With the recent signing of two deals collectively worth up to more than $1 billion, Medarex Inc. has turned its attention to a collaboration agreement with MedImmune Inc. to develop two antibodies to treat autoimmune diseases.

The antibodies - MDX-1103 and MDX-1333 - are believed to target areas that might be involved with systemic lupus erythematosus disease activity. The products are in preclinical development, but the companies expect to file investigational new drug applications with the FDA within the next 18 months.

Medarex will receive a $15 million up-front payment, and MedImmune is responsible for the continued development of the two candidates.

"It allows us to accelerate the development of attractive products with a highly experienced antibody company," said Donald Drakeman, Medarex's president and CEO, "and to be able to participate in the commercialization of those products in the future."

The agreement gives Princeton, N.J.-based Medarex the option of co-developing the products once they reach the starting point for pivotal trials. In return, Medarex would receive co-promotion rights in the U.S. and a profit-sharing arrangement if the products reach the market. If Medarex chooses not to co-develop the products, it would be entitled to receive milestone payments and royalties.

Clarencia Stephen, MedImmune's public relations manager, said Medarex's antibodies fit in nicely with her company's focus.

"The collaboration helps bolster MedImmune's core immunology and antibody programs," Stephen told BioWorld Today. "And we believe they can potentially address a large unmet medical need for safe and effective treatments for lupus."

Drakeman said specific financial details, regarding each company's share of profits, are undisclosed. He classified the royalties for Medarex as "substantial."

In preclinical studies, MDX-1103 has been shown to bind to multiple interferon-alpha subtypes, while MDX-1333 has been shown to block the Type I interferon receptor 1.

"The interferon-alpha pathway has been very strongly associated with lupus," Drakeman said. "These two antibodies interrupt that pathway in different ways, one by blocking the receptor and the other by binding to interferon-alpha itself."

Since interferon-alpha attaching to the receptor seems to be the pathway, Drakeman said that if the compounds "can interrupt that association, then we can have a good therapeutic effect," in lupus.

The deal with Gaithersburg, Md.-based MedImmune follows two very large agreements completed by Medarex in recent months.

Earlier this month, Medarex signed a potential $530 million deal to partner its Phase III metastatic melanoma product, MDX-010, with New York-based Bristol-Myers Squibb Co. The companies also are investigating the product in additional tumor types, and the collaboration includes an investigational gp100 peptide vaccine, MDX-1379, which will be developed for use in combination with MDX-010 in melanoma. Under the agreement, Medarex received $50 million up front, and could receive the rest upon the achievement of regulatory and sales-related milestones. It could potentially share in 45 percent of U.S. profits. (See BioWorld Today, Nov. 9, 2004.)

Less than two months earlier, Medarex entered its first large collaboration, worth a potential $510 million, with New York-based Pfizer Inc. for the discovery and development of up to 50 antibody products over 10 years. Medarex plans to use its UltiMAb human antibody technology to create the products against Pfizer's disease-associated targets. Pfizer made an initial $80 million cash payment to Medarex and purchased $30 million in Medarex stock. (See BioWorld Today, Sept. 21, 2004.)

Drakeman said Medarex has more than 50 partnering agreements that have helped the company gain attention.

"We are very much in the flow of traffic in the pharmaceutical and biotechnology industries," he said, "and, because we know the companies and the key individuals, we've been able to nurture relationships that have led to these partnerships."

Medarex's UltiMAb technology generates a range of fully human antibody products for the company and its partners. A total of 20 such products are in clinical trials, with the most advanced, MDX-010, in Phase III testing with MDX-1379 for melanoma. In August, the company agreed with the FDA on a special protocol assessment for that trial. It should complete in the first half of 2006.

Aside from focusing on lupus candidates with Medarex, MedImmune began recruiting patients a few weeks ago in a pivotal Phase III study of Numax for respiratory syncytial virus (RSV) in high-risk infants. The study is comparing the drug's safety and efficacy with Synagis, MedImmune's RSV product approved in 1998. The company also completed enrollment of 8,500 children in a pivotal trial comparing the cold-adapted intranasal influenza vaccine, trivalent (CAIV-T), with the injected product as a potential advance in FluMist. (See BioWorld Today, Oct. 22, 2004, and Nov. 2, 2004.)

Medarex's stock (NASDAQ:MEDX) closed at $10.32 Tuesday, unchanged, while MedImmune's stock (NASDAQ:MEDI) lost 44 cents and closed at $26.45.