Among the slew of challenges in drug development, there’s this: how can you efficiently get a big molecule, like a protein or nucleic acid, into a cell?
That quandary has bedeviled a number of efforts to make and deliver drugs over the years, but it has also provided room for creative thinkers—including one from MIT who’s trying to prove it only requires giving a cell a gentle squeeze.
That’s the thinking behind SQZ Biotech, a startup coming from discoveries that Armon Sharei, a postdoctoral fellow at Harvard Medical School, made at the labs of MIT’s Bob Langer and Klavs Jenses. The company just received the largest prize in the five-year history of the Boston accelerator, MassChallenge—$400,000 in non-dilutive grant money—and some high praise from Scientific American, which called its technology one of the year’s top breakthroughs. With a CEO and 11 other employees, SQZ will soon find out if it can turn that promise into a profitable business.
SQZ is currently situated in the Boston seaport district offices of MassChallenge, which runs a non-profit accelerator program and competition that doles out $1 million in grants to its top new startups each year.
To go from seedling to startup, says CEO Agustin Lopez Marquez, SQZ is looking to raise $3 million to $5 million for a Series A round. That amount of cash would help develop its technology not only as an academic research tool but potentially as a way to deliver immunotherapies—treatments that train the immune system to fend off cancer and other diseases.
SQZ first needs to conduct animal studies to prove to pharma companies that by getting “stuff” into cells (as the startup describes via a cartoon on its website), it can elicit a powerful immune response that shrinks tumors.
It’s a tall order, but SQZ has big names backing its quest. MIT’s Langer and Jensen are both co-founders and sit on its board, as do Oxford Bioscience Partners managing partner Jonathan Fleming and Amy Schulman, a Polaris Partners venture partner and former head of Pfizer’s consumer healthcare business.
Schulman’s recent addition suggests that a Series A round might include Polaris—after all, the Boston firm has been a major backer of several Langer co-founded startups, like Bind Therapeutics (NASDAQ: [[ticker:BIND]]), Momenta Pharmaceuticals (NASDAQ: [[ticker:MNTA]]), and Selecta Biosciences, to name a few.
“It would make sense, but there’s nothing concrete yet,” Marquez says.
It turns out the work behind SQZ was an accidental discovery. Sharei was working on a method to make a more efficient and productive version of microinjection—a microscopic way to puncture single cells and inject them with a substance. The idea was to push cells through a tiny channel, and poke them with a needle sitting perpendicular to the channel as the cells were passing through.
What Sharei found, however, was that the cells moved too fast for the needle. So he and his colleagues slowed cells down by making the channels they passed through even smaller—squeezing them—so the needle could poke them. The system started working, but as the scientists fortuitously found out, it was the squeeze itself, not the needle, that was opening the cells.
“In hindsight this was a fantastic accident, because that system was pretty expensive and difficult to assemble, while [our technology] is so simple,” Marquez says.
That led to what SQZ calls “CellSqueeze,” which is essentially a microfluidic chip made of silicon and glass, slightly bigger than a cell-phone chip, that can be used to squeeze cells just enough to open up their membranes so molecules, like proteins, can get inside without killing them.
Here’s how it works. A scientist mixes cells with a molecule of interest—say, a drug prospect they want to test. The mixture is put into a reservoir and pushed, by the pressure of nitrogen gas, through the tiny channels in the chip. The constrictions open up the cell membranes, and they remain open for a few minutes after they exit the channels. The cells are still in the mix, which allows the molecule of interest to sneak inside.
The cells then close up, and the researcher scoops them up to do whichever kind of assay is needed. SQZ has 16 different chip designs for different sizes of cells and constrictions. The chips can squeeze about a million cells per second, and the technique can be applied to a host of different cell types, like stem cells or immune cells.
SQZ has already sold CellSqueeze as a research tool to Harvard University, MIT, Massachusetts General Hospital, and the University of Pennsylvania. In those deals, SQZ supplies both the chips, which are disposable (and thus a recurrent revenue), and a system that dials up or down the amount of pressure from nitrogen tanks (which most labs have). SQZ also trains people how to use them.
Marquez wouldn’t divulge the pricing details. He does say, however, that the $1 million in angel funding SQZ has raised from
