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Arrowsmith Challenges Scientific Establishment With New Approach for Brain Cancer

Xconomy Seattle — 

Much has been written about personalizing cancer drugs by giving them to patients with a genetic profile that makes them likely to respond to treatment. But what if doctors could tailor cancer drugs a different way, confining standard chemotherapy to a precise organ or cancerous region, without sending the drugs flowing throughout the rest of the body and causing side effects?

This idea has been around a long time, without a lot of success to show for it. But I heard about a new variation on this theme being developed at a Seattle-based startup called Arrowsmith Technologies. It is the brainchild of Jefferson Foote, a former scientist at the Fred Hutchinson Cancer Research Center, and an expert in making antibody drugs.

Arrowsmith draws its inspiration, and name, from the 1926 Sinclair Lewis novel that tells the story of a scientist who grows disillusioned with the medical establishment. In this case, Foote is striking out on his own for a vision that’s yet to catch on with the crowd. His goal is to make antibody drugs that are injected directly into the brain, where they can latch onto chemotherapy and keep it confined there where it can kill cancer cells. If this works as intended, it means that patients would be exposed to a low dose of chemotherapy in the brain, and they could avoid the peaks and valleys of concentration in the blood that cause many side effects, and the need for frequent repeat doses, Foote says.

“If you have a tumor in your belly, why should your hair fall out?” Foote says. “If you can direct your drug to the tumor, you can avoid that.”

This is all at the very early stages of development—Foote is still toiling in the lab for the right antibody to take into animal tests—but he has high hopes that this could offer a new paradigm for treatment of brain cancer. About 22,000 people in the U.S. were diagnosed with brain tumors a year ago, and about 13,000 died from the disease, according to the American Cancer Society.

Foote has been working on various ways to get commercial support for his work since he left the “Hutch” in 2004. Foote has a distinguished scientific pedigree, having earned his doctorate in biochemistry at UC-Berkeley, and then doing his postdoctoral fellowship in Cambridge, UK, during the 1980s. He worked there under a pair of giants in the field of antibody therapeutics—Nobel Laureate Cesar Milstein and Greg Winter.

Foote has spent much of his career thinking about how to “humanize” antibodies to make it so the body’s immune defenses don’t reject these drugs as foreign invaders. This was a big problem with the early generations of antibodies that were made with mouse proteins. Improvements have been made with modern antibodies like Genentech’s trastuzumab (Herceptin) and bevacizumab (Avastin), so plenty of scientists questioned whether Foote was wasting his time trying to solve a problem that was already conquered. The work struggled to win much financial support under the peer review grant system. His response was that the current crop of antibodies still cause immune-reactions in at least one out of 100 patients, so there’s still room for improvement.

This work eventually yielded some intellectual property, which eventually spun into a Mountain View, CA-based company called Absalus. That company was acquired by Australia-based EvoGenix in April 2005, which gave Foote an investment return that provided enough financial security to start Arrowsmith in 2007. (In what surely has to go down as one of the more creative financing tools, Foote is paying the company bills by doing expert witness work a couple days a month on antibody drug patent disputes, he says.)

Arrowsmith’s lead project is to develop an antibody that will bind with topotecan, a common chemotherapy drug, to keep that in a steady, low dose in the brain, killing cancer cells. If the antibody is injected directly into the brain, it will be trapped there and prevented from circulating through the body, because it’s a large molecule that can’t cross the blood-brain barrier, Foote says.

So far, Arrowsmith hasn’t collected any investment from venture capitalists, who want to see more data showing that this technique for confining chemotherapy in the brain works in animals.

Even though he’s a lone scientific rebel of sorts, Foote says he can’t do everything himself. He has been joined in the company by Cynthia Figge, a former vice president at McCaw Cellular, and a past president of Sustainable Seattle. Figge handles the business side of things, while Foote works in a Fremont lab to develop antibodies with the right properties. He figures he’ll have a good drug candidate to take into animal trials within a year, so he can generate the kind of data that investors or a biotech company partner will want to see.

No other company is using antibodies in the quite same way, to confine chemotherapy to the brain, Foote says. But there are lots of competitors working on improved drug delivery, or various technologies to help cancer drugs last longer in the body, or reduce side effects. If Arrowsmith is successful, it could change the way a lot of scientists think about how antibodies can be used to treat disease.

“Instead of having peaks and valleys, we want to see if there’s a Goldilocks level of drug in the body that’s not too high or too low,” Foote says.