BioWorld International Correspondent

LONDON - Oxford BioMedica plc made significant progress with its gene therapy portfolio, agreeing to a comprehensive deal for the commercialization of its LentiVector technology for use in research, and announcing it has achieved the industry's Holy Grail of generating cytotoxic T-cell responses with the cancer immunotherapeutic TroVax.

Meanwhile, partner Wyeth Pharmaceuticals said an antibody-conjugated chemotherapeutic based on Oxford BioMedica's technology will enter the clinic next year.

In the technology deal, partner Sigma-Aldrich will invest $5 million in Oxford BioMedica and make an undisclosed up-front payment, annual maintenance payments and royalties on sales. Initially, Sigma-Aldrich will use the LentiVector technology for the delivery of RNA interference (RNAi) in the reagent and research tool market but it has first rights also to negotiate a license for other products based on the technology.

Oxford BioMedica has agreed previously to a string of research licenses for LentiVector, but Alan Kingsman, CEO, told BioWorld International, "This is significantly bigger than anything we have done before, and there is a genuine intention that the two companies work together." The Oxford-based company has revenues of around £1 million (US$1.8 million) annually from technology licenses, and Kingsman expects that to grow to £2 million to £3 million annually.

He added that the agreement is a significant endorsement of the LentiVector technology and reflects the fact that lentiviruses are acknowledged as one of the most adaptable vectors, capable of delivering genes to a wide range of cell and tissue types. "It has become almost universal to use lentiviral vectors," Kingsman said, "and our patents in the field are very broad. While this deal has no effect on existing licensees, we won't do anything in the field of RNAi."

Kingsman said that giving Sigma-Aldrich the exclusive right to sublicense LentiVector for research purposes allowed Oxford BioMedica to put business development of that market to the side and concentrate on finding a development partner for TroVax, its cancer immunotherapy product that is based on LentiVector.

New data released last week showed that all 23 colorectal cancer patients who completed the Phase IIb trial in which TroVax was administered in combination with chemotherapy mounted a T-cell response. Of those, 70 percent were cytotoxic T-cell (CD-8) responses. In some patients, those were at levels comparable to those observed in response to infectious disease pathogens.

"The single most important thing in the trial, apart from the evidence of impact on tumors, was the CD-8 data," Kingsman said. "The industry as a whole believes [CD-8] will be the antitumor effector, rather than the antibody response."

Kingsman has set the target of licensing TroVax within the next 12 months, and he said the CD-8 data have made a difference to the "quality of interaction" with potential partners.

"We have had a couple of really quite significant meetings, where a lot of the discussion has focused on CD-8," he said.

TroVax targets the 5T4 tumor antigen, which is widespread on solid tumors. In a further endorsement, Wyeth last week presented preclinical efficacy data of its 5T4 antibody-targeted chemotherapy product and announced plans to start Phase I trials in 2006.

The data showed the targeted calicheamicin is cytotoxic to tumor cells expressing 5T4 and inhibited tumor growth in various in vitro models. The license with Wyeth is valued at $24 million in up-front and milestone payments, plus royalties on sales. Moving into Phase I will trigger a milestone payment to Oxford BioMedica.

"It really shows stunning efficacy in the preclinical models," Kingsman said. "It shows the targeting works, and there is a big therapeutic window before you get toxicity."