John Maraganore - Alnylam

A leading voice in a reinvigorated RNA field

Name: John Maraganore
Title: CEO, Alnylam Pharmaceuticals

Everyone wanted to brush aside RNA interference as yet another dazzling lab discovery with no place in treating human diseases, but John Maraganore has never backed down from his belief in the big idea that the gene-silencing tech could be turned into powerful new drugs.

Maraganore, the chief executive of Alnylam Pharmaceuticals ($ALNY), has shown his industry counterparts how an unwavering devotion to a bold vision pays off in biotech. He has led his company from its infancy, through a cycle of hype fueled by a Nobel Prize in 2006 for RNAi discoveries, and beyond a recent era of doubt that followed a series of pharma cutbacks in gene-silencing research such as Roche's ($RHHBY) big exit from the RNAi field in 2010.

Cambridge, MA-based Alnylam endured setbacks and questions about its future after Novartis ($NVS) ended a research collaboration with the company in 2010, with the biotech undergoing staff reductions in recent years that have brought its workforce down from a peak of 225 employees to about 130 today. Investors have worried whether the company and others in the field could effectively deliver short interfering RNA molecules into target cells to silence disease-causing genes.

Over the past year, Alnylam put some of those worries to rest, with Maraganore and his colleagues turning in upbeat human data from early trials of RNAi therapies against a major cholesterol target known as PCSK9--recently the subject of a licensing deal--as well as a culprit in the rare genetic condition transthyretin (TTR)-mediated amyloidosis. The company's lead drug that targets TTR, ALN-TTR02, is in midstage development with a pivotal trial slated to kick off this year if the Phase II study goes well.

After tumbling for years, Alnylam's stock price more than doubled over the past year.

"I think rumors of our death were highly overexaggerated," Maraganore told FierceBiotech last month.

"I think if you look at 2012," he continued, "it really was a transitional year for the company because we generated really convincing human data. People look at those data and say, 'Wow, you can do RNA interference in humans.' There's no doubt about that."

Maraganore has inspired his peers who are undertaking their own risky journeys into the unknown with biotech ventures. Kevin Starr, a partner at Third Rock Ventures and an Alnylam director, followed Maraganore's career through his time as a leading researcher at Biogen Idec ($BIIB) and later as an executive with Millennium Pharmaceuticals.

At Biogen, Maraganore invented the blood thinner Angiomax, now manufactured by The Medicines Company ($MDCO), which recently licensed Alnylam's PCSK9 program.

"[Maraganore] is one of the few that effectively integrates science and business and truly understands the value equation in the life cycle of a company and a therapeutic," Starr, who was corporate controller at Biogen and then operations and financial chief at Millennium, said via email. "He knows we are in a 'long-odds' business and has the passion to believe that nothing is impossible."

-- Ryan McBride (email | Twitter)

John Maraganore - Alnylam