Avila Therapeutics May Have Found “Achilles’ Heel” of Hepatitis C Virus

4/27/09

Avila Therapeutics emerged from stealth mode in December and told Xconomy about its secret sauce to systematically create permanent, covalent bonds with protein disease targets. Now the Waltham, MA-based biotech (pronounced AH-vill-uh) reports that its experimental drug for hepatitis C virus may be able to wipe out multiple variations and mutated forms of the virus.

The firm’s drug, dubbed AVL-181, is a small molecule protease inhibitor intended to silence a key protein for the survival and replication of the virus. The drug targets a region of the protein that the company believes is common among many known forms of the virus, even those that are resistant to standard treatments, meaning that the firm may have found an “Achilles’ heel” of the protein, says Nagesh Mahanthappa, vice president of business development and operations at the biotech. Over the weekend, the company presented results of a study, in which infected mice were treated with the drug, at the European Association for the Study of the Liver meeting in Copenhagen, Denmark.

“When we look across all known published genetic sequences of the hepatitis C protease, from a variety of mutants, we find that the particular site where we get bond formation with our drug is constant,” Mahanthappa says. “It remains possible that that site is somehow critical for the protease’s normal function, or the general fitness of the virus.”

It’s early in the game to draw any conclusions about Avila’s hepatitis C drug, which to date hasn’t yet advanced to clinical trials. Yet the fact that the startup may have found a new weakness in the virus, making the drug effective across drug-resistant and mutated strains, could help the drug stand out among the 40-odd other hepatitis C treatments in development. With industry embracing a cocktail approach to treating the disease, Mahanthappa says, there’s a possibility that Avila’s drug could be useful in combination with other drugs to combat difficult-to-treat variations of hepatitis C, which is a chronic liver disease that affects 170 million people worldwide.

The study presented over the weekend showed several potential benefits of Avila’s hepatitis C drug over existing treatments. For one, it had no significant impact on other proteins, boding well for how safe the drug could be for humans. Another potential perk is that the drug appears to work for 24 hours or more, meaning it could be taken once a day rather than several times a day. Yet there were many new hepatitis C drugs presented at the medical conference and most of the companies presenting those other drugs promised improvements over existing therapies as well. Cambridge, MA-based Vertex Pharmaceuticals (NASDAQ: VRTX) is generally considered the front-runner in the race to develop the first protease inhibitor for hepatitis C, called telaprevir. That drug is now in the third and final stage of clinical trials needed before it can win FDA approval to start selling in the U.S.

For Avila, the hepatitis C protease inhibitor is one of two drugs that are neck and neck for top position in the biotech’s young pipeline, Mahanthappa says. The other, called AVL-291, is a small molecule kinase inhibitor that could be used to treat immune system cancers such as non-Hodgkin’s lymphoma and B cell chronic lymphocytic leukemia. The company’s earlier plan was to begin human clinical trials of its hepatitis C drug by late 2009, but Mahanthappa says that the company now wants to wait until mid-2010 to start its first clinical trial. The company also hasn’t decided which of its drugs to enter into clinical trials first. The reason for waiting an extra half year to begin clinical trials is to make the firm’s existing capital last longer. The firm wants to raise more venture capital before it launches an initial clinical trial and—in case you’ve been living under a rock and don’t know—the climate nowadays for completing such financings is pretty awful.

Avila is now in the midst of raising another round of financing, Mahanthappa says. The firm has previously recieved $21 million in venture capital from lead investor Abingworth Management as well as Polaris Venture Partners, Atlas Venture, and Advent Venture Partners.

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