Agios, Seeking to Starve Cancer Cells to Death, Wins Support from Brain Tumor Foundation

Cancer cells can essentially get addicted to food, and Agios Pharmaceuticals thinks it has a groundbreaking way to starve them to death. Now it’s getting some help to test the idea from a foundation started by the family of AOL founder Steve Case.

The Cambridge, MA-based biotech company is announcing today that it has secured a grant of about $180,000 from Accelerate Brain Cancer Cure (ABC2), the Washington DC-based foundation founded by the Case family in 2001. Agios CEO David Schenkein, who got to know Case and the foundation when he ran cancer drug development at Genentech, filled me in on why he thinks this news matters even though the dollar amount isn’t huge.

Agios (pronounced AH-jee-ose) got up and running in July 2008 with a $33 million Series A venture round, to pursue its vision of blocking the super-fast metabolism of those hungry cancer cells. The company published its first big paper in Nature last month, in which it showed in tumor samples that an enzyme previously thought to be an innocent bystander in brain cancer patients can flip into an overactive, mutated mode, and create a metabolite that nourishes tumors. This begs a lot more questions, and the cash from ABC2 will enable Agios and its collaborators at UCLA to answer three important questions in brain cancer patients, Schenkein says. How much of the metabolite gets made? What tissues is it found in? And is there a connection between high levels of this metabolite and a worsening clinical outcome?

If those answers point Agios in the right direction, it will be off to the races toward developing a new drug for about 70 percent of brain cancer patients with a mutated form of the gene, called IDH1. About 22,000 people in the U.S. are diagnosed with cancer of the brain and central nervous system each year, and almost 13,000 die from the disease each year, according to the American Cancer Society.

“We are turning the field upside down,” Schenkein says. “The science is potentially transformational.”

Of course, doing something potentially transformational also carries risks. Agios will have to have a deep understanding of the biology of the pathway before developing a drug to shut it down. And the company will have to make drugs that are extremely specific to the target of interest, and which don’t hit similar structures on cells that are carrying out the usual metabolic functions we all need to live. Agios is working on “extremely targeted” small molecule drugs to block the enzyme targets it has in mind, Schenkein says.

But these are clearly heady days at Agios. There was a lot of can-do optimism in the air when I visited the company’s office on Sidney Street in early November, just a few weeks before the Nature paper came out on IDH1. I talked with a couple of key Agios employees, Lenny Dang, the director of biochemistry, and John Evans, the director of business development and operations.

While a lot of companies have pinched pennies this year, Agios has moved aggressively, even though it was born just a couple months before the financial crisis hit hard in September 2008. Agios has 27 employees in Cambridge, who work with a team of 30 chemists in China and India.

Agios sees itself carving out a whole new niche within the cancer drug development world. There are drugs that choke off the blood supply to tumors, and block rapid-fire proliferation signals that are a hallmark of tumors. While there’s growing interest in starving cancer cells to death by blocking metabolic pathways, there isn’t a drug on the market to point to that has proven an approach like this can work.

Part of the mission this year has been to “lock up” the intellectual property around cancer metabolism so that Agios can be in a dominant position as the field matures over time, Evans says. “We want to be the IP gateway for cancer metabolism like Alnylam is for RNAi,” he says.

Other pharmaceutical companies are interested in cancer metabolism, but “nobody has built the scientific engine we have now,” Schenkein says. Over time, the strategy will be to form partnerships with bigger companies to help pay the R&D bills, although Schenkein wasn’t making any promises about a deal being imminent. When I asked about how much cash he had left in the bank, he noted, “We still have significant runway ahead of us.”

The employees didn’t sound concerned about hitting their milestones. The operation runs 24/7 with its offices in other parts of the world, Dang says, so experiments are running all the time and data is constantly pinging around the world via phone, e-mail, and Skype. “It’s an awesome place for science here,” Dang says.

“We have a bold vision,” he adds. “We’re not afraid to fail, which is how you need to be if you want to transform medicine. David [Schenkein] really gets that tone, and that vision. We want to build the leading cancer metabolism company.”

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