LONDON — Chiroscience Group plc has agreed to a research and licensing agreement with a leading oncology company, Bristol-Myers Squibb Co., to develop oral cancer drugs based on matrix metalloproteinase (MMP) inhibitors.

The pharmaceutical company has taken worldwide rights to Chiroscience's two second-generation MMP inhibitors, D2163, which entered Phase I trials in December 1997, and D1927, which is due to enter the clinic in March 1998. In addition the partners have entered a three-year collaboration to find new, more selective MMP inhibitors.

No financial terms were disclosed, but Andy Richards, director of business development at Chiroscience, told BioWorld International, "This is a very important deal. It's the biggest we've done, and one of the bigger deals in the sector."

Richards said it was a significant endorsement of Chiroscience's MMP inhibitor program. "The important thing is not that this is an endorsement of MMP inhibitors, because almost all the major pharmaceutical companies already have an interest," he said. "The big statement is, this is the leading oncology company, moving into MMP inhibitors in a big way, putting its clinical clout and muscle behind our program."

Bristol-Myers Squibb, of New York, will take on the development and all the development costs for the two licensed compounds. Chiroscience, of Cambridge, U.K., will receive development milestones for all products, and royalties on sales. Bristol-Myers Squibb will have rights to new MMP inhibitors for cancer treatments while Chiroscience will retain rights to develop its MMP inhibitors for all other areas, which include osteoarthritis, osteoporosis, multiple sclerosis and atherosclerosis.

The research collaboration will focus on understanding the role of MMPs in different tumors, at different stages of development and in different patient subsets in order to develop compounds with different selectivity profiles.

MMPs are enzymes that are overexpressed in tumors, supporting their growth, spread and metastatic processes. Chiroscience claims that its two second-generation MMP inhibitors are more selective than first-generation compounds such as Oxford, U.K.-based British Biotech plc's marimastat, which is currently in Phase III in a wide range of tumor types. Chiroscience said this will give them an improved safety profile and may also increase efficacy.

The collaboration with Bristol-Myer's will involve using genomics technology developed at Chiroscience's Darwin division, in Bothell, Wash., to look at expression profiles of different members of the MMP family in well-defined tumor samples.

"This will enable us to have a directed clinical program, selecting patient subsets," said Richards. It also will provide feedback to drive the selection of more selective inhibitors.

"When you are selecting on the basis of an animal model, you go for compounds that show a broad spectrum of action," he added. "Using feedback from the clinic, there are three routes to greater selectivity."

These are: selecting inhibitors to MMPs which are associated with particular cancer types; selecting inhibitors to MMPs which play a role in a particular stage of the development of cancer, for example, in angiogenesis or metastatic processes; and looking for individual patient differences in expression of MMPs.

Richards said Chiroscience has been researching MMP inhibitors for three years. "We have already got large numbers of compounds; the question is how to apply them."

He anticipates the new drugs will be used in combination with existing therapies, including chemotherapy, radiotherapy and surgery. "The strength of Bristol-Myers Squibb is its huge amount of clinical experience to get these regimes right, so we end up with the best use of these kinds of compounds," Richards observed.

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