Glossary and definitions 02

Table of contents 03

Report objectives 05

Report scope 06

Report methodology 07

About the authors 08

Companies cited in this report 09

What we got right, what we got wrong 10

Who should be interested in this report? 11

Yole Group’s related reports 12

Executive summary 13

Context 51

• A problem to solve
• Limitations of alternative methods (2D cell culture, 3D cell culture, organoids, animal models, bioprinting)
• The big picture: huge potential in a huge market
• Future vision: personalized medicine
• What is an organ-on-chip?
• What makes OOC technology important?
• Body-on-a-chip: connecting several organs for a comprehensive understanding
• Organ-on-chip disease models

Market forecasts 79

• How are OOC companies generating revenue today?
• Business models
• Assumptions
• Market data and forecasts: comparison between the 2017 report and this report
• Market data and forecasts, in value and units
• ASP evolution

Market trends 96

• Relationship between OOC developers and pharmaceutical companies
• Applications beyond the pharmaceutical industry
• OOC won’t replace current workflows in the foreseeable future
• What’s the demand from end-users?
• Market status
• The OOC market paradox
• Where are we today?
• What do we expect?

Market share and supply chain 123

• Organ-on-chip companies – geographic location
• Organ-on-chip ecosystem
• 2018 market share, in value
• Evolution of OOC companies’ revenue
• Fundraising table
• Manufacturing: who’s working with whom?
• Possible market evolution and structuration
• Appearance of dedicated OOC CROs
• Value chain: cost of making a functioning organ-on-chip

Technology trends 137

• Who’s doing which organs: matrix
• Most widespread organ models (ranking)
• Current limitations
• Two types of OOC: chips and plates
• Different OOC types for different drug development stages
• From chip to plate
• Different OOC types at different prices
• Different flow-control modalities
• Where does microfluidics add value?
• Materials and manufacturing
• Emergence of new materials
• Towards an increased use of silicon in OOC?

Company profiles 176

Conclusions 186

Yole Développement presentation 189

A RAPID PACE FOR A HIGH-POTENTIAL MARKET

Organs-on-chips (OOC) has the potential to enable better predictive, physiologically-relevant in-vitro drug testing. This could save hundreds of millions of dollars in development costs, reduce drug development time, and avoid failures due to lack of predictiveness from alternative models like 2D cell cultures and animals. Burgeoned by these promises, the OOC market increased 4-fold from 2016 – 2018 (from $7.5M to $29.6M), and will grow at a CAGR2018-2024 of 35,3%. Many new players are entering this market with new organ models, and most players that were present two years ago have made noticeable progress. Top players like Mimetas and TissUse now have recurring sales and a consistent revenue stream, and many players are leveraging their OOC devices to provide testing services to their partners in the pharmaceutical, cosmetics, and consumer goods industries – for testing the efficacy and safety of new drugs and products.

Evolving regulations in certain countries and industries have spurred a push towards the use of in-vitro models instead of animal models. In the pharmaceutical industry, the real potential of the technology conclusively lies in the promise it holds for personalized medicine. Indeed, it could be possible to create individually-tailored OOC with a patient’s own cells, allowing a substance’s effects to be predicted on an individual basis. In this report, Yole Développement’s (Yole) analysts explain how reaching such milestones could create a real inflexion point, causing the OOC market to skyrocket. However, this is a long-term vision that will not materialize over the next five years.

TOO MANY EXPECTATIONS, TOO MUCH HYPE?

Since OOC holds great promise, the associated expectations are extremely high. Personalized medicine, fully replacing current in-vitro and in-vivo models, for disease modelling? We have entered a phase where end-users don’t expect such results yet – but they do expect reproducibility and automation. Though OOC companies claim to have positive feedback from end-users overall, the comments from end-users are more restrained. The problem is that most OOC models are still “proof-of-concept”, whereas end-users prefer industry-grade models with validated processes and outcomes. In this report, Yole’s analysts explain the reasons for such negative feedback, and what the end-users’ expectations are.

OOC technology is intriguing, but it is struggling to generate a consensus. Consequently, OOC companies strain to find the ideal business model: most end up adopting a hybrid business model combining product sales and services, because even though different users have different demands, OOC firms cannot say “no”. Ultimately though, each company must find the right balance inspired by its strengths, instead of trying to please every customer.

The OOC industry’s maturation could signal the beginning of contract research organizations’ (CROs) involvement. Today, CROs seem minimally involved in the OOC field, and are waiting for more evidence of the technology’s potential. However, CROs are usually the privileged subcontractors of the pharmaceutical, cosmetics, and consumer goods industries for safety and efficacy testing – and in a midterm future, they will certainly be the primary users of OOC in order to perform testing services for the pharma industry. Also, they will work closely with OOC companies to learn how to best use their models. That said, it’s too early to speculate, and additional data must be generated to prove OOC’s relevance over the gold standards CROs have used for decades.

ORGANS-ON-CHIPS IS A MULTIDISCIPLINARY FIELD, AND VARIOUS PARAMETERS WILL SHAPE TOMORROW’S TECHNOLOGY

Organs-on-chips can take various shapes and appearances, depending on their purpose. The drug development process is long and complex, and the needs are not the same at the early drug-screening stages as they are in the late preclinical trial stages. Thus, we see some players specializing in plate formats for automation and high throughput, while others prefer developing single independent chips.Some players develop key solutions based on single organ models, while others propose multi-organ models to assess metabolic interactions between organs. Every technology is different and has specific application domains.

On the materials side, important changes are happening. Two years ago, Yole’s analysts were concerned about the ability of OOC companies to switch from PDMS devices in order to scale-up production. Today, it appears that most companies have successfully managed this transition, or at least engaged with the right partners early enough to avoid the problems young companies usually face at this stage. At the moment, polymer is the preferred material, but some companies use glass. The next step could be the integration of more silicon pieces: indeed, sensing directly at the cell level is a necessity, but right now only a few companies are moving in this direction. This is why silicon is not commonly used in OOC. Yole’s analysts expect this to change by 2024, and in this report they detail the evolution of the materials mix, along with various other technical aspects such as the added-value of flow control and vascularization of organs, the emergence of new materials combining the preferred properties of several existing ones, the importance of cell sources, and more.

4Design Biosciences, AIM Biotech, Allevi, Alnylam, AlveoliX, Amgen, Amore Pacific, Ananda Devices, Aspect Biosystems, Astellas, AstraZeneca, AxoSim, BASF, Barcelona Liver Bioservices, Beiersdorf, BeOnChip, Bioclinicum, Biogen, BiomimX, BI/OND, Bristol-Myers Squibb, Charles River, Charles Stark Draper Laboratory (Draper), CN Bio Innovations, CorSolutions, Covance, Creo Bioscience, Curiochips, DARPA, Denz Bio-Medical, Eli Lilly, Elveflow, Emulate, EpiSkin, ESA, Fluigent, Galapagos, GlaxoSmithKline (GSK), Harvard Medical School, Hesperos, Hurel Corporation, ICON plc, imec, InSphero, INTENZE Products, Iontox, IQVIA, Javelin Biotech, Jiksak Bioengineering, Johnson & Johnson, Kirkstall, L’Oréal, Massachusetts Institute of Technology (MIT), Merck, MicroBrain Biotech, Microfluidic ChipShop, Micronit, Mimetas, MiniFAB, NASA, NCATS, NIH, Nortis, Organovo, Parexel, Parker Hannifin, Pfizer, Philip Morris, PimBio, Roche, Sanofi, Seattle Bioscience, Seres Therapeutics, Sigma-Aldrich, StemoniX, Stratec Consumables, Sun Bioscience, Syneos Health, Synvivo, Tara Biosystems, Tebu-bio, TissUse, Vanderbilt University, Vertex Pharmaceuticals, WYSS Institute, Xona Microfluidics, Yale University, and more.