Giant pharmaceutical companies and biotech startups are seizing opportunities to advance their oncologic immunotherapy business and provide patients with more-effective treatment options.

As checkpoint inhibitors and other cancer immune therapies continue to advance in the clinic, giant pharmaceutical companies and nascent biotechs are positioning themselves to make the most of these agents.

Merck and Bristol-Myers Squibb both have FDA-approved checkpoint inhibitors on the market to treat melanoma—pembrolizumab (Keytruda) and nivolumab (Opdivo), respectively—and are pushing to expand their approved uses. (For example, nivolumab was approved in March to treat advanced squamous non–small cell lung cancer.) Novartis has gained ground on competitors by buying GlaxoSmithKline's cancer portfolio, investing in Aduro Biotech (Berkeley, CA), and hiring a leader in the field, Glenn Dranoff, MD, PhD, this past spring from Dana-Farber Cancer Institute in Boston, MA, to head their efforts.

These companies are also developing first-line therapies, as well as reexamining their portfolios to find other drugs—some already FDA-approved, others not—that might prove effective in combination with checkpoint inhibitors. Research presented at major conferences this year supported the idea that patients will see greater benefits if checkpoint inhibitors are given together or in combination with targeted therapies, chemotherapies, or cancer vaccines. Companies are testing many combinations to determine which are most effective against which types of cancer.

“The trend toward consolidation in cancer—where a single pharma company can offer a suite of agents covering a range of cancers and combinations—is definitely real,” says Bruce Booth, a partner in Atlas Venture, a Cambridge, MA–based venture capital firm specializing in life sciences and technology.

Dranoff agrees, saying it makes sense to have a wide range of therapies in-house that can be tested in combination. He notes that Novartis now has programs in checkpoint inhibitors, cancer vaccines, and CAR T cells, in addition to treatments such as imatinib (Gleevec) that are directed at specific genetic defects.

“I think there's enormous potential for coupling,” Dranoff says. “That's going to be a theme of the work we'll be doing.”

Large companies are also buying and partnering with start-ups to augment their pipelines, says Booth, referring to a flurry of recent sales, including AbbVie's $21 billion purchase of Pharmacyclics (Sunnyvale, CA) to acquire the hematologic oncology drug ibrutinib (Imbruvica). In June, Celgene and Juno Therapeutics of Seattle, WA, announced a 10-year collaboration to develop CAR T-cell therapies, a deal that will net Juno about $1 billion. In addition, Novartis has invested $250 million in Aduro Biotech, an immune therapy company developing small molecules to activate the STING pathway, which may detect tumor cells and trigger an aggressive antitumor response.

Meanwhile, young biotechs, such as Jounce Therapeutics of Cambridge, MA, are advancing the science on other immune modulators. However, these biotechs have to be more selective, says Jounce CEO Richard Murray, PhD. They cannot cast a wide net, testing many compounds, like large pharmaceutical companies can.

“Biotech probably has to really start pushing the boundaries of where some of these new pieces of biology and therapeutic paradigms might emerge,” says Murray, whose company is pursuing T cell–directed therapy, as well as therapies aimed at macrophages and other cell types that may initiate or improve the immune system's antitumor response.

“A balancing approach between the more established space and the new frontier … makes sense,” he says.

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