Overview of the current challenges in biomarker commercialisation, to kick off the scientific advisory board meeting with the multidisciplinary Interreg BIC project team.

1. Biomarker innovation gaps:
setting the scene
BiC Advisory Board meeting
Copenhagen, 28 Nov 2018
Prof Alain van Gool
Professor Personalized Healthcare
Head Translational Metabolic Laboratory
Strategic advisor of the executive board
Coordinator Radboudumc Technology Centers

2. My path in translational health research
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
Knowledge
validation &
application
Knowledge
translation
Knowledge
exploitation
Fundamental
knowledge
Universities IndustryUniversity medical
centers
Applied Research
Institutes
1991
2018
• Basis in molecular biology
• Academia, pharma, medical center, applied research institutes
• Biomarkers / Omics / technologies
• Mechanisms of disease
• Translational medicine
• Personalized healthcare
2

3. My current roles
Scientific lead DTL-Technologies (NL)
Chair EATRIS Biomarker Platform (EU)
Professor of Personalized Healthcare
Head Translational Metabolic Laboratory
Strategic Advisor Executive Board
Coordinator Radboudumc Technology Centers
PI Biomarker Development Center (NL)
Coordinator Netherlands X-omics Initiative (NL)
Co-initiator of Health-RI (NL)
3

4. 4 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

5. Exponential developments – lab technology
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
5

6. 6
Exponential developments
- digital biomarkers
6

7. Exponential developments - data
7 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

8. Role of molecular biomarkers in Personalized Healthcare
Personalized diagnosis
Personalized therapy
= Personalized healthcare
+
Patient participation
X-Omics
Therapy monitoring
8 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

9. Genomic impact in Personalized Health(care)
Personalized medicine:
B-RAFV600E drugs for melanoma
Personalized health:
BRCA-driven preventive surgery
9 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

10. Precision medicine in genetic-metabolic disease – current
Personalized diagnosis
Genomics
(WES)
Metabolomics
(IEM panel)
New disease
mechanisms
Personalized therapies
Nature Genetics 2018
NEJM 2014
Nature 2016
NEJM 2014
Genet Med 2017
10 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

11. Precision medicine in genetic-metabolic disease - future
Personalized diagnosis
Genomics
(WGS)
Metabolomics
(more panels)
New personalized
therapies
Glycomics
Glycoproteomics
Deep Learning
Artificial Intelligence
System biology
Nature Genetics 2016 Pilot 2017
New disease
mechanisms
11 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

12. 12 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

13. However … 3 innovation gaps !
innovation
1. Research to research
2. Research to diagnostics
3. Research to society
13 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

14. Innovation gap Research to Research
{Freedman et al, PLOS Biology, 2015}
• About 50% of scientific findings cannot be reproduced
• Multiple reasons (practical variations, financial/scientific incentives, etc)
• Gap in translational innovations.
• Bad for science, economics and society
14 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

15. Categories of errors leading to irreproducibility
{Freedman et al,
PLOS Biology, 2015}
15 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

16. “It is simply no longer possible to believe much of the clinical
research that is published, or to rely on the judgment of trusted
physicians or authoritative medical guidelines.
I take no pleasure in this conclusion, which I reached slowly and
reluctantly over my two decades as an editor of The New
England Journal of Medicine.”
Marcia Angell, MD
Former Editor-in-Chief NEJM
Oct 2010
16 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

17. Critical component in biomarker R&D: Data
{Wilkinson et al,
Nature Scientific Data, 2016}
Need to increase quality in:
• Data capture
• Data stewardship (FAIR)
17 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

18. DATA STEWARDSHIP: INTEROPERABILITY IS KEY
If data are interoperable … … analytics provide new knowledge
18 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

19. … but not all data is useful data !

