BioWorld International Correspondent

PARIS - The Strasbourg-based gene therapy company Transgene will concentrate its research and development effort henceforth on its most promising drug candidates in the area of immunotherapies for cancer as part of a refocus of its corporate strategy on "product-based development of therapeutic candidates."

Phase II trials of two such therapies will start later this year, as will Phase I trials of two others.

At the same time, Transgene said it is looking for partners for the joint development of gene therapy candidates for cardiovascular disease. It also confirmed that it will continue development of a gene therapy for improving quality of life for sufferers from Duchenne's disease with the financial support of the French Muscular Dystrophy Association.

On the other hand, development of its gene therapy for cystic fibrosis remains suspended while it continues to look for a more effective vector. In effect, a company spokesman told BioWorld International, Transgene's new strategy focus does not imply any curtailment of its upstream research into gene therapy vectors; it will continue developing the different families of vectors that constitute its technology platform, with particular emphasis on vaccinia virus, adenovirus and synthetic vectors.

In the oncology field, Transgene has two cancer vaccines in clinical development. One uses the Muc1 antigen for the treatment of breast, prostate, lung and other cancers. Phase I and II trials of this treatment in breast and prostate cancers have been completed using an early generation vaccinia vector, but a new formulation of the Muc1 vaccine product using a new generation vector based on the modified virus ankara (MVA) strain has shown improved efficacy and safety in both preclinical and Phase I trials. The company has thus decided to discontinue development of the virus vector, while Phase II clinical trials of the second-generation product, MVA-Muc1-IL2, are scheduled to begin in the fourth quarter in Europe and the United States.

Its second cancer vaccine candidate is based on the expression of two antigens from the human papilloma virus. The safety of this therapy has already been demonstrated in Phase I clinical trials, and Phase II trials in cervical cancer are due to commence in the fourth quarter in Europe and Mexico.

The company's other family of cancer treatments are immune enhancement gene therapies entailing the injection of the vector carrying the appropriate cytokine directly into the tumor. Phase I and II clinical trials of one of these candidate therapies involving the use of interleukin-2 with the cellular Vero vector, Vero-IL2, established proof of principle for this approach. This cellular vector has since been replaced by an improved adenovirus vector delivering the IL-2 gene, Ad-IL2, and Phase I trials of one version of the product developed for the treatment of solid tumors will get under way shortly.

Transgene is developing a second immune enhancement therapy that combines this vector with the cytokine interferon gamma. This product is expected to enter Phase I trials this year.

In the cardiovascular field, Transgene has established the therapeutic potential of two genes that it selected in mid-2000 from the gene database of Human Genome Sciences Inc., of Rockville, Md. The two genes are AngioPro, or connective tissue growth factor-2 (CTGF-2), and VasoSten, or tissue inhibitor of metalloproteinase (TIMP-4). Preclinical trials using animal models confirmed their therapeutic effectiveness for treating severe cardiovascular conditions, but Transgene has decided that it needs either to team up with a biopharmaceutical company specialized in cardiovascular disease, or create a specialist spin-off for the development of these therapies.

The spokesman also confirmed that Transgene is to go ahead with its planned capital increase aimed at raising at least EUR60 million (US$52 million) before the end of June, but declined to say whether it would take the form of a public share offering, as originally planned. Transgene's share price recently plummeted to as little as EUR11 from its March 2000 high of almost EUR110. Following the clarification of its corporate strategy and the announcement of its 2000 results, however, it picked up to over EUR16.

Transgene is a subsidiary of bioMérieux-Pierre Fabre, which was created at the end of last year by the merger between bioMérieux, part of the Alain Mérieux group that originally spawned Transgene, and Pierre Fabre, another privately owned French pharmaceutical company.