Immuno-oncology is all the rage these days, and it’s easy to see why. Breakthroughs in harnessing the power of our body’s natural defenses are unlocking new ways to fight cancer, and producing some of the most promising results the field has seen to date.
But it’s not as if someone has magically cracked the code already; cancer is a shifty, maddening foe, and there’s plenty of room for new ideas. A small, Lexington, MA-based startup called ImmuneXcite is built around one such notion: launching an immune assault on tumors by recruiting one of the body’s first lines of defense, cells known as neutrophils.
To be clear, it’s early days for ImmuneXcite and its technology. Today, at the American Association for Cancer Research’s annual meeting in Philadelphia, the startup is talking up the results it’s seen in preclinical tests. The AACR limelight is occupied by therapies from Bristol-Myers Squibb, Merck, Novartis, and others that are already impacting patients. By comparison, ImmuneXcite likely won’t begin its first human clinical trials until next year, according to CEO Yaniv Bejerano.
But the startup’s approach is noteworthy. While most immune-based cancer treatments currently on or nearing the market focus on enlisting so-called T-cells, ImmuneXcite uses a molecule from a fungus to help coax neutrophils—an aggressive, invader-killing type of cell—into the fray as well.
That approach grew from a discovery made at the Whitehead Institute by Ifat Rubin-Bejerano (Bejerano ’s wife) while she was studying how neutrophils interact with fungi. Neutrophils, the most common type of white blood cell, are one of the immune system’s first responders. They patrol the bloodstream and other tissues looking for infections, and once they find a bacterium or fungus, they swallow it up, kill it, and then self-destruct—which serves as an alert for other immune cells to race to the scene.
Neutrophils have never been effectively harnessed to combat cancer, however, in part because their aggressive nature makes them potentially dangerous. Activating a system-wide neutrophil attack could be disastrous; the trick is to recruit them in a targeted way, without overdoing it.
Rubin-Bejerano discovered the beginnings of a system for doing just that at the Whitehead. She took plastic beads, and coated them with various sugars normally found on the cell walls of fungi. The neutrophils were drawn to a specific sugar, beta- 1,6-glucan; it was neutrophil bait. She and Bejerano then took meetings with scientists and medical professionals to think of the best way to use that technology. An MIT investigator, Daniel Kohane, suggested chemically linking these sugars to an antibody, which could act as a targeting agent that would lead neutrophils to invaders they might not recognize otherwise—essentially the antibody would serve to attach the neutrophil bait right on to the surface of the targeted cells.
Kohane was specifically thinking of tuberculosis, which neutrophils don’t normally attack; But Rubin-Bejerano and Bejerano thought, what about cancer? The idea was particularly appealing because there are already a number of antibodies against specific tumors in commercial use and in development; piggybacking on that technology could potentially provide new treatments for a host of cancers.
The pair were able to raise about $8 million from angel investors and a variety of grants (from the National Cancer Institute, the Massachusetts Technology Transfer Center, the Massachusetts Life Science Center and others) to back the idea, forming ImmuneXcite in December 2011 around the technology, which it calls “mAbXcite.” Bejerano is the president and CEO; Rubin-Bejerano, who left academia to pursue the idea full-time, is the CSO. Whitehead founding member Gerard Fink chairs the company’s scientific advisory board, which also includes oncology specialists from Johns Hopkins University (Charles Drake, Drew Pardoll), former Genzyme CSO Alan Smith, and immunology expert K. Frank Austen.
ImmuneXcite is starting out by strapping the fungal sugar to two different well-known cancer antibody drugs: cetuximab (Erbitux), and trastuzumab (Herceptin). That makes for a tricky business model, however: ImmuneXcite doesn’t have any rights to these drugs, so it would have to either wait for them to go off patent, cut deals to license their use, or find other antibodies to work with. (The startup doesn’t intend to make its own antibodies). Bejerano says the company is discussing “several approaches” to addressing that problem, like in-licensing antibodies that have shown they can get to their targets, but which haven’t been that effective as stand-alone molecules in clinical testing.
The big opportunity for ImmuneXcite may be to get in on the evolving mix and match game going on with cancer immunotherapy drugs. There’s currently much excitement around the new wave of so-called checkpoint inhibitors—drugs like nivolumab (Opdivo, from Bristol-Myers) and pembrolizumab (Keytruda, from Merck) that release a brake that otherwise stops T cells from attacking tumors. But these drugs don’t work for everyone, and so companies are testing them in combination with a variety of other molecules, searching for ones that boost the checkpoint inhibitors’ effectiveness.
That could be a perfect niche for ImmuneXcite’s drugs. “We already know that [checkpoint inhibitors] aren’t effective in large numbers of cancer patients—but we might be able to make those drugs effective by virtue of getting the immune storm to begin with this approach,” says Keith Flaherty, the director of developmental therapeutics at Massachusetts General Hospital’s Cancer Center, who isn’t affiliated with ImmuneXcite but is familiar with the company’s technology.
“That’s why we’re seeing a lot of interest from pharma,” Rubin-Bejerano says. “You can bring T cells to new tumors, release brakes if needed, and get responses in more people in more indications.”
That’s yet to be seen, of course. ImmuneXcite has some key challenges ahead of it as it moves into human testing. Flaherty points to a few in particular. On the efficacy side: sure, cetuximab and trastuzumab are known to be able to get to tumors, but when those molecules are linked to a sugar will they have the same success, or will they get cleared out by the body first? And on the safety side, will these conjugates create too powerful of an immune storm?
The answers to those questions, and others—like which antibody ImmuneXcite will ultimately use first—are coming soon. Bejerano says ImmuneXcite aims to raise a funding round this year, which would get the company to its first clinical trials. By then, we’ll see if ImmuneXcite has been able make some noise in the fast-growing immuno-oncology field.
“Every time I’m speaking with a company I’m surprised how many approaches people can come up with to use [these] sugars,” Rubin-Bejerano says. “It’s very exciting.”