By Mary Welch

Corixa Corp. has reason to celebrate as two corporate partners, Pasteur Merieux Connaught and SmithKline Beecham plc, extended their vaccine-related research agreements.

Pasteur Merieux Connaught, of Lyon, France, is continuing a collaboration to investigate use of an infectious disease vaccine adjuvant, while SmithKline, of London, is renewing its exclusive option to license a tuberculosis vaccine.

"It's usually good news when a partner extends its agreement," said Steven Gillis, president and CEO of Seattle-based Corixa. "It can mean they like what's going on." Corixa's research focuses on T cell vaccines for cancer and infectious diseases.

The larger of the two deals involves SmithKline, which signed an agreement in October 1995 to fund Corixa's discovery of antigens for a tuberculosis vaccine. The original deal, worth up to about $22 million in up-front technology access fees, research support and milestone payments, gives SmithKline exclusive worldwide rights to use any or all antigens. In Japan, the two firms would be co-owners of the vaccine.

In extending the collaboration, SmithKline will provide additional research funding through May 1999 and will retain its exclusive option to license any discovered antigens in the tuberculosis (TB) program through August 1999.

T cell, Antibody Methods Find TB Genes

Using a variety of techniques that utilize T cells and antibodies, Corixa has identified multiple genes within the specific bacteria that cause TB. It has identified more than 60 candidate TB gene products that trigger helper T cell responses in vitro.

"We have identified genes, filed patents, expressed the gene products and tested them in combination to determine if they can prevent the TB infection in animals such as mice and guinea pigs," Gillis said. "We have identified several excellent antigens for a vaccine and are narrowing the field to see which antigens are best to combine and take into the clinic. We hope to have a vaccine ready to test by the end of this contract extension."

Once thought no longer a threat to the Western world, TB is coming back strong as a result of drug-resistant strains, Gillis said. In fact, it is the leading infectious disease killer in the world, with over 8 million new cases diagnosed each year.

The deal with Pasteur Merieux, the subsidiary of Paris-based Rhone-Poulenc Group extends a research agreement until Dec. 31, 1998, to study Corixa's protein adjuvant, Leishmania elongation initiation factor (LeIF). The pact includes an option to license exclusive use of LeIF in influenza and respiratory syncytial virus, and a non-exclusive license to use the adjuvant in HIV, TB and malaria. Specific terms were not disclosed.

LeIF, when combined with certain antigens, is designed to stimulate stronger antibody and T-cell responses than the antigen alone would elicit. LeIF is a protein produced by the parasite Leishmania, which is carried by sandflies. In preclinical studies, LeIF has been shown to be a unique protein stimulator of a Th1 helper T cell response to fight diseases. It appears to work by both upregulating the important costimulatory factor, B7.1, and by inducing significant production of IL-12.

Gillis said Pasteur Merieux will pay a fee for each disease indication it chooses to pursue using LeIF. "We are working with [Pasteur Merieux] to evaluate the efficacy of the protein and hopefully, during this extension, finish off the experiment. When Phase I is started is up to them," he added.

While Pasteur Meriuex has an exclusive option for influenza and respiratory syncytial virus, Corixa is pursuing licensing agreements with other companies for indications such as HIV, TB and malaria.

"These two agreement extensions are different and involve different technologies," said Gillis. "The agreement with SmithKline covers a recombinant subunit vaccine of the TB virus, and with PMC the relationship deals with our adjuvant technology."

Corixa's stock (NASDAQ:CRXA) closed Friday at $4.656, up $0.093. *