cancer immunotherapy treatments—drugs that spur on the immune system to fight cancer.
Progress in immunotherapy over the past several years has started to change the way certain cancers are treated, but there is still a long way to go. So-called checkpoint inhibitors, which help unmask tumors so the immune system can fight them, for instance, have racked up FDA approvals in skin, kidney, and other cancers, but “the ugly truth,” as Haney says, is that most patients don’t respond to them. Researchers and firms across the globe are trying to figure out why, and unearth the best way to counteract the tricks cancer uses to evade our body’s defenses.
The latest cancer immunotherapy reality check came last week, when Bristol-Myers Squibb (NYSE: [[ticker:BMY]]) disclosed that nivolumab (Opdivo), the top-selling checkpoint inhibitor, failed a Phase 3 trial in lung cancer. The news was a setback for Bristol, of course, but more broadly speaking, it offered further evidence that checkpoint inhibitors will likely need help from other drugs to boost their effectiveness. That means a huge opportunity remains for companies that can produce the best pairing for drugs like nivolumab and Merck’s (NYSE: [[ticker:MRK]]) rival pembrolizumab (Keytruda).
Opdivo’s failure, “while surprising, is not shocking, in that we’re still learning how to use these therapies,” Jacks says.
Enter the newer wave of companies and immunotherapy approaches, like the one Dragonfly is developing. Several of these companies are trying to bring the innate immune system—our body’s first line of defense against foreign invaders—into the cancer fight. Checkpoint blockers affect T cells, members of the adaptive immune system, which learns to remember threats and eliminates them when they return. But there are potentially powerful cancer killers in the innate immune system as well—macrophages, neutrophils, and more—and in the Boston area alone, companies like Jounce Therapeutics, Surface Oncology, and ImmuneXcite are trying to develop drugs that spur them on. These startups have gotten the backing of large companies like Celgene, Novartis, and Sanofi.
Dragonfly’s focus is on natural killer (NK) cells, innate immune system sentinels that help the body battle viruses, parasites, and tumors, and alert other immune cells of threats. The company’s name is a nod to NK cells; Haney calls dragonflies pound for pound “as ferocious as anything in nature.” UC Berkeley’s Raulet is an expert in NK cell research, and Jacks has been focusing on their role as cancer fighters and immune cell recruiters. Dragonfly says it is developing biologic drugs that simultaneously target NK cells and cancer. Jacks won’t divulge specifics, but he calls the drugs “biological linker molecules” that connect NK cells to tumor cells. When this happens, the NK cells both fight the tumor cells and bring T cells into the mix.
“They substantially enhance the performance of the immune system, and they’re powerful killers on their own basis,” Haney says of NK cells. “In that sense they offer things that T cells don’t.”
Such a powerful tool comes with risks—what if too strong of an immune storm is created, for instance? And other players, such as France’s Innate Pharma and Los Angeles-based NantKwest, are developing methods of activating NK cells or stimulating them with drugs. But Haney says getting NK cells to “be productive, stay productive, and not be disruptive” forms the basis of the new company. If Dragonfly can prove this concept, the strategy might apply to a broad range of cancers, he says.
“We think we’ve got a bit of an edge based on what we’ve done and how we’re thinking about it,” Jacks says.
Dragonfly is anywhere from six to 12 months away from having its first drug programs, Haney says, so it will likely be a while before the company produces human clinical data. And Jacks acknowledges that until that data arises there is a “burden of proof” to show that NK cells can provide the cancer-fighting punch Dragonfly believes they can.
“The same was true of T cells if you dial the clock back 10 or 15 years ago,” Jacks says. “There was skepticism, and then everything flipped.”
