PARIS - The Strasbourg-based gene therapy company Transgene has selected two more genes from the gene database of Human Genome Sciences Inc. (HGS), with which it concluded a 10-year research collaboration agreement in March 1998.

The two genes are AngioPro, or connective tissue growth factor-2 (CTGF-2), and VasoSten, or tissue inhibitor of metalloproteinase (TIMP-4), which Transgene plans to develop as novel gene therapy drugs for severe cardiovascular conditions. They were originally identified by HGS using its proprietary gene discovery technology, but their biological function and therapeutic potential were determined in functional genomics research undertaken jointly by the companies. Since then, Transgene has established their therapeutic effectiveness in preclinical trials of animal models.

AngioPro is a potent angiogenic factor with potential for treating peripheral and coronary artery disease. In a gene therapy experiment in rabbit models of peripheral ischemic disease, Transgene demonstrated that transfer of the AngioPro gene using an adenoviral vector stimulates new blood vessel formation and increased blood flow. At equivalent doses, the adenovirus AngioPro therapy was more effective than an adenoviral vector expressing the VEGF-1 gene.

The potential therapeutic applications of the VasoSten gene, which inhibits processes responsible for the destruction of tissues and assists in tissue regeneration, are in restenosis (obstruction of blood vessels such as coronary and peripheral arteries) following angioplasty. In preclinical models, Transgene showed that local delivery to injured arteries of an adenoviral vector expressing the VasoSten gene blocks restenosis in those blood vessels.

For these experiments, Transgene used the improved second generation of adenoviral vectors it developed under a research collaboration with Schering-Plough Corp. concluded at about the same time as its agreement with HGS, of Rockville, Md. That collaboration called for the development of a new generation of adenoviral vectors for the transfer of the p53 tumor suppressor gene in particular and triggered an initial milestone payment of $1 million from Schering-Plough in June.

Transgene said it intends to continue development of gene therapies with the VasoSten and AngioPro genes using both these adenoviral vectors and its proprietary non-viral vectors. These are only the second and third genes that Transgene has selected from the HGS database, the first one being p53. Its agreement with HGS gives Transgene the right to license up to 10 genes for the development and commercialization of gene therapies and provides for HGS to receive milestone and royalty payments for each gene therapy product brought to market. The deal also provides for the two companies to choose whether to share late-stage clinical development of particular products and subsequently co-market them.

On the signing of the agreement, HGS acquired a 10 percent equity stake in Transgene, while Transgene made an up-front payment to HGS of FFr155.4 million (US$24 million), representing an initial license fee plus a first installment of research funding. No money changed hands as a result of the selection of the latest two genes.

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