MIT Angels, Walnut Angels, and Maine Angels—along with the $400,000 in grant money and $150,000 from the founders themselves—is supposed to get SQZ to profitability based on the research tool sales. Marquez expects to be there by early next year.
So why would academic researchers or pharma companies need a technology like this? Labs already have several methods to open up cells, like electroporation, which electrocutes cells. And biopharma researchers can fill liposomes, little bubbles made out of cell membranes, with drugs to deliver them. Other approaches like gene therapy (where a corrected gene is injected into the body to replace a defective one) or chimeric antigen receptor therapy (CAR-T, where T-cells of the immune system are souped up to identify and attack cancer cells) are delivered with viruses.
But Marquez says SQZ can exploit inefficiencies and niches where current technologies don’t work well. Getting large molecules inside cells is “a very hot and niche market for us because we’re not competing head to head against [other established technologies],” Marquez says. “We’re just bringing something new that couldn’t be done before.”
Sharei says that high throughput electroporation techniques, for instance, while effective at delivering some nucleic acids to cells, have difficulty elsewhere. “Cellular toxicity and incompatibility with non-nucleic acids such as proteins” are challenges, he says, whereas SQZ’s technology induces more temporary disruptions to the cell membrane that enable “almost any material of interest to be delivered to virtually any cell type.”
For a pharmaceutical company, this might mean partnering with SQZ to take a molecule of interest and see how a cell reacts to it. Or, for companies trying new therapeutic methods like messenger RNA or CRISPR/Cas9 where efficient drug delivery is a major challenge, SQZ will try to market CellSqueeze as a potential solution. (Marquez says the company has partnerships with “some of” those companies, including an mRNA therapeutics developer, though he wouldn’t name names).
We asked the opinion of several people deeply involved in cutting-edge therapeutics that will require clever ex-vivo delivery solutions. In general, the reaction was both positive—that is, conceptually it could work and be useful for a variety of applications—but still very much wait-and-see, with many technical questions outstanding.
“Finding new methods of doing non-viral delivery into cells ex-vivo is very important,” says Matthew Porteus, a Stanford University professor and clinician who specializes in pediatric blood cancers, and a scientific founder of London, UK-based Crispr Therapeutics. “So this is very exciting. The caveat is that they have to show that it will work better than electroporation.”
Another scientist immersed in CRISPR/Cas9 work—Andy May, the chief scientific officer of Caribou Biosciences in Berkeley, CA, and a board member of Intellia Therapeutics—agrees with Porteus that the electroporation bar is set high, but May notes “not all proteins work well with electroporation.”
Before Caribou, May was director of R&D at microfluidics company Fluidigm (NASDAQ: [[ticker:FLDM]]). From his decade of background in that business, he’s eager to see how SQZ builds the architecture of its chips—the size of the channels, for example—to accommodate the mixtures of cell types that come in more challenging clinical settings.
Beyond selling its technology to others, SQZ has a bigger goal in mind: cancer immunotherapy. The company aims to use CellSqueeze as a medium to create a next-generation version of Dendreon’s sipuleucel-T (Provenge). Dendreon (NASDAQ: [[ticker:DNDN]]) extracts a patient’s dendritic cells, which “teach” the soldiers of the immune system, the T-cells, what to look for, and incubates them with a genetically engineered protein found on prostate cancer cells called PAP. When those incubated dendritic cells are re-infused back into the patient, they alert T-cells to find and kill cells with PAP.
SQZ envisions CellSqueeze as a more efficient way of delivering antigens (substances like those PAP proteins that spark an immune response) into dendritic cells.
Marquez says CellSqueeze might elicit a greater response from the immune system’s T-cells than Dendreon’s method. In mice, for instance, he says CellSqueeze “basically activated every single T-cell.” Of course, that’s in mice, where cancer has been cured a million times over. SQZ has a lot more to prove.
“When we talk to pharma, they want to see that not only can you activate these T-cells, but that they can have a tumor effect,” Marquez says.
That’s where the animal studies come in. Marquez notes that those experiments will be a critical moment for the company. If the data are impressive, SQZ might contemplate the long, capital-intensive route of making its own therapeutics. Until then, however, it’ll try to amass the credibility to cut more licensing deals and grow itself brick by brick—starting with a Series A round.
“That’s happening as we speak,” Marquez says.
Alex Lash contributed to this report.
