Accelerator’s New Startup, Xori, Aims to Use Chicken Cells to Make Better Antibody Drugs

Accelerator’s New Startup, Xori, Aims to Use Chicken Cells to Make Better Antibody Drugs
Luke Timmerman 5/14/09
Accelerator’s latest company has a vision of turning the world of antibody drug development upside down. The tenth company to roll out of the Seattle-based biotech startup machine, Xori, aims to turn lab dishes of chicken cells into factories for making better, faster, cheaper antibody drugs. Xori also represents the fulfillment of a sort of romance, but we’ll get to that later.
The company (pronounced Chore-ee) is founded on technology developed by Nancy Maizels, a professor of immunology and biochemistry at the University of Washington. The usual crew of Accelerator’s investors are backing it—Alexandria Real Estate Equities, Amgen Ventures, Arch Venture Partners, OVP Venture Partners, PPD, and WRF Capital. I heard the gist of this story during a group interview with Maizels, Accelerator president David Schubert, and Accelerator’s chief scientific director, Patrick Gray. (The exact amount wasn’t disclosed, but Accelerator usually invests less than $5 million in new companies.)
Antibody drugs that can specifically seek out diseased cells, while sparing healthy ones, are one of the biggest advances in the 30-year history of the biotech industry. Genentech became the industry’s most valuable company, worth more than $100 billion, largely because of three of these targeted medicines for cancer—marketed as Avastin, Rituxan, and Herceptin. The antibody drug market is expected to generate $30 billion in worldwide sales in 2009, with an annual growth rate of 14 percent through 2012, according to Datamonitor.
With that much money on the line, there’s a huge interest in coming up with more efficient ways of creating and selecting more antibody drug candidates. There are literally hundreds of specific targets scientists have identified on cells for these kinds of “smart bomb” therapeutics. But it’s time-consuming and expensive work—it can take a year’s worth of effort in the lab, and $10,000 or more—just to come up with a new antibody to begin the gauntlet of experiments, Maizels says.
Current industry standards require scientists to inject mice with a certain protein target, wait for them to develop antibodies against it, and then collect antibody drug candidates. One of the problems is these antibodies need to be made to incorporate more human DNA, so that when they are given to humans, they aren’t rejected by the immune system as foreign invaders.
Xori sees its edge in using genetically modified chicken cells in petri dishes, instead of going through the arduous process with mice. The chicken cells are loaded with human DNA from whatever target scientists want to hit, and the chicken cells can start pumping out antibodies in a matter of hours. If Xori is successful, it could yield antibodies that can be effective at far lower doses, which will work with fewer injections, and which might be able to hit targets on cells that mouse-derived antibodies never could, Maizels says.
“It’s a wonderful idea, and I’m excited to see how it will work,” said Leroy Hood, president of the Institute for Systems Biology, and a director of Accelerator.
Like all Accelerator companies, Xori will have to hit certain milestones over the next 24 months if it wants to win another round of funding. Maizels is keeping her day job at the UW, and the day-to-day work
of the company will be led by Larry Tjoelker, a former scientist at Bothell, WA-based Icos, MacroGenics, and Theraclone Sciences (another Accelerator company.) Xori’s goal will be to show that it can prove its concept works in animals, Gray said.
For Accelerator, Xori represents the first new company it has bankrolled in 2009, and the tenth overall since its founding in 2003. It’s the second time Accelerator has made a foray into the world of antibody drug development (Theraclone was first), and the second time it has supported a technology that originated at the University of Washington, after Seredigm.
So how is this technique really different and special? Others have certainly been working hard to make better, faster, cheaper antibodies—including Merck through its purchase of Lebanon, NH-based GlycoFi, and Bothell, WA-based Alder Biopharmaceuticals.
What Maizels’ lab has developed that’s different is a genetically modified line of chicken cells to serve as the host for creating antibodies. These cells are designed to allow genes to evolve quickly and to select the exact structure of the molecular target—and then create ideal antibodies that bind tightly against them, she says.
Standard antibody techniques might only yield five to 20 different antibody candidates that can hit a certain target-even though biology says there could potentially be many more. Many good candidates made during the standard mouse-based process get weeded out, never binding properly with a target on cells, Maizels says. That’s because the body has a natural tendency to develop antibodies against foreign invaders like viruses, but not against normal cells. The problem is that many diseased cells, like, say, tumors, look a lot like healthy cells to the immune system. Overcoming this tendency is a challenge that scientists refer to as breaking “tolerance.” Since chicken cells are quite different from both humans and mice, they should allow Xori to avoid this problem with tolerance, and help identify many antibodies with great potential as drugs that would otherwise fail the early scientific screens, Maizels says.
“It has the potential to treat diseases that we can’t treat now, so it’s an important thing for us to do,” Maizels says.
Like a lot of Accelerator’s investments, there’s not a lot of hard data to support the notion that this works in animals, much less in people. Accelerator was drawn to the idea because it has the potential to be applied to many different drugs, not just one, and antibody drugs represent such a big market, Schubert says. It also has other key ingredients, such as its passionate founder, and a core expertise in immunology that is one of the strengths of the Seattle biotech scene, Schubert says.
Schubert also told an interesting little backstory about how this deal came together. Usually, Accelerator gets ideas from the Institute for Systems Biology, a referral from Hood or another ISB faculty member, through its own research, or from investor referrals.
This case was a little different. Schubert first heard about the technology about 18 months ago while having a regular monthly lunch with a friend of his from business school, Aaron Coe of Seattle-based Calistoga Pharmaceuticals. Coe, who happens to be a second cousin of Maizels, told Schubert that she was doing some interesting work that might soon be ready for private investment.
So Schubert and Gray decided to take a look for themselves. “I’ve never seen Pat as excited at first blush about a technology as he was with this,” Schubert says. The passion never waned for the investors during the year this deal took to assemble, even though it’s common to go through highs and lows, like with a romance, Schubert says.
Maizels laughed out loud at the analogy. Apparently, she never expected to get dumped. “David has a different view of romance than I do,” she said with a laugh.