20. However … 3 innovation gaps !
innovation
1. Research to research
2. Research to diagnostics
3. Research to society
20 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

21. Biomarker innovation gaps !
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
• Too much biomarker discovery
• Too little development to application
21 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

22. Biomarker innovation gaps: some numbers
~ 5 biomarkers/
working day
1 biomarker/
1-3 years
1 biomarker/
2-10 years
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Eg Biomarkers in time: Prostate cancer
May 2011: 2,231 biomarkers
Nov 2012: 6,562 biomarkers
Oct 2013: 8,358 biomarkers
Nov 2014: 10,350 biomarkers
Oct 2015: 11,856 biomarkers
Nov 2016: 14,481 biomarkers
Oct 2017: 15,463 biomarkers
Oct 2018: 16,501 biomarkers
22 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

23. Choice for biomarker scientists: discover or confirm?
23 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

24. Good example of multi-laboratory biomarker validation
3 biomarkers:
• Aβ42
• T-Tau
• P-Tau
24 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

25. Good example of multi-laboratory biomarker validation
25
Adoption of best biomarker practice ???

26. However … 3 innovation gaps !
innovation
1. Research to research
2. Research to diagnostics
3. Research to society
26 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

27. 3 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?
27 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

28. Translation is key in Personalized Healthcare
Personal profile data
Knowledge
Understanding
Decision
Action
28 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

29. Towards a personalized data-driven GPS for health
• Monitor on background
• Alert when you are at risk
• Advice what to do
29 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

30. Next: focus on prevention ?
30 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

31. 31 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018
Getting into ethical considerations

32. Moving forward from quantity to quality
innovation
1. Research to research
2. Research to diagnostics
3. Research to society
32 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

33. Partners in biomarkers innovation
33 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

34. 1. Focus on the end user: the patient / citizen
34 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

35. 2. Interpret data with self-normalisation
healthy disease disease +
treatment
A
healthy disease disease +
treatment
100%
Normalisation of responders
C
Subgroups
B
healthy disease disease +
treatment
100%
Individual data through self-monitoring
D
treatment time
35 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

36. 3. Do realize there is no single one reflection of health
• Funhouse mirror effect
• Multiple sources of your
data
• Omics
• EPD
• Diagnostics
• Wearables
• Health apps
• Commercial health tests
• Social media
• Surrounding
• Each give an (incomplete)
image of you
• How to deal with this for
personal health?
{Mira Vegter, Hub Zwart, Alain van Gool, in prep}
36 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

37. 4. Be open to alternative therapies
Higher efficacy / less side effects
37
Pharma-Nutrition
37 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

38. 5. Progress further through collaboration
38 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018 www.radboudumc.nl/research/technologycenters

39. European
national
local
39 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

40. Netherlands X-omics Initiative
www.x-omics.nl
• Access
• Helpdesk / training
• Collaboration
40 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

41. Netherlands X-omics Initiative
Push omics
technologies
• Resolution
• Sensitivity
• Coverage
Genomics
Proteomics
Metabolomics
• Quality
• Standards
• Data FAIR
at source
X-omics
• Study design
• Sample handling
• Data cataloging
• Quality
• Expertise
• Best practice
• Data integration
• Data analysis
• Best practice
• Access
• Helpdesk / training
• Collaboration
41 Alain van Gool, Healthy Brain Chort day, Nijmegen, 2 Nov 2018

42. 6. Join forces in biomarker activities
Europe
USA
{Asadullah et al, Nature Reviews Drug Discovery, Dec 2015}
42 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

43. Collaboration towards Good Biomarker Practices
{van Gool et al, Nature Reviews Drug Discovery, Apr 2017}
COST action CA16113
http://clinimark.eu
43 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

44. 7. Collaboration towards nationwide programs
44 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

45. 8. And learn from other fields!
45 Alain van Gool, BiC SAB, Copenhagen, 27 Nov 2018

46. Acknowledgements
Translational Metabolic Laboratory
Hans Wessels
Dirk Lefeber
Karlien Coene
Leo Kluijtmans
Richard Rodenburg
Jolein Gloerich
Anouk Suppers
Purva Kulkarni
Roel Tans
Esther Willems
Ron Wevers
and others
Edwin Cuppen
Albert Heck
Thomas Hankemeier
Peter Bram ‘t Hoen
Daniella Kasteel
and others
Collaborators/funders
Human Genetics Nijmegen
Marcel Nelen
Alexander Hoischen
Lisenka Vissers
Christian Gillisen
Han Brunner
and others
alain.vangool@radboudumc.nl
www.radboudumc.nl/en/people/alain-van-gool
www.slideshare.net/alainvangool
CarTarDis
Irene Keularts
Hans Scheffer
and others
Rainer Bischoff
Theo Luider
and others