Roche is the world’s biggest maker of cancer drugs, but it hasn’t moved into cellular immunotherapy, one of oncology’s most promising new treatments that turns our own immune cells into cancer killers. Today the Swiss company is taking the plunge by turning to tiny Boston startup SQZ Biotech and working on a form of immunotherapy they say may overcome some of the field’s most significant limitations.
The companies aren’t saying how much Roche is paying SQZ (pronounced “squeeze”) at first, but the biotech could ultimately earn more than $500 million as they develop cell therapies together for a broad range of cancers.
Cell-based immunotherapy has been moving fast. By modifying T cells, the immune system’s attack dogs, to seek and destroy tumors, companies like Juno Therapeutics (NASDAQ: JUNO), Kite Pharma (NASDAQ: KITE), Novartis (NYSE: NVS), Cellectis (NASDAQ: CLLS) and others have entered clinical trials and produced promising results for patients with certain blood cancers. These treatments are known as chimeric antigen receptor T cell, or CAR-T, therapies.
A number of questions remain about cellular immunotherapy, however: how many cancers it can impact, how scalable the technology is, whether these treatments can be manufactured in a cost effective way. All need to be answered in the next few years as therapies advance towards potential FDA approval.
The allure of the field has attracted a number of larger players: Pfizer has partnered with Cellectis, Celgene (NASDAQ: CELG) has teamed with Bluebird Bio (NASDAQ: BLUE) and Johnson & Johnson has inked a deal with Transposagen Biopharmaceuticals.
Now, finally, comes Roche. It generated about $25 billion in sales from its cancer drugs alone in 2014, and has the wherewithal to gobble up any of the major cell therapy makers. So why is its first foray into the field a smaller bet on a startup company with an unproven technology?
A Roche spokesperson says that the company has been monitoring the cell therapy space for awhile looking for methods that can expand the use of these treatments into an “array of tumor types and indications,” and that SQZ’s technology, while early, “is a step in this direction.”
“It’s demonstrated the ability to overcome many of the long standing challenges in the field of intracellular delivery,” the spokesperson says.
Instead of genetically engineering changes into T cells and unleashing them in the body, as the high-profile CAR-T methods do, Roche and SQZ are looking to modify B cells as a way of super-charging a patient’s T cells.
Here’s how: Also part of the immune system, B cells are adept at taking bits of invasive or pathogenic material called antigens—such as fragments of proteins from tumors—and “presenting” them in just the right way to T cells, akin to the way a police dog will be presented a fragment of clothing to sniff as a way to identify a suspect or missing person.
SQZ has made a chip that can be used to sort cells, one by one, and insert material into cells without killing them. Roche and SQZ want to take antigens from a patient’s tumor, insert them into the patient’s B cells—all done outside the body—then give the “stuffed” B cells back to the patient. The theory is that the modified B cells would train the body’s T cells to hunt down the cancer.
“I think [the approach] is really interesting, it’s something that should be investigated,” says Justin Taylor, an assistant member at the Fred Hutchinson Cancer Research Center in Seattle and an expert on B cells, who isn’t involved with SQZ.
Taylor says the big question is how effectively the modified B cells would train T cells. Would those “trained” T cells be as effective as genetically modified T cells? “I don’t know how strong the evidence is for B cells being a particularly strong driver of [T cell] responses…[but] it seems feasible,” Taylor says. “B cells have all the right machinery.”
If this approach were proven to work—and to be clear, SQZ does not yet have any evidence in humans that it will—there could be a few benefits over current cell therapy methods, says SQZ CEO and founder Armon Sharei. If they were directed at B cell malignancies such as a variety of leukemias, for instance, these therapies—unlike CAR-T treatments—should spare the healthy B cells.
Second, modified B cells could target a broader range of cancers—solid tumors such as breast, ovarian, and lung—with targets deep within tumors, not just on the surface. That so far has been a limitation of the T cell therapies.
Third, Sharei says that these treatments could be produced “much, much faster” than CAR-T therapies, which can take a few weeks to turn around. “It could very well be a few hours, or a day,” he says.
Taylor says that B cells haven’t really been investigated in this fashion before. Sharei contends that is because it’s very hard, “if not close to impossible” to alter B cells with the help of a virus, and electroporation—a common biopharma tool that essentially zaps cells open with electricity—tends to kill or damage them.
Taylor agrees: “Historically, modifying B cells has been a bit difficult.”
SQZ’s technology supposedly overcomes these hurdles by giving cells a gentle squeeze, just enough to open their membranes so proteins can get inside without killing the cells. Says SQZ executive chairman Amy Schulman, a partner at SQZ investor Polaris Partners: “What this tackles is a fundamental challenge that cuts across both immuno-oncology and many other diseases, which is essentially, how do you make the material you want to get into the cell have access to the cell?”
Sharei and Schulman won’t say which cancers SQZ and Roche are targeting first, which tumor-associated proteins they’re selecting, or when to expect the first treatment in a clinical trial.
The deal is a stamp of validation for SQZ. It’s only two years old, but it burst onto the scene by winning $400,000, the largest prize in the five-plus year history of the Boston accelerator MassChallenge last year. SQZ followed up with a $5 million Series A round from Polaris Partners, 20/20 Healthcare Partners and others in June.
Sharei discovered the technology at the labs of MIT’s Bob Langer and Klavs Jensen, who are both co-founders.
SQZ initially aimed to license the technology to universities and hospitals for research, but eyeing bigger profits, it changed course earlier this year and decided to focus on developing therapies—either on its own, or via deals with biotech and pharma companies. The Roche deal is the first it has announced.
Separately, SQZ also said today that former Vertex Pharmaceuticals chief technology officer Mark Murcko and XTuit Pharmaceuticals president and CEO Garry Nicholson have joined its board of directors. Arlene Sharpe, the head of immunology at Dana-Farber Cancer Institute, was named to its scientific advisory board, which already includes MIT professors Darrell Irvine, Tyler Jacks, and Christopher Love, and Harvard University professor Ulrich von Andrian.