BioWorld International Correspondent

LONDON - Oxford Biomedica plc announced positive interim Phase II results of its TroVax gene therapy cancer treatment as an adjunct to standard care, showing that patients mounted an immune response despite being on chemotherapy.

Eleven of 13 patients who reached the interim stage in two trials had immune responses to the cancer antigen 5T4, after receiving the gene for the 5T4 antibody delivered by a poxvirus vector.

Alan Kingsman, Oxford's CEO, said in an analyst meeting the results answered a very important question.

"Can you stimulate an immune response in the context of chemotherapy, which can be immunosuppressive?" he asked. "We have concluded that chemotherapy does not affect the immune response to TroVax, and we are very pleased with that."

The trials, in patients with Stage IV colorectal cancer, are due to complete recruitment in the next four weeks. In the first trial, patients received TroVax with irinotecan, 5-fluorouracil (5FU) and leucovorin; in the second, patients received TroVax with oxalplatin, 5FU and leucovorin.

The results released last week relate to patients who had received four out of eight injections of TroVax and eight of 12 cycles of chemotherapy in the study protocol.

"The trials have already passed their primary endpoints, with no adverse events," Kingsman said.

The company expects to report full safety and immunological results in mid 2005. At that time, tumor response rates will be evaluated.

Oxford Biomedica is preparing for pivotal trials and has manufactured 12,000 doses of TroVax. It is in discussions with potential partners and has promised a deal within the next 18 months. The company had £26.2 million (US$46.8 million) cash as of June 30, enough to last until the second quarter of 2007.

Two other Phase II trials of TroVax are ongoing, one of which is sponsored by Cancer Research UK. In the States, the U.S. South Western Oncology Group (SWOG) is due to start a 120-patient Phase II trial in renal cancer at Columbia University before the end of 2004.

"With all the products that the North American biotechnology industry generates, they have chosen to put money behind TroVax," Kingsman said. "It's like having a major partner without giving any value away."

In the SWOG study, TroVax will be administered with standard care - the biologic IL-2. "We are very excited by this, and believe we may see an interesting synergy between TroVax and IL-2," Kingsman said.

Unlike some other cancer antigens, 5T4 is highly tumor-specific and does not occur on normal cells. It occurs on more than 75 percent of solid tumors, which Kingman said will make TroVax relevant in a range of cancers.

Oxford Biomedica's approach has been to show the treatment can be effective in a number of different contexts, from early to late-stage disease, and in combination with standard therapy or alone, to increase the appeal to potential partners. It commissioned a U.S. and European market survey of the most common chemotherapy regimens, choosing the two most popular for its trials.

In an earlier Phase I/II study of TroVax alone, patients mounted both an antibody and a cytotoxic T-lymphocyte response. Ten of the 17 patients exceeded the expected survival time by more than 50 percent. The latest analysis from the trial, released last week, showed a correlation between the strength of the immune response and survival.

Oxford, UK-based Oxford Biomedica also reported that its partner Wyeth is preparing for clinical studies of an antibody-chemotherapeutic conjugate, which uses 5T4 to deliver the cytotoxic calcheamicin. The leukemia treatment Mylotarg uses the same principle, and Oxford Biomedica believes that the ability of the 5T4 antibody to solid tumors will give the Wyeth product broad applicability.

"We have not talked about this product too much in the past because we didn't know if it would get through all the barriers Wyeth set up for it," Kingsman said. Manufacturing scale-up now is under way, and pre IND work is ongoing.

"[Wyeth is] barreling on, in moving this forward," he said.

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