Boston Startup Leads Charge In Burgeoning Biocare Industry

Cellcor's new approach to immunotherapy links patient and lab; the firm's success is tied to skirting the FDA bottleneck BOSTON--What do you get when you cross research with clinical care? The answer, immunologist Michael Osband says emphatically, is a new industry--"biocare." His Boston-based company, Cellcor Therapies Inc., is one of about a half-dozen firms worldwide that are developing therapies tailor-made in the laboratory for individual patients. It's been eight years since Michael Osband, then a professor at Boston University, started down the road to biocare. He was experimenting with in vitro immunization of human lymphocytes: taking out white blood cells, sensitizing them to a particular antigen, then putting them back into the body, where their enhanced properties could be put to use. He discovered that lymphocytes, once removed from the body, could be treated in ways that would be harmful in the body, but not to cells in a petri dish. With autolymphocyte therapy, a patient donates lymphocytes twice. The first time, the cells are stimulated to produce activating chemicals called lymphokines (what Cellcor scientists call autokines). The second set of cells are incubated in a soup of these lymphokines for several days and then injected back into the patient. The lymphokines stimulate the disease-fighting capabilities of these cells. The patient may temporarily experience fever and chills from the treatment. But he or she is spared the toxic side effects that other experimental immunotherapies can invoke. "We think it's a far more effective approach," says Osband. --E.P. Osband and his business partner, Gary Cashon, coined the word biocare as a way to help promote a service side to the burgeoning biotechnology business. They define biocare as a team effort among scientists using the latest molecular techniques and insights to hone a patient's ability to battle diseases like cancer. Rather than develop a drug that is packaged and sold, biocare firms combine clinical and laboratory services in developing treatments for patients. By Osband and Cashon's definition, those services can include cultivation of skin for grafting onto burn victims, in-vitro fertilization procedures, or, in Cellcor's case, immunotherapy against cancer. Cellcor's success in developing autolymphocyte therapy for kidney cancer, they say, shows just how promising biocare can be. The two men hope the concept will catch on with investors and consumers. If it does, hundreds of biotechnologists someday will be able to apply their talents to this new approach to medicine. "There's a whole sector of biotechnology that is much more process-oriented and much more complex," explains Cashon, a microbiologist who is president and CEO of Cellcor. "It is going to be very useful for producing sophisticated products, but each product will be for a single patient. It probably falls outside any medical specialty." Biocare is such a new idea that few industry analysts have thought much about its potential as a spinoff of biotechnology. Even the U.S. Food and Drug Administration has yet to decide how to regulate what companies like Cellcor have to offer. "Biocare is sort of a self-defined thing by a few companies," says Kurt Gunter, chief of the cytokines branch in FDA's Center for Biologics Evaluation and Research. "It's one way of classifying all these activities. But they are all quite different, and we look at each thing on a case-by-case basis." Osband, Cellcor's vice president, and Cashon hope that biocare may one day rival pharmaceuticals as a thriving healthcare industry. But right now this approach to health-care has one major advantage: speed. Because its services are not classified as drugs, they are not required to meet the stringent federal requirements for new drugs. And that means companies like Cellcor can enter the marketplace much more quickly than companies that need approval from the FDA. Michael Osband, when he's not seeing patients, shows up for work in khaki pants and a polo shirt that he doesn't bother to tuck in. He certainly doesn't look the part of the founder of a new--and potentially very profitable--medical industry that he calls biocare. Osband entered Yeshiva University in New York as an English major. But by his junior year he was hooked on medicine, enrolling in a special undergraduate medical school program at Johns Hopkins University. He finished his medical degree at Yeshiva's Albert Einstein College of Medicine, followed by a fellowship in hematology and oncology and tumor immunology at Children's Hospital Medical Center in Boston, the Dana-Farber Cancer Institute, and Harvard Medical School. Although trained as an oncologist, the 41-year-old Osband functions as an immunologist in the laboratory. Like many