2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van Gool

Personalized Health(care): more than just targeted medicines

Professor of Personalized Healthcare Head Radboud Center for Proteomics, Glycomics and Metabolomics Coordinator Radboud Technology Centers

Senior Scientist Integrator Biomarkers

Prof Alain van Gool

Opening Radboud Translational Medicine Nijmegen, 9 Dec 2015

My background in personalized health(care)

8 years academia (NL, UK)

(molecular mechanisms of disease)

13 years pharma (EU, USA, Asia)

(biomarkers, Omics)

4 years med school (NL)

(personalized healthcare, Omics, biomarkers)

4 years applied research institute (NL, EU)

(biomarkers, personalized health, nutrition)

1991-1996 (PhD)

1996-1998 (post-doc)

2009-2012 (visiting prof)

1999-2007 2007-2009 2009-2011

2011-now

2011-now (prof)

2 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

A person / citizen / family man (adventures in EU, USA, Asia)

Source: Chakma, Journal of Young Investigators, 16, 2009

Principle of Personalized/Precision/Targeted Medicine

3

Molecular biomarkers as key drivers to select right patient for right drug at right dose at right time: Companion Diagnostics


Example: Personalized Medicine in melanoma

Key biomarkers: Stratification: BRAFV600E DNA mutation assay Mechanism: P-ERK Cyclin-D1 Efficacy: Ki-67 18FDG-PET, CT Clinical endpoint: progression-free survival (%)

{Source: Flaherty et al, NEJM 2010} {Source: Chapman et al, NEJM 2011}


Companion diagnostics in current drug labels

Metabolism

Efficacy or safety

{Source: www.fda.gov (June 2013)}

= molecular biomarker that indicates the right patient for right drug at right dose at right time


Exponential developments in biomarker technologies

• Next generation sequencing • DNA, RNA • Risk analysis and therapy selection

• Mass spectrometry

• Proteins, metabolites • Monitoring of disease and treatment effects

• Imaging • Non invasive images, real time • Spatial view of intact organs and organisms

500

1000

1500

2000

m/z

5 10 15 20 25 30 35 40 Time [min]


Emerging companion diagnostics

Good examples personalized medicine in Oncology and Neurosciences:

• Cyp450, Her2/neu, BRCA, BRAF, EGFR, EML4/ALK, etc

Emerging companion diagnostics, also linked to non-drug therapies:

• Volker: Intestinal surgery → XIAP → Cord blood

• Beery twins: Cerebral palsy → SPR → Diet 5HTP

• Wartman: Leukemia → FLT3 → Sunitinib

• Gilbert: Healthy → BRCA → Mas/Ovarectomy

• Snyder: T2Diabetes → GCKR, KCNJ11 → Diet, exercise

• Lauerman: Scotoma, leg → JAK2 → Aspirin

• Bradfield: Healthy → CDH1 → Gastrectomy

Coming up: metabolic biomarkers, imaging biomarkers


Rational selection of best targets and biomarkers works

The 5R’s assessment:

• Right Target

• Right Tissue

• Right Safety

• Right Patients

• Right Commercial Potential


9

Optimal Personalized / Precision / Targeted Medicine

People are more than linear pathways

People are more than linear pathways

{Source: Barabási 2007 NEJM 357; 4}

• People are different • Different networks and influences • Different risk factors • Different preferences


Personalized health(care) in a systems view

12


Societal need in efficient personalized health(care)

{Source: prof Jan Kremer}

Towards cost effective care, less cure


Personal need in efficient personalized health(care)

It’s personal !

‘I want to stay healthy.’ ‘If not, how do I get healthy?’


My route to Personalized Health(care)


Analogy: TOMTOM

GPS to a location

Amsterdam

Traffic jam

Amsterdam

Route 1 Route 2

= Default Traffic jam near Utrecht Alternative route


Personalized Health(care) model

GPS to health

Health

Route 1 Route 2

= Default First signs of disease risk

Alternative route

Now

Disease risk

Health

Now

Health



18

New data (generators, owners)

Key aspects of personalized health(care)

‘I want to stay healthy. If not, how do I get healthy?’

1. What to measure?

2. How much can it change?

3. What should be the follow-up for me?


1. What to measure?

Discovery Clinical

validation/confirmation

Diagnostic

test

Number of

biomarkers

Gap 1

Gap 2

Gap 3

• Too much biomarker discovery • Too little development to application

Alain van Gool, Workshop Neuroinformatics and personalized health care , Nijmegen, 26 Nov 2015 21

Biomarker innovation gaps!

Biomarker innovation gaps: some numbers

5 biomarkers/ working day

1 biomarker/ 1-3 years

1 biomarker/ 3-10 years

?

Eg Biomarkers in time: Prostate cancer May 2011: n= 2,231 biomarkers Nov 2012: n= 6,562 biomarkers Oct 2013: n= 8,358 biomarkers Nov 2014: n= 10,350 biomarkers Oct 2015: n = 11,856 biomarkers

Discovery Clinical

validation/confirmation

Diagnostic

test

Number of

biomarkers

Gap 1

Gap 2

Gap 3


2. How much can it change? Personalized Intervention

of patients-like-me Personal thresholds of persons-like-me

Big Biomarker Data

Molecular Non-molecular Environment …

Ho

meo

sta

sis

A

llo

sta

sis

D

isease

Time

Disease

Health

Selfmonitoring

Adapted from Jan van der Greef, TNO (2013)

Personal profile

Personalized health

Personalized medicine


3. What should be the follow-up for me?

Personal profile data

Knowledge

Understanding

Decision

Action


Translation is key in Personalized Healthcare !

