AIDS

Vaccines

Research and make vaccines

for children and adults that

protect against infectious

diseases

Consumer Healthcare

Categories include: Wellness,

Skin health, Oral health and

Nutrition

4

4bn packs of medicines

in 2014

800m

doses of vaccines

in 2014

18bn packs of consumer healthcare

products in 2013

84 Manufacturing facilities in 36 countries in 2014

Major research

and development

facilities in

3 continents

More than 100,000 employees

Source: “About us,” gsk.com, accessed 18 May 2015

Accelerating innovation through collaboration

30 Internal Discovery Performance Units

External innovation engines are those collaborations that are greater than £10m in value and are focused on assets that are currently pre-POC. The

collaborations include in-licenses, option arrangements and technology arrangements focused on producing new molecules.

MD Anderson

Cancer Center

IMI (consortium)

As of 26 May 2015

40 External innovation engines

Areas of interest for future collaboration

Dermatology Immuno-oncology

Cell & Gene Therapy Inflammatory Diseases

Neurodegeneration

HIV & Infectious

Diseases Respiratory

Bioelectronics Metabolic & CV Diseases Platform Technology

GSK – UK Academic Research Partners

Birmingham Cambridge

Southampton

Edinburgh Glasgow

Cardiff

Dundee

Sheffield

Leicester

GSK currently has >500

active research collaborations

ongoing with UK Universities.

Two way exchange of knowledge &

technology

Newcastle

Durham

Leeds

Ulster

Belfast

York Hull

Nottingham Loughborough

Warwick

Manchester Liverpool

Buckingham Oxford Reading

Hertfordshire Essex

Canterbury

Brighton Portsmouth

Surrey Bristol

Exeter

Bath

Lancaster Bradford

Cranfield Ipswich

Country No.

Austria 1

Belgium 4

Denmark 4

France 16

Germany 21

Greece 1

Ireland 10

Italy 4

Netherlands 4

Norway 2

Spain 4

Sweden 4

Switzerland 15

EUROPEAN ACTIVE AGREEMENTS BY COUNTRY

Spain

Portugal

UK

Iceland

Ireland

Germany

France

Switzerland

Italy

Austria

Belgium

Holland

Norway

Sweden

Denmark

Lux

Poland

Czech R.

Hungary

Slovenia Croatia

Corsica

Sardinia

Sicily

Bosnia & Herz

Slovakia

Serbia

Albania

Greece

Macedonia

Bulgaria

Romania

Ukraine

Belarus Russia

Lithuania

Latvia

Estonia

Finland

Russia

Moldova

Turkey

Crete

GSK Agreements by State

IO

AL

IN 5

GA

NY (15)

NC (13)

MD (6)

PA (18)

MA (30)

CA (13)

MI

TX (6)

CO

WA(13)

MO (3)

IL (5)

FL(2)

NJ(2)

VA DE

1 Agreement

CT(3)

April 2013-June 2015 (RCAs and Licenses)

5-9 Agreements

2-4 Agreements

More than 15 Agreements

10-13 Agreements

OH (10)

Massachusetts MA(30)

Pennsylvania PA(18)

New York NY(15)

North Carolina NC(13

California CA (13)

Washington WA13

Ohio OH10

Maryland MD(6)

Texas TX (6)

Illinois IL5

Indiana IN5

Connecticut CT3

Missouri MO3

OKLAHOMA OK3

TENNESSEE TN3

Florida FL2

GEORGIA GA2

NEW JERSEY NY2

Alabama AL1

Colorado CO1

IOWA IO1

Michigan MI1

Virginia VA1

TN(3)

OK3

Top 15 companies by REF analysis and

collaboration data

Top 40 companies ( 15/40

Pharma)

MRC Collaborations reported through Researchfish

420 Other On-going Collaborations

Why Collaborate ?

