When Did Organs-on-a-Chip Become Human-on-a-Chip?
Drug discovery is one of the keystone themes we cover on Nanalyze, and we’re not just talking about finding new cannabis dispensaries in the smoking Pacific Northwest. Creating novel medicines from scratch to treat disease isn’t cheap. A study published this year calculated it costs an average of $1.3 billion to develop a new drug – and that sounds like a bargain compared to previous estimates of more than $2 billion. The new scientific guesstimate covers most of the recent decade, so maybe all of those AI drug discovery companies like Atomwise and Insilico Medicine are starting to pay dividends by rapidly identifying the best molecule for the job. Another shortcut in the drug discovery process that’s gaining traction – at least judging by the number of companies crowding the space – is the application of microchip manufacturing to create what’s known as organs-on-a-chip.
What is Organs-on-a-Chip?
While the technology varies, organs-on-a-chip generally encapsulate human cells into a microchip structure. These micro devices include multiple hollow channels lined with organ-specific cells, along with other types of cells that reproduce the circulatory system. Experiments usually involve introducing a fluid containing a drug, chemical, other cells, or whatever constituent required for response is being studied. In effect, they are artificial organs that researchers can use to test the effects of medicine, chemicals, and foods. Some of these medical devices can even replicate the physical activity of human organs, such as the breathing motion in the lungs:
While scientists can already perform experiments on cells in vitro (the proverbial test tube or otherwise outside the body), organs-on-a-chip is the only method that can maintain the original cellular function for prolonged periods of time with a much broader range of applications.
How Does Lab-on-a-Chip Fit In?
The idea of inserting human cells onto a microchip to mimic organs like the lungs or kidneys for research is based on something called microfluidic technology. Microfluidics is synonymous with a term we’re more familiar with – lab-on-a-chip. One of the hottest IPOs this year involved Berkeley Lights, a company that offers an R&D sandbox for analyzing cells en masse which will help find the right cellular machinery for everything from drug discovery to synthetic biology. The lab-on-a-chip concept has been an area of active investigation since the 1990s but thanks to advances in things like automation (increasing throughput) and nanotechnology (shrinking it all down), the technology is now becoming scalable and profitable.
What is Human-on-a-Chip?
The primary use case behind organs-on-a-chip is that scientists can more realistically test how a drug will affect a particular organ like the stomach without killing a bunch of twitchy-nosed mice in the process. Of course, the human body is a holistic system, so what might be good for the gut could prove to be toxic to the liver. Enter human-on-a-chip, or body-on-a-chip, which links multiple organ chips together to analyze an experiment’s effects on the whole system.
The line is blurring between the two concepts, at least when it comes to the terminology itself; companies that have developed specific organs-on-a-chip technology sometimes use the more encompassing human-on-a-chip term.
Companies Developing Organ- and Human-on-a-Chip Technology
About five years ago, we covered some of the companies working on organs-on-a-chip technology. During the course of our research for this article, we uncovered more than 20 startups and private companies developing various riffs on the organ-on-a-chip platform, with more than a few taking it to the next level with human-on-a-chip integrated systems. In this article, we’ll revisit old friends and introduce you to a few new ones that have taken recent funding.
We’ll start with the company that most would consider to be the leader in the field – Emulate
Most Well-Funded Organ-on-a-Chip Startup
We first wrote about Emulate way, way back in 2014 when excitement was building around Organovo (ONVO) and its 3D bioprinting technology. At that time, we wondered if organs-on-a-chip would compete with 3D bioprinting. The more likely scenario now is that 3D bioprinting would complement organ-on-a-chip technology as a manufacturing process. While Organovo has been on a steady slide since then, Emulate has amassed more than $142 million in funding, including a round of debt financing for $19.3 million back in March. Its investor roster is diversified, including government agencies like the National Institutes of Health (NIH), nonprofits including ALS Finding a Cure, and traditional venture capital firms like Founders Fund.
A spin-out from the Wyss Institute, Boston-based Emulate originally got its start from a $37 million R&D grant that the shadowy government agency known as DARPA gave to Harvard University to create organs-on-a-chip to study physiology outside the body. That was eight years ago. Today, the company is pushing toward commercialization with a broad portfolio of products. Its flagship platform consists of two hardware components – organ chips and the Zoë Culture Module. The latter is a lab-ready instrument that automates experiments for up to 12 of the company’s organ chips, which comes in three flavors – kidney, intestine, and liver.
Emulate claims that the platform has already been installed by 150 customers, including 10 of the top 25 biopharmaceutical companies in the world. It is still developing new chips, including a brain model, and colleagues at its alma mater are working on a device called the Interrogator, which is a human-on-a-chip platform that can link 10 organ chips at once.
Getting to the Heart of Organ Chip Technology
Emulate’s platform is the prototype for organs-on-a-chip technology. Then there’s the Tell-Tale Heart organ-on-a-chip device from New York-based TARA Biosystems. Founded in 2014, the biotech startup has raised a total of $21.3 million, including a $10 million Series A earlier this summer in June. The company has developed the Biowire2 platform by engineering mature heart cells from stem cells that can beat like a real human ticker, enabling a wide range of cardiac experiments for drug discovery during preclinical drug trials.
