LONDON - Oxford GlycoSciences plc announced progress on two fronts last week, with a further patent filing on proteins associated with breast cancer and publication of the first clinical trial results on its lead compound, OGT 918, in the treatment of Gaucher's disease.

The latest patent filing, together with two others made in the past two months, covers proteins found on the surface membranes of breast cancer cells, within breast cancer cells and serum protein markers of breast cancer. They were discovered using the company's proteomics technology, and represent potential targets for antibody therapy, small-molecule drugs and diagnostics.

OGS, based in Abingdon, Oxfordshire, said its approach to the discovery of disease-associated proteins represents a new and holistic approach to understanding disease at the molecular level. Raj Parekh, chief scientific officer, said the breast cancer study "is the first time a proteomics study of this breadth has been performed in any disease. We set out to run a broad study designed to find proteins implicated in breast cancer by looking in actual tumor tissue from patients with the disease."

The work was carried out in collaboration with the Ludwig Institutes of Cancer Research in London, which collected and purified the tumor material.

OGS said its approach to detecting disease-associated proteins is more effective than other genomics technologies because it can detect where the proteins actually are located. "Proteomics can identify those proteins which are actually present on cell surfaces, or are actually secreted into the serum, by analyzing these proteins directly," said Martin Page, director of biology. "This can decrease the uncertainty associated with genomics-based predictions of which proteins in a cancer cell may offer potential as targets for drug treatment or markers for monitoring therapy."

The OGT 918 trial involving 28 patients who were treated for one year was published in the Lancet. Overall, it was concluded that OGT 918 improved key clinical features of Type 1 Gaucher's disease, could be used as a monotherapy, and has additional potential as a treatment combined with the existing enzyme replacement treatment.

There were significant reductions in the volume of the liver and spleen (a key measure of response to treatment in glycolipid storage disorders in which unmetabolized material accumulates in lysosomes), a trend to improvements in blood counts, and a reduction in chitotriosidase, a protein marker of the disease.

Current treatment of Gaucher's disease involves intravenous administration of replacement enzyme every two weeks to remove excess glycolipid stored in the body. OGT918, taken orally, is a glucosyltransferase inhibitor, slowing the generation of glycolipid in the body to reduce the amount stored. OGT 918 has orphan drug status in the U.S.

Further trials are under way, including a study in which patients who are currently receiving enzyme injections are randomized to receive either enzyme, OGT 918 or both in combination. The company said it is on track to file for U.S. and European approval in 2001.

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