Particle accelerators are used as tools of archaeology that tell you the approximate age of King Tut. But Seattle-based Accium Biosciences has hit upon a way to use these tools to improve everyday prescription drug development.
I discovered this enormous cylinder—which weighs a whopping 15 tons—on a tour last week of Swedish Medical Center’s new comprehensive brain tumor treatment center at James Tower. (More on the brain tumor application later.) The machine, actually called an accelerator mass spectrometer, is one of just three tools in the world that’s sensitive enough to break down a blood, urine, or tissue sample to count individual atoms. It can say how much of a drug is being absorbed into the body, how fast it gets there, and how quickly it breaks down, even in the slightest traces. The machine, which Accium (sounds like Axiom) set up in January 2006, is now being used under contracts with five of the world’s 10 largest drugmakers, and it’s booked around the clock from now through much of December, says Accium president and founder Ali Arjomand.
So how did we make the transition from using these things for archaeological carbon-14 dating to the pharmaceutical business? The story starts when Arjomand was studying for a doctorate in nutrition at the University of California-Davis in the early 1990s. He learned about the accelerator at Lawrence Livermore National Laboratory, and made arrangements to run experiments that looked at folic acid absorption in the body, which was unknown. The machine could detect trace amounts of this vitamin, which other instruments couldn’t, and the findings partly led the U.S. government to raise the recommended daily allowance of folic acid for pregnant women.
“It was a landmark experiment,” says Arjomand. He had ideas of how this might be commercially applied, but didn’t pursue them. “In ’98, ’99 and 2000, it was too early to build a business. Even though the technology was rock solid, only about 1 percent of all scientists in the pharmaceutical industry had heard of it.”
Arjomand moved to Seattle in 2000 to do something completely different, joining Mukilteo, WA-based CombiMatrix, a maker of DNA microarray chips. He stayed there until 2004, while keeping an eye on what was happening with accelerator mass specs.
While he was doing business development at CombiMatrix, the one other site in the world that had an accelerator mass spec for drug development started getting some commercial use and acceptance from European regulators, he says. It was at York University in the U.K., which eventually spun off a company called Xceleron to perform contracts for pharma companies. American pharmaceutical companies sought out some of the capacity at Livermore, but the machine there wasn’t really geared up to meet the demand, he says.
So Arjomand decided to try to meet it. He figured he needed to pull together $2.5 million to $3 million to have a new machine built for his company by the one manufacturer in the U.S., National Electrostatics of Middleton, WI. He got about $700,000 for the business from angel investors, friends, and family, which was good enough for a down payment on the machine and to support him and one other employee for about a year while it was under construction.
During that year, Arjomand went around to venture capitalists, who mostly weren’t interested in his idea of a fee-for-service model with the pharmaceutical industry because it doesn’t have the same home-run potential as selling a proprietary machine on a desktop, he says. Pharma companies already have liquid chromatograph mass spectrometer machines, at about $300,000 to $400,000, from companies like Applied Biosystems and Agilent Technologies. They are workhorses that do much of this same job, Arjomand says. A more expensive accelerator machine could only be justified if those workhorses weren’t sensitive enough in all cases, for drugs that use tiny doses, or drugs that are poorly absorbed in the body, he says.
Arjomand found one local VC, Loretta Little of WRF Capital, who liked the idea, and was able to confirm that there was interest from big drugmakers in such a machine, Arjomand says. WRF ended up leading a round worth almost $2.5 million at the end of 2005 so that Arjomand could install the machine and get the business really going.
It was a bootstrap operation until then, but Arjomand realized that he needed to settle on a location because with a 15-ton machine, that takes engineers a month to put together, it’s not something you plan to move when you outgrow your initial office space in two years. So, he scouted locations, and found a friendly ear in David Sabey, the real estate developer who built the refurbished James Tower at 550 17th Avenue, the old Providence Hospital.
When Arjomand met with Sabey, the developer fell for the tool immediately, and even decided to invest in the company. “He said something like, ‘This is a gonzo machine. I want that machine in my building,'” Arjomand says.
Then Accium set up shop. The business model is built on service. A pharmaceutical company runs an initial clinical trial for safety in about a dozen people, and sends all sorts of blood, urine, or tissue samples to Accium. It pays something like $100,000 to $250,000 to run all the samples through the machine, and gets a report about a month later. It’s the sort of result the company can then send to FDA to answer its questions about how the drug is absorbed and metabolized.
That side of the business has become cash-flow positive on operations in its third year, and now supports an operation of 14 employees, Arjomand says. The company hasn’t drawn much attention because pharmaceutical companies generally don’t like to publish the results with the machine in peer-reviewed journals, although that may still come, he says. “If they find a good thing, the pharmaceutical companies like to keep it to themselves. They don’t like to let competitors know they’re doing this,” he says. That’s why Accium doesn’t disclose its customer names.
Within the next six months, Accium will have to decide whether to order a second machine to keep up with demand, Arjomand says. And, it’s thinking about doing a spin-off business which would use the machine for personalized diagnostics.
That’s the medical angle that I heard Greg Foltz, a neurosurgeon at Swedish, describe on the tour last week. In the same building as Accium, he’s cutting out brain tumors, and giving post-operative chemotherapy to patients. The comprehensive center is analyzing those tumor samples for all sorts of genomic abnormalities, on next-generation sequencing machines and microarrays from Applied Biosystems. But the accelerator mass spec can answer a different question. It can take a tumor sample and look at how much of the chemotherapy got to its target, and whether a second rough, or a higher dose is necessary, Foltz says.
Arjomand has an even grander vision of using the machine for predictive medicine. The idea is that a patient walks in to see the doctor, gets diagnosed with a brain tumor, and doctors consider treatment options. It’s possible to give the patient a tiny “pre-dose” of chemo that’s harmless, take a tumor sample after surgery, to see just how efficiently he or she metabolizes this drug. “By the time they are recovering from surgery, we could know the right dose of chemotherapy they should be on,” he says.
That work is being supported with a grant from the National Institutes of Health, so it will still be a few years before we’ll know how useful that may be for patient care. The pharmaceutical industry service model will continue to pay the bills in the meantime.
In the future, Accium will probably end up being acquired by a contract laboratory or clinic as demand continues to climb, he says. The market still has a lot of room to grow. “Only about 1 percent of pharmaceutical industry scientists had heard of this back in 2000, and now about 60 percent to 70 percent have heard of it,” he says. “But less than 2 to 3 percent have actually used it in a study.” As word spreads at trade shows, he said he’s going to need a new machine. “There are periods when we are running it day and night.” None of that work is going to enlighten us on ancient civilizations, or end up on the cover of National Geographic, but it might help people get new medicines they otherwise wouldn’t get.