scientists, he was intrigued by the therapeutic potential of monoclonal antibodies and frustrated by the limitations of producing them from mice. As a result, he and his colleagues at the Joint Clinical Immunotherapy Program of Boston University and New England Baptist Hospital started to make monoclonal antibodies using B cells from humans. Once Osband discovered he could get these B cells to make antibodies, he immunized them against antigens found on kidney tumor cells. Then he put those cells back into a patient with kidney cancer. "After about six months, the tumor shrank dramatically," says Osband, who immediately shifted his efforts from making monoclonal antibodies to developing autolymphocyte therapy. He thinks that his five years of scientific training are more than a match for what he might have learned in a graduate Ph.D. program. He also likes having one foot in academia and the other in industry. "Industry brings a reality test that academia doesn't have," he says. "It is industry that will make biomedical research come out of the lab." --E.P. Since its formation in 1987, Cellcor has developed a treatment for metastatic kidney cancer, a disease that kills about 10,000 people a year in the United States. The method uses autolymphocyte therapy, a technique that encourages the patient's own immune system to slow the progression of the disease. This treatment is considered to be biocare because the "medicine" is derived by laboratory manipulation of the patient's lymphocytes. Because it's not a substance that is mass produced and packaged--part of the conventional definition of a drug--the treatment did not have to undergo FDA scrutiny. That definition offers the company a shortcut along the path to profitability. While that's a big boost to any startup, the real challenge for Cellcor is to prove that its approach is not merely some 21st-century form of medical quackery, but a viable treatment for harnessing the immune system to battle cancer. Osband has been building his case for biocare for almost a decade, carrying out his initial studies with support from Boston University. In 1987, after a search for additional funding, Osband's institution turned over the patents for its unique methods to Hillman Medical Ventures, a Pennsylvania venture capital firm, and entered into an agreement with that company. During the next three years, $20 million was spent on two clinical studies and a controlled, multicenter trial. Today, Cellcor stands ready to open its first clinic. The results speak for themselves, says Osband. Typically half the patients with metastatic kidney cancer die within eight months of diagnosis. But in a 90-patient multicenter study, according to Osband, more than half of the 45 patients who received the therapy were still alive after 20 months. And toxicity levels are "amazingly low," says Robert Krane, chairman of urology at Boston University, who conducted much of the clinical research. The results of the study were published last spring in Lancet (335:994-8, April 28, 1990) and Urochemotherapy (35:417-22, May 1990). "When you are looking at risk-to-benefit ratios, the risk is obviously much lower and the benefits may be much greater," says Krane. Therapies that use interferon or interleukin 2 are either not very effective or very toxic, he adds. In any case, according to Krane, they lack the controlled studies that have been done on autolymphocyte therapy. But Cellcor's success is not without its critics. For some, the results appear too good to be true. "It's such an extraordinary difference [in survival]," says David Parkinson, head of biologics at the National Cancer Institute. Parkinson has reviewed hundreds of clinical trials, and says he rarely has seen such dramatic improvements. And he questions whether survival rates can be used to judge a treatment's effectiveness. Parkinson also believes that the results are difficult to interpret. "It's not clear what is being accomplished immunologically," he says. He is puzzled by the fact that survival was not always accompanied by a shrinking of the tumor. And he wonders why this treatment--which involves activation of relatively few lymphocytes with low concentrations of lymphokines--seems to do so much more than immunotherapies that activate far larger numbers of lymphocytes and use higher dosages of lymphokines. "In the absence of other data, it's hard to comment," he adds. Others stress the need for more experiments. "It's an interesting study; it needs to be confirmed," says Richard Kradin, director of immunotherapy at Massachusetts General Hospital. "There's a lot of variation in how long people live with this disease. The interval studied in the Lancet study was relatively short." Cellcor officials, however, are undaunted. "They fail to recognize that this was our third clinical study," says