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Innovation economy

Start-ups working on new ways of taking medicine

Entrega Inc. scientists (from left) Robert Langer, Jonathan Behr, and Colin Gardner see a bright future for its product.JIM DAVIS/GLOBE STAFF

The Boston biotech community shows up at work every Monday to nudge forward new treatments for diseases like rheumatoid arthritis, Parkinson’s, and macular degeneration, a major cause of blindness.

And almost all of them will need to be delivered through the business end of a sharp needle, either just under the skin, or directly into a vein. Within the biopharma industry, this class of injectable drugs is growing faster than any other; sales are predicted to hit $200 billion by 2015, according to IMS Institute for Healthcare Informatics, a research firm in Danbury, Conn.

That’s why an idea from a new company, Entrega Inc., could represent a giant leap. It promises to deliver many of these “large molecule” drugs — the kinds of protein-based pharmaceuticals that already generate billions of dollars for local companies like Genzyme and Biogen Idec — inside a capsule. Currently, they can’t be offered in capsules because the body’s digestive process would break down the drugs, and not enough would make it into the bloodstream.

Entrega is working on “a big idea, and it’s very, very high risk,” says Robert Langer, an MIT professor and serial entrepreneur who serves as chairman of the Boston start-up’s scientific advisory board. “But if it’s successful, it would be very high reward. Pharmaceutical companies have spent billions working on less-painful ways to deliver these drugs, and I’d think that 95 percent of patients would probably prefer a capsule to an injection.”


Entrega’s approach isn’t too different from the way nicotine patches work when affixed to the skin. Except Entrega is designing miniature circular patches — the company calls them wafers — that would be packed into a capsule.

Once swallowed, the capsule carries its cargo of drug-infused patches through the stomach and into the small intestine, where it dissolves and releases the wafers. They then attach themselves to the lining of the small intestine. A backing material protects each patch from the digestive enzymes whose job it is to break down the kinds of proteins it is carrying. Over the course of several hours, the patch delivers the drug through the wall of the small intestine; then it lets go and is excreted.


Langer calls it a simple idea that still needs a lot of refining. It originated at the lab of Samir Mitragotri at the University of California Santa Barbara; Mitragotri did part of his training at Langer’s lab on the MIT campus.

The company has been testing the new approach as a needle-free way to deliver fertility drugs, insulin, and cancer treatments. But human clinical trials probably won’t begin for two or three years, says Jonathan Behr, the company’s chief operating officer. Entrega is a spin-out from Enlight Biosciences, a Boston incubator of science-oriented start-ups that has financial backing from several major drugmakers, including Lilly, Merck, and Pfizer.

A handful of other local companies have been prospecting in adjacent plots, some for years, trying to hit upon more convenient and effective ways to deliver drugs. (Many of them have links to Langer and another MIT professor, Michael Cima.)

Kala Pharmaceuticals of Waltham, founded in 2009, raised $11.5 million last month to continue its work on a new kind of nanoparticle that can carry drugs across the thin barrier of mucus that protects your eye. The particles might carry drugs to treat chronic inflammations, or a form of macular degeneration that can today only be slowed with — ouch! — an injection into the eyeball every month for the rest of your life. Other than a needle, says chief executive Guillaume Pfefer, “there’s just no elegant way to deliver drugs to the back of the eye.”


SpringLeaf Therapeutics, a Boston company, raised almost $20 million for a new kind of battery-operated, wearable patch that would enable patients with weakened immune systems to get the proper dose of immunoglobulin at home, instead of going to a hospital or clinic to be hooked up to an intravenous machine. But the company, founded in 2007, hasn’t yet gotten a clinical trial underway, and swapped chief executives last September. (Company executives didn’t return phone calls or e-mails seeking comment.)

Waltham-based MicroCHIPS started designing an implantable, computer-controlled miniature pharmacy back in 1999, and has since raised more than $70 million. The device, which is smaller in diameter than a quarter and the thickness of a stack of four of the coins, can be slipped under the skin in an outpatient procedure.

Its surface has 200 tiny reservoirs that hold doses of a drug that can be released on a set schedule, or by a doctor using a wireless remote control. It was tested in women with osteoporosis in 2011, as an alternative to daily injections of a synthetic hormone intended to increase bone density.


Company CEO Robert Farra says the device will be capable of dispensing drugs inside the body for a decade or more. But it hasn’t yet been approved for sale by the Food and Drug Administration.

Many talk about needle-free delivery of large-molecule drugs as one of the “holy grails” of the biotech industry, not only making products easier to use as they are prescribed, but also potentially extending the length of patent protection by formulating and packaging the products in different ways.

Entrega’s Behr also points out that there are plenty of approved injectable drugs to treat conditions like chronic pain or HIV, but they aren’t widely prescribed because patients prefer pills.

And, he adds, “There are these hugely promising drugs being developed that are going to be painful for patients to take. We’re hoping to create a solution that’s attractive to both patients and the industry.”

For the needle-phobic, that solution can’t arrive soon enough.

Scott Kirsner can be reached at Follow him on Twitter @ScottKirsner.