A study just published in July seemed to validate all those R&D dollars. Scientists tested whether the teeny tiny heart would react the same way as a human heart with eight types of drugs known to increase the strength of cardiac muscle contractions. Apparently, the heart organ model didn’t miss a beat. In the same month, TARA announced a partnership with VantAI, a computational drug discovery company that uses machine learning to map genes to diseases. Together, the pair hope to identify novel drug targets linked to cardiac disease and test new therapies.
Platform for Human-on-a-Chip Studies
London-based CN Bio is another biotech startup that has benefited from U.S. federal dollars via DARPA through a joint five-year, $26 million grant with MIT. That’s in addition to the $11.5 million the company has raised in disclosed funding, including a $9 million venture round back in March. In 2018, after licensing the technology from MIT, the company launched the PhysioMimix platform. The printer-sized device allows scientists to conduct organ-on-a-chip studies to test new drugs, food, and chemicals on living human organ models. That same year, in a paper published in Nature Scientific Reports, researchers demonstrated that the machine could perform human-on-a-chip studies with up to 10 organ chips that contain as many as two million cells. In one experiment, the researchers modeled how drugs can cause unexpected stress on the liver by making the gastrointestinal tract “leaky,” allowing bacteria to enter the bloodstream and produce inflammation in the liver.
More recently, the company is focused on using its proprietary liver-on-a-chip to find novel drugs for diseases like alcoholic hepatitis in collaboration with Imperial College London. The liver chip can run experiments for more than a month, modeling a range of human liver diseases and their progression.
An Organ-on-a-Chip for Modeling Snake Venom
A Dutch startup called Mimetas has been making some waves in the organs-on-a-chip industry. Founded in 2013, the company has raised about $32.4 million, including $3.5 million last year. The company’s flagship product is OrganoPlate, which supports customized disease and toxicology models for the kidney, liver, gut, brain, and a range of oncological applications. It claims to work with the majority of the global top-50 pharmaceutical companies, in addition to chemical, food, and consumer goods companies.
Mimetas has also done some out-of-the-chip investigations in academia, including an experiment published in the journal Cell about how its platform could be used to model the glands of venomous snakes for developing easier and cheaper antidotes.
Organ-on-a-Chip Enables Gene Sequencing
Another company that has come up in our previous coverage around Organovo is InSphero, a Swiss startup founded back in 2009. It has raised about $35.2 million in total disclosed funding, including an undisclosed amount of grant money last year and $10 million in 2018. InSphero’s flagship organ-on-a-chip platform is called Akura Flow, which appears to be finally heading toward commercial production after nearly a decade of development. Sounds like it can handle both organ- and human-on-a-chip applications. In addition, InSphero says its device is the first in the industry to allow users to extract 3D microtissues for gene sequencing or other downstream uses.
Organ-on-a-Chip for Neurological Drug Discovery
Leave it to the folks at New Orleans-based AxoSim to put a Cajun spin with an organ-on-a-chip platform that focuses on drug discovery for neurological disease. Founded in 2014, the biotech startup has raised $4.1 million in disclosed funding, with a couple of rounds last year, including a $1.1 million venture round and an undisclosed Seed round. Its Nerve-on-a-Chip platform currently boasts two technologies – BrainSim and NerveSim. AxoSim claims the latter is the first to replicate nerve growth in an in vitro setting to study the underlying causes of neurological diseases. In a successful study published earlier this year, scientists used a rat nerve model to see if it would respond to four kinds of cancer drugs that often cause neurological side effects.
The Original Human-on-a-Chip Company
That’s how Orlando, Florida-based Hesperos describes itself in all of the marketing material. In fact, it has trademarked “Human-on-a-Chip,” and developing its multi-organ chip systems has been the focus of the company’s recent R&D efforts and scientific publications. Founded in 2015, it has raised $4 million in disclosed funding, with the NIH kicking in an undisclosed amount of grant money last year.
Like just about every biotech company in 2020, Hesperos has pivoted its
press outreach efforts to understanding more about the novel coronavirus that causes COVID-19, based on a study published this summer that was a collaboration with Hoffmann-La Roche, a Swiss multinational healthcare company, and the University of Central Florida. The paper suggested that the company’s Human-on-a-Chip platform can be used to investigate immune responses for multi-organ systemic diseases such as COVID-19. Using what Hesperos refers to as “immunity-on-a-chip,” the three-organ system could be used to understand how the body’s immune system overreacts to infection, possibly helping to find a treatment more quickly.
It would seem that the biotech sector devoted to modeling disease treatments using organ- and human-on-a-chip technologies is rapidly progressing. However, the industry is still quite young. Funding is relatively modest and generally lacks any big names, especially from the pharmaceutical side. Money that is flowing into the sector is largely coming from government grants and related sources, which reflects the fact that most of the activity is still focused on R&D. Similarly, the press releases tout the latest published research rather than major financial deals. Even big names like Emulate are only now beginning to commercialize its products after more than a decade of development.
However, there are obvious signs that the sector is starting to shift from peer-reviewed to profit-driven, as the science solidifies and companies figure out how to scale. You remember the study we cited at the beginning of the article that said the average cost to develop a new drug is $1.3 billion? More than 40% of that is spent on preclinical work, meaning organ- and human-on-a-chip technologies could have an outsized impact on drug discovery research in the coming years.
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