XOMA Ltd. halted development of its Phase I heart drug, causing the company to lose 40 percent of a potential equity investment from partner Millennium Pharmaceuticals Inc.

The company stopped development of its humanized monoclonal antibody known as MLN2201 following results from a Phase I trial. The compound was in development for conditions related to inflammation of the heart and blood vessels. Phase I results showed the compound did not meet predetermined criteria for safety, tolerability, pharmacokinetics and pharmacodynamics.

"We have really stringent guidelines when evaluating products," said Laura Zobkiw, manager of corporate communications and investor relations at Berkeley, Calif.-based XOMA. "You want to make sure you're putting all of your resources and time on products that have the best chance of getting to market.

"That is our goal - if something's not going well to our satisfaction, that we make the decision to end things quickly," she told BioWorld Today.

XOMA formed the collaboration with Cambridge, Mass.-based Millennium in November 2001 to focus on two products for certain vascular inflammation indications: MLN2201 and CAB-2, a recombinant protein that inhibits complement activation. XOMA was to be responsible for development activities and related costs for both products through Phase II trials. Then, Millennium had the right to further develop and commercialize the products. XOMA had the option to participate in the development program and profit sharing, or, if it chose, to be entitled to royalty and milestone payments. (See BioWorld Today, Nov. 27, 2001.)

As part of the original collaboration, Millennium had an obligation to purchase up to $33.5 million worth of common stock at XOMA's option. With the termination of MLN2201's development, that obligation has been reduced to $20.1 million worth of common stock - a 40 percent reduction.

XOMA initiated the Phase I trial of MLN2201 in June. MLN2201 is directed toward the beta-2 subunit of integrins found on the surface of leukocytes.

"There are no plans, as far as both companies are concerned to date, to study that product in any additional indications," Zobkiw said. The decision to terminate development was jointly made by representatives of both companies.

"With the termination of this product, CAB-2 now is the sole focus of that collaboration," she added. And although CAB-2 is in preclinical development, "It is one of our goals through the year to get that in the clinic as quickly as possible," she said.

XOMA also is working on earlier-stage programs focused on antibodies and other compounds developed to treat acne, cancer and retinopathies.

Within the last few weeks, the company released news that it had initiated a Phase I/II trial with Children's Medical Center Dallas to study Neuprex in pediatric patients with congenital heart abnormalities requiring open-heart surgery associated with cardiopulmonary bypass. Neuprex is an injectable form of a modified recombinant fragment of bactericidal/permeability-increasing (BPI) protein. The company also initiated a Phase I trial at the end of September of XMP.629 as a topical treatment for acne. XMP.629 is a synthetic peptide compound derived from BPI protein.

"That is one of our more promising products," Zobkiw said, explaining that some of the resources saved from dropping MLN2201 will go toward XMP.629, as well as Neuprex.

In the nearer term, XOMA might soon see the fruits of its labor with Raptiva. Last month, an FDA panel voted in favor of approval of the antibody, which was co-developed by Genentech Inc., of South San Francisco, to treat moderate to severe plaque psoriasis in adults. An analyst estimated U.S. sales could reach $178 million by 2008. XOMA is entitled to 25 percent of U.S. revenues, with Genentech receiving the rest. (See BioWorld Today, Sept. 10, 2003.)

A Millennium spokesperson could not be reached for comment. The company's shares (NASDAQ:MLNM) rose 13 cents Friday to close at $17.33. XOMA's shares (NASDAQ:XOMA) dropped 10 cents to close at $8.05.