COLLABORATIVE RESEARCH's PROUROKINASE CONTRACT WITH SANDOZ
COLLABORATIVE RESEARCH's PROUROKINASE CONTRACT WITH SANDOZ accounted for $ 3.1 mil. of the firm's $ 11.8 mil. in revenues during fiscal 1987 (year ended Aug. 31), the Bedford, Massachusetts-based R&D firm reported in its most recent annual report. Collaborative Research licenses prourokinase to Sandoz and supplies the compound for clinical trials. At a January Hambrecht & Quist health care conference, Collaborative Research Chairman and CEO Orrie Friedman reported that the Sandoz agreement, in addition to involving the supply of prourokinase for clinical trials, includes the development of two new production methods for the clot dissolving agent. "Our second generation production methods, which will bring the cost of producing prourokinase down to a very low number, both use recombinant technologies," Friedman explained. "One is the production in mammalian cells, other than the kidney cells in which we now produce it. The most exciting one is the production in yeast, which we are already doing, because that has the potential of reducing the cost of producing prourokinase very dramatically." Sandoz begin clinicals with prourokinase (Sandolase) in West Germany and the U.S. in 1986. The thrombolytic is now in Phase II studies. Friedman noted that Sandoz recently expanded testing to include a combination of urokinase and prourokinase after the discovery that the clot lysis rate is accelerated by a small bolus dose of urokinase at the beginning of treatment. "It turns out that when used in combination with a small priming dose of urokinase, prourokinase is essentially free of the complications . . . that attend the use of TPA [tissue plasminogen activator]," Friedman said. Prourokinase "is essentially free of bleeding complications . . . and as far as the reocclusion of the cleared arteries, which is a problem in the use of TPA, so far, in the few hundreds of cases [in which prourokinase has been used], it is a very rare appearance," he added. Collaborative Research also has a contractual arrangement with Shell Oil's Triton Biosciences subsidiary for development of a natural interleukin-2 product. In vitro studies with Collaborative Research's interleukin-2, Friedman said, indicate that the substance may have a better side effect profile than recombinant interleukin-2. The differences "relate to the ability of the product to stimulate the growth and maintain the cytotoxicity of samples of lymphokines," Friedman explained. If the preclinical results carry over into the clinic, Friedman said, "it will enable clinicians to deploy significantly high critical concentrations of activated lymphocytes against an existing tumor in the individual in order to effect therapy without the necessity of either repeatedly [having to provide] leukopheresis, which is a requirement with the administration of the recombinant materials, and without the necessity of having to administer the drug to the patient, which is the source of the . . . complications that attend the present efforts of interleukin-2 immunotherapy." At least one other firm, Interleukin-2 Inc., is working on a natural IL-2 product. In the near term, Collaborative Research plans to expand its line of diagnostic tests. The diagnostics, which are based on the firm's genetic map ("The Pink Sheet" Oct. 19, T&G-5), currently include tests for three forms of cystic fibrosis, paternity, Y chromosome abnormalities, leukemia/lymphoma differentiation and adult polycystic fibrosis. In its annual report, the company also noted that in early 1988 it plans to introduce a series of ELISA assay tests that allow researchers to quantitate the level of lymphokines and growth factors present in biological fluids. New tests using Collaborative Research's enzyme membrane immunoassay technology are also under development. Ciba-Corning, under an arrangement with Collaborative Research, currently markets a thyroxine test based on the firm's technology.
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