Synta, Developer of New Class of Cancer Drugs, Eagerly Awaits Results From Key Trial

Nothing really buys time for patients with terminal forms of melanoma, a type of skin cancer. Not chemotherapy, not targeted antibody drugs, not genetic-based antisense treatments. But Lexington, MA-based Synta Pharmaceuticals should find out within weeks whether or not it has made a breakthrough with a new approach.

Synta (NASDAQ: SNTA) is on pins and needles now, as it awaits results early this year from a final-stage clinical trial that will determine whether its experimental drug, elesclomol, can slow down the spread of metastatic melanoma. The study, called Symmetry, enrolled 630 patients who got the Synta drug in a once-weekly intravenous infusion along with paclitaxel chemotherapy or the chemo drug alone. If successful, Synta could apply for FDA approval before the end of this year.

This trial is the first major test for a new class of cancer drugs Synta is developing. The treatment is designed to amplify the amount of oxidative stress in the body, which is thought to nudge cancer cells past a breaking point in which they trigger a self-destruct mechanism known as apoptosis. This same effect does little to healthy cells, because they contain lower levels of these reactive oxygen molecules, and they have a natural ability to send in anti-oxidants to keep them in balance. If the Synta technique works in this trial, it could offer a new form of treatment with minimal side effects for patients with multiple forms of cancer. Melanoma alone was diagnosed in 62,000 people in the U.S. last year, and is estimated to kill 8,400 people annually, according to the American Cancer Society.

“We have 200 people at the company, and I’ve never seen people so excited and full of energy in my life,” says Synta CEO Safi Bahcall. “To use the football analogy, we are inches from the goal.”

Synta has been on an unusual corporate journey to get to this point. Bahcall, formerly a pharmaceutical and investment banking consultant at McKinsey & Co., spotted an opportunity to build a new company in 2001. What he found was a group of 50 medicinal chemists in the Boston area who were working at a research branch of a joint venture owned by Japanese pharmaceutical company Shionogi. The chemists, led by Lan Bo Chen, a professor of pathology at Harvard Medical School, had spent a couple of decades scouring the world of chemistry for unique compounds that might have potential as cancer treatments. They had built a deep library of compounds, with chemical screening capabilities, he says.

The catch was that the team was all about pure science, Bahcall says. They had no animal testing capability, much less clinical trial development skill or marketing muscle. The parent company wasn’t focused on cancer drug development, so the scientists were frustrated they couldn’t get their work to move forward, Bahcall says. “It was a very difficult parent-daughter relationship,” Bahcall says. “It was an incredible diamond in the rough.”

Bahcall lined up meetings with some of his New York investment contacts. “I said to them, ‘We have an amazing opportunity here, a drug discovery engine sitting on a terrific pipeline. It’s all early stage, but what you have here is the heart and soul of a small Merck.” They bought into the idea, and he raised $75 million for a buyout in 2002 to start the company.

That got Synta started in its quest to build an independent biotech company. It added all the necessary skills, animal testing, clinical, regulatory affairs, intellectual property, legal, finance and manufacturing. The company went public in 2007. And it settled into a bet on a lead compound, elesclomol.

In multiple lab tests, this drug was found promising because it can boost the amount of free radicals inside cancer cells, without causing harm in healthy cells, Bahcall says. Essentially, cancer cells are thought to be on the verge of having so many free radicals that if pushed a little further, they will self-destruct.

Bahcell uses a handy analogy to explain how this works: “A cancer cell is like a car moving at 150 mph with a needle stuck in the red zone. A normal cell is like a car safely driving at 50 mph and the engine revving in the green zone. Our drug reaches inside there and cranks up the engine even more. If you do that with the cancer cell, you reach inside the engine like that it blows up, stalls out. If the car is safely moving at 50 mph, you crank up the engine you tap on the brake, and you’re fine.”

Synta chose melanoma as its first disease, because it’s one form of cancer that dances really close to the edge of having too many free radicals in cancer cells. But this same principle is thought to be at work in prostate cancer, breast, and ovarian cancer cells as well, Bahcall says.

Results from a mid-stage study of the drug for 81 patients with melanoma were encouraging. It found that patients on a combination of the Synta drug and paclitaxel were able to remain stable without their disease spreading for about twice as long as patients who got the paclitaxel alone (3.7 months, compared with 1.8 months). The results were better for patients who had gotten no prior chemotherapy, than for patients who had relapsed after an earlier round of chemo.

The bigger ongoing trial, called Symmetry, is designed the same way, Bahcall says. It is statistically designed to show that the Synta drug and paclitaxel keeps tumors from spreading for five months, compared with three months in the chemo-only control group, he says.

Investors appear to be in a wait-and-see mode for this trial, as shares fell 9 percent in 2008 (although that’s holding up better than a lot of biotech companies.) If the results are positive, Synta and its partner, GlaxoSmithKline will start gearing up to market the product. Given the history of failure of experimental melanoma drugs from New York-based Pfizer (NYSE: PFE), Princeton, NJ-based Medarex (NASDAQ: MEDX) and Berkeley Heights, NJ-based Genta, anything that reaches its endpoint will generate a lot of attention.

“It’s unlike any drug that’s ever been developed for cancer. When we have positive data, it’s going to be an explosion not only in the treatment of melanoma but also in the science,” Bahcall says. “This opens up a whole new field of science.”

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