More than a simple handshake was required to complete a multifaceted agreement between Northwest Biotherapeutics Inc. and Medarex Inc., supplying the former with funding to continue operations for at least a year and positioning the latter for an almost simultaneous agreement with Millennium Pharmaceuticals Inc.

Princeton, N.J.-based Medarex acquired from Northwest therapeutic development and commercialization rights to MDX-070, a fully human antibody to PSMA (prostate specific membrane antigen). Medarex also gained from Northwest rights to two additional cancer-related disease targets, as well as certain patents related to the acquired targets for the development and commercialization of antibody-based products, including fully human anti-PSMA antibodies to potentially treat prostate cancer. Medarex then entered into a royalty-free, worldwide, nonexclusive cross-license agreement with Cambridge, Mass-based Millennium for certain patents relating to antibodies against PSMA.

"I think that PSMA is one of the most exciting targets for cancer therapy that exists right now," Medarex President and CEO Donald Drakeman told BioWorld Today. "We think this is a very exciting opportunity for us to, essentially in one fell swoop, consolidate the product rights and settle out the intellectual property issues."

Drakeman declined to disclose terms of the Millennium deal, which centers on the companies' respective patents involving the same subject matter, but he said Medarex plans to quickly further MDX-070's development.

"We now expect to file an investigational new drug application within the next two weeks and move this rapidly through clinical trials and toward commercialization," Drakeman said. "I think this product, like most new cancer treatments, will enter Phase I/II trials in late-stage patients, but beyond that we'll need to await details."

As part of the Northwest exchange, Medarex will receive 2 million shares of Northwest's common stock at an undisclosed price and warrants to purchase an additional 800,000 shares at market value. Northwest's stock (NASDAQ:NWBT) closed Tuesday at 29 cents, though Wednesday its shares jumped 52.3 percent, or 15 cents, to close at 44 cents. The Bothell, Wash.-based company, which went public a year ago at $5 per share, has cut its staff from 64 to 18 employees in the past six months. Further internal streamlining to reduce the company's burn rate is allowing Northwest to move forward with sufficient funding to continue operations through next year, Northwest President and CEO Daniel Wilds told BioWorld Today.

"We were looking at opportunities through which we could restructure the company and secure enough funding for next year," Wilds said. "So we took a look at our portfolio of technologies, and in that portfolio we had this nice relationship with Medarex."

The deal provides Northwest with $3 million in funding, potential future royalties, and certain diagnostic rights for two of the three cancer-related disease targets being acquired by Medarex, targets previously co-owned by the companies. Northwest also will reacquire all development and commercialization rights to five potential additional cancer-related disease targets, previously granted to Medarex. Included among the targets is CXCR4, a potential antibody, antisense and small-molecule target found in preclinical studies to be overexpressed in multiple cancers and to be involved in the growth and spread of tumors.

"This is an extremely valuable target," Wilds said.

Northwest, which in the past several months has withdrawn a pair of investigational new drug applications for studies of its dendritic cell-based cancer drug in brain and lung cancer and suspended a Phase III trial of its DCVax Prostate, continues to push toward establishing a position in antibody-based diagnostics and therapeutics. Two months ago, upon completing Phase III enrollment, Northwest said it would sell some fixed assets and consider options for the future. (See BioWorld Today, Oct. 11, 2002.)

But Wilds said yesterday's reacquisition of the target rights signaled forward movement for Northwest.

"We'll continue to talk with some strategic partners about their potential commercialization," Wilds said, adding that Northwest also is seeking a partner to take forward development of its DCVax Brain drug to treat glioblastoma multiforme, for which the FDA has approved a Phase II trial. He said the candidate also received orphan drug designation.

In a prior agreement, Medarex and Northwest had agreed to share the therapeutic development and commercialization rights and obligations with respect to MDX-070 and the additional targets.

Drakeman said Medarex would pursue development of MDX-070 on its own, as eight fully human antibodies based on Medarex technology continue in clinical trials.

"Our fully human antibody technology has advanced rapidly, and there are now several products from that technology in Phase II trials as well as a number in Phase I," he said.

The company features an in-house program for its MDX-010 compound, now in Phase II studies to treat prostate cancer and melanoma. An internal Phase I/II program continues for MDX-060 to treat Hodgkin's disease.

Medarex and its partner, GenMab A/S, earlier this week filed in Europe an application to begin a clinical trial of HuMax-Inflam, also known as MDX-018, to treat an undisclosed autoimmune disease.

Two other products being developed in partnership with Copenhagen, Denmark-based GenMab include HuMax-CD4 and HuMax-IL15, both in Phase II trials to treat autoimmune and inflammatory diseases. Medarex also is working in partnership in Phase I programs at Centocor, a unit of New Brunswick, N.J.-based Johnson & Johnson, and at Basel, Switzerland-based Novartis AG.

Medarex's stock (NASDAQ:MEDX) on Wednesday fell 18 cents to close at $4.35, while Millennium's shares (NASDAQ:MLNM) dropped 47 cents to close at $9.44.