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 06/12/2016
Hype Cycle for Emerging Technologies Organ on a chip has created high expectations Gartner, Inc. Stamford, CT 06902 USA
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 Slide from Dr. Barry Pallotta , Program Manager in DARPA’s Biological Technologies Office
Market opportunities in Drug Discovery Organ on chip goal is to replace HTS or animal 06/12/2016
Concept of Multi-Organ-Chip Edinburgh 2014 Materne 7
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’ 06/12/2016
Organisation Chip Picture Controller Comments 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 Hurel (USA) Chip has in-built microfluidic pumps. Complex controller needed. MIT / CNBio CNBio offer as a service (USA / UK) Chip is 96 well plate format. Works in a standard incubator with rocker plate Mimetas (NL) Chip is size of cigarette Pack, chamber is 24 well plate size Control system uses Pneumatic pumping Chamber is 24 well plate format and in volume production with custom peristaltic pump
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 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 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 06/12/2016
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 0 – 2D single cell type model Physiologically relevant organoids 5 – 3D spheroid like model 9 – functional differentiated organoid +3 – liver Multiple organoids available +2 – cardiomyocytes + 2 – kidney +1 – other organs 2 – manual transfer of conditioned media Connected organoids 6 - flow of media between chambers 9 - recirculating flow of media 1 – 2 to 3 days Long term culture /homeostasis 5 – 28 days 10 – 90days+ 2 – in house only Easy to use / no bubbles / no leaks 5 – available for external use / licence 9 – already in use multiple sites 2 – skilled postdoc researcher Robust/repeatable 5 – fully trained lab technician 9 – standard laboratory methods 1 – single chambers Scale to volume progress 5 – 6 well chambers 7 – 24 well chambers 0 – no cost data available Economics 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 2 - research laboratory Organisation culture 4 - research division in commercial organisation 8 - dedicated start up company 2 – industrial partners in research consortium Market engagement 4 – sales to academics 6 – sales to industrial innovators 9 – sales to majority market 1 – in house prototyping Design for manufacture 4 – industrial prototyping 6 – industrial preproduction 9 - volume manufacture process +3 - research grants only Ability to attract +4 - Venture Capital investment +3 - Sales revenue 0 - no business plan Sound business model 5 - CRO Research model only 7 - products only 9 - products and service 1 - burning investors capital Profitability 6 - break even 8 - profitable TOTAL SCORE
Report Card : Example Technical Scores Measure of progress Indicative Scores W H C M T K 0 – 2D single cell type model Physiologically 4 4 3 3 6 6 5 – 3D spheroid like model relevant organoids 9 – functional differentiated organoid +2 – liver Multiple organoids 8 3 3 4 6 5 +2 – cardiomyocytes available + 2 – kidney +1 – other organs 2 – manual transfer of conditioned media Connected organoids 3 4 3 3 5 5 6 - flow of media between chambers 9 - recirculating flow of media 1 – 2 to 3 days Long term culture 4 6 4 2 4 4 5 – 28 days /homeostasis 10 – 90days+ 2 – in house only Easy to use / no 3 4 4 4 6 6 5 – available for licence bubbles / no leaks 9 – already in use multiple sites 2 – skilled postdoc researcher Robust/repeatable 3 4 4 3 5 6 5 – fully trained lab technician 9 – standard laboratory methods 1 – single chambers Scale to volume 3 6 6 8 3 3 5 – 6 well chambers progress 7 – 24 well chambers 0 – no cost data available Economics 3 5 3 5 3 5 3 – cost estimates available 7- on sale / cost match animals
Report Card : Example Commercial Scores Measure of Indicative Scores W H C M T K progress Organisation 2 - research laboratory 8 7 6 8 6 6 4 - research division in commercial organisation culture 8 - dedicated start up company 2 – industrial partners in research consortium Market 8 9 6 6 5 6 4 – sales to academics engagement 6 – sales to industrial innovators 9 – sales to majority market Design for 1 – in house prototyping 4 5 5 6 4 6 4 – industrial prototyping manufacture 6 – industrial preproduction 9 - volume manufacture process +3 - research grants only Ability to attract 9 6 8 8 7 6 +4 - Venture Capital investment +3 - Sales revenue 0 - no business plan Sound business 8 7 7 7 5 7 5 - CRO Research model only model 7 - products only 9 - products and service Profitability 1 - burning investors capital 4 5 6 2 2 6 6 - break even 8 - profitable
Overall Scorecard Result Name Technical Technical Commercial Commercial score ranking score 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
Leading 43 Commercialistion? 41 39 Leading 37 Commercial score Technical Approach ? Wyss 35 Hurel CNBio 33 Mimetas TissUse 31 Kirkstall 29 27 25 25 27 29 31 33 35 37 39 41 Technical score
60 Commercial & Technical Success 50 2017 - 2020 40 Commercial score Wyss Hurel 30 CNBio Mimetas TissUse 20 Kirkstall 10 0 0 10 20 30 40 50 60 70 80 Technical score
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