Frontrunner in Organ-on-a-Chip

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For several years, manufacturers have been developing organs‑on‑a-chip (OoC) technology, whereby engineered or natural tissues are grown inside microfluidic chips allowing them to maintain tissue-specific functions. Today, OoCs encompass an array of tissues and organ functionality including the blood-brain-barrier (BBB), central nervous system (CNS), heart, intestine, liver, lung, kidney, muscle, and skin to allow pharma to better understand the underlying pathophysiology of diseases and to determine the effect of drugs in vitro (1).

Advances in tissue engineering, microfabrication, and biocompatible microfluidic chambers alongside the governmental (2) and regulatory (3) appetite to seek animal-free innovations in the drug development process has fuelled further interest and investment in this marketplace. According to market research, the global OoC market is forecast to be worth US$388 million (€354 million) by 2028 increasing from US$82 million (€75 million) in 2023, with a compound average growth of 36.4% from 2023 to 2028 (4).

Market leaders carving out a niche in the OoC market

Several players have already carved out niches in the OoC field. CN Bio Innovations, a spin-out from Oxford University in the United Kingdom, was founded in 2008 and became one of the first companies in this space with OoC technology licensed from Massachusetts Institute of Technology and Vanderbilt University. CN Bio has developed a range of single OoC technologies including the gut, liver, or lung, and recently launched the PhysioMimix platform, a system that can co-culture human cells (e.g., gut/liver) in open-well plates to recreate human organs. Importantly, multiple devices can be connected together to generate a ‘body-on-a-chip’ device whereby microchannels allow different organs to interact with one another (5).

Another player in the field of OoC, TissUse, was founded in 2010 and is a spin-off from Technische Universität Berlin. The biotech company produces models of human organs for preclinical drug testing based on this patented technology. Like CN Bio, TissUse has developed a multi-organ system or human-on-a-chip technology to allow potential interaction of one organ with another. This technology has been used in drug development, consumer products, cosmetics, and food and nutrition products to help predict absorption, distribution, metabolism, and excretion (ADME) and toxicity (6).

Netherlands-based Mimetas was founded in 2013 and has raised more than US$25.2 million (€23 million) in series A and B funding (7). In March 2022, it launched a three-dimensional (3D) OrganReady Coco-2 assay consisting of 38 intestinal tubules that facilitate the pre-clinical assessment of ADME, safety, and toxicology of new chemical entities (NCEs) and later the same year won the Dutch Innovation Award in recognition for its innovative technology (8). In July 2021, it entered into a strategic partnership with Roche to develop in vitro models of inflammatory bowel diseases and hepatitis B viral infections, which it successfully completed in March 2023. Mimetas has also teamed up with Astellas Pharma to utilize its Organoplates for high throughput (HT) in vitro screening of Astellas’ next-generation immune-oncological therapies (9). Mimetas continues to push the frontiers of OoC and recently launched its off-the-shelf solution, OrganoReady consisting of 3D Adult Stem Cell (ACS)-derived tubular organoid assay derived from either the colon or kidney for use in preclinical research (10).

In the United States, microfluidic start-up Emulate was established in 2014 and became one of the first companies to develop the Liver-Chip for predictive toxicology (11); the technology was developed at the Wyss Institute for Biological Inspired Engineering at Harvard. Like other OoC companies, Emulate is now researching personalized medicines through a human-on-a-chip approach. New York-based TARA BioSystems was also created in 2014, a spin out from Columbia University and became one of the market leaders in heart-on-a-chip technology. It was recently acquired by Valo Health in April 2022, enabling it to expand its cardiac disease modelling capabilities (12). Meanwhile, Florida-based Hesperos a global contract research organization (CRO) has ventured into the OoC space and now offers clients inhouse safety and efficacy testing services. It has developed a multi-organ in vitro platform, ‘human-on-a-chip’ technology, to allow drug developers to investigate patients’ response to drugs during pre-clinical and clinical development. Hesperos has forged collaborations with Roche and Sanofi to pre-clinically evaluate NCEs for ADME and toxicity; these data have been used to support investigational new drugs (IND) files (13,14).

Newcomers in the OoC field attracting investor attention

As the field of OoC moves forward at a pace, several European start-ups have recently entered the arena and gained investor attention.

NETRI focusing on neurology. In March 2022, Lyon-based NETRI, attracted €8 million series A funding to help develop its novel high throughput (HT) compartmentalized microfluidic brain-on-a-chip and skin-on-a-chip technology for use by the pharma and cosmetic industry (15). The NeoBento HT 96-well plate contains between 16 and 24 chips that are interconnected by microchannels (e.g., tunnels or grooves) allowing cells to be co-cultured and recreate physiological interactions. Unlike other OoC technologies, the microchannel grooves allow continuous connection between compartments allowing research to study axotomy, the gut brain axis, the neuromuscular junction, and innervated skin and evaluate therapeutic agents for neurological conditions such as multiple sclerosis and neuropathies. NETRI’s microfluidic chips can also be used to mimic physiological barriers such as cell membranes to allow companies to assess how substances are transported across the cell membrane including the blood brain barrier.

In September 2022, NETRI teamed up with Axion Biosystem to develop a HT microchip that is compatible with multielectrode arrays (MEA) (16). In March 2023, the companies launched the NeoBento MEA a HT 96-well plate that enables electrophysiological recording of cells in vitro; this allows pharma to remotely stimulate the cell and monitor synaptic activation in isolated cell populations (17). The technology is currently designed for use in peripheral nerve injury (peripheral neuropathic pain and allodynia, nociceptive pain) and sensitive skin syndrome as well as the evaluation of neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease) and other neurological disorders. NETRI has adopted a modular approach that allows the OoCs to be combined to create multi‑organ or multi‑organoid formats and these can be customized to clients’ requirements, enabling them to rapidly and cost‑effectively screen NCEs and select the most appropriate drugs to move forward into clinical development (Figure 1) (18).

Figure 1: NETRI high throughput organs-on-chip platform, NeoBento, for drug discovery and cosmetic testing. FIGURE IS COURTESY OF NETRI.

Bi/ond personalizing treatment. In March 2022, Netherlands-based Bi/ond, secured US$4 million (€3.6 million) investment from leading industrial venture firm FORWARD.one to develop its proprietary inCHIPit and the reusable comPLATE platforms that combine 3D microfluidic cell culture within a microchip for applications in kidney research, oncology, and cardiac simulation (19). The inCHIPit is an open well system that can be loaded with a variety of cells or tissues (e.g., pluripotent stem cells, organoids, ex vivo tissues, spheroid, or microtissues) and each well is connected to microfluidic channel via a porous membrane, which allows cells to be stimulated in vivo and viewed optically. Bi/ond is currently evaluating its technology to predict treatment response and personalize therapy. For instance, the company has forged a collaboration with the Leiden University Medical Centre (Netherlands) to culture heart OoCs so that patients’ response to therapy can be predicted, and the company is working with the Erasmus University Medical Center (Netherlands) to generate OoCs containing patient tumour tissues to assess their response to chemotherapy (19).

What does the future hold for OoC?

As OoC manufacturers continue to embrace the adoption of new biomaterials and fabrication techniques such as lithography and 3D bioprinting this will allow companies to increasingly customize multi-OoC systems with the desired functionality and will provide high content imaging and/or electrophysiological readouts (1). To date, the use of OoCs has primarily focused on drug development; however, they also offered considerable potential throughout preclinical and clinical development, providing new ways to model diseases, including rare disorders, monitor pharmacokinetic and pharmacodynamic properties of NCEs, and guide the personalization of treatment in the clinic based on genotypic-phenotypic characteristics. Given the recent regulatory move to reduce animal testing (3) the field of OoC looks ripe for innovation and further investment.

References

1. Leung, C.M.; de Haan, P.; Ronaldson-Bouchard, K.; et al. A Guide to the Organ-on-a-Chip. Nat. Rev. Methods Primers, 2022, 2, 33.
2. European Commission. JRC Supporting Alternatives to Animal Testing. EC.europa.eu, News Release, 7 April 2022.
3. Wadman, M. FDA No Longer Needs to Require Animal Tests Before Human Drug Trials. Science, Article, 10 Jan. 2023.
4. Market Data Forecasts. Global Organ-on-Chip Market Size, Share, Trends, COVID-19 Impact and Growth Analysis Report—Segmented by Type (Heart-on-chip, Human-on-chip, Intestine-on-chip, Kidney-on-chip, Liver-on-chip and Lung-on-chip), Application and Region (North America, Europe, Asia-Pacific, Latin America, Middle East and Africa)—Industry Forecast from 2023 to 2028. Market Report, March 2023.
5. CN-Bio. PhysioMimix OOC Microphysiological Systems. CN-Bio.com, accessed 3 April 2023.
6. TissUse. Technology. Tissuse.com, accessed March 2023.
7. Mimetas. MIMETAS Secures 20 Million Dollar Series B Financing. Mimetas.com, Press Release, 11 April 2018.
8. Mimetas. MIMETAS Elected Most Innovative Company of the Netherlands. Mimetas.com, Press Release, 2 Nov. 2022.
9. Mimetas. MIMETAS and Astellas Enter into Strategic Partnership on Immuno-Oncology. Mimetas.com, Press Release, 28 March 2023.
10. Mimetas. MIMETAS Launches Ready-to-Use 3D Adult Stem Cell Organoid Tubules. Mimetas.com, Press Release, 7 March 2023.
11. Ewart, L.; Apostolou, A.; Briggs, S.A.; et al. Performance Assessment and Economic Analysis of a Human Liver-Chip for Predictive Toxicology. Commun. Med. 2022, 2, 154.
12. Valo. Valo Health Acquires TARA Biosystems Creating First of its Kind Vertically Integrated Cardiovascular Platform. ValoHealth.com, Press Release, 5 April 2023.
13. Hesperos. Hesperos Shows Potential for In Vitro Approach to Replace Conventional Animal Efficacy Studies for Rare Neuromuscular Disorders. Hesperosinc.com, Press Release, 19 April 2022.
14. Hesperos. The Original Human-on-a-Chip Company. Hesperosinc.com, accessed 3 April 2023.
15. NETRI. Lyon-Based Industrial Start-Up NETRI is Finalizing an €8 million Series A Funding Round. NETRI.com, Press Release, 3 Mar. 2022.
16. NETRI. NETRI and Axion BioSystems Announce Organs-on-Chip Collaboration. NETRI.com, Press Release, 8 Sep. 2022.
17. Business Weekly. Axol Bioscience and French Partner Unveil Organs-on-Chip Innovation. News Release, 3 Jan. 2023.
18. NETRI. Modular Integration. NETRI.com, accessed 3 April 2023.
19. Bi/ond. Bi/ond Secures Over $4M in Funding—Bi/ond. Gobiond.com, Press Release, 8 Mar. 2023.

About the author

Cheryl Barton is director of Pharmavision, info@pharmavision.co.uk.

Article details

Pharmaceutical Technology Europe
Vol. 35, No. 5
May 2023
Pages: 16–17, 30

Citation

When referring to this article, please cite it as Barton, C. Frontrunner in Organ-on-a-Chip. Pharmaceutical Technology Europe, 2023, 35 (5), 16–17, 30.