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.

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

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

Hype Cycle for Emerging Technologies

Gartner, Inc. Stamford, CT 06902 USA

Organ on a chip has created high expectations

High expectations: organ on a chip will provide a more effective way to test

safety and efficacy of new drugs

Slide from Dr. Barry Pallotta, Program Manager in DARPA’s Biological Technologies Office

There is a real market need !

Could be a $ multi-billion market by

2020

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Market opportunities in Drug Discovery

Organ on chip

goal is to replace

HTS or animal

Concept of Multi-Organ-Chip

Edinburgh 2014 Materne 7

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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’

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

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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

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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

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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

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!

Given the right environment human cells can grow, differentiate and form organ-like structures

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

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

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

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

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

TOTAL SCORE 31 36 30 32 38 40

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

TOTAL SCORE 41 39 38 37 29 37

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

25

27

29

31

33

35

37

39

41

43

25 27 29 31 33 35 37 39 41

Co

mm

erc

ial s

core

Technical score

Wyss

Hurel

CNBio

Mimetas

TissUse

Kirkstall

Leading Commercialistion?

Leading Technical

Approach ?

0

10

20

30

40

50

60

0 10 20 30 40 50 60 70 80

Co

mm

erc

ial s

core

Technical score

Wyss

Hurel

CNBio

Mimetas

TissUse

Kirkstall

Commercial & Technical Success

2017 - 2020

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!