Respiratory syncytial virus or RSV for most people can seem like a lingering chest cold, but for people with compromised immune systems or infants and the elderly, RSV can send them to the hospital and even to the grave.
The virus is responsible for 1 million hospitalizations worldwide each year and more than ten times as deadly than the flu for infants. Efforts to develop a drug to stop RSV, though, have been evasive. Trellis Bioscience thinks it’s onto a solution.
The South San Francisco, California based-biotech company has discovered an antibody that targets a protein on the surface of RSV known as the G protein. Researchers at the Centers for Disease Control and Prevention had figured out the mechanism of how that protein fools the immune system by displacing a key modulator of the immune system that triggers a response to invaders.
Because of the way RSV works and the ability of the G protein to mutate, people are generally unable to effectively fight the virus with their own immune system after they have been previously exposed to it. Year after year, seasonal exposure to the virus will still get people sick. But they do produce antibodies to the virus in very small quantities.
Trellis, using its technology called CellSpot, was able rapidly hunt through 10 million antibody producing b-cells from blood samples of dozens of healthcare workers and others with exposure to RSV to find the rare antibody with desired characteristics to fight the virus.
“CellSpot makes possible for the first time very large screening libraries in such a way that we are able to gain an order of magnitude more information than was previously available,” said Brian Cunningham. “That ability makes it practical to screen, for instance, human blood.”
A Powerful Platform
Trellis has identified a lead antibody and plans on advancing it into the clinic in the second half of 2009. Though AstraZeneca markets its antibody Synagis as a prophylactic against the virus in premature babies, there is currently no treatment for RSV. But the greater promise of Trellis lies in CellSpot.
“You can pick a needle out of a haystack here,” said Jim Broderick, a partner with Morgenthaler Ventures, an investor in Trellis. “These guys can identify and quantify millions of protein secreting cells simultaneously and through their screening technology pick out the one out of ten million with the attributes you want.”
That’s significant, said Broderick, because some of the most important targets for drugs today aren’t strong immunogens so they don’t necessarily generate a vigorous and robust b-cell response. For these difficult targets, standard screening techniques may not be able to detect the best antibodies. In fact, Trellis has been able to screen large collections of antibodies that other companies have given up on and find antibodies that were too rare for conventional screening technology to detect.
In one project for Redwood City, California-based PDL BioPharma, the company was able to screen a library of antibodies to find ten candidates for a cancer target that PDL was pursuing. PDL had previously scanned the same library without much success.
“A lot of projects stop just because we can’t screen that deeply,” said Bob DuBridge, head of new technologies for PDL BioPharma. “We had a very difficult target. We spent months and months trying to screen antibodies to it and we found one crummy one. They found ten and a few of them were pretty good. So that project went from ‘we’re going to drop it’ to ‘okay, we’re going to progress because we’ve got the reagents to move forward.’”
An Efficient Process
CellSpot uses plates coated with a desired protein and takes a large volume of antibody producing b-cells to capture their footprint. The cells are washed away and the plate is treated with fluorescent nanoparticles that light up remaining antibodies with desired characteristics. The process not only allows a large number of antibodies to be screened at once, but also to simultaneously screen for multiple attributes such as affinity and specificity. The company can pull the desired antibody producing b-cell simply by appearance.
Trellis said it can develop a lead antibody to a target in a matter of six weeks. That’s far faster than the estimated year it can take to develop a mouse-derived antibody to do the same as it must be engineered so it is safe for humans.
Bruce Keyt, vice president of research and CTO for Trellis believes because the CellSpot can identify antibodies from human blood, “there are safety and efficacy bonuses.” He said these antibodies will have “negligible to zero” side effects.”
The 25-person company is currently in the process of raising a third round of venture funding. It’s raised $25 million to date and expects to raise an additional $20 million in the current round. The latest funding should carry it through the early-stage clinical trial for its RSV antibody and will advance two preclinical programs under way in cancer to target “well validated” targets. The company is also reviewing a number of different potential programs, and expects to take it through mid-stage clinical trials before finding a partner for it.
“We expect in each case it may well be different depending on the disease, the need and the interest of potential partners,” said Trellis’ Cunningham. “This one we expect to take through phase II clinical trials and partner it at that point, although we might do a small regional deal. In general it will vary with each target and each disease, but most we will probably take to the clinic, if not into the clinic.”