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To Infinity and Beyond: Julian Adams on Missteps and His New Job

Xconomy Boston — 

Julian Adams left Boston pharma Millennium Pharmaceuticals in 2003 having accomplished a rare feat. A medicinal chemist by training, Adams helped shepherd along a drug known as bortezomib (Velcade) that was the first-ever approved inhibitor of the proteasome, the cell’s garbage disposal unit. It was an approach most people thought would never work.

“Everybody was convinced, except for Julian Adams, that if you block this target people would melt away and die,” Alnylam Pharmaceuticals CEO John Maraganore, a former Millennium executive, told Xconomy a few years ago. “Except for Julian, who stuck with it.”

Adams was indeed proven right. Bortezomib is now a widely used treatment for people with the aggressive, deadly blood cancer multiple myeloma, and the main reason Takeda bought Millennium for $8.8 billion in 2008. The drug’s widely told story, from the labs of Harvard University to a tiny startup, ProScript, and eventually Millennium, became a shining example of fast drug development—eight years from discovery to approval, and a speedy four-month FDA review.

A number of folks who had a hand in bortezomib’s success at Millennium—Maraganore, Mark Levin (Third Rock Ventures), David Schenkein (Genentech, Agios Pharmaceuticals), Nick Leschly (Bluebird Bio), Alan Crane (Polaris Partners) among them—went on to lead other companies or take up other prolific positions in biotech. Adams was no different. In 2001, he had a beer with his longtime friend and ex-Millennium colleague Steve Holtzman, who had formed a startup, Infinity Pharmaceuticals (NASDAQ: INFI). Adams was drawn in by Holtzman’s pitch. Why not build, from scratch, a research and development organization “in his image,” Adams recalls?

Adams dove in. He was named Infinity’s head of R&D in 2003, and over the next 13-plus years, tried to execute on that vision—to form a collaborative early stage research and clinical development team, rather than two disparate groups—and build off his success at Millennium. What he encountered instead was a humbling roller coaster. (More on that and his latest job, in the Q&A below.)

Infinity’s plan to develop small molecule drugs for cancer never quite panned out. Two drugs that seemed promising early on eventually failed clinical trials in pancreatic, lung, and stomach cancers. A third program, a blood cancer drug called duvelisib—not discovered by Infinity, but acquired through a licensing deal with San Diego, CA-based Intellikine in 2010—became its best prospect. It felt validated when pharma giant AbbVie (NYSE: ABBV) wrote a $275 million check in 2014 to bet on duvelisib’s future. Yet, AbbVie just months later paid $21 billion for Pharmacyclics and a drug, ibrutinib (Imbruvica), that competed directly with duvelisib.

“We were stunned that that happened,” Adams says.

The writing was on the wall. By the time duvelisib’s big test produced results in June 2016, the competition had blown by Infinity, and so-called PI3 kinase inhibitors, like Infinity’s drug, were no longer hot commodities. Even though duvelisib hit its main goal in a mid-stage trial, the results weren’t good enough to compete with drugs already on the market—the bar had gotten higher. The company closed its research and discovery work, and lost the AbbVie partnership. Two months later, it sold duvelisib to another biotech, Verastem (NASDAQ: VSTM), for a pittance—nothing up front, and up to $28 million in future payments.

Adams left in January, and Infinity now operates with a “skeleton” staff of about 20 to 30 people working on the company’s final shot—a drug called IPI-549 in Phase 1 testing, Adams says. Shares currently trade at roughly $3 apiece.

Adams has his share of regrets about his time at Infinity—it grew too fast, he says, and he blames himself for plenty of mistakes, even as “mundane” as making a key hire that didn’t work out, or not vetting certain clinical trial sites well enough. But failure is the norm in drug development, not the exception. The Infinity setback hasn’t consumed him.

“I’m undaunted, I still want to do this,” he says. ”Managing failure is part of being a scientist.”

For now, that means taking all of his experiences and applying them as more of a mentor, consultant, and investor. In January, Adams became the president and chief scientific officer of Israeli venture firm Clal Biotechnology Industries. From an office in Cambridge, MA, he’s overseeing the firm’s biotech investments—five of which are in the Boston area—and is executive chairman of one, Vedantra Pharmaceuticals. Adams is helping startups develop research and development plans, raise cash, and more.

Xconomy spoke with Adams about his ups and downs at Infinity, his new role at Clal, and his plans going forward. Edited excerpts from the conversation follow below.

Xconomy: You say you wanted to build an R&D organization at Infinity “in your own image.” What did that mean?

