Four years ago, Sugen Inc. chief executive officer Stephen Evans-Freke painted a rosy picture of his biotechnology companys future. "Were fortunate in being the world leader ... in signal transduction-based drug discovery," Evans-Freke said, speaking at a health care conference. "We think we can make an awful lot of money for our stockholders over the next 2 to 3 years."
Within a year of making that statement, Evans-Freke had departed, and Sugen had ceased to be an independent company, absorbed into Pharmacia & UpJohn. Now Sugen, based in South San Francisco, will vanish completely, a casualty of the $57 billion Pfizer-Pharmacia merger, completed April 16. "Most of the employees will sort of disappear, they will go to other companies," predicted Sugen co-founder Axel Ullrich, Ph.D., of the Max Planck Institute of Biochemistry in Martinsried, Germany. "The coherence of the whole approach will get lost."
Sugens demise worries many cancer researchers. "The intellectual impact is really a great loss," said Percy Ivy, M.D., a senior investigator at the National Cancer Institutes Cancer Therapy Evaluation Program. "You just dont see that kind of commitment to scientific and data-driven drug development." The company was unique among cancer therapeutics firms, "a model for how you run a company, and how to develop targeted therapies for cancer," said Tony Hunter, Ph.D., a prominent kinase expert at the Salk Institute for Biological Studies in La Jolla, Calif.
The Sugen shutdown is just the most obvious sign of Pfizers contraction in cancer research, as the worlds largest drug company moves to absorb Pharmacia and downsize its operations for the sake of operational efficiency and investor returns. Pfizer is shutting down discovery operations and cancer clinical development at the former Upjohn Pharmaceuticals site in Kalamazoo, Mich., eliminating cancer drug discovery at the former Parke-Davis laboratories in nearby Ann Arbor, and is pondering the future of cancer research at Pharmacias former research laboratories in Nerviano, Italy. Pfizer officials said they will move as many oncology programs and people as possible to company facilities in La Jolla and in Groton, Conn. But a reduction in cancer research and a loss of scientific personnel and program continuity, at least in the short term, are certain.
A Biotech Pioneers Rise and Fall
Although Sugen never produced an FDA-approved cancer drug, the company pioneered the field of tyrosine kinase inhibitors for cancer, an approach that all large drug companies now pursue vigorously. Sugen scientists "had a depth of knowledge that was exceptional," said Ivy. "They had an incredible grasp of what would need to be done to get validated molecular therapies."
Sugen founders Ullrich and Joseph Schlessinger, Ph.D., were among the worlds top signal transduction researchers when they founded the company in 1991. Ullrich had cloned the Her-2/neu and epidermal growth factor receptors, among others, while at Genentech in the early 1980s. Sugen, when it was founded, was the only company openly pursuing kinase inhibitors, although Ciba-Geigy also had a small program that would eventually yield the Novartis cancer drug Gleevec.
Targeting receptor kinases was not a popular approach in 1991, since most companies did not view them as "druggable." Sugen scientists decided to target the ATP (adenosine triphosphate) binding site, an approach considered foolhardy by many scientists, who thought such drugs would be nonspecific and extremely toxic. "Even in the company, some of the senior people did not believe in this [approach]," said Ullrich. "But we pursued the track anyway."
Despite its lead in kinases, Sugen was upstaged in drug approvals. Gleevec and AstraZenecas Iressa were the first small molecule kinase inhibitors to reach market. Research on Sugens most advanced drug candidate, the VEGF receptor inhibitor SU-5416, was discontinued in February 2002 after disappointing phase III results. Another VEGF receptor inhibitor, SU-6668, now appears stalled in development. Meanwhile, Genentechs Avastin, a monoclonal antibody against VEGF itself, demonstrated substantial survival benefit when combined with chemotherapy in colorectal cancer patients in a study presented at the May meeting of the American Society of Clinical Oncology. Ironically, it was Sugen scientists who, in 1994, first validated the VEGF receptor as crucial for tumor angiogenesis.
Sugen now has a third-generation VEGF receptor inhibitor, SU-11248, in the clinic, and the company presented encouraging phase I results at the ASCO meeting. SU-11248 "very much figures into our forward plan," said Mike Morin, Ph.D., Pfizers director of cancer drug discovery in Groton. But Sugens extensive kinase discovery and preclinical programs are at risk, said Ullrich. "Its really sad that, at this point when really all this is peaking, the whole long-term plan was destroyed," he said.
Pfizer Takes Over
Pfizer officials say that Sugens most valuable cancer programs will continue. "We were really very excited about some of the technologies at Sugen, and also excited about some of the discovery programs," said Martin Mackay, Ph.D., Pfizers senior vice president of worldwide discovery. "The technologies, the intellectual property, really will be captured and will be put to good use."
Thats not likely, said Ullrich. "[Sugen] has accumulated a big patent package and tremendous know-how that cannot simply be transferred to a new company context without losing most of its value," he said. Ullrich is also worried that the roughly 20 patents his laboratory has transferred to Sugen will get lost in Pfizers vastness and will never be mined for their therapeutic potential. Sugen also filed patent applications on more than 140 kinase and phosphatase DNA sequences generated by the companys Human Kinome project, the catalog of all 518 kinases that was published last December 6 in Science. These now belong to Pfizer.
The loss of a company with 350 employees, all focusing on kinases, is substantial, said former Sugen president Laura Shawver, Ph.D., now CEO of Phenomix, a San Diego biotechnology company. Pfizer "is very committed to cancer," she said, but Sugens programs will be hard to move wholesale to other sites. "How will [Pfizer] fairly evaluate them if all the Sugen employees scatter to the winds, or choose to stay in the Bay Area and not take Pfizer jobs?" she asked.
Pharmacia, unlike Pfizer, left Sugen largely intact as a stand-alone entity after the 1999 merger. "One of the beauties of a small company [is] you can be very fast, very flexible in making decisions and moving," said former Sugen president Peter Hirth, Ph.D., now CEO of Plexxicon, a Berkeley, Calif., biotechnology company. "This was really poetry in motion." Sugen scientists also published frequently, with almost 300 scientific papers to their credit. "They were free scientific thinkers, they were grounded in fact and data," said Ivy. "They felt what they did would withstand public scrutiny."
Pfizer scientists publish far less often, but company officials say the companys size gives its researchers resources that small companies cannot duplicate. "If I look at our compound file, our screening prowess, the technologies that we can bring to bear, theres great advantage," said Mackay. And Pfizer is hardly a newcomer to the kinase field, having developed OSI-774 (Tarceva), an epidermal growth factor inhibitor later divested to OSI Pharmaceuticals as a government condition to Pfizers takeover of Warner-Lambert in 2000. At Pfizer, "there are probably 20 or more discovery projects targeting kinases," said Morin. "Weve been doing this very quietly for at least 10 years."
But Sugen will be missed. "They were a company that we loved dealing with, because they really were driven by the science of drug development," said Ivy, who coordinated an NCI clinical development grant to Sugen. The companys demise, she added, "saddened all of us, because it was a wonderful kind of intellectual partnership."
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |