BioWorld International Correspondent

LONDON - Oxford BioMedica plc is revamping its business strategy following the signing of a potential $690 million deal for its lead gene therapy product, TroVax, with Sanofi-Aventis SA in March.

The company will seek to retain more value through co-promotion deals and move to a fully integrated model by building its own sales and marketing operation.

"After the Sanofi deal, we took the opportunity to step back and look at the company and its strategy," said Alan Kingsman, CEO. "There's no biotech that has delivered substantial value without being fully integrated. We will do that, moving cautiously."

The Oxford, UK-based company reached the first development milestone in its TroVax collaboration last week, enrolling the 350 patients in a Phase III trial in renal cancer. That triggered a payment of €9 million (US$12.5 million) to add to the up-front payment of $38.6 million. Oxford BioMedica expects payments associated with the Sanofi deal to bring it to sustainable profitability in 2009.

The money is allowing the company to accelerate development of its key products and broaden the pipeline, Kingsman told an analysts' meeting called to discuss the company's six-month financial results. In particular, Kingsman is very optimistic about getting permission to carry out a Phase I/II trial of Prosavin, a gene therapy for Parkinson's disease.

Prosavin consists of the gene for dopamine delivered with Oxford BioMedica's LentiVector delivery construct. The product is designed to be administered by a stereotactic, MRI-guided injection into the striatum. In animal models, a single treatment delivered long-term benefits. The animals showed significant improvements in two weeks and returned to normal by five to eight weeks. To date, the effect from a single injection has been maintained for 20 months.

"That is, there is essentially a complete reversal of the condition. We and a number of people in Parkinson's disease are very excited about this," Kingsman said. The company has filed an application with the French regulator AFSSAPS (Agence Francaise de Securite Sanitaire des Produits de Sante), and Kingsman is hopeful that will lead to the first patient being treated before the end of 2007.

The 18 subjects in the trial will be patients failing on standard L-dopa therapy, but not experiencing debilitating side effects. The trial will be dose escalating and placebo controlled. Given the preclinical findings, Kingsman expects initial results at about eight weeks

"We believe that if we see the sort of efficacy in man that we see in animals, we can move straight from Phase I/II to Phase III."

Following on from Prosavin, in 2008, Oxford BioMedica expects its Retinostat gene therapy for retinopathy to enter the clinic, further broadening the company away from its focus on oncology. The company also has made moves to expand its preclinical portfolio. It has taken rights to use the same anti-angiogenesis genes used in Retinostat in cancer, and has revived an AIDS project that dates from the early days of the company, but was parked as being of less commercial value when retroviral therapies were launched.

In addition to triggering the first milestone in the Phase III trial of TroVax in renal cancer, the study received the go-ahead following the first review by the data safety monitoring board. That trial will recruit 700 patients. Meanwhile, Paris-based Sanofi-Aventis expects to start a 1,000-patient trial in metastatic renal cancer in 2008, while another 3,000-patient trial of TroVax as an adjuvant in early stage colorectal cancer already is under way. That study is funded by the UK Department of Health and the UK Medical Research Council.

Mike McDonald, Oxford BioMedica's medical officer, claimed TroVax is the best-in-class cancer vaccine. "As each month goes by, our view on this strengthens," he said.

The safety profile is being maintained as the product moves into large multicenter studies, and antibody and/or cellular responses are induced in most patients, with a strong correlation between immune response and clinical benefit, he said.