Aileron Develops New Class of Drugs To Go Where None Could Before

If Aileron Therapeutics is on the right track, it will turn “stapled peptides” into a biotech industry buzzword along the lines of RNA interference. The Cambridge, MA-based company says its technology, like RNAi, is starting to show in animal tests that it can work against diseases where conventional drugs don’t.

This company, whose name is inspired by the hinged wing flaps that stabilize an aircraft, got its start in 2005. It began with technology from the late Stanley Korsmeyer and Loren Walensky, a pair of biologists from Harvard Medical School and the Dana-Farber Cancer Institute, combined with chemistry contributions from Gregory Verdine of Harvard University. Aileron has raised $20 million since inception from the venture investing arm of Novartis and Apple Tree Ventures. Aileron’s aim is to develop what it calls “stapled peptides” as a new class of drugs that block all sorts of interactions between proteins in the body that can’t be affected by conventional small-molecule chemicals or genetically engineered protein drugs.

“If you look at the pharmaceutical industry today, there are about 10,000 diseases, and 500 to 600 targets that are druggable with conventional small molecules,” says Aileron CEO Joe Yanchik. “We believe we can open up opportunities for thousands of new targets.”

Conventional small-molecule chemical drugs, like Pfizer’s atorvastatin (Lipitor) usually need “a nice deep pocket” on the targeted protein for the compound to settle into, Yanchik says. The problem is that only about one-tenth of proteins have this kind of pocket, while many more have long, flatter pockets inside that are “like a hot dog bun, for lack of a better term,” Yanchik says.

Engineering peptides, which are small protein fragments, to have better properties than other drugs is not a new idea—they are critical players inside cells, and have been studied for decades. A few peptide drugs are already on the market, such as Amylin Pharmaceuticals’ and Eli Lilly’s exenatide (Byetta) for diabetes. But most peptides have no chance as drugs, because once they get absorbed, they get chewed up by enzymes in the body that render them useless within minutes, Yanchik says.

Aileron’s insight is that the body’s enzymes can only do this when peptides—which are folded-up chain-like molecules—become unraveled. So it is designing ways to chemically “staple” the peptides into the proper folded shape. The end product, Yanchik says, will resist being chewed up by enzymes, will be efficient at penetrating cells, and will bind tightly and long enough to its target to have the intended effect.

The work is still in very early stages. Aileron hopes to bring forward its first drug candidate—likely a leukemia or lymphoma treatment—into clinical trials within one year, Yanchik says.(Indeed, Aileron recently got a paper published in Nature which showed it could identify a new target on cells to trigger apoptosis, or programmed cell death—a mechanism that firms like Genentech (NYSE: DNA) and Amgen (NASDAQ: AMGN), have been working on for years as a means of treating cancer.)

Unlike the compounds that many other companies are developing, Aileron’s drugs have the ability to hit a wide variety of targets on cells, which might make them potentially more effective than compounds that only hit one specific target Yanchik says. The trade-off, though, is that in theory Aileron’s drugs could have unforeseen side effects by affecting healthy cells. Company scientists haven’t seen those effects in animal studies, he says.

So far, Yanchik says he’s seen enough evidence that the drugs are potent and stable in animals to move ahead with an expansion plan. The company has been on a pace of hiring a new person once every three weeks this year, and now has a staff of 21. Yanchik is looking to raise more capital to expand the company, and is talking with pharmaceutical companies that might be interested in becoming partners. Drug companies are aware of the Aileron work, and likely trying to mimic some of it in their own labs, Yanchik says. “We believe we’re on the edge of something important here,” he says.

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