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Organ on a Chip Report Card Assesses Progress of Key Players
- 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
- 6. 06/12/2016 Market opportunities in Drug Discovery Organ on chip goal is to replace HTS or animal
- 7. Concept of Multi-Organ-Chip Edinburgh 2014 Materne 7
- 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!
- 14. Given the right environment human cells can grow, differentiate and form organ-like structures
- 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
- 22. 25 27 29 31 33 35 37 39 41 43 25 27 29 31 33 35 37 39 41 Commercialscore Technical score Wyss Hurel CNBio Mimetas TissUse Kirkstall Leading Commercialistion? Leading Technical Approach ?
- 23. 0 10 20 30 40 50 60 0 10 20 30 40 50 60 70 80 Commercialscore Technical score Wyss Hurel CNBio Mimetas TissUse Kirkstall Commercial & Technical Success 2017 - 2020
- 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!