Julian Adams: Often there’s a big silo between what research does and what development does. I wanted to see if I could bridge the gap and build a kind of organization that would seamlessly discover, but also develop, drugs. It would be the same people connected to both ends of the spectrum.

X: How much of that do you feel you accomplished?

JA: I realized it was very difficult to scale. Once we got to 125 or to 150 people it was harder and harder to have development and research in the same room learning from each other. It works on a small scale, and many startups are forced to do it that way, but when you’re doing multiple projects and have a pipeline to build, it’s very hard. The development [team] has a different phenotype than the research team—they don’t quite speak the same language.

X: Infinity had three key clinical failures in 2009, 2012, and 2013, with two different cancer drugs. What do you remember about them? How do you break news like that to the company, and rally employees you know will be devastated?

JA: [In 2012, when saridegib failed], I was on a business trip and was called back, I came back at 11 pm at night. We spent all night writing the press release, and were trying to figure out what to say to the company in the morning. I stood up in front of the company and said, “This is a noble failure. Who even dares to try to treat pancreatic cancer? It’s a graveyard for many drugs, and here we are. We did everything right, except the biology is way more complicated than what we thought our [drug] could do.”

I said, “Let’s go back to the lab and work on the next problem.” There’s nothing I can do about the past, I can only look to the future and to new ideas. That’s not to say that everybody bought into this—some people left Infinity and transitioned to other places—but I would say the vast majority of people enjoyed the community of Infinity and felt like it was an enriching enough experience to continue on to the next problem.

X: That next shot turned out to be duvelisib, but you were way behind other companies already. How do you weigh investing in a program like that, knowing how fast the competition is moving?

JA: We had hoped that maybe our drug had features that would comport to better activity, that maybe being second or third to market would be ok. When we in-licensed duvelisib, none of these drugs were approved. It’s a footrace, let’s run with the big boys, we said, but it turned out that 4 out of 4 competitors all reached the market before us.

X: Including ibrutinib, which AbbVie bought by acquiring Pharmacyclics six months after your deal.

JA: That was totally unanticipated. We were stunned that that happened, and I think that that’s just bad luck. AbbVie had made a corporate decision to go and get a marketed drug that directly competed with our program. There are scientific and clinical risks, and there are also business risks. We had managed our risks fairly effectively to the 15-year life of the company. But this was just kind of a giant killer for us.

I had made the pitch to [AbbVie’s] head of oncology that if we combined our drug with venetoclax (Venclexta, a drug co-developed by AbbVie and Genentech) that we would have a shot at curing [the blood and bone marrow cancer] chronic lymphocytic leukemia. The reason we did the AbbVie deal was to try to enable that experiment, and it never got done. That for me is a big regret, as a researcher and as someone trying to work in this horrible disease.

X: So you had no indication AbbVie had other plans?

JA: No. They couldn’t talk to us about venetoclax, and they couldn’t talk to us about the Pharmacyclics drug by virtue of their partnerships with other companies. So AbbVie was never able to share with us, even in the aftermath, why they made certain decisions. We were swept away with the success of the other drugs. And let me make no bones about it—the other drugs were very successful.

X: How did you deal with the setbacks?

JA: We have to separate ego from the work we do. If you come up with an idea and carry it out and see a drug to a successful approval, that obviously feels very good and everyone loves you, but it’s sort of like making movies. Steve Holtzman used this analogy all the time: Steven Spielberg makes great hit movies, but not every movie that Spielberg makes is even good. Yet you’ll remember “Schindler’s List,” and “E.T.,” and not all his crappy movies, right? I feel the same way. We are not guaranteed that our theory and hypotheses hold up. Managing failure is part of being a scientist.

X: Did you think about retiring when it was clear your time at Infinity was up?

JA: I‘m the worst retiree in history. I really thought, this is it, I’m 62 years old, time to hang it up, maybe join a couple of boards just to stay involved, but be effectively retired. But I just have so much curiosity in science and drug discovery and development, and so many scientific interests. I realized there’s no way I’m gonna retire. I’m gonna start a new chapter in my life.

X: So you joined Clal, does that make you a venture investor now? A consultant?

JA: I guess I’m in a venture role, but I’m very much in a scientific and leadership role too—helping to raise capital, make good decisions on science and R&D, and then just general leadership experience and ability to hire and attract good people. I see this as an ongoing process of my education. I am learning how to start and support new companies, and do so at a different capacity, where I’m not the on-the-ground R&D director for these companies.

X: Does that mean you’re done as an entrepreneur?

JA: Absolutely not, I am incubating an idea right now. I love science, and I’m still capable of having an idea and I want to see it through. I ain’t done yet.