Cancer drugs make almost everyone sick as a dog from toxic side effects, yet they have a hit-or-miss record when it comes to killing cancer cells. Jim Olson is a pediatric oncologist, so he’s well aware of the suffering and waste created by this approach. He prescribes these nasty toxins for young kids with only a slim chance of benefit.
What if he could invent a way that doctors could tell whether a tumor was responding to a certain kind of treatment, or whether the cancer cells were resisting it? Maybe doctors could move more quickly, quit wasting everyone’s time, and switch to a drug that might actually work.
Olson, a researcher at the Fred Hutchinson Cancer Research Center and physician at Seattle Children’s Hospital, has led a team that has developed a prototype device that works in mice. The technology has been spun out into a new company called Presage Therapeutics. The company hopes to introduce a new way of personalizing cancer treatment that any physician can use, without having to know anything special about a patient’s genetic profile.
Cancer treatment is a big business, with a global market worth $66 billion a year, and predicted to grow to $84 billion by 2012, according to Cowen & Company. There’s a lot of talk about bringing down costs, and waste, by personalizing cancer treatment based on genetic profiles of people who are more likely to respond. One example doctors are debating is whether to prescribe Eli Lilly’s cetuximab (Erbitux) or Amgen’s panitumumab (Vectibix) strictly for patients with a normal form of a tumor growth gene called KRAS. That’s because analyses on clinical trials show that about 60 percent of patients have mutated forms of KRAS, and they get no benefit from the drug, and lots of side effects. Yet a lot of people get these drugs—at tens of thousands of dollars a pop—without any realistic chance of benefit.
“There’s a huge hunger out there among patients about how they’re doing on a given drug,” Olson says. Referring to the genetic approaches toward personalizing cancer treatment, he says, “The promise of that has not been realized.”
But the Presage method doesn’t depend on that kind of sophisticated genotyping like with the KRAS example, or on biomarkers of which genes are turned on or off. Here’s how the technology is supposed to work:
A prototype, which Olson showed me in his lab, has five porous needles with holes along the sides. These five needles can deliver five different kinds of chemotherapy drugs—or combinations of experimental biotech treatment—to different localized regions of the tumor. The drugs are made to seep out within a small radius of the needle, so doctors can see how different regions of the same tumor respond to different drugs. If one part of the tumor is clearly being killed by a certain drug combination, and the other four aren’t having much effect, the doctor will know which drug to prescribe with confidence.
“We see this as dramatic innovation in cancer care,” says Thane Kreiner, Presage’s founding CEO.
Doctors have tried for decades to simulate how an individual’s tumors will respond to certain drugs, after they’ve been surgically removed and tested in the lab dish, Olson says. But as any biologist will tell you, tumors behave differently in a lab dish than they do inside the body in real time. Using the Presage method, doctors can watch how a tumor is responding inside the body to a given drug, Olson says.
This idea hasn’t exactly gone mainstream just yet. It has been funded for years by charitable donations given to the Hutchinson Center, precisely for the kind of off-the-wall ideas with big potential that don’t tend to attract peer-reviewed federal research grants.
“The grants we’ve written were rejected,” Olson says. “They said we were overly ambitious. I don’t know how you can be overly ambitious when you’re trying to cure cancer.”
Presage is getting started with a group of about 10 employees who are all working for equity, without salaries, Olson says. Kreiner, a former senior vice president of sales and marketing with Santa Clara, CA-based Affymetrix (NASAQ: AFFX), has known Olson for years through that previous company. When Olson told him about this idea last fall, Kreiner, now a consultant, was intrigued enough to take the lead and build it into a company.
The next steps for Presage are to finish up technology development work to make the device cheap and simple so that any doctor can use it, and make it pump drugs properly, Olson says. Presage envisions a business model in which tumor samples injected with the multiple drugs get surgically removed. They would be shipped in a formaldehyde mixture to prevent the tumor from decaying. The package would be sent to a central lab for analysis to ensure accuracy and a quick response to the physician, Olson says.
Presage hopes to raise $3 million in a Series A financing. It also hopes to get $2.4 million through a Small Business Technology Transfer grant from the Small Business Administration. That should help the company complete its final engineering, and start clinical trials about 18 months later. The initial clinical trial has been designed in patients with mantle cell lymphoma, because they don’t have long to live, and so a clinical trial can provide an answer relatively quickly. Presage hopes to show its method allows doctors to pick drugs that help people live longer than they otherwise would when the doctor is using his or her best judgment.
Oliver Press, a lymphoma expert at the Hutch, is one of the investigators eager to see how this might work in a clinical trial, Olson says. Kreiner and Olson have talked to venture capitalists about it, although they think the idea is still too early-stage for most VCs, especially in the economic downturn.
Further in the future, Olson said he can imagine selling this device to pharmaceutical and biotech companies, who might use it as a drug discovery tool. A cutting-edge RNA interference treatment, say, could be compared side-by-side in a mouse tumor with a standard chemotherapy, or scientists could mix and match for the best combinations. I wondered if it might even be used to deliver chemotherapy drugs more uniformly throughout a 3-D tumor than a needle with a single hole pumping out drug through the end.
But Olson, even though he’s a scientist trained to think about many possibilities, brought me back to the single original application. He insists the technology should be used initially to help doctors pick the right cancer drug for a patient, and quit using the wrong ones. It was a disciplined move that I would expect more of a seasoned businessman than a researcher.
“To be successful, we will have to have a single focus,” Olson says.