It’s an age-old problem with drug development: no matter how good a drug looks when tested in animals or petri dishes, there’s no guarantee it’ll have the same effect on a person. That unpredictability has delayed or doomed countless drug prospects—and drives up the cost, and time, it takes to make a successful therapeutic.
A new startup called Emulate, spun out of Harvard University’s Wyss Institute, wants to improve the odds and recalibrate how preclinical testing is done—by using what it claims is the most comprehensive “organ on a chip” and software system created to date.
Today, Cambridge, MA-based Emulate is officially ramping up with a $12 million Series A round that it’ll partly use to move out of Harvard University’s Wyss Institute for Biologically Inspired Engineering—where it’s been incubating—and try to set up shop in Kendall Square, says CEO James Coon. Venture firm NanoDimension is leading the financing, with additional contributions coming from Cedars-Sinai Medical Center and Swiss billionaire Hansjorg Wyss, the founder of the Wyss Institute.
Emulate will now start out on a difficult quest. It’ll try to prove that pharmaceutical companies and biotechs can reliably use its thumbnail-sized microchips in preclinical drug tests, rather than relying on in vitro or animal studies. It’ll try to show that its chips are different, and superior, to similar technologies being developed or sold by a number of other companies. And then Emulate will try to branch out into other industries, like using its microchip systems to test the safety of cosmetics or agro-chemical products.
It’s a big challenge—and the idea of organs on a chip has been around for years. But Emulate believes it’s got a chance because it’s based on the work of Harvard professor Donald Ingber, one of the pioneers in the field, who’s also the Wyss Institute’s founding director. The company has been incubated within the Wyss Institute for around five years, where scientists and an assembled in-house executive team have raised more than $40 million in grant money from the FDA and the Defense Advanced Research Projects Agency (DARPA). They also brought in industry researchers early on to help direct the design of the founding technology.
“We’ve been able to put a lot of resources around this,” Coon says.
Coon, a former AstraZeneca and GlaxoSmithKline employee and entrepreneur-in-residence at the Wyss Institute, and senior staff scientist Geraldine Hamilton (now president and chief scientific officer) are leading the company. Both Coon and Hamilton were executives of Research Triangle Park, NC-based CellzDirect, which Invitrogen bought for $57 million in 2008.
What Emulate has come up with is a way to manufacture tiny systems that mimic the functions of real organs—lungs, livers, and guts, among others—on microchips. Those chips can be used to run experiments and test how, in theory, a human organ would react to a potential drug. Take Emulate’s lung chip, for instance. It’s a small, flexible polymer with hollow channels running through it. Those channels contain a porous membrane in the middle that is infused with human lung cells on one side, and capillary blood cells on the other. Emulate uses mechanical forces to make the chip contract and expand, mimicking breathing. The chip has air running through the top, above the lung cells, and blood underneath the membrane, to approximate a real lung.
Coon says researchers can then use these chips as part of a “plug and play” system to create disease states and infections, test how these mini-organs would react to a drug, and then analyze the results. A lab instrument provided by Emulate, for example, maintains and feeds the cells on the chip. And the company’s software enables researchers to design an experiment and analyze the data that come out. The idea is that this process would be simple—and give drug companies a more representative indicator of how a real patient’s organ would respond to a potential therapeutic than isolated cells in a petri dish, or the reactions of animals.
“What we wanted to do really early on was create a platform that really automated this process, that made it easy to use, that made it plug and play, that made it robust and reproducible,” Coon says. “Ultimately, we’re trying to cut down on clinical failures.”
Ideally, Coon says, Emulate’s goal is to have this type of technology used by academic labs, research labs, and drugmakers across the globe—something of a new standard for preclinical testing. Its big idea down the road is to link a bunch of these chips together to create a system that mimics the whole human body, rather than just using models of individual organs (the DARPA grant was designed to fund that project). But of course, there are big hurdles Emulate has to overcome before it can really get there.
Perhaps the first, and biggest, of those challenges is that Emulate has to show pharmaceutical companies, biotechs, and most importantly, regulators, that its system is easy to use, scalable, and reliable enough to trust in preclinical tests. To do that, Emulate is going to have to amass data, and lots of it, showing that its system works.
In one such study that Emulate points to, it created a disease model for pulmonary edema—an uncommon, but potentially deadly side effect of cancer treatment with interleukin-2, in which fluid fills up the lungs. Emulate then tested a drug GSK was developing to treat the condition. The drug, a so-called transient receptor potential vanilloid 4 (TRPV4) channel blocker, reversed symptoms when tested on the chip—as well as in a separate study GSK ran in animals published in Science Translational Medicine at the same time. Additionally, Emulate says it found something that animal studies hadn’t—that breathing exacerbated the fluid leakage caused by IL-2 therapy.
Emulate will need more examples like that to help build its case to potential industry customers. Coon says the feedback he’s gotten from such companies so far is positive, and that the startup is confident it’ll have a big impact on early preclinical testing methods—in vitro studies—“right out of the gate.” It’s the animal studies further down the preclinical drug development road that’ll be tougher for Emulate to break into, he says, because that’s when regulators get involved, and “years of studies” would be required to appease an agency like the FDA.
“That’s going to take a longer period of time,” Coon says.
Then there’s the competition. Emulate is by no means the first company to try the organ-on-a-chip approach. But the technology has never been scalable, comprehensive, or user-friendly enough to really make an impact on preclinical drug testing in the pharmaceutical industry. Still, technological advances and government initiatives like the National Institutes of Health’s Microphysiological Systems Program—a wide search for methods like organs-on-chips to improve preclinical drug testing—have led to a number of academic groups and companies with competing systems that are either already on the market, or on their way. Among them: Seattle startup Nortis, a University of Washington spinout; North Brunswick, NJ-based Hurel Corp., which uses an organ on a chip method to replicate liver tissue; and Netherlands-based Mimetas. San Diego-based Organovo Holdings (NYSE: ONVO) and others also aim to use 3-D printing techniques to help speed up preclinical drug development.
What makes Emulate stand out? Coon points to a few things. First, he contends that Emulate’s chips can provide a more detailed and representative level of biological function: “Technologies that are out there, they focus on cells, they focus on a combination of cells in the matrix,” while Emulate’s chips include the cells, the blood flow, and recreating the mechanical forces that drive organ function—like breathing on a lung chip, or the compression of an intestinal tract, Coon says.
“That’s tough to do,” he says.
He also notes that some competitors are looking at individual organs, while Emulate is moving towards a larger, integrated approach (like the body-on-a-chip concept). Coon adds that the company aims to move into personalized medicine by using patient sample cells to construct patient-specific organs on its chips.
These advantages, of course, have yet to be proven with industry adoption and revenue. That’s the task that awaits Emulate as it moves out of the Wyss Institute and smack into the middle of Boston’s biotech ecosystem. Emulate has some time to get its bearings—the $12 million should last about two years, according to Coon—but now that it’s moved on from a science project to a full-fledged company with venture investors, it’ll have to deliver.
“Our team will be transitioning out [of the Institute] in the coming months, and we’re going to hit the ground running,” Coon says.