John Maraganore: From “Prototypical Geek” To Canny Alnylam Chief

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an order disguised as a suggestion: take up business development. Vincent was a big proponent of taking young, talented people and rotating them through different areas of biotech—business, strategy, and medicine—to turn them into better general managers. He clearly felt that Maraganore had potential. But Maraganore was dismayed. His heart was in the lab—and he felt ill-suited to trade a lab coat for a suit and tie.

If he wanted to stay at Biogen, though, he had no choice.

“It soon became apparent to me that he wasn’t giving me the option,” he says. “He was like, ‘this is your job if you want to stay here.’”

At first, Maraganore hated it. He’d had no business training. He didn’t think he could make the right judgment calls. But he turned out to be a natural. Within months, “his instincts take over and he becomes one of the best business guys we’ve had in the company,” Starr says.

Maraganore liked how the job was “incredibly linked” to the science, how there were new, different things to learn, and how he could really have a big impact. In retrospect, he says, Vincent’s mandate was an “amazing gift.”

Former Biogen CEO Jim Vincent

Former Biogen CEO and chairman James Vincent

“Like many things in career development, sometimes you have to do something that you’re not happy with or don’t want to do to really learn something new that can help shape you for the future,” he says.

One of Maraganore’s first big tasks—secretly, he says, the thing he cared the most about—was to find a new home for bivalirudin. He went to most every pharma company in the world looking for a deal. They were all skeptical. Why didn’t Biogen want the drug, they asked?

For about two years, no one was even remotely interested. Finally, Maraganore found two venture capitalists, MPM Capital directors Clive Meanwell and Scott Johnson, who were starting up a company called The Medicines Co. (NASDAQ: MDCO) that aimed to buy up drugs from biotech and pharma and develop them. They loved bivalirudin, and bought it in March 1997 for a pittance—$30 million up front, and royalties.

It was a watershed deal for The Medicines Co. The FDA approved bivalirudin in 2000. Now known as Angiomax, it’s been used in more than 5 million people around the world, generates over $500 million annually, and is the core product of a public company worth almost $2 billion to this day.

Maraganore, meanwhile, felt like he’d done his job for Biogen once he’d sold the drug. After a 10-year stint, new science, again, was calling—the early genomics craze started gaining steam. Sequencing technologies were emerging. Biotech companies were looking for novel proteins that could be better Epogens, or G-CSF’s, or interferons. Maraganore was passionate about genomics, but Biogen, he says, was hesitant to commit to a big investment. Mark Levin, then the CEO of Millennium Pharmaceuticals, was vocal about genomics and how it would change medicine. So Maraganore, who’d met Levin through Sato, began having lunch meetings with him. Levin was recruiting him hard, and after bivalirudin was shipped out, Maraganore left Biogen to join him.

The move helped turn Maraganore into a true biotech business executive. He’d spend the next five or so years at Millennium helping to make deals, large (COR Therapeutics, $2 billion) to small (Cambridge Discovery Chemistry, $53 million), to industry-changing (LeukoSite, $635 million). Starr quips even his fashion tastes had expanded from the “J Crew catalog” to items with “a little bit more European influence.” He bought more suits. His personal life took off. He met a new love at a bar in 1999, and married her three years later.

MaranganoreVolleyballStill, the geeky scientist resided underneath. Maraganore was liable to pull up to Jillian’s, a local pub and sports bar in Boston, with a fancy car and a leather bag carrying a custom pool cue. Meeting some buddies like Starr after work, he’d whip a cigar out, put the cue together—and then scratch on the break.

Perhaps the most significant deal Maraganore helped negotiate at Millennium was its buyout of LeukoSite—the deal that turned Millennium into a commercial success. For his part, Maraganore concedes today that this was partly good fortune. Millennium was really interested in LeukoSite for the cancer drug alemtuzumab (Campath) and a second antibody drug. It valued a third drug, PS-341, or bortezomib, “at zero.” The drug had only been tried in a few patients at the time, and was an inhibitor of the proteasome, the cell’s garbage disposal unit—an approach most people thought would be fatal.

“It was a very scary program,” Maraganore says. “As people said back then, it was ‘inconsistent with life’ to [inhibit the proteasome].”

As luck would have it, people were wrong. Bortezomib, now known as Velcade, worked. By inhibiting the proteasome, bortezomib turned out to activate the cell death pathway in some cancer cells. The FDA approved bortezomib in 2003, making it the first proteasome inhibitor ever to market. It’s since become a mainstay treatment for multiple myeloma, bringing in billions of dollars every year. (Millennium later sold Campath, on the other hand, to ILEX Oncology, which was subsequently acquired by Genzyme.) Bortezomib was so successful it ultimately led Japanese pharma giant Takeda to acquire Millennium for $8.8 billion several years later.

Maraganore, however, never witnessed the commercial success of Velcade first-hand. Like many other big names who’ve since gone on to lead other companies or take up other prolific positions in biotech—like Levin, David Schenkein (Genentech, Agios Pharmaceuticals), Julian Adams (Infinity Pharmaceuticals), Alan Crane (Polaris Partners), Nick Leschly (Bluebird Bio), and Starr—Maraganore got a new opportunity off of Velcade’s success. While regulators were considering approving it in 2002, he got a call from Sharp, who had just started a new company with VC firms Atlas Venture, Arch Venture Partners, Polaris, and Cardinal Partners, in an emerging field of science, RNA interference. The company’s name: Alnylam. Sharp wanted Maraganore to come on board as CEO.

Most drugs on the market today are either small molecules or proteins. Around the turn of the century, however, RNAi began to electrify scientists across the globe because it offered, at least theoretically, a way to create a whole new class of drugs that could treat diseases that those other medications couldn’t touch.

The idea: to essentially silence disease-causing genes before they can make the proteins that trigger diseases. The technique—which involves introducing short, synthetic strands of RNA into cells—was first discovered by two U.S. scientists, Andrew Fire and Craig Mello, in 1998, winning them the 2006 Nobel Prize. But a team led by scientist Thomas Tuschl at the Max Planck Institute for Biophysical Chemistry in Germany became the first to publish a peer-reviewed paper in Nature, in 2001, describing how to introduce synthetic RNA molecules into human cells. Other labs around the globe were following fast.

Maraganore talked with Sharp and with Atlas partner and friend Peter Barrett, and met with then Alnylam CEO Christoph Westphal. He became smitten with RNAi. He remembers days driving to and from work at Millennium where his mind would … Next Page »

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One response to “John Maraganore: From “Prototypical Geek” To Canny Alnylam Chief”

  1. Bill Massey says:

    John is the real deal. A humble, bright visionary. Proud to know him.