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Avila Comes Out of Stealth to Talk Bonds, Covalent Bonds

Xconomy Boston — 

Remember that 10th grade chemistry lesson on the difference between covalent and ionic bonds? Me neither. But I got a refresher on the topic last week from Avila Therapeutics, a Waltham, MA-based startup that thinks this chemistry is crucial to creating a new class of more effective drugs.

Avila has kept a pretty low profile since it was founded last year. It has hired 23 employees so far, and raised $21 million from Polaris Venture Partners, Atlas Venture, Abingworth Management, and Advent Venture Partners. Now it’s starting to emerge from stealth mode, with some preliminary data on its drugs being presented over the weekend at the American Society of Hematology. The company also named former ImClone Systems CEO Daniel Lynch as its executive chairman. I got a chance to learn more from Lynch and Nagesh Mahanthappa, Avila’s vice president of corporate development and operations.

Avila (AH-vill-uh) was founded by Juswinder Singh, a computational chemist formerly of Cambridge, MA-based Biogen Idec. The company’s goal is to develop conventional small-molecule drugs that can be made into oral pills, but with a twist. These molecules are intended to form covalent bonds with their cellular targets. The idea is that covalent bonds form stronger connections that can completely shut down the targeted receptor. Most drugs form van der Waal or ionic bonds, Mahanthappa says. Those interactions are “dynamic,” which means the drug bounces in and out of the target. As a result, such ionic bonds don’t completely block inhibit the biological function the drug is supposed to stop, he says.

“Those drugs aren’t like a key and a lock, it’s frequently bouncing in and out,” he says. “We form a permanent bond. It sits in there like a lock. We get silencing of the target.”

A few drugs already use this covalent approach, like the heartburn medication omeprazole (Prilosec), and even an oldie like penicillin, Mahanthappa says. But that was more the result of serendipity than from designing the drugs to work that from the outset, as Avila is attempting to do, he says.

I asked Mahanthappa if it’s really desirable to have such a strong bond hanging onto the target. Couldn’t that linger in the body and cause side effects if it’s not metabolized? That’s something the company has considered, so it’s specifically aiming for targets that don’t last in the body more than a day or so. That means an Avila drug could be given once a day as a pill, do its job with tight binding and then have to be re-dosed the following day, he says.

The company’s lead candidate in development is for hepatitis C, the liver infection, and should be ready to enter clinical trials by the end of 2009, Mahanthappa says. Another candidate in animal testing, AVL-101, is designed to block the activity of excess B cells (a type of white blood cell) by hitting a target called BTK. This could accomplish something similar to what Genentech and Biogen Idec’s hit antibody drug, rituximab (Rituxan) does. The big difference would be that if Avila’s drug can be proven effective, against B-cell driven lymphomas and autoimmune diseases, the pill form would offer an alternative to rituximab, which is delivered intravenously.

Avila claims to have developed all its intellectual property around this technique in-house, and since it hasn’t been around long, it doesn’t have patents in hand yet. But Lynch said part of the reason they are starting to talk publicly about their work is the increasing confidence that their patent applications will be approved.

This, of course, is all about vision and dreams in the early days, and Avila knows it has lots to prove. I asked Lynch why he decided to join this company as opposed to any other startup biotech. He didn’t try to hold back on expectations. “This is a huge, huge opportunity that has not been exploited practically,” Lynch says. “To create a new class of small molecules, to be a part of that is exciting to me.”