West Coast Editor

On the same day it disclosed - after trading hours - the second failure of ABX-IL8, a monoclonal antibody that blocks interleukin-8, Abgenix Inc. chalked up another transgenic mouse deal, this one with Corvas International Inc.

The bad news for Fremont, Calif.-based Abgenix: ABX-IL8 failed in a Phase IIb psoriasis trial to meet its primary endpoint of improvement in PASI scores. In January, the same drug failed to meet its primary endpoints in a Phase IIa study in rheumatoid arthritis. (See BioWorld Today, Jan. 7, 2002.)

Development of the drug will not go forward in RA, psoriasis or anything else, Abgenix said. The planned study in melanoma has been scrapped, and an ongoing Phase IIa study in chronic obstructive pulmonary disease will end.

The company did not return phone calls throughout the day.

The good news: In the Corvas deal, disclosed early, Abgenix will use its revenue-generating transgenic mouse and screening technologies for discovery and development of fully human monoclonal antibodies against a pair of selected antigens from Corvas' lineup of membrane-bound serine proteases.

Specifically, the companies are going after serine proteases associated with the growth and progression of solid tumors - and San Diego-based Corvas, at least, was feeling like a winner Tuesday.

"It's a brand new target area," said George Vlasuk, vice president of research and development and chief scientific officer for Corvas.

"This is a different type of strategy, since these are functional proteins, enzymes - they're not receptors," Vlasuk told BioWorld Today. "Most antigens that have been worked on by Abgenix and others have been receptor antigens. We have a little more stringent requirement on the screening assay."

The terms call for Abgenix, of Fremont, Calif., to use its XenoMouse and/or XenoMax (which uses microplate-based assays to quickly scan the immune repertoire of an immunized XenoMouse) for generating and selecting antibodies against the targets provided by Corvas.

Next, the companies will study the candidates in vitro and in vivo, retaining rights to co-develop and commercialize or, if they choose, to develop and commercialize on their own whatever antibody products are discovered. If they elect to work together on the products, costs and profits would be shared equally.

Abgenix and Corvas may expand the deal to a multi-antigen collaboration that would include additional serine protease antigens owned by Corvas or licensed to the company.

Vlasuk acknowledged that the investor question about such deals has to do with how far away the companies might be from a drug.

"That depends on how you define a drug," he said. "It's still in a mouse somewhere [right now]. Usually this kind of collaboration is at least a year and a half to two years away from entering the clinic."

Corvas has another deal with Dyax Corp., of Cambridge, Mass., disclosed last fall. It also focuses on serine protease inhibitors for cancer, using phage display technology provided by Dyax, which also Tuesday signed a deal with London-based AstraZeneca plc (see story in this issue).

With Abgenix, Vlasuk noted, Corvas has the option to expand the deal to other targets. "We haven't talked about that with Dyax," he said, although Corvas considers Dyax and Abgenix its two main collaborations at this point.

Memorably bad news came out of another deal last month, when Corvas' stock tumbled 47.3 percent on news that partner Pfizer Inc., of New York, disclosed that preliminary analysis of a Phase IIb study of UK-279,276, a neutrophil inhibitory factor, in ischemic stroke showed that it failed to meet its primary endpoints and therefore did not support a Phase III trial. Corvas' stock (NASDAQ:CVAS) ended that day at $3.15. (See BioWorld Today, April 25, 2002.)

"We won't know what [Pfizer's] plans are for the drug until mid-year," Vlasuk said. Corvas is scheduled to begin a Phase IIb trial of its anticoagulant, rNAPc2, in acute coronary syndrome in the second half of this year, while keeping its main focus on cancer.

"We think we have a leading position in this area, and we're trying to expand our options," Vlasuk said, adding that the company has a small-molecule program in-house. "We've got lead molecules and we've put them into animals," he said. "Right now we're focused on cancer, but this family of proteases anchored to the cell's surface is probably involved in other diseases as well."

Regarding the failure of Abgenix's ABX-IL8, