Oxford BioMedica plc
Established in 1995, the Company specialises in the development and application of gene-based therapeutics and immunotherapeutics for the treatment of disease in the areas of Oncology, Viral Infection, and Neurobiology and in Gene Discovery. Oxford BioMedica plc was floated on the Alternative Investment Market of the London Stock Exchange in December 1996. Currently Oxford BioMedica has corporate collaborations with Aventis, AstraZeneca, IDM, Modex Therapeutics, Nycomed Amersham and Virbac. BioMedica's first clinical product, MetXiaŽ is in Phase I/II clinical trials for late-stage breast cancer (BC1) and ovarian cancer (OC1). Recently it received ethical approval form the UK Gene Therapy Advisory Committee for a Phase I/II clinical trial of its cancer vaccine TroVaxT in colorectal cancer. The TroVaxT clinical programme is expected to commence shortly.

MetXiaŽ gene therapy for cancer
A common strategy for the treatment of cancer is to administer cytotoxic (or cell killing) drugs in an attempt to destroy the tumour. Cyclophosphamide is one of a group of drugs that is taken by the patient in the form of an inactive prodrug. The prodrug travels through the body to the liver where enzymes convert it to the active, cytotoxic form. This approach affects the whole body and leads to the familiar adverse side effects of cancer chemotherapy because the cytotoxic drug destroys normal cells on its way from the liver to the tumour. In addition, because the activating enzymes are present only in the liver, high doses of prodrug must be given to achieve therapeutic levels of the cytotoxic drug at the tumour site. Often the therapeutic effect is compromised by the toxicity.

Oxford BioMedica's MetXiaŽ addresses these problems by delivering the gene (CYP2B6) directly to the tumour. Once incorporated into the genetic material of the tumour cells, this gene produces the liver enzyme that converts the cyclophosphamide pro-drug to its active form within the tumour. The aim is to achieve high concentrations of activated cyclophosphamide locally in the tumour while minimising circulating levels of the drug. It is anticipated that this will lead to substantially increased sensitivity of the tumour to the drug and to an ability to reduce the dose of cyclophosphamide, thereby reducing adverse side effects.

In a variety of preclinical models, BioMedica has shown that delivery of the human CYP2B6 gene to tumours, using MetXiaŽ, does indeed increase their sensitivity to cyclophosphamide and leads to enhanced tumour cell killing. The Company is now engaged in Phase I/II clinical trials in breast cancer (BC1) and ovarian cancer (OC1). The results reported on 6 November 2000 confirm that the gene transfer achieved in preclinical models also occurs in the cancer patients in the BC1 trial. The implication for the efficacy of the product of this level of gene transfer will be evaluated in further studies.

MetXiaŽ represents a platform technology which can be developed in a number of ways; firstly as a product in its own right, secondly as a component of a combination product that induces the immune system to destroy tumours and finally, in selected formulations to achieve tumour targeting. The collaborative agreement signed today with Valentis, is an example of the third of these options.