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Biological Chemistry

Movers And Shakers

C&EN talks with Jay Bradner, physician-scientist turned R&D chief

The new president of Novartis Institutes for BioMedical Research discusses his approach to innovation

by Lisa M. Jarvis
May 16, 2016 | A version of this story appeared in Volume 94, Issue 20

Jay Bradner
Credit: Novartis
Photo of Jay Bradner.
Credit: Novartis

When Jay Bradner got the call from a Novartis board member asking whether he’d be interested in leaving academia to become the research chief for the big pharma firm, he wasn’t exactly feeling a career itch. The physician-scientist and serial entrepreneur was having a particularly good year. Discoveries—several of which would go on to become well-funded companies—seemed to be streaming out of his Harvard Medical School labs. “We were just getting warmed up,” he says.


Education: Harvard University, A.B., 1994; University of Chicago, M.D., 1999

Career highlights: >130 publications, >30 patents

Companies founded: Acetylon Pharmaceuticals, C4 Therapeutics, Shape Pharmaceuticals, Syros Pharmaceuticals, and Tensha Therapeutics

Did he want to leave that well-oiled academic engine behind to take on the weight of a 6,000-plus-person research organization? “It didn’t require any thought at all,” Bradner says. “Charles Sawyers was halfway through the sentence when, in my mind, I said, ‘Yes.’ ”

Bradner officially left his joint appointments at Dana-Farber Cancer Institute and Harvard for Novartis in January and took over as president of Novartis Institutes for BioMedical Research (NIBR) in March. The past two months have been a whirlwind: He’s crisscrossed the globe to visit Novartis’s R&D hubs to get to know its research culture and pipeline. “In effect, I’m learning our pipeline through the oral history of its innovators,” a method that is giving him a crash course in how a huge organization does science.

Some might regard that task as daunting. Novartis’s pipeline is rich in Bradner’s area of expertise, oncology, but he also needed to learn about fields outside his comfort zone, such as neuroscience and musculoskeletal disease.

Bradner, however, seems downright giddy when talking about digging into the details of Novartis’s vast research activities. “It’s not overwhelming; it’s just intoxicating,” he says. If you like structure-activity relationships, “there’s no better job in the world than the job I’ve just taken.”

This is not the first time that a thirst for knowledge has driven him into entirely new areas. After finishing his training as a hematologist, Bradner threw himself into learning chemistry with Harvard’s Stuart Schreiber. Bradner’s Harvard labs subsequently combined synthetic organic chemistry, protein biochemistry, assay development, chromatin biology, and computer science.

The end result was a team that Bradner describes as “a biotech company built at Harvard to create knowledge.” The goal wasn’t, he says, to generate drugs but to use small molecules to study the circuitry of enhancer-promoter communication. Yet roughly once per year, a technology would emerge from his research that was ripe for commercialization. During his tenure at Harvard, he cofounded five oncology-focused biotech firms—the most recent, C4 Therapeutics, raised $73 million.

But the serial entrepreneur is also notorious for preaching the gospel of open science. After Bradner’s lab discovered JQ1, the first small molecule known to block the epigenetic enzyme bromodomain 4, in 2009, he decided to make the compound freely available to other researchers. The move stemmed from his own frustration at the lack of access to compounds before his lab had synthetic chemistry capabilities. No strings were attached when he sent out samples to other researchers. “We just asked them, please, not to eat it,” he jokes.

What happened next came as a surprise: Although not required to collaborate, labs that received the compound always came back to Bradner to share their data. “Like opening the first door of a threshold, people instinctively open the second door,” he says.

At no small expense, his lab ended up sending JQ1 to 450 labs around the world. That access appears to have sped up the development of drugs against the target. Since the discovery of JQ1, the field has seen 79 patent applications from at least 29 institutions related to bromodomain inhibition. Today, 10 bromodomain inhibitors are in clinical testing.

It was an honorable experiment in how to accelerate knowledge around a target and quickly generate a drug pipeline, but many wonder how that approach to open science will translate to an industrial setting. Now at NIBR, Bradner is trying to push the boundaries of how industry researchers think about collaboration.

“I’ve challenged our scientists to propose models of open innovation that would be well-suited to our institute,” Bradner says. He grins and adds that he has his own ideas about what could work, but he wants to hear from Novartis scientists first.

As part of that challenge, Bradner is trying to get Novartis researchers to reflexively tap into ideas and technologies discovered outside their labs. “To date NIBR has done this pretty well, but we need to do better,” Bradner says. He calls science “a team sport” and ultimately wants scientists who do cutting-edge work to pick Novartis out of the many potential collaborators in the industry.

This talk of open innovation doesn’t mean he’s not excited by what he’s seen inside Novartis’s own labs. His predecessor, Mark Fishman, left him with “a well-manicured” research organization, and he’s been impressed with what its researchers are achieving. “NIBR scientists have accomplished feats of discovery that even I have thought were beyond the reach of chemistry,” he says. Visiting labs and digging into the early pipeline, he says he’s had to “absolutely recalibrate my own idea about what is druggable and what is undruggable.”

Broadening that knowledge network through open collaboration, he says, “could be a way to turn $9 billion of R&D into $90 billion by extending the scope and reach of our science.”

Doing more with those research dollars will be vital for Novartis. Bradner has stepped into the job at a time when the company needs more than ever to pump out promising new drugs. In February, a generic version of Novartis’s blood cancer pill Gleevec rolled out in the U.S. Lauded as one of the first—and 15 years later, one of the only—cases of a personalized treatment truly transforming cancer care, Gleevec generated $4.7 billion in revenues last year, making it the company’s biggest-selling drug. And sales of Entresto, a new heart failure treatment that was expected to help offset the Gleevec loss, have trickled in since its approval last year.

Bradner appears up for the challenge. As he told a group of reporters last month with his characteristic enthusiasm, every day he gets excited about a new piece of data or a glimpse of a potential breakthrough. “There’s no question that it is like Christmas every day in this job.”  


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