By Randall Osborne

SAN FRANCISCO — Therion Biologics Corp.'s cancer vaccine program got a major boost from Pasteur Merieux Connaught (PMC) with the signing of a deal potentially worth more than $25 million.

PMC is making an initial, undisclosed equity investment in privately held Therion and will pay up to $25 million as scientific, clinical and regulatory milestones are met.

Therion, of Cambridge, Mass., has six therapeutic cancer vaccines in Phase I/II clinical trials: four for melanoma, one for colorectal and lung cancer, and one for prostate cancer. The firm expects to have about eight new products ready for clinical trials in the next two years.

"That seems like an awful lot for a small company of 30 individuals that's been operating on a cash burn of about $3 million per year," said Dennis Panicali, president and CEO of Therion, during a presentation at the 16th Annual Hambrecht & Quist Healthcare Conference here.

Vaccines can be created quickly with the company's technology, based on pox virus vectors, Panicali said, and much research already has been done through agreements with the National Cancer Institute.

"It takes less than nine months for us to go from a gene to having a virus or vaccine in a vial that can go into the clinic," Panicali said. "These things cost pennies to produce, at least at the clinical level, and are eminently scalable in the future."

Part of the deal with PMC, of Lyon, France, is a cross-licensing pact that gives the big pharma partner exclusive rights to certain of Therion's therapeutic cancer vaccines, and gives Therion access to certain pox virus vector technologies controlled by PMC and its affiliate, Virogenetics Corp., of Troy, N.Y.

The French vaccine maker PMC, a subsidiary of Rhone-Poulenc SA, of Paris, gains rights to develop, manufacture and commercialize Therion's therapeutic melanoma and carcinoembryonic antigen-based (CEA) vaccines.

CEA is a protein secreted by solid tumors. In Phase I trials, Therion's lead product for colorectal and lung cancer, known as TBC-CEA, caused an enhanced and specific immune response to CEA. Therion's vaccines for melanoma are designed to stimulate an immune response to MART-1 and gp100, antigens common in melanomas.

Pox Vectors Are The Linchpin

The linchpin of Therion's technology is its collection of pox vectors.

"They all have slightly different properties that can be used in combination," Panicali said. "And we can put multiple genes into these vectors." New generations will be worked out with PMC, he added. One vector that has shown satisfying results is the fowlpox virus. (See BioWorld Today, June 17, 1996, p. 1.)

"We're designing our vaccines to elicit a cellular response and an antibody response," Panicali continued. A large DNA virus is used, into which are inserted antigens, costimulatory molecules or cytokines. "These can be highly regulated in terms of temporal expression — when they're expressed and how much is expressed," he said.

Therion is developing several more melanoma antigens into vaccines. An investigational new drug application will be filed this year with the FDA for the fowlpox version of a prostate cancer vaccine, which will be used with an existing vaccine already under study. Clinical trials will begin this year for Therion's first vaccine for breast cancer and ovarian cancer.

The company also is working on a preventive AIDS vaccine, with funding from the National Institutes of Health. Therion's first generation of AIDS vaccines will soon move from Phase I to Phase II trials, Panicali said, and research is starting on the second generation.

Data from cancer vaccine trials will be presented at conferences this spring and summer, and PMC's agreement with Therion may be followed by more vaccine deals between the two companies, Panicali said. "They understand the nature of vaccines," he said. "They understand the biology. I'm very pleased." *