By Karen Pihl-Carey

Valentis Inc. and Boehringer Ingelheim International GmbH formed a 15-month collaboration to focus on gene therapy for rheumatoid arthritis.

Boehringer's interest in a partnership grew when Valentis demonstrated the feasibility, safety and efficacy of interleukin-10 and interleukin-1 receptor antagonist protein (IRAP) and other gene therapies through its collaboration with the University of Pittsburgh.

"They wanted to see if we could generate the same efficacy with their genes," said Ben McGraw, chairman, president and CEO of Valentis. "The collaboration is around working with our delivery systems and Boehringer Ingelheim's genes and the goal is to show that we can create a product that they would decide is appropriate for clinical development during this phase of the collaboration."

Boehringer Ingelheim, of Ingelheim, Germany, did not want any specifics released about its gene therapies, McGraw said. The companies are not disclosing any financial terms, including whether they include up-front payments or milestones.

"They were adamant we can't say anything about that," McGraw told BioWorld Today. "They're funding the work that we're doing here and through the University of Pittsburgh."

Ingelheim and Burlingame, Calif.-based Valentis will evaluate Valentis' delivery and expression systems with Boehringer's genes in several animal models of rheumatoid arthritis. Boehringer will fund the research for up to 15 months. By that time, the company hopes to have enough research together to file an investigational new drug application, McGraw said.

Through the Valentis and University of Pittsburgh collaboration, researchers completed a Phase I trial with nine patients for rheumatoid arthritis earlier this year. Results showed that the gene medicine tested was well tolerated and resulted in gene expression in the treated joints.

Valentis has formed a separate agreement with the University of Pittsburgh, enabling the school's researchers to perform certain aspects of the collaboration with Ingelheim.

Rheumatoid arthritis affects more than 2 million people in the U.S. and is a disabling disease that causes pain, swelling, stiffness and loss of function in the joints, according to the Arthritis Foundation. Gene medicines may be an advantage over current treatments, Valentis said, because they can be administered less frequently and they have the potential to stop cartilage destruction.

Valentis was formed through the merger of Megabios Corp., of Burlingame, Calif., and GeneMedicine Inc., of The Woodlands, Tex., which was completed in March. The two companies decided to pool their nonviral gene-delivery technologies through a stock swap that gave Megabios 59 percent of the new company and GeneMedicine 41 percent. (See BioWorld Today, Oct. 27, 1998, p. 1.)

Valentis merged with PolyMASC Pharmaceuticals plc, of London, earlier this year in a deal worth $19.8 million in Valentis stock. PolyMASC intrigued Valentis with its Vira-MASC program, which PEGylates viruses used to deliver genes, conserves viral infectivity and offers improved tumor targeting for cancer gene therapeutics. The PolyMASC technology is expected to be applicable to arthritis. (See BioWorld Today, May 26, 1999, p. 1.)

Valentis is working with Glaxo Wellcome plc, of London, on a cystic fibrosis transmembrane regulator gene for the treatment of cystic fibrosis. Glaxo completed a Phase I/II trial.

Valentis also has partnerships with F. Hoffmann-La Roche, of Basel, Switzerland, to develop gene-based immunotherapeutics for cancer, specifically squamous cell carcinoma of the head and neck, based on the interleukin-2 (IL-2), IL-12 and the interferon-alpha (IFNa) genes. IL-2 is in a Phase II trial, while IL-2 plus superantigen B is in a Phase I/II program. IL-12 and IFNa also are in Phase I/II trials. In the fourth quarter this year, Valentis plans on initiating clinical trials of IL-2 plus chemotherapy, McGraw said.

The company also is working with Eli Lilly & Co., of Indianapolis, on a gene-based therapeutic for treating breast and ovarian cancer using the BRCA-1 gene.

Valentis stock (NASDAQ:VLTS) closed Monday at $6.375, up 37.5 cents.