Agreement

Oxford Biomedica PLC 6 June 2000 For further information, please contact: Oxford BioMedica plc Professor Alan Kingsman, Chief Executive Tel: +44 (0)1865 783 000 City / Financial Enquiries David Simonson / Melanie Toyne Sewell Tel: +44 (0)207 606 1244 Scientific / Trade Press Enquiries Sue Charles / Katja Stout, HCC de Facto Tel: +44 (0)207 496 3300 OXFORD BIOMEDICA ANNOUNCES COLLABORATION EXTENSION WITH AVENTIS PHARMACEUTICALS INC. ON GENE THERAPY FOR CARDIOVASCULAR DISEASE Oxford, UK - 6 June 2000: Oxford BioMedica plc announced today that it had extended the scope of its collaboration with Aventis Pharmaceuticals Inc. (formerly Rhone Poulenc Rorer). The original agreement with Oxford BioMedica, signed in December 1998, gave Aventis Pharmaceuticals rights to use Oxford BioMedica's Hypoxia Response Element (HRE) in gene therapy products for cardiovascular disease. Aventis Pharmaceuticals is developing products for coronary artery disease and peripheral arterial disease as part of its cardiovascular gene therapy programme. The HRE is being used as a switch to regulate gene expression in these product programmes. Under a new agreement, Aventis Pharmaceuticals will also have access to BioMedica's proprietary LentiVectorr gene delivery vectors in cardiovascular gene therapy product research and development programmes. In addition, Aventis Pharmaceuticals has exercised an option under the agreement of December 1998 to include an additional angiogenic gene in its development of cardiovascular disease products using BioMedica's HRE. Commenting on the agreement with Aventis Pharmaceuticals, Alan Kingsman, BioMedica's Chief Executive said: 'Oxford BioMedica has a long-standing relationship with Aventis Pharmaceuticals dating back to 1997, in both gene therapy and genomics R&D. We are pleased with the progress we have made in these interactions with Aventis Pharmaceuticals and are particularly pleased that Aventis Pharmaceuticals has chosen to extend, in two ways, the collaboration with us in cardiovascular disease. 'This new deal also further strengthens our belief in the value and versatility of our LentiVectorr technology in a range of therapeutic and genomics areas. Aventis Pharmaceuticals has access to world-class gene therapy technology through its Gencell group, and it is an endorsement of BioMedica's leading position in this field that they have again chosen to work with our product components.' Notes to Editors 1. Oxford BioMedica plc Established in 1995, the Company specialises in the development and application of gene-based therapeutics using advance gene delivery technologies for the treatment of disease in the areas of 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. 2. 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 Rhone-Poulenc S.A. 3. Hypoxia Response Element in Aventis Pharmaceuticals 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 Pharmaceuticals 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. Financial details of the new collaborative agreement have not been disclosed. 4. LentiVectorsr 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 LentiVectorsr do not give rise to detectable adverse side effects including inflammatory responses. Lentivirus vectors are constructed from two sources: primate viruses e.g. human or simian immunodeficiency virus (HIV or SIV) non-primate viruses e.g. feline and bovine immunodeficiency viruses (FIV and BIV), and one of the most simple, equine infective anaemia virus (EIAV). Oxford BioMedica's pEGASUST vectors are based on EIAV. 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. 5. Worldwide web This release is also available on the Worldwide Web at http://www.oxfordbiomedica.co.uk
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