Share risks & rewards

Harness other sources of funding

Access knowledge & new thinking

Build global links

Networking

Recruitment

Think longer term

Criteria for selection of collaborative projects

Strategic fit to GSK research

Quality of science in the proposal

Availability of facilities and resources

High likelihood of useful new information or

technology arising

Timing with respect to deliverables

Value for money

Process for Internal Approval of Research Collaborations

Industrial scientist discusses proposal with academic to identify areas of common interest

Assumes role of industrial champion & discusses project with Academic Liaison

Review project priorities with respect to resources & budget

Academic Liaison negotiate & implement agreement

Use standard agreements wherever possible

What does Industry want from Universities?

Access to ………..

Industry-friendly lateral thinking academics

Know-how

Potential recruits

An awareness of developing technology

To address the big industry challenges…………

Critical mass of strategic thinking scientists

A multi-disciplinary approach to problem solving

Effective project management

Points for Academia to consider when choosing an Industrial Partner

Is the industrial scientist likely to make a significant

intellectual contribution to the project?

Does the company have a good track record for

collaborations with academia?

Does the industrial scientist have access to knowledge or

technology which may contribute towards the aims of the

proposed research?

Is the industrial partner well placed to exploit intellectual

property arising from the collaboration in an efficient &

effective way?

Review scientific literature & company's web site & annual

report to provide useful information

D

R

A

F

T

-

N

O

T

F

O

R

E

X

T

E

R

N

A

L

V

I

E

W

Innovation examples

involving engineering in

GSK Collaborations

Bioelectronic medicines – the vision

19

Complementing molecular medicines with

electrical impulses

20

Image source::http://jn.physiology.org/content/jn/98/4/2244/F6.large.jpg; http://www.frontiersin.org/files/Articles/62833/fphar-04-00103-r2/image_m/fphar-04-00103-g007.jpg

Healing Spark: Hack body electricity

to replace drugs

New Scientist Feb 2014

Stop popping Start zapping

Major types of medicines don’t do it alone – they tap into

nature’s control systems

21

Signalling control Neural control

Small molecules leverage

intra- and extra-cellular

signalling cascades

Immune control

Bioelectronic medicines

will leverage the nervous

system

Image source: http://en.wikipedia.org/wiki/Ligand_(biochemistry); http://www.rndsystems.com/resources/images/6295.gif; http://www.empowher.com/media/reference/x-linked-

adrenoleukodystrophy

Vaccines and antibody

drugs leverage the

immune system

The nervous system lends itself to wide-reaching class of

precision medicines

22

Image source: Atlas of Human Anatomy, 5th edition, Frank H Netter; Mosby's Medical Dictionary, 8th edition

vs

Objectives of GSK Bioelectronics R&D

1. Identify specific nerve circuits

that control or effect organ

dysfunction and diseases.

2. Understand these nerve circuits

and signals, and how they can

differ in healthy and diseased

states.

3. Develop implantable devices

(‘neural interfaces’) that can attach

to nerves and enable precision

recording/stimulation to influence,

and ultimately treat, disease state.

Anatomy

Physiology

Engineering

Visceral peripheral nerves reach a multitude of organs

implicated in chronic diseases

Bioelectronic Medicines 24

A broad body of activity during the last 2 years

• A research network (30-40 academic collaborators)

seeking pre-clinical proof of principles across a range of

chronic diseases, and visceral nerve interface designs

• Building of a research toolkit for visceral nerve

interrogation from rats to man, including the “Innovation

Challenge”

• Building in house capabilities (LAS Stevenage)

• Venture funding to nurture start-ups with early

manifestations of bioelectronic medicines and enabling

technologies

• Engagement with the broader ecosystem of public and

private parties to support foundational research and effective

translation (NIH, DARPA, Welcome Trust, EPSRC)

25

Exploratory research

Pre-clinical discovery

Experimental medicine

Therapeutic development

Interfaces to the nerve will be key to success

Bioelectronic Medicines 26

Biocompatible

Functional

Novel

• Softening

• Conformational

• Biological

• Functional

separation

• High-density

• Embedded probes

• Optogenetics

• Nanoparticles

• Electrical impedance

tomography (EIT)

Image sources: Reeder et al, Adv. Mater. 2014, 26, 4967–4973; Chew et al, Sci Transl Med 5, 210ra155 (2013); Flytzanis et al, Nat Commun. 2014 Sep 15;5:4894

2 mm

grain

of rice

Figure 1: Image of a fullywireless, cellular-scale LEDsystem for optogenetics,wrapped around a grain ofrice to illustrate its size andflexibility (left) and implantednear the sciatic nerve in amouse model (right).

Our device goal: specific, small and smart implants

Defining features

27

Why

• Selectively address one circuit that control one

function without side effects Specific

• Close the loop enables personally optimised and

adaptive treatment Smart

• Facilitate broad access through minimally invasive,

safe, quick implantation Small

Today’s reference point are “metal can and leads” devices

28

Source:CVRx; SetPoint Medical; inspiresleep.com; N Engl J Med 2014;370:139-49; http://www.bariatricnews.net/?q=news/11179/vbloc-therapy-new-dawn

However, miniaturisation is starting

29

Low-power, miniaturised components from consumer

electronics can accelerate this further

30

Source: Apple; http://www.smartdatacollective.com/sites/smartdatacollective.com/files/IoT%202.png

The pre-clinical and clinical evidence is emerging

Source: New York Times, May 23, 2014; Koopman, F. A. et al. Arthritis Rheum. 64 (suppl.), abstr. 451 (2012).

DAS28 in 8 RA patients that had failed on methotrexate after

vagus nerve stimulation

Acetylcholine signalling in Ach in splenic nerve induces phenotypic changes in macrophages & monocytes =

decreased sensitivity to pro-inflammatory signals

Global Summit seeks to bring together research leaders from multiple key disciplines

3

CRACK IT Solutions – connecting technology

developers with new partners, users and markets

World Health Statistics, 2009

Smoking in China

Men Women

67%

4%

%

70

60

50

40

30

20

10

350 million smokers

GSK Sponsor 3Rs Prize

Mouse mini-livers from adult mouse stem cells

Meritxell Hutch, Gurdon Institute

Working with instrument manufacturers

• High spatial resolution

– to study compound distribution in organelles

– Initially ca 200 nm & ultimately ca. 50 nm

• High mass resolution

– identify drug and metabolites (study metabolic degradation of compound)

– identify endogenous molecules

• Ability to maintain tissue & cellular morphology

– Cryostage?

– Freeze fracture?

– Study structural changes in cell

• High resolution optical system

– Locating cell types in tissue section

– Determining precise location of ion image

Confidential Property of GlaxoSmithKline

3D nanoSIMS

World beating Label Free Molecular Imaging

• NPL - Prof Ian Gilmour

• GSK - Dr Andy West

• ION-TOF - mass spectrometers for imaging

• Thermo ScientificTM - OrbitrapTM mass analyzer for high-

performance identification of substances.

• University of Nottingham - Profs Morgan Alexander, Martyn

Davies & Clive Roberts

• University of Illinois at Chicago. - Luke Hanley

3D nanoSIMS – major new project

• Scan speed up to 18 Hz

• Resolving power up to

240,000 at m/z 200

• Sub ppm mass accuracy

New analyser

50 nm LMIS

Argon cluster beam

Designed for laser

post-ionisation

Press release Dec 2013

Thermo Scientific™

Q Exactive™ HF Orbitrap

mass spectrometer

£4.5m Strategic Capability Programme –

National Measurement System BIS

surface analysis (top) & depth profile (bottom) of

villus, 1.5 m spatial resolution

500 x 500 μm²

total

235.07 u

400 x 400 μm²

184.11 u

235.08 u

Phosphocholine head group

Compound specific fragment

Compound specific fragment

Sum of all ions in MS (TIC)

Epithelial cells

(enterocytes)

Lamina

Propria

Villus edge

Confidential Property of GlaxoSmithKline

Confidential Property of GlaxoSmithKline

View from above

Side view

Epithelial cell

Lamina Propria Enterocytes

GSK McLaren Collaboration (15th Sept 2011)

McLaren – dynamic learning culture based on self-

examination & attention to detail e.g. rapid design & prototyping to continuous monitoring of car &

performance

Brand-new state-of-the-art learning facility “the McLaren GSK

Centre for Applied Performance” next to McLaren Technology

Centre in Woking, Surrey (2013)

Advanced

Telemetry

Pre & Post

Race

Analysis

Design

Simulate/

Race

Real-time

Data Capture,

Management &

Visualisation

Why McLaren? Telemetry & data analytics expertise

Telemetry expertise:

500 sensors per car

Creating over 1100 channels at up to

1000Hz

1,400,000,000 DATA POINTS IN

RACE

...IN REAL TIME

What makes a Great Strategic Partnership

World-leading science

Regular & honest communication

An appreciation of each others capabilities

Trust – must have effective Chinese walls

Clear scientific programme setting out aims & objectives

Publications

Thanks for listening Malcolm.7.skingle@gsk.com

Our long-term vision is microscopic medicines that speak the electrical language of the body

Illustration of a future medicine selectively modulating the firing patterns in the carotid sinus nerve

GSK seeks step changes from today’s large neuro-stimulation devices both in biology and technology

To From

Large devices

affecting

neural tissue

with simple

waveforms

Miniaturised

devices

reading and

writing

naturalistic

signal

patterns

Targeting the

brain, spinal

cord, and

nerve trunks

with broad

effects

Targeting

small

“peripheral”

nerves that

are close to

and specific

to organs

Image sources: http://patients.dartmouth-hitchcock.org/pain_mgt/spinal_cord_stimulation.html; http://www.bbc.co.uk/news/health-12274271; Mosby's Medical Dictionary, 8th edition

GSK seeks step changes from today’s large neuro-stimulation devices both in biology and technology

To From

Large devices

affecting

neural tissue

with simple

waveforms

Miniaturised

devices

reading and

writing

naturalistic

signal

patterns

Targeting the

brain, spinal

cord, and

nerve trunks

with broad

effects

Targeting

small

“peripheral”

nerves that

are close to

and specific

to organs

Image sources: http://patients.dartmouth-hitchcock.org/pain_mgt/spinal_cord_stimulation.html; http://www.bbc.co.uk/news/health-12274271; Mosby's Medical Dictionary, 8th edition

The exploratory research projects GSK currently integrate focus on three CONVERGING areas

Biology –

Disease

spectrum

Neuroscience –

treatment code Neural engineering –

Peripheral neural

interface

Material science –

biocompatibility, energy and biosensors

Electronics–

low-power

circuits, data

transfer and

management

Neurosurgery –

Minimally invasive,

precision

procedures

2013-14 GSK research

investment focus

GSK’s three-pronged approach to activate the field of bioelectronic medicines research

1. Exploratory research in a network of 20 funded groups in academia and

small companies around the world (40 full time researchers)

2. Dedicated venture fund to support start-ups pursuing early manifestations

of bioelectronic medicines and enabling technology platforms ($50m)

3. Integration of a broader research community that lay the foundation for

bioelectronic medicines

1. Global summit with research leaders to set research roadmap

2. $1m innovation prize

3. Engagement with public and philanthropic funding bodies

1

2

3

Key Performance Indicators

People exchange in both directions

Reagent exchange

Access to technology platforms

Access to well phenotyped tissue

Amount of grant funding leveraged

Number of interactions between

consenting adults

Publications in top journals

Sharing science A selection of GSK Nature publications in 2012

Peripheral nerves at the centre of translation

51

While brain research is…

Therapeutic circuit tuning will start in the periphery

• Arguably the biggest scientific challenge of our time

• Critical for understanding most neural circuits

• A centre stage for innovative tool development

• Chronic diseases affecting billions

• Near-organ nerves lower level of complexity

• More reliable animal models of disease

• Objective clinical endpoints

• Potential for lower-risk surgery

Image source: Mosby's Medical Dictionary, 8th edition

A broad body of activity at the onset of this journey

• A research network across a range of chronic

diseases, visceral nerve interfaces, and next-

generation device technologies and architectures

• Building of a neuromodulation toolkit for

visceral nerve interrogation from rats to man,

including the rapidly progressing “Innovation

Challenge”

• Venture funding to nurture start-ups with early

manifestations of bioelectronic medicines and

enabling technologies

• Engagement with the broader ecosystem of

public and private parties seeking to ensure

foundational research and effective translation

Bioelectronic Medicines

52