“I’m afraid you’re

suffering from an

increased IL-1β and

an aberrant miR843

expression”

Adapted from:

?


Shared decision making

Select personalized therapy

Treatment options

Succ

ess

rate

s

Example from Prostate cancer patient guide


{Source: Peep Stalmeier}

Shared decision making

Treatment options

Pro’s

Con’s

Select personalized therapy

Example from Prostate cancer patient guide


{Source: Peep Stalmeier}

Flipping the coin

Via the ónly constante in

healthcare: The patient Via HC ICT systems


{Source: Lucien Engelen}

http://www.hereismydata.com/

Patient

Radboud Personalized Healthcare

A significant impact

on healthcare

Molecule

Population


Orientation across the spectrum from molecule to man to population

Ori

enta

tio

n a

cro

ss

the

spec

tru

m o

f d

isea

ses

Researcher

Research Theme

Te

chn

olo

gy

C

ente

r

Research support by Technology


www.radboudumc.nl/research/technologycenters

Genomics

Bioinformatics

Animal studies

Stem cells

Translational neuroscience

Image-guided treatment

Imaging

Microscopy

Biobank

Health economics

Mass Spectrometry

Radboudumc Technology

Centers Investigational

products

Clinical studies

EHR-based research

Statistics

Human performance

Data stewardship

Molecule

Flow cytometry


About 250 dedicated people working in 18 Technology Centers, ~2000 users (internal, external), ~150 consortia www.radboudumc.nl/research/technologycenters/

• Proteins • Metabolites • Drugs • PK-PD

• Preclinical • Clinical

• Behavioural • Preclinical

• Animal facility • Systematic review

• Cell analysis • Sorting

• Pediatric • Adult • Phase 1, 2, 3, 4

• Vaccines • Pharmaceutics • Cyclotron • Radio-isotopes • Malaria parasites

• Management • Analysis • Sharing • Cloud computing

• DNA • RNA

• Internal • External

• Early HTA • Evidence-based

surgery • Field lab

• Statistics • Biological • Structural

• Preclinical • Clinical • Economic

viability • Decision

analysis

• Experimental design • Biostatistical advice

• Electronic Health Records • Big Data • Best practice

• In vivo • Functional

diagnostics

• iPSC • Organoids

32

• Cyclotron

Technology Center Investigational Products

www.radboudtranslationalmedicine.nl/

GMP licensed production of clinical grade therapeutic materials

• Radio isotopes

• Cell therapies (cells, vaccins)

• Pharmaceutics

• Malaria parasites


{Source: Anne de Goede, Frans Pieters + team}

Technology Center Imaging

• State-of-the art (pre)clinical imaging equipment and expertise:

CT, MRI, US, PET/CT, SPECT/CT, photoacoustic imaging, fluorescence imaging

• Strongly linked to RTC Microscopy

• Covers spectrum from molecule to man to population

• Hardware, software, expertise, innovation, impact


{Source: Otto Boerman, Chris de Korte, David Norris, Sven Lafebre, Peter Friedl + team}

http://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.ru.nl/donders/organization/organization/&ei=QwxvVK3kPIf2OozvgagD&bvm=bv.80185997,d.ZWU&psig=AFQjCNFKo5Vdth9Czt5MgBUjLZ_8w4rqcA&ust=1416650177185352

http://biomr.runmc-radiology.nl/images/7/79/Biomed_research_RUN-MC_4.jpg

Technology Center Image-guided treatment • Integrated workflow with imaging guidance in operation rooms • Field lab environment to drive innovations

{Source: Jurgen Fütterer, Maroeska Rovers, Mathias Prokop + team}

Access

Combination of • Science • Technology • Business • Innovation • Impact in health

www.radboudumc.nl/research/technologycenters/

(1H2015: 1.900 unique visitors, 26.000 page views) 36 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

Working together on the Radboud campus

(Spin-out) companies


https://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCO74-vG96ccCFQK1FAodwiYJnw&url=https://curastagao.wordpress.com/2013/05/22/jaarlijks-zelfde-aantallen-van-nhtv-en-han/&psig=AFQjCNHwYTFOi0x4_qdtM16YHQ3oiXdhkw&ust=1441871985852225

Radboud Research Facilities • Shared facilities across Radboud campus, also made part of Gelderland facilities • Initiated by funding 6.2M Eur Gelderland + 6.2M Eur Radboud University/ Radboudumc

www.ru.nl/radboudresearchfacilities/ 38 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

Working with other networks Region, nation, Europe, world


Takehome message

• Strategic focus on implementing Personalized Healthcare

• Strong technological and methodological infrastructure

• Continuous exploration of functional networks


Acknowledgements

Ron Wevers

Jolein Gloerich

Hans Wessels

Dirk Lefeber

Monique Scherpenzeel

Leo Kluijtmans

Lucien Engelen

Nathalie Bovy

Paul Smits

Maroeska Rovers

Bas Bloem

the Technology Centers

and many others

www.radboudumc.nl/personalizedhealthcare

www.radboudresearchfacilities.nl

www.radboudumc.nl/research/technologycenters

[email protected]

[email protected]

www.linkedIn.com

www.slideshare.net/alainvangool

Many collaborators

Jan van der Greef

Ben van Ommen

Bas Kremer

Lars Verschuren

Ivana Bobeldijk

Marjan van Erk

Carina de Jongh

Peter van Dijken

Peter Wielinga

Robert Kleemann

Suzan Wopereis

and many others And funders

CarTarDis


http://www.erasmusmc.nl/index.htm

Health & Medicine

2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van Gool