It’s not every day on the biotech beat that we find a startup has been inspired by the 1984 rock mockumentary “This is Spinal Tap.” But that’s a true story behind the founding of Eleven Biotherapeutics, the latest high-profile startup in the Boston biotech cluster.
Cambridge, MA-based Eleven Biotherapeutics is emerging from stealth mode today with its volume dialed way up, as they say in the movie, past 10 on the amplifier, to 11. The company has raised $35 million in its Series A round, attracted prominent backers from Third Rock Ventures and Flagship Ventures, and assembled a five-man band of big-name scientific founders. The money and brainpower is being channeled into a company that seeks to engineer proteins with ideal properties for treating autoimmune diseases and blood clotting disorders.
Eleven is led by interim CEO Mark Levin, a founding partner with Third Rock and the former CEO of Millennium Pharmaceuticals. He’s joined by Cary Pfeffer, a partner at Third Rock, who is serving as interim chief business officer, and Burt Adelman, the former executive vice president of R&D at Biogen Idec, who is now the interim head of R&D at Eleven. I spoke with Pfeffer yesterday afternoon to get the scoop.
“We are developing substantially improved next-generation biologic drugs,” Pfeffer says. Like in the movie, “the concept is to go one better than the maximum on the amp, which is 10.”
This is all still at a very early stage. Eleven isn’t saying anything specific yet about which drugs are its lead candidates, which diseases they are designed to treat, where the intellectual property for this comes from, or exactly how far along its programs are in development. But with $35 million in hand, Eleven has the cash to hire a team of 25 to 30 people for its R&D team, and an ambitious goal of going through the early steps of development to reach a clinical trial in three years.
The strategy at Eleven is to assemble a portfolio of drugs, using a wide variety of best practices in protein engineering, not just one single technology platform like many other companies, Pfeffer says. The technologies are not proprietary to Eleven. The company sees its advantage being in the scientific insights of its founders, and their ability to harness so many different protein engineering technologies to drug candidates in the pipeline, Pfeffer says.
The initial plan is to develop a number of programs with low, medium, and high risk. That means Eleven plans to acquire a couple of drug candidates that are in some early phase of clinical trials, develop some internal drug candidates that are made to hit targets that have been validated by other drugs, and then put some resources toward drugs that block higher-risk, novel targets on cells.
While protein drugs are made by incubating inside living cells—and that brings an inherent amount of unpredictability when dealing with Mother Nature—Eleven is seeking to capitalize on advances that have given scientists more control over the properties they want, and don’t want, in the protein drugs that they create.
For example, it’s now possible to engineer protein drugs from scratch so they can hit a specific target without causing a potentially dangerous immune-system reaction, Pfeffer says. Other technologies are making it possible to develop proteins that last longer in the bloodstream and therefore require less-frequent injections. Deeper understanding of the structure and function of targets on cells is making it possible to engineer drugs that will specifically hit the intended target, while avoid a similar target that may cause side effects, he says.
The opportunity for improvement in treating autoimmune diseases, in which the immune system goes haywire and starts attacking healthy cells like it does viruses, is immense. Protein drugs already make up a $10 billion market for one autoimmune disease, rheumatoid arthritis. Drugs like Amgen’s etanercept (Enbrel) and Roche’s tocilizumab (Actemra) are just a couple examples of rheumatoid arthritis drugs that have proven the usefulness of a couple of targets, known as tumor necrosis factor (TNF) and interleukin-6 (IL-6), respectively. But that’s really just the start for autoimmune drugs. There are something like 80 different autoimmune diseases, and they’re estimated to affect as many as one in 12 Americans, according to the National Institutes of Health.
While Eleven isn’t saying much about the specific targets it has in mind for autoimmune disease, it has revealed one of them—the Th17 pathway. Another Cambridge, MA-based company we’ve written about recently, Lycera, also has its sights on this pathway as a target for conventional orally-delivered small molecule drugs.
The scientific founders of Eleven, and their backgrounds, may offer some additional clues about what the company is up to. K. Dane Wittrup of MIT is known for his expertise in the engineering of monoclonal antibody fragments; Casey Weaver of the University of Alabama has expertise in studying the biology of Th17; Gregory Verdine of Harvard University brings chemistry experience and deep knowledge of protein interactions; K. Christopher Garcia is known for his research into the structure and function of inflammatory proteins called cytokines; and Reza Dana is a prominent ophthalmologist at Harvard Medical School (which offers another clue of a disease category Eleven is focused on).
Getting prominent people on a scientific advisory board doesn’t mean much if they don’t contribute, so I asked Pfeffer how much these people are bringing to the company. They’ve all kept their academic day jobs, but they have committed “multiple days per month” to work together on the company over the past seven or eight months, in addition to fielding occasional calls to discuss issues at length with Eleven’s management team, Pfeffer says. “They have all signaled their willingness to spend substantial amounts of their time with the company,” Pfeffer says.
As is usual at Third Rock, Levin and Pfeffer plan to get deeply involved personally in the operations of the company during its infancy—serving as interim management for maybe six to 18 months, Pfeffer says—until they hand the baton to a permanent executive team. But before I hung up the phone, Pfeffer insisted he and Levin are very much enthused about this new idea.
“One of the reasons we are so excited is that there have been a number of biotech companies over the past five to seven years that get founded on one technology platform,” Pfeffer says. “The thing Eleven has is that we’re building products from Day 1, and we don’t just use one technology, but we’ve brought in a lot of expertise in protein engineering. We’re identifying the issues and bringing multiple technologies to work on it. It’s a dramatically different approach.”
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