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Concert Pharmaceuticals, Flush With Well-Timed Venture Round, Aims for Hot Flashes, HIV

Xconomy Boston — 

Concert Pharmaceuticals caught my eye a few weeks back with something unusual—an experimental drug for the hot flashes women get during menopause, without the risks of standard hormone-replacement therapy.

I didn’t have a chance to interview CEO Roger Tung last month when his Lexington, MA-based company took this drug into its first clinical trial, so a follow-up was in order. Tung bears watching because he was one of the people who left Merck with Joshua Boger in 1989, and became employee No. 9 at Cambridge, MA-based Vertex Pharmaceuticals, where he stayed until 2005.

Tung’s new company got off to an auspicious start the next year with a long list of venture capital backers, and he has shown good timing. Tung raised a $37 million round in May for Concert that will help it weather the financial storm through 2010, he says

So what does Concert have under the hood? It takes existing drugs that have well-understood safety profiles, replaces a few hydrogen atoms with deuterium atoms to change how they are metabolized, and sees if that can give the drugs enhanced properties such as fewer drug-drug interactions or more stable absorption, Tung says. (It also creates a newly-patentable set of compounds for Concert.) The company’s lead candidate, CTP-347, is a modified form of paroxetine, long marketed by GlaxoSmithKline as the anti-depression drug Paxil. This drug is off-patent, and reached $3 billion in annual sales at its peak, so a lot is known about its safety profile. Nobody had ever developed it for hot flashes, and no alternatives for hot flashes exist beyond hormone-replacement therapies, which many women avoid because of the risks (a bit more on this below).

“I wanted to create a differentiated compound with real benefit for medicine, strong reimbursement profile, lower development risk, and shorter timelines,” Tung says.

By taking paroxetine and replacing certain hydrogen atoms with deuterium, Concert believes it has found a way to get the benefits against hot flashes without the side effects. Wyeth’s Pristiq, another anti-depression drug, showed a benefit last year against hot flashes in a clinical trial and a trial published in the Journal of the American Medical Association suggests paroxetine may work for hot flashes at lower doses than for depression, Tung says. The Concert drug has another advantage of minimizing the older paroxetine’s action against a key liver enzyme for drug metabolism, CYP2D6. That enzyme is needed to break down tamoxifen, a drug taken by millions of menopausal women to prevent breast cancer. Interfering with that enzyme can cause what amounts to a traffic jam in the liver, leading to side effects. It only makes sense that any new drug for hot flashes will have to behave well in tandem with tamoxifen.

Hormone replacement therapies like Wyeth’s Prempro work against hot flashes, but the landmark Women’s Health Initiative results in 2002 showed the drugs can raise the risk of breast cancer and heart attacks for some women. An estimated 8 million women quit taking the hormone-replacement meds after that study, Tung says, so there’s a big potential market here for something perceived as less risky.

The deuterium itself is not a problem, because it’s cheap and widely available, derived from sea water. Concert’s chemists were able to synthesize it into the new drug so quickly that they zipped through animal tests and entered the clinic in two years, Tung says. Results from this early-stage trial will be available in the first half of 2009, which will give the company an idea about whether it can avoid bad drug-drug interactions.

Concert’s second candidate is a protease inhibitor for HIV, modified with deuterium, which might be able to help patients simplify their dosing schedules. CTP-518 is designed to be more stable in the bloodstream, avoiding the peaks and valleys of concentration in the blood that sometimes allow the HIV virus an opportunity to replicate, Tung says. A more stable drug may also help patients quit taking a combination med called ritonavir that causes increased cardiovascular risk and nausea, prompting as many as one-fifth of patients to go off their meds, Tung says. This new compound might offer the same kind of convenience as Gilead Sciences’ highly successful Atripla, the first drug approved as a single daily pill for HIV, Tung says.

Since Concert’s first drug just entered the clinic, its investors will have to be patient to wait for results. The latest round of investors includes Adage Capital Management, SR One, Mediphase Venture Partners, and Westfield Capital Management, as well as existing investors that include Three Arch Partners, TVM Capital, Skyline Ventures, Brookside Capital Partners Fund, Flagship Ventures, Greylock Partners, New Leaf Venture Partners, QVT Fund, and Alexandria Real Estate Equities.

The proof of how well Concert alters drugs, as always, will come from animal tests, and eventually clinical trials. The HIV candidate could be in the clinic by the end of 2009, and the hot flashes drug could be in a mid-stage effectiveness study next year, Tung says. If Tung’s timing continues to be spot-on, then he’ll have promising signs of effectiveness in hand that he can use to raise more cash, just as the markets turn around. But Tung doesn’t sound that confident. He says he’s keeping the operation lean, with 40 employees now, while maybe hiring 10 more over the next couple years. “We’re really fortunate to have raised our financing in the spring,” he says.