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AesRx Navigates “Valley of Death” to Get Sickle Cell Drug Into Trials

Xconomy Boston — 

Last week, Newton, MA-based AesRx announced that it has begun human trials of its lead drug, Aes-103, to treat sickle cell disease. To biotech observers, this may not have seemed like a big deal—sickle cell is a rare disease that affects only about 75,000 people in the U.S.—but for AesRx CEO Stephen Seiler, just getting this far is a major achievement. Seiler founded the company in 2008 and tried to raise $10 million in venture financing to advance the drug through “pre-clinical” (animal) trials. But he had to give up. “Everyone said, ‘This is sexy technology, but we don’t fund pre-clinical drugs anymore,'” Seiler says.

So Seiler, who bought the drug from a New Jersey company that had gone bankrupt, nurtured its early development with about $1.5 million in angel funding, money from his own pocket, and a $750,000 loan from the Massachusetts Life Sciences Center. Then, in November 2010, AesRx (pronounced ES-er-ex) formed a partnership with the National Institutes of Health, which committed an undisclosed amount of money to help advance the drug through pre-clinical studies and the first human trials. “It was a huge step towards getting us through the Valley of Death,” says Seiler, quoting terminology that CEOs often use to describe the chronic lack of venture funding for early-stage biotechs.

Seiler says Aes-103 is the only drug in development that targets the underlying cause of sickle cell disease. The condition, which is inherited, is caused by abnormal hemoglobin, the oxygen-carrying protein in red blood cells. The red blood cells become distorted into a sickle-like shape, causing pain, organ damage, infections, and other complications that can turn fatal. AesRx’s drug, called 5-hydroxymethyl-2-furfural (5HMF), is derived from sugar and designed to prevent blood cells from sickling.

There is one anti-sickling drug on the market already, but it has such harsh side effects it can’t be used in children—a huge proportion of the patient population. If Aes-103 proves safe in the healthy adult volunteers participating in the first trial, the company will design trials in children, Seiler says. “It’s important to get this intothe pediatric setting,” he says. The FDA has granted the drug “orphan” status, which may help speed its path through the regulatory process.

Nevertheless, that process won’t be an easy one for AesRx. Sickle cell disease is an unpopular target for drugmakers because the FDA has traditionally set too high a bar for the endpoints they must prove in clinical trials, Seiler says. For example, the agency has traditionally expected drugmakers to show that their compounds prevent hospitalizations for severe episodes of pain. “That’s not appropriate because many of these patients are now treated on an outpatient basis,” meaning they never check into the hospital, Seiler says. “The treatment modality is disappearing, so the endpoint should be disappearing, too.” He says AesRx is working with the FDA to establish more reasonable endpoints for the Aes-103 trials.

If all goes well, AesRx could complete Phase 1 and 2 trials by the end of next year and start Phase 3 trials in the first quarter of 2013, Seiler says. He hopes that a Big Pharma company will show some interest in partnering with AesRx to fund the later-stage trials. Seiler was particularly encouraged on October 11, when drug giant Pfizer (NYSE: PFE) formed a $340 million development deal with GlycoMimetics, a Gaithersburg, MD-based company that’s in Phase 2 trials of a drug to treat “vaso-occlusive crisis,” the episodes of extreme pain that sickle cell can cause. “Over the last two years there’s been a huge amount of interest from companies like Pfizer in orphan diseases,” Seiler says.

For now, Seiler says, AesRx has enough money to make it through 2012. At that point, he says, the company will need to “look at the next step.” After all, he knows he can’t rely on government funding forever. “The goal of the NIH is to take you across the Valley of Death,” he says, “and no further.”

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