Aileron CEO Hails Expanded Roche Deal as a Validation of Stapled-Peptide Drug Technology

Xconomy Boston — 

Yesterday, Cambridge, MA-based Aileron Therapeutics announced that a collaboration it had formed with European drug giant Roche in 2010 has been expanded. The companies, which have been working together on two programs focused on turning Aileron’s “stapled peptide” technology into cancer treatments, have now added a third program focused on inflammatory diseases. The financial details weren’t disclosed, but the original agreement was already quite lucrative for Aileron: Roche vowed $25 million to the biotech over the first two years of the partnership. And Aileron is eligible for up to $1.1 billion in milestone payments—one of which it said yesterday it recently received.

Stapled peptides are fragments of proteins that are linked in a way that’s designed to stabilize them, so they don’t degrade too quickly in the body. And rather than attaching to targets on the surface of cells—like many drugs do—Aileron’s compounds are designed to penetrate cell’s outer membranes so they can more effectively hit disease targets.

Aileron CEO Joseph Yanchik believes Roche’s support will be vital to advancing the entire field of stapled peptides. “Until a year ago, all discussion about stapled peptides as a drug platform was coming out of the academic world and our presentations,” he says. “People wanted to see a large pharma company, with all its skepticism, believing it could have success with this technology. This is the first validation that stapled peptides are valuable.”

Aileron has taken a deliberately slow approach to proving out the idea of stapled peptides and finding the right partner to take it forward. The company was founded in 2005 on technology developed by a Harvard chemist and two biologists from Harvard Medical School and the Dana-Farber Cancer Institute. The basic concept is to combine the best properties of conventional, small-molecule chemical drugs with large-molecule protein drugs in a way that eliminates the shortcomings of both. “Small molecules can’t occupy the whole surface of cells,” says Steven Kafka, Aileron’s chief operating officer and chief financial officer. “Large molecules can’t actually get inside of cells.” Plus most proteins unravel in the body and are chewed up by enzymes within minutes, rendering them useless as therapies.

So Aileron’s scientists have spent much of the last five years figuring out how to staple peptides—fragments of proteins—together so they’re not only resistant to degradation, but they’re also effective at penetrating cell membranes and binding to disease targets within those cells. “This is a difficult thing to do because you improve one property and end up losing another,” says Tomi Sawyer, Aileron’s chief scientific officer. “We’re able to break through that threshold to get bothpotency and favorable properties,” such as minimal side effects, he says. The ability to get protein-based drugs into cells, he adds, expands the potential opportunities for combating diseases “exponentially.”

At first, though, it seemed that to achieve the right potency, stapled-peptide drugs would have to be administered once a day by IV, says Yanchik. “That works in oncology. But other diseases? Forget it.” So Aileron’s scientists worked hard to improve the amount of time the molecules stay active in the body before degrading. “We’ve gotten half lives to one week and beyond,” Yanchik says. That’s vital for treating patients with inflammatory diseases, because they often have to take drugs chronically, for years on end. Once Roche saw the half-life improvement, Yanchik says, “We were able to convince them that this was applicable to inflammatory diseases.”

Last year, Aileron moved its staff of 40 to an office on Albany Street that’s designed to facilitate open interactions between biologists and chemists. The scientists work together in a sprawling lab, with wall-to-wall windows facing the outside. “Typically labs have the chemistry department sitting over here and the biology department over there, or maybe in an entirely different building,” Kafka said while taking Xconomy on a tour of Aileron in September. “What we’ve tried to create is a place where a biologist finishes an experiment, has an insight, and can turn around and talk to the chemist who designed the molecule in the first place.”

“There’s lots of interaction among the staff,” adds Sawyer. “It’s really a pleasant and productive place to come to work. You don’t feel like you’re stuck in a cave somewhere.” And because all the scientific disciplines are together in one building, he says, the company is able to move quickly from concept to finished molecule.

Aileron raised $40 million in a 2009 Series D financing round that brought its total funding to $60 million. The Series D included a syndicate of Big Pharma venture capital units. Among them were the VC arms of GlaxoSmithKline, Eli Lilly, and Roche. Yanchik says Aileron started talking to Roche’s R&D folks first, and later was introduced to the Roche venture fund. About a year after Roche made the investment, the company’s R&D folks stepped up with a separate drug-development deal.

Yanchik says Aileron’s management team spent many months picking the right partner. “Too often a biotech company is reduced to being a contract-research organization, and that’s usually the beginning of the end,” he says. “We wanted to be an equal partner.” Roche has afforded Aileron that opportunity, as well as sharing its expertise in protein biology, oncology, and developing drugs across “diverse modalities,” Yanchik says.

Aileron has a big list of goals it hopes to achieve over the next year. Yanchik says the company plans to start disclosing the exact disease targets it’s working on and to publish results of its research. The company also hopes to hit at least one more milestone in the Roche development deal, and to lock up a second partnership with another drug company. “We did one partnership and focused on making it work,” Yanchik says. “We’ve had to be patient, but we think it’s paying off. This technology is becoming ripe.”