Cashon. One reason for the skepticism, he says, is that Cellcor has all but ignored oncologists and instead worked mainly with urologists, who represent a smaller, more focused community. Company scientists are beginning to analyze the immunological data as well, he adds, and may enlist outside immunologists to analyze what is really happening inside the body during these treatments. At the same time, Cellcor's researchers are looking for ways to broaden the uses of its services. Boston University's Krane believes this therapy can help those suffering from many other, more common disorders. "Autolymphocyte therapy can theoretically be applied to other tumor systems," he says. "There are a lot of diseases that are immunological, and there may be immunological ways of dealing with them." One possibility is prostate cancer and other tumors. Until then, Cellcor hopes to build a network of clinics to ensure the quality of its services. The company also plans to operate centers (possibly within hospitals) where patients and cells are treated in the same place. "We want to integrate the clinical and laboratory facility in one seamless hole," says Osband. This integration, he says, is the essence of biocare, covering in vitro fertilization, tissue banks, bone marrow transplants, and a host of newly developed treatments. Cellcor Therapies Inc. 1256 Soldiers Field Road Boston, Mass. 02135 (617) 782-2204 Founded: 1987 Senior Officers: Gary W. Cashon, President and CEO Michael E. Osband, Executive Vice President and Chief Technical Officer Joe Gulla, Vice President of Sales Bill Aliski, Vice President of Governmental Affairs Esteban Celis, Vice President of R&D Susan Ross, Vice President of Clinical Services Gary duMoulin, Vice President of Quality Assurance Financial Information: Cellcor is a closely held private venture between Hillman Medical Ventures and Boston University, which in return for surrendering patent rights has a 5 to 10 percent equity in the company. Hillman Medical Ventures says it has invested about $20 million in developing the therapy. Major Product: Autolymphocyte therapy for metastatic kidney cancer, with investigations into the use of the therapy for prostate cancer. Employees: 55 total; 8 with Ph.D.'s or M.D.'s The proliferation of such treatments and centers may force the FDA to take a stand on these services. The agency could decide to regulate Cellcor's facilities in a manner similar to blood banks. Or it might view the procedure as a surgical one, in which hospital review boards and the medical community take the place of the federal government. At the same time, it may define manipulated cells as biological products, subject to the same review as a new drug. "It's difficult to define what the biological product is," FDA's Gunter explains. "Right now, we're wrestling with where we want to draw the line." The federal agency's jurisdiction covers technologies and products of public health concern that cross state boundaries. But with biocare, there are no clear-cut answers about how and what should be regulated and, sometimes, no interstate activity. Such ambiguity has its advantages for a company like Cellcor. For now, autolymphocyte therapy does not have to go through the regulatory bottleneck that ensnares many innovations in the field. "It can cut a couple of years off the time of development," says Cashon about the possibility of avoiding FDA oversight. "That's very important in the early life of a company, when it needs to show a return on the investment made." But the uncertainty of the company's status can work against it as well. Industry observers say that the company might have to rethink some of its strategies if the FDA decides to regulate Cellcor's therapy as a product and not as a service. In the meantime, potential investors might hesitate to back a company or industry where the regulatory burden is still undefined. "In the absence of a decision, the whole industry will be put on hold," complains one industry source who asked not to be identified. In any case, Cashon says that Cellcor is financially healthy and that it expects to show a profit in the next few years. But at $20,000 a treatment, it will take 1,000 patients to pay off the initial investment. And a planned network of centers in such cities as Atlanta, Chicago, and Los Angeles exists only on paper, casting doubt on Cellcor's goal of operating 15 to 20 such centers by the end of 1991. Even so, the company believes that the Lancet article makes a convincing argument for the potential of biocare. "It's an example of what can come about with a high degree of focus," says Cashon. "It's somewhat high risk, but I think we've created a very useful, valuable treatment."

Boston Startup Leads Charge In Burgeoning Biocare Industry

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