Oxford BioMedica plc
Established in 1995, the Company specialises in the development and application of gene-based therapeutics using advanced gene delivery technologies for the treatment of disease in oncology, viral infection and neurodegenerative disease. Oxford BioMedica plc was floated on the UK Alternative Investment Market of the London Stock Exchange in December 1996.

Aventis Pharmaceuticals Inc.
Aventis Pharmaceuticals is the U.S. business of Aventis Pharma AG, the pharmaceutical company of Aventis S.A. (NYSE:AVE). Aventis Pharmaceuticals, with headquarters in Parsippany, N.J., focuses its activities on important therapeutic areas such as cardiology, oncology, anti-infectives, arthritis, allergy and respiratory, diabetes, and the central nervous system.

Aventis Pharma is dedicated to treating and preventing human disease through the discovery, development, manufacture, and sale of innovative pharmaceutical products aimed at fulfilling unmet medical needs. The corporate headquarters of Aventis Pharma is in Frankfurt, Germany. Aventis Pharma comprises Aventis Pasteur, a world leader in vaccines, with corporate headquarters in Lyon, France, and Aventis Behring, a world leader in therapeutic proteins, with corporate headquarters in King of Prussia, Pa.

Aventis S.A., one of the world's leading life sciences companies, is focused on two core business areas: pharmaceuticals and agriculture. With global corporate headquarters in Strasbourg, France, Aventis employs nearly 90,000 people in 120 countries. Aventis S.A. was launched in December 1999 through the merger of Hoechst AG and Rhône-Poulenc S.A.

Hypoxia Response Element in Aventis gene therapy products
The Hypoxia Response Element, to which Oxford BioMedica has exclusive rights, is a sophisticated control mechanism that can switch genes on or off in response to oxygen levels in the tissues of the body. Aventis will use HRE in gene therapy approaches to treat coronary artery disease and peripheral arterial disease by stimulating growth of new blood vessels in areas where existing blood vessels have become diseased, and have ceased to function. Hypoxia is an intrinsic phenotype of ischaemic diseases. The HRE system is designed to ensure that any new blood vessels will grow only where they are needed and will not continue to grow once a normal blood supply has been established.

Under the December 1998 agreement, Oxford BioMedica could receive payments up to $18 million through a combination of access, milestone and research funding payments and equity subscriptions, in addition to royalties on sales of products containing the HRE once they reach the market.

LentiVectors®
In gene therapy, the aim is to deliver a gene and its necessary regulatory elements (the gene construct) to the cell surface, using a vector to mediate the transfer across the cell membrane and, in some cases, into the nucleus. A new and potentially very powerful vector system is based on lentiviruses, which have similar features to retroviruses in the ease of manipulation, predictable integration and reliable gene expression and regulation. However, their main advantage over retroviruses is the ability to function in non-dividing cells or cells that are dividing slowly - a feature of many tissues of the body. In addition, BioMedica has found that its LentiVectors® do not give rise to detectable adverse side effects including inflammatory responses.

Lentivirus vectors are constructed from two sources:

Most lentiviral vector development to date has focused on the HIV-1-derived system, as HIV is the most thoroughly characterised of the lentiviruses. However concerns over the use of HIV-based vectors for diseases other than HIV infection are leading to the use of non-primate viruses such as EIAV.