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Alnylam s Maraganore on Leaving Millennium to Guide an RNAi Therapeutics Startup


At A Glance

Name: John Maraganore

Age: 40

President and CEO

Senior Vice President of Strategic Product Development at Millennium—1999–2002

General Manager at Millennium BioTherapeutics—1997–1999

Director of Molecular Biology, Director of Market and Business Development at Biogen—1987–1997


Maraganore joined Alnylam from Millennium Pharmaceuticals last December with a promise to help the company build up its pipeline and forge alliances with biopharmaceutical partners. After the company’s announcement last week that it had inked a five-year therapeutics-development deal with Merck, marking the first partnership between a big pharma and an RNAi-as-therapeutics firm, Maraganore appears on track to deliver. RNAi News spoke with him recently about how he made the move from Millennium to Alnylam, and what he feels needs to get done to make the company a success story.

How did you end up making the move to Alnylam from Millennium?

The story starts back in 2001, when Phil Sharp gave me a call. I had known Phil from my time at Biogen, because Phil was a founder of Biogen. Phil called me and said “I’m working here with a number of assistant professors and postdocs, and we’ve discovered something pretty important around RNA interference.” I had no idea what RNAi was when he called because I had been out of the lab for sometime; I’ve a PhD in biochemistry, but have been focused more on the business side for the last 13 years of my life. So, I said, “Phil, that sounds very interesting,” and I did some quick reading on [RNAi], and I said [to Sharp], “Why don’t you cover over to Millennium and talk to us about this new technology.”

So Phil and Tom Tuschl, Phil Zamore, and Dave Bartel came over in the spring of 2001 and met with a pretty broad group of the Millennium team and, for the first time, presented to the Millennium team the discoveries around RNA interference as applicable to mammalian cells. People on the Millennium team were aware of the observations of RNAi in the context of C. elgans and other model organisms, but they at Millennium, amongst the rest of the world, were of the belief at the time that RNAi was not an active mechanism in mammalian cells. So, people at Millennium were just stunned by Tom Tuschl, who gave the presentation, and his findings …

We caucused after Phil Sharp et al. left the company, and [Millennium] actually went to Phil with a very specific proposal to consider starting up a company … Millennium will acquire the intellectual property [Sharp and his colleagues] developed for the purpose of target validation … have an equity stake in the [new] company, and leave the therapeutic rights … with the company …

Phil very graciously thought about it … and said, “That’s a good idea, but as we talked about it internally, we think the right thing to do is offer the technology broadly through MIT’s technology license office to biotech and pharmaceutical companies that want to use the technology for target validation, and we’re going to ourselves hold onto the therapeutic rights and figure out what we want to do with them.”

At Millennium, we took a license to the MIT technology, and began using RNA interference very broadly in the context of Millennium’s overall target validation efforts … In the meantime, I continued with my Millennium job and Phil continued with his life.

In early 2002, Christoph Westphal, at Polaris, and John Clarke, at Cardinal Partners, began to assemble their thoughts on building a therapeutics-focused company around RNA interference, and they brought Phil Sharp, with Phil Zamore, Dave Bartel, and Tom Tuschl, together … and started the company in June of 2002. Around two months into that, Phil and I reconnected … and Phil said, “John, it would be a delight to have you come on board as CEO.”

This was back in August of 2002. I spent some time doing some due diligence on the technology…and then made the tough decision to leave Millennium, because Millennium is truly a great company … But the Alnylam opportunity was just too fundamentally good …

Was the transition difficult?

No, I didn’t find it difficult at all … for a number of reasons. One is I’ve known Phil Sharp for 17 years … and having that sort of history with somebody, and relationship, and trust, and everything else, is a great start.

And I also had experience in building new companies, because when I joined Millennium I joined a subsidiary company, which, albeit majority owned by Millennium, was capitalized separately, and had a separate governance structure, separate board … So [coming to Millennium] really, to some extent, was like going back to that experience, which I really enjoyed.

I’ve had the pleasure and the opportunity for working both in a small company environment and a big company environment, and I’ve enjoyed both in many ways. But I must say, the small company environment is in many ways more pleasurable, it’s more fast-moving, it’s more dynamic, decisions get made quicker. That was a major attractive feature of joining Alnylam.

What do you feel is the biggest near-term challenge facing you in your new position?

First and foremost, it’s always about building the strongest team, and integrating the team so that they work great together. For me, people always come first in terms of the challenge any CEO has … We’ve been able to hire and recruit an unbelievably strong team of people…but there’s always challenges in terms of continuing to build the company from a people standpoint …

Beyond that, the key things for us are truly demonstrating that this technology can work in the context of therapeutics. I think it’s fair to say that while there’s very significant promise and very significant progress that we and others have made, the real proof points for this technology working require clinical trials. So, a big focus of our activities [is] clearly addressing the near-term challenges of this technology, which in my mind are largely around the delivery hurdles for siRNAs …

The third component is … continued deal making and partnerships as part of how we build our company. It takes hundreds of millions of dollars to build a successful biotechnology company, so you really can’t be successful with private equity financing or, even if you’re a public company, through secondary offerings and convertible debt offerings because it’s far too dilutive … You really need to work with pharmaceutical companies and partners to assemble the right critical mass, to assemble the right commitment, to assemble the right levels of funding to build a great company.

Let’s see if we can go through these point by point. Are you still adding to your staff?

Modestly. We now have a company of 60 employees. We are being careful about how rapidly we build the company, because we want to avoid making the mistake that’s often made in biotech companies … of … getting too porky in terms of how rapidly we build. The team that we have right now of 60 people is about the size that is needed to execute on our plans. We will add more people in areas that are related to downstream activities such as preclinical, manufacturing, clinical, et cetera this year and next year as part of building our company. But it is a relatively conservative growth because we want to be careful and judicious about how rapidly we build the company.

You had said earlier this year that you expect Alnylam to have a drug in the clinic in the next two to three years. Has that timeline changed or gotten more specific?

No. We can’t get more specific, in my mind, because when we make a commitment on the timing, we want to make sure we can live up to that commitment. In my mind, we, nor anybody, can yet really say that the appropriate pharmaceutical challenges of delivery have been addressed …

We expect by year’s end to be able to have a little more transparency on what specific siRNA structures are going to be optimal for achieving efficient delivery, such that we can give more precise timelines and more precise information about specific targets that we’ll go after.

As for partnerships, after the Merck deal, are there any other discussions going on? Is anything else in the works?

Oh, yeah. We’re unbelievably busy. We’ve got a large number of discussions that are ongoing with other potential pharmaceutical and biotechnology partners. I think it’s fair to say that the Merck deal provides a very positive momentum and validation of our company in light of the fact that it’s an important validation point for other companies that are having discussions with us. They recognize that…Merck has done a fair amount of due diligence around our intellectual property, actually a very extensive amount of due diligence around our intellectual property, and they recognize that Merck, as a company that everybody has a high regard for…is a very positive and important validating point…

We expect to have additional deals done. We’re not providing any specific timeframe for that at this point in time, but I don’t think it’s going to be a long time away before we have our next major partnership completed.

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