7 Companies Helping Exclude Animals From Drug Discovery Research

by Natalia Honchar    Contributor        Biopharma insight / Biopharma Insights

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Topics: Emerging Technologies   
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Are there alternatives to using animals in drug discovery? Even though right now it still seems like a milestone which is almost impossible to avoid, there is a way to not only save the animal lives, but also enhance the drug discovery research by introducing more human-relevant physiological systems. 

In this article we are going to focus our attention around the organ-on-a-chip systems, recent advancements in the sphere and discuss to which extent we can compare such organ chips to the human. In few words, organs-on-chips are constructed from engineered or natural tissues grown inside microfluidic chips, which creates the close-to-physiological cells interplay, mimicking the liquid flow, its pressure and concentration gradients of chemicals.

The standard organs-on-chips are built as cavities containing tissues, connected with channels, where it all together is integrated with electrical connectors, electrodes and microelectrodes. The assembled chip should have a liquid circulating and tissues functioning and “communicating” as it would be occuring in a living body. For example, the heart tissue would contract, liver tissue would produce a set of enzymes, and the “brain” would be protected with a blood-brain barrier.

Are there alternatives to using animals in drug discovery? Even though right now it still seems like a milestone which is almost impossible to avoid, there is a way to not only save the animal lives, but also enhance the drug discovery research by introducing more human-relevant physiological systems. 

This challenge comes along with multiple uncertainties about how much we can rely on the data obtained from such alternative non-animal systems, do they really reflect all the complexity of the living organism and can the drugs be approved for clinical trials just from the research done in microphysiological systems and organoids. 

The term “microphysiological systems” covers biology and engineering developments aiming to mimic the human organ or (most often) human organ systems, while having it all in a controlled in vitro environment. Such systems are also called “organ-on-a-chip” and various derivations of this name. Nature journal in biomedical engineering has a notable collection of articles under the category of “Microphysiological systems”, featuring over 20 Nature publications describing intestine-on-chip, multi-organ chip, neurovascular-unit-on-a-chip, human-airway-on-a-chip, human-glioblastoma-on-a-chip and many more. 

At the same time, there is a less complex model from the engineering point of view, which may assist in excluding animals from the drug discovery research -- organoids. They represent the 3D structure of the corresponding organ unit and can be grown from primary tissue cells, embryonic stem cells, or induced pluripotent stem cells. Unlike conventional 2D cell culture, which lacks the organ anatomic microstructure and cell microenvironment, organoids stand comparatively closer to the physiologically relevant systems. Despite some advantages and the prospective use of organoids for high-throughput drug screening, they suffer from heterogeneity and often lack some essential physiological components, pushing the organoids further away from the clinically representative and reliable models.

RELATED: 3D Printed Muscle Tissues for Drug Discovery With Mantarray™ Platform by Curi Bio

In this article we are going to focus our attention around the organ-on-a-chip systems, recent advancements in the sphere and discuss to which extent we can compare such organ chips to the human. In few words, organs-on-chips are constructed from engineered or natural tissues grown inside microfluidic chips, which creates the close-to-physiological cells interplay, mimicking the liquid flow, its pressure and concentration gradients of chemicals.

The standard organs-on-chips are built as cavities containing tissues, connected with channels, where it all together is integrated with electrical connectors, electrodes and microelectrodes. The assembled chip should have a liquid circulating and tissues functioning and “communicating” as it would be occuring in a living body. For example, the heart tissue would contract, liver tissue would produce a set of enzymes, and the “brain” would be protected with a blood-brain barrier.

Let’s review some of the companies pushing boundaries in this field:

Hesperos

Orlando-based company Hesperos was founded in 2015 and now is focused on creating the custom organ-on-a-chip systems, according to the specific research requirements. They raised a total $5.9M through multiple grants from National Institutes of Health (NIH) and National Center for Advancing Translational Sciences (NCATS).

The company’s organs-on-chips are designed to assess efficacy and toxicity profiles of the tested drugs, while using low volumes and amounts of materials. The maintenance in the serum-free media also mimics the blood circulation, according to Hesperos. 

The services of the company include both pre-developed available models, and the ones customized by the client, where the last ones can fit in up to 5 various tissues. The available models include such essential systems as neuromuscular junction (which assists in drug development for neurodegenerative diseases), blood-brain-barrier (which helps to assess the permeability for the drug) and many more. In the case of custom organs-on-chip they can include almost any organ, barrier tissue, or tumor, as Hesperos states. 

Quris

Quris is an Israel-based artificial intelligence (AI)-driven company, founded in 2019. After two funding rounds, with the last seed round in 2022, they raised a total $28M from multiple investors. 

Quris aims to reduce the drug development costs by predicting the safety profiles of the drugs, for which they developed a Bio-AI Clinical Prediction Platform. The company claims to have a disruptive approach: instead of using few organs on chip, they train their algorithm with the data from patient-on-chip.

The high-throughput system allows the analysis of thousands of drugs using patients-on-chip, where nanosensors assist with a continuous monitoring of the responses from each “organ representative” in a chip. Afterwards, the machine learning algorithm is trained with the data generated. Such a system allows to target the broad genomic diversity, which is achieved with multiple stem cell derived patient-on-chip-systems, for which Quris also collaborates with the New York Stem Cell Foundation. 

