Millennium Pharmaceuticals Inc and Xenova Group plc have signed a license agreement for the development and North American commercialization of Xenova's novel compounds, which have a unique mechanism of action including dual inhibition of topoisomerases I and II, for the treatment of solid tumors in cancer. The program includes three molecules; XR11576, XR5944, and XR11612. XR11576 is an oral agent that has entered Phase I clinical development with the first patients screened for study entry. The two additional compounds are in preclinical development.

Under the terms of the agreement, Millennium will acquire development and exclusive marketing rights to the topoisomerase program in North America in exchange for an upfront payment of US$11.5m (£7.8m) as well as future milestone payments and royalties following the achievement of specific development and sales goals. Xenova retains commercialization rights for all products arising from this topoisomerase collaboration outside the United States, Canada and Mexico, including marketing in Europe and the rest of the world. Xenova will retain responsibility for performing development activities associated with the program, which will be funded by Millennium commencing in 2003, to the end of Phase II clinical trials. Thereafter, Millennium will assume responsibility for subsequent development activities in North America and Xenova will retain development activity responsibility for the rest of the world.

Additionally, Millennium has the right to market in North America any improvements or additional products based on the same topoisomerase inhibitor technology, in which case Xenova will receive further milestones and royalties on the sales of such products. Additional terms of the agreement were not disclosed.

Topoisomerases are enzymes that are critically involved in the replication of DNA during the process of cell division and that play a key role in the proliferation of cancer cells. Topoisomerase inhibitors comprise a major and established class of cytotoxic anti-cancer agent that is widely used to treat cancer patients. Topoisomerase inhibitors that inhibit either topoisomerase I or II are used to treat a number of different tumor types: camptothecins (topoisomerase I inhibitors) for colorectal cancer; anthracyclines (topoisomerase II inhibitors) for breast, ovarian, bladder cancer and Non Hodgkin's Lymphoma; etoposide (topoisomerase II inhibitor) for lung cancer. Given the differing roles and expression of the two types of enzymes within the cell cycle, inhibitors of both topoisomerase I and topoisomerase II (dual inhibitors) are expected to have potentially significant therapeutic advantage over agents targeting one type of topoisomerase alone.

In addition, dual inhibitors may circumvent mechanisms of drug resistance and may also have a broader spectrum of activity as expression levels of the two enzymes are variable between different types of cancers, as suggested by Xenova's preclinical data of the three molecules.