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Organ on a chip
1. 06/12/2016
Organ on a chip:
A Commercialisation Report Card
Trying to make an objective assessment on the
status of a new technology (and avoid the hype)
Dr JM Wilkinson, Dr K Davidge
Kirkstall Ltd.
2. 06/12/2016
Content
• Challenges facing new technology introduction
• Hype vs reality
• Market need
• Key factors for tracking success
• Introducing a Report Card Format
• Trial run with status of some key players
• Recommendations for 2017
3. 06/12/2016
Some challenges for new technology
• New technology must meet a market need
• Winning grants is helpful but is not same as
winning customers
• $ millions from VC’s does not guarantee success
(money does not change the laws of physics)
• Early engagement with customers is essential
4. Hype Cycle for Emerging Technologies
Gartner, Inc. Stamford, CT 06902 USA
Organ on a chip has created
high expectations
5. High expectations:
organ on a chip will provide a more effective way to test
safety and efficacy of new drugs
There is a real market need !
Could be a $ multi-billion market by
2020
8. 06/12/2016
A Multitude of Approaches
• There is little standardisation
• Players are mainly start-up companies commercialising
OOC prototypes developed in the universities
• Mainly plastic materials
• Different chamber and plate sizes
– Hurel, CN Bio, Mimetas use 96 well plate size
– TissUse and Kirkstall use 24 well plate size
– Wyss/Emulate has custom plates for each organ
• Pneumatic, Peristaltic, & Syringe pumps as well as
gravity fed
• In general the control systems are more complex than
the ‘chips’
9. Organisation Chip Picture Controller Comments
Hurel (USA)
MIT / CNBio
(USA / UK)
Mimetas (NL)
Chip is size of cigarette
Pack, chamber is 24 well plate size
Control system uses
Pneumatic pumping
Chip is 96 well plate format.
Works in a standard incubator
with rocker plate
Chip has in-built microfluidic
pumps. Complex controller
needed.
CNBio offer as a service
Each organ chip is developed
by a different group so not
clear how they will
interconnect.
Technology only available as a service from Hurel who now focus on
delivery of ready seeded 24 and 96 plates
Chamber is 24 well plate
format and in volume
production with custom
peristaltic pump
10. 06/12/2016
Key Requirements to replace animals
• Biological
• Physiologically relevant organoid models
• Connected organoids
• Long term culture /homeostasis
• Practical
• Easy to use and fast to set up
• Robust/repeatable
• No bubbles/blockages
• Scale
• 100’s animals/drug lead not 10,000’s as in HTS assays
• Economical
• Capital and consumable cost < animals
• Replacing HTS will require much lower cost
11. 06/12/2016
Some Technical Challenges
• Obtaining representative human cells
• Media selection for co-culture of different cells
• Seeding cells inside microstructured chambers
• Getting adequate nutrient and oxygen to cells
• Connecting multiple chambers and flowing
media
• Getting enough biological material for an
accurate assay
12. 06/12/2016
Cells for human on a chip?
• Animal cells may be easy to obtain and keep
alive – but they are not moving us forward
• Human tumour derived cell lines are easy to
culture but are not representative of healthy
tissue (basically cancer cells)
• iPSC (Induced Pluripotent Stem Cells) look
promising but expensive and tough to grow
• Human Donor Tissue is gold standard but
cryopreservation does compromise function
13. Review Article : Organs-on-chips at the frontiers of drug discovery
Esch, Bahinski & Huh, Nature Reviews Drug Discovery 14, 248–260 (2015)
Cancer cells
Cancer cells
Cancer cells
Vascular cells
Heart cells
Cancer cells
Liver cells
Vascular cells
Cancer cells
Cancer Cells
Cancer cells
Liver Cells
Why so many tumour derived cancer cells? They are tough to kill!
15. Report Card Format : Technical Factors
Measure of progress Indicative Scores
Physiologically relevant organoids
Multiple organoids available
Connected organoids
Long term culture /homeostasis
Easy to use / no bubbles / no leaks
Robust/repeatable
Scale to volume progress
Economics
16. Report Card Format : Technical Factors
Measure of progress Indicative Scores
Physiologically relevant organoids 0 – 2D single cell type model
5 – 3D spheroid like model
9 – functional differentiated organoid
Multiple organoids available +3 – liver
+2 – cardiomyocytes
+ 2 –kidney
+1 – other organs
Connected organoids 2 – manual transfer of conditioned media
6 - flow of media between chambers
9 - recirculating flow of media
Long term culture /homeostasis 1 – 2 to 3 days
5 – 28 days
10 – 90days+
Easy to use / no bubbles / no leaks 2 – in house only
5 – available for external use / licence
9 – already in use multiple sites
Robust/repeatable 2 – skilled postdoc researcher
5 – fully trained lab technician
9 – standard laboratory methods
Scale to volume progress 1 – single chambers
5 – 6 well chambers
7 – 24 well chambers
Economics 0 – no cost data available
3 – cost estimates available
7- on sale / cost match animals
17. Report Card Format : Commercial Factors
Measure of progress Indicative Scores
Organisation culture
Market engagement
Design for manufacture
Ability to attract
investment
Sound business model
Profitability
TOTAL SCORE
18. Report Card Format : Commercial Factors
Measure of progress Indicative Scores
Organisation culture 2 - research laboratory
4 - research division in commercial organisation
8 - dedicated start up company
Market engagement 2 – industrial partners in research consortium
4 – sales to academics
6 – sales to industrial innovators
9 – sales to majority market
Design for manufacture 1 – in house prototyping
4 – industrial prototyping
6 – industrial preproduction
9 - volume manufacture process
Ability to attract
investment
+3 - research grants only
+4 - Venture Capital
+3 - Sales revenue
Sound business model 0 - no business plan
5 - CRO Research model only
7 - products only
9 - products and service
Profitability 1 - burning investors capital
6 - break even
8 - profitable
TOTAL SCORE
19. Report Card : Example Technical Scores
Measure of progress Indicative Scores W H C M T K
Physiologically
relevant organoids
0 – 2D single cell type model
5 – 3D spheroid like model
9 – functional differentiated organoid
4 4 3 3 6 6
Multiple organoids
available
+2 – liver
+2 – cardiomyocytes
+ 2 –kidney
+1 – other organs
8 3 3 4 6 5
Connected organoids 2 – manual transfer of conditioned media
6 - flow of media between chambers
9 - recirculating flow of media
3 4 3 3 5 5
Long term culture
/homeostasis
1 – 2 to 3 days
5 – 28 days
10 – 90days+
4 6 4 2 4 4
Easy to use / no
bubbles / no leaks
2 – in house only
5 – available for licence
9 – already in use multiple sites
3 4 4 4 6 6
Robust/repeatable 2 – skilled postdoc researcher
5 – fully trained lab technician
9 – standard laboratory methods
3 4 4 3 5 6
Scale to volume
progress
1 – single chambers
5 – 6 well chambers
7 – 24 well chambers
3 6 6 8 3 3
Economics 0 – no cost data available
3 – cost estimates available
7- on sale / cost match animals
3 5 3 5 3 5
20. Report Card : Example Commercial Scores
Measure of
progress
Indicative Scores W H C M T K
Organisation
culture
2 - research laboratory
4 - research division in commercial organisation
8 - dedicated start up company
8 7 6 8 6 6
Market
engagement
2 – industrial partners in research consortium
4 – sales to academics
6 – sales to industrial innovators
9 – sales to majority market
8 9 6 6 5 6
Design for
manufacture
1 – in house prototyping
4 – industrial prototyping
6 – industrial preproduction
9 - volume manufacture process
4 5 5 6 4 6
Ability to attract
investment
+3 - research grants only
+4 - Venture Capital
+3 - Sales revenue
9 6 8 8 7 6
Sound business
model
0 - no business plan
5 - CRO Research model only
7 - products only
9 - products and service
8 7 7 7 5 7
Profitability 1 - burning investors capital
6 - break even
8 - profitable
4 5 6 2 2 6
21. Overall Scorecard Result
Name Technical
score
Technical
ranking
Commercial
score
Commercial
ranking
Wyss 31 #5 41 #1
Hurel 36 #3 39 #2
CNBio 30 #6 38 #3
Mimetas 32 #4 37 #4=
TissUse 38 #2 29 #6
Kirkstall 40 #1 37 #4=
Beware !
Trial Scores only – not really objective at this point
24. 06/12/2016
Recommendations
• Refine the scoring criteria
• Add weighting factors? – which criteria are more
important
• Use some independent assessors
• Revisit scoring and ranking each year to track
progress
Thanks for your attention!