Emulate

Founded in 2013, Emulate is a Boston-based company developing organ-on-a-chip systems for various research and drug discovery purposes. By now, they raised a total $224.3M from multiple investors, with the last $82M Series E round led by Northpond Ventures.

Emulate has multiple organ-on-a-chips in their portfolio, specializing on a deeper understanding of the organ function itself, rather than the complex interplay of multiple organs. With the chips for kidney, liver, lung, brain and more, the company claims to effectively predict toxicology profiles or inflammatory responses for the patients. For example, the brain chip contains 5 cell types, forming the human neuro-vascular unit model, which is representative for the blood-brain barrier, cell microenvironment and multicellular diversity. 

The major application fields defined by Emulate include ADME-Tox, infectious diseases, immunology & inflammation, microbiome and more. For example, using an organ-on-a-chip system helped to study Shigella infection, since the mechanical forces have an essential role in the disease's pathogenesis, hence the chip system could become a highly representative model compared to conventional in vitro models.

Cherry Biotech

Cherry Biotech is a French company founded in 2014, having few vectors of R&D, the main of which is microfluidic technology for organ-on-a-chip systems. They claim to predict efficacy and safety of any molecule based on human tissues and their technology, while removing the animals from the clinical research. 

Cherry helps to mimic physiological and pathological culture conditions in vitro, bringing organ-on-a-chip closer to the level of clinical studies. The company developed an incubator-free microphysiological system, which assists with a temperature control while performing live imaging. This could be essential for the long-term live monitoring of the drug influence on the organ-on-a-chip, while removing the possible impact of temperature fluctuations on the obtained results. Cubix control and culture units are connected with integrated software and can be compatible with multiple culturing systems. 

Mimetas

Mimetas is a Dutch company based in Leiden, which specializes in developing organ-on-a-chip models for drug development. Founded in 2013, they raised $32.4M from multiple investors. 

The company provides OrganoServices for compound profiling or screening in the human-relative models. Combined with their OrganoPlates, the screening can be performed for multiple compounds using just one plate. 

Mimetas has such essential models as blood vessel integrity, angiogenesis and blood-brain-barrier toxicity and small molecule transport. Their proprietary OrganoFlow platform drives precisely-controlled perfusion flow in the OrganoPlate, simulating the physiological conditions. 

TissUse

A Berlin-based company TissUse was founded in 2010, aiming to develop a unique multi-organ-chip platform for drug discovery and research, to both have a more human-relative system and reduce the number of animals used for the drug discovery. 

TissUse offers to test drug toxicity, ADME profiles and efficacy using their organ-on-a-chip developments. The available models include skin-liver, intestine-liver, liver-cardio, skin-lymph node, blood-brain-barrier, intestine-muscle and many more. By the customized combination of various organs on chip TissUse aims to satisfy various individual research and drug discovery needs. 

The company also provides various control units, such as HUMMIC Starter and Autolab, which makes the chips management process faster and more convenient, which could be important for large-scale experiments. At the same time, ​​HUMIMIC ActSense can assist with reading out the various signals from multi-organ-chips. 

Netri

French company Netri was founded in 2018 with a specific focus of developing brain-on-a-chip technology. When diving deeper into one specialization, the company developed the portfolio with various applications for their brain-on-chip, such as assessment of the synaptic toxicity, axonal transport, neural network activity and others. 

Netri offers the NeuroFluidics line of products, which can become an instrument for the research of various neurological disorder models. The variety of chip’s architecture, number of chambers and their connectivity helps to create the custom models for specific needs. 

The company also owns several technological approaches to accelerate neuroresearch, so their brain-on-chips have 3D deposition chambers with advanced microchannels and membranes; the detection and recording of electrophysiological signals can be performed with Micro Electrode Arrays; additionally NeoBento plates can assist with a high-throughput research. 

Conclusion

Organ-on-a-chip technology has substantial potential to solve multiple problems in the drug efficacy and toxicity evaluation, but not all of them, at least not yet. Even now this technology already helps to push the drugs to the clinical trials, especially when the required model for testing is highly specific, as it was demonstrated by Hesperos in case of chronic inflammatory demyelinating polyneuropathy.

Organ-on-a-chip can indeed be a more relevant model to estimate the drug efficacy for the human body. There are several reasons which support this claim: for chips the tissues can be grown from the individually collected patient cells, enabling the personalized approach. Overall, there are unique molecular signatures which drastically differ between animals and humans, therefore the drug can be a “good fit” for a human but show no desired activity in the animal model.

At the same time, the estimation of systemic toxicity with in vitro models, even such an advanced model as organ-on-a-chip, remains a challenge. This is mainly an echo of lacking the complete understanding of the living organism complexity, and all the technical obstacles which come along with trying to build the simplified-but-complex-enough system even out of the currently available knowledge.

It will take decades before organs-on-chips might become a dominant technology for drug testing, fully replacing animals. Today chips can help to estimate the approximate ranges of safe but effective drug concentration (therapeutic window), assess possible drugs interactions, confirm proof of concept and still have multiple characteristics of the human body, unlike organoids or, especially, 2D cell cultures. Therefore this already can significantly cut down the number of animals used and R&D costs spent for the drug development.

Topics: Emerging Technologies   

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