Aiming to expand its portfolio of potential new drugs, Human Genome Sciences Inc. of Rockville announced a major deal yesterday that gives it access to one of the more intriguing technologies of the genetic era.
The company formed an alliance with Abgenix Inc. of Fremont, Calif., to develop custom-designed antibodies that target diseases. The companies said they are shooting to find "dozens" of new drugs, many for diseases that are now untreatable or for which treatment is poor.
The collaboration will depend on Abgenix's "XenoMouse," a strain of laboratory-engineered mice that have human genes inserted into them. When exposed to germs or other microscopic foreign particles, the mice produce antibodies that closely resemble those a human being would produce. The mice are a fast, efficient way to come up with designer antibodies that can be given to people as treatments.
"This adds another arrow to our quiver in our drug-development plans," said William Haseltine, chairman and chief executive of Human Genome Sciences. "It is a very nice way to complement our existing skills."
Human Genome Sciences has already discovered thousands of genes and is puzzling out the roles they play in health and illness. Some of those genes can be used as templates to make proteins that may work as treatments, and the company is pursuing that strategy--with a compound that could radically speed wound healing, for instance.
But in other cases, the genes the company has found play a role in illness--they are sometimes said to be "over-expressed" in diseased tissues. In those instances, the need is for a way to in effect turn the genes off in an attempt to lessen the severity of the ailment.
Custom-designed antibodies are one way to do that. An antibody is a protein made by the body's immune system that binds to and neutralizes foreign invaders. A monoclonal antibody is a laboratory creation that works much the same way, but can target a broader set of microscopic particles, can be mass-produced in vats and can be given by injection in high concentrations.
Monoclonal antibodies are produced initially in mice, and for years they failed to work because they looked too much like mouse antibodies. When they were given to people, their immune systems would produce antibodies to the antibodies, neutralizing the treatment.
In the last few years, scientists have begun to solve that problem in various ways, making monoclonal antibodies appear more human and resulting in a string of important new drugs. These include an entirely new way of fighting breast cancer and the most successful drug ever developed against Crohn's disease, a debilitating bowel ailment.
Abgenix's XenoMouse, the culmination of a $40 million development program, represents one of the most elegant solutions to the problem. Scientists zeroed in on the genes that tell an animal how to make antibodies, switched off the mouse's version of those genes and inserted human ones in their stead.
The result is that when exposed to a foreign invader, including a human protein, the mouse mounts a strong immune response complete with antibodies. But because the mouse's genes have been tweaked, those antibodies closely resemble human antibodies. Once the mouse produces a template, the antibodies can be grown in quantity and tried as treatments.
The goal of the collaboration between Human Genome Sciences and Abgenix is to produce antibodies to disease-related human proteins. When injected, the antibodies should neutralize the proteins and, with luck, make the patient better. At least two cancer drugs developed this way have already come to market, and a strong focus of the collaboration will be to create antibodies that target cancer growth factors.
Inviting targets, Haseltine said, will include the major human cancers--those of the breast, prostate, lung and colon--as well as rarer cancers, like those of the brain, for which current treatments are notably poor. Particularly in the major cancers, "we think adding antibody therapies may make a life-and-death difference," he said.
Financial terms of the collaboration were not disclosed in detail, and the potential value to the companies is difficult to calculate. The companies said they would pay fees to each other based on a complex series of goals and milestones.
Both Abgenix and Human Genome Sciences are closely followed on Wall Street, and investors have proven willing to fund their research programs lavishly. In trading on the Nasdaq market yesterday, Abgenix shares jumped 17 percent, to close at $60.12 1/2, and Human Genome Sciences rose 8 percent, closing at $120.87 1/2.
Abgenix's stock price was probably influenced not only by the Human Genome deal but also by a separate collaboration it announced with Chiron Inc. and by positive test results on a potential treatment for psoriasis.