Human-on-a-chip: the holy grail of organs-on-chips developers – An interview with TissUse

In-development drugs have a very high failure rate in clinical trials. In many cases, drugs have different effects on 2D cell cultures and animals compared to humans. Around 90% of drugs validated on animals during pre-clinical trials fail during human clinical trials. Thus there is a need for solutions that enable better predictive, physiologically-relevant in-vitro drug testing. This could save hundreds of millions of dollars in development costs and avoid major timeline delays for a single drug. In many cases, cell models, 3D culture models, and animal models do not adequately represent human biology. Consequently, a large part of the total pharma R&D budget is spent on drugs that ultimately fail in human clinical trials. Over the past decade, organ-on-chip technologies have emerged, holding the potential to solve these issues. These are micro-engineered devices lined with living human cells, which model and reconstitute the physiological and mechanical functions of a human organ.

In its recent report Organs-on-Chips Market and Technology Landscape 2019, Yole Développement (Yole) provides a comprehensive analysis of the organ-on-chip market, which increased fourfold from 2016-2018, from $7.5M to $29.6M. It will expand at a 28.6% Compound Annual Growth Rate (CAGR) from 2018-2024. In this context, Marjorie Villien and Sébastien Clerc, Technology & Market Analysts at Yole and co-authors of the report, had the opportunity to interview Reyk Horland, Head of Business Development at TissUse, one of the organ-on-chip market leaders. During their discussion, Horland shared in-depth insights about TissUse’s position and strategy, along with a more high-level vision of the organ-on-chip technology improvements and adoption over the coming years.

Marjorie Villien (MV): Please introduce yourself, the story behind TissUse and where the company stands today.

Reyk Horland (RH): My name is Reyk Horland and I am responsible for the business development at TissUse. TissUse was founded in 2010 as a spin-off from the Technische Universität Berlin. Back then the original concept of developing a Multi-Organ-Chip system was funded by the German Ministry for Education and Research (BMBF) under their GO-BIO initiative. This unique program supports high risk/high reward projects in the German life science sector to demonstrate a proof of concept of an idea before further developing and commercializing it.
Since then, TissUse has established itself on the market as a leading provider of contract services and products under the HUMIMIC brand.

Sébastien Clerc (SC): What are TissUse’s Organ-on-Chip (OOC) models and products? What differentiates TissUse from the other OOC companies?

RH: In comparison to many other groups, TissUse has focused its efforts on the development of a multi-organ solution capable of emulating the systemic arrangement and interactions of multiple organ models. This does not exclude the use of our Multi-Organ-Chips for the study of single organ function, as most prominently shown with our bone marrow-on-a-chip model.

There are currently three different chip types commercially available: HUMIMIC Chip2, Chip3 and Chip4. The number in the name implies the maximum number of organs that can be cultivated on the chip in a common microfluidic circuit. The chips are designed with full flexibility in mind. At present customers can select from 16 established human organ models and 9 established organ combinations to be used in the chips.

The next generation chip design under development will integrate over 10 different induced pluripotent stem cell (iPSC)-based organ models on one chip. These Body-on-a-Chip or Universal Physiological Templates (UTP) should be capable of generating highly predictive data, aiming for Phase I/II co-clinical trials. It should allow for the establishment of Patient-on-a-Chip models for personalized medicine approaches.

MV: A whole human body on a chip could be a real revolution in drug development and personalized medicine. How difficult is it to build different organ models and connect them together? Are the outcomes very different from individual organ models?

RH: In our experience in working with single- and multi-organ models we very often see what Aristotle coined as “The Whole is Greater than the Sum of its Parts”. A very good example of this is the combination of a pancreatic islet model with a liver model. Both models behave differently in single cultures compared to the co-culture systems in terms of insulin production and glucose regulation as well as long-term cell viability.

Normally, single organ models are already well established. It takes some time and knowledge to set up a multi organ system, which is one of the core areas of expertise of TissUse.

SC: TissUse currently offers chips to build 2-OOC, 3-OOC and 4-OOC models. How far in time are we from a whole human body on a chip? Will there be major differences between what you offer today and what you envision?

RH: TissUse’s HUMIMIC Chip XX/XY system is currently in its prototyping stage with first biological experiments having already been conducted. We estimate another two years before we will be able to reliably and reproducibly generate substance exposure data with our UTP model. We believe that this new system will eventually be capable of generating highly predictive data in the preclinical phase thereby replacing certain animal studies as well as substituting Phase I/II clinical trials.

MV: Some organ-on-chip developers provide testing services, others sell hardware dedicated for cell culture, and some even try to sell hardware with the cell culture on it. What does TissUse offer its customers?

RH: TissUse employs a two-step business model by offering a product business to its customers through a high value development service.

TissUse collaborates with cosmetics and pharmaceutical companies and offers service contracts to create custom solutions for safety evaluation of drug candidates, cosmetics and chemicals, and pre-clinical human disease modelling. The company concluded its first cosmetics industry contract in 2013. Since then, a wide range of customers from pharma and consumer product industries have been involved in the use of TissUse technologies.

TissUse’s products address the needs of companies that generate systemic human test data for discovery programmes. We see an exponential growth in technology transfer to customer sites and, consequently, the product business due to increasing customer’s confidence acquired within the service contracts.

SC: TissUse is one of the rare OOC players to use glass, or actually a PDMS and glass combination, in its devices. Can you comment on this choice and on the advantages and drawbacks of the materials you are using? Overall, which materials do you expect to be the OOC industry’s materials of choice in the future, and why?

RH: Presently we are still getting a high number of requests for customized chip designs. Here, our current manufacturing PDMS-based procedure allows us to prototype and produce any new customer specific chip design with a certain organ arrangement within a short time period due to a proprietary rapid prototyping procedure established at TissUse. Non-specific binding tests to establish saturation levels to achieve targeted free substance concentrations are used. Glass background supports superior high-end live imaging. In the future, for specific applications we plan to switch to high-end medical plastic materials in order to optimize scalability of the production process.

MV: There is certainly a gap between academic work on organs-on-chips and their use in the industries like pharmaceuticals or cosmetics. Why is there this gap between the technology and the users’ expectations? What are the remaining challenges?

RH: Many of the organ-on-a-chip models of academia are only developed until a proof-of-concept stage. These highly promising models often lack commercial device and chip manufacturing background and required qualification background of the biological models and assays.   acceptable for industrial portfolio decision making. Here suppliers and CROs need to bridge the gap with their experiences.

SC: At Yole, we feel that the hype around the organs-on-chips has decreased a little bit over the past two years. Some end-users have started being impatient for the technology to unleash its full potential. As a provider of organs-on-chips, do you feel this in the discussions with and feedback you have from your customers? What will be the consequences?

RH: Expectations for the overall potential of organ-on-a-chip systems certainly have been decreased to levels that are more realistic. In our experience, however, this has actually been a boon for the organ-on-a-chip community as a whole. End-users now have a more in-depth understanding of the technology and are therefore able to apply it better in a “fit for purpose” approach.

While a couple of years ago you still needed to convince people about the usefulness of organ-on-a-chip systems, we now see in general an increasing confidence in the technology. This is also reflected in the increasing number of customers who decide to invest in our technology without prior experience in it.

SC: We were surprised to observe that the Contract Research Organizations (CROs), to which the pharmaceutical companies subcontract the large majority of their drug development tests, are not active in the field of organs-on-chips yet. How do you explain that?

RH: CROs are certainly keeping an eye on the development in the organ-on-a-chip field. However, for CROs organ-a-on-chip is still a relatively new technology with very few assays currently available that do meet industry standards. We believe that this will change in the near future with more and more assays being further optimized to meet the high quality requirements of industry end-users.

MV: How do you expect current organ-on-chip leaders to evolve in the future? Are they going to be acquired by end-users or CROs? Will some of them merge? Can they survive and become large players by themselves?

RH: This is certainly a subject for debate and wide speculation. Companies are now settling into their key market segments, and there is unquestionably a lot of potential for significant growth enabling them to become large players on their own. Judging from other examples in the life science industry an acquisition by end-users or CROs or even potential mergers are also viable scenarios. On the other hand, a lot of organ-on-a-chip technologies offered today is actually complementary to each other due to different areas of application e.g. in the drug development process. Therefore, strategic alliances between several players in the market are also likely. There are definitely interesting times ahead of us.

SC: Is there any other industry trend you would like to highlight?

RH: Not a trend per se but organ-on-a-chip development is immensely helped by the huge interest regulatory agencies like the FDA are taking. Their extremely valuable input could very much accelerate the process to regulatory acceptance of organ-on-a-chip based assays thereby leading to a paradigm shift in drug development.

MV: What can we expect from TissUse in the future? Any announcements to share?

RH: We are very proud that we have recently been certified under the ISO EN 9001-2015 as the first dedicated Organ-on-a-Chip company. This ISO standard ensures that TissUse products and services meet the highest customer needs through an effective quality management system. We will also launch our HUMIMIC AutoLab to the market in the near future. The system is capable of running long-term assays of up to 24 chips in a fully automated fashion. Automation will dramatically increase quality and reproducibility of data thereby facilitating industrial and regulatory acceptance of our multi-organ-chip assays.

Since 2010 Reyk Horland is actively involved in the development of TissUse’s Multi-Organ-Chip platform for culture analysis of drug candidates, cosmetics, chemicals and consumer products. He currently holds the position of Head of Business Development at TissUse. Prior to TissUse Reyk studied Biotechnology at the Technische Universität Berlin and specialized in Medical Biotechnology. During his academic career he was involved in various tissue engineering programs, all with a focus on commercialisation of the respective products.

As a Technology & Market Analyst, Medical & Industrial Imaging, Marjorie Villien, PhD., is member of the Photonics & Sensing activities group at Yole Développement (Yole).
Marjorie contributes regularly to the development of imaging projects with a dedicated collection of market & technology reports as well as custom consulting services in the medical and industrial fields. She regularly meets with leading imaging companies to identify and understand technology issues, analyze market evolution and ensure the smart combination of technical innovation and industrial application.
After spending two years at Harvard and prior to her position at Yole, Marjorie served as a research scientist at INSERM and developed dedicated medical imaging expertise for the diagnosis and follow-up treatment of Alzheimer’s disease, stroke and brain cancers.
She presents to numerous international conferences throughout the year and has authored or co-authored 12 papers and 1 patent.
Marjorie Villien graduated from Grenoble INP (France) and holds a PhD. in physics & medical imaging.

Sébastien Clerc is a Technology & Market Analyst in Microfluidics, Sensing & Actuating at Yole Développement (Yole).
As part of the Photonics & Sensing team, Sébastien has authored a collection of market and technology reports dedicated to microfluidics and other micro-devices for both market segments: medical (including diagnostics, pharmaceutical, biotechnology, drug delivery, medical devices) and industrial (including environment, agro-food).
At the same time, he is involved in custom projects such as strategic marketing, technology scouting and technology evaluation to help academic and industrial players in their innovation processes. Thanks to his technology & market expertise, Sébastien has spoken in more than 20 industry conferences worldwide over the last 4 years.
Sébastien Clerc graduated from Grenoble Institute of Technology (Grenoble INP – Grenoble, France) with a Master’s degree in Biomedical Technologies. He then completed his academic studies with a Master’s degree in Innovation and Technology Management in the same institute.

Organs-On-Chips Market and Technology Landscape 2019
Market growth is pushing changes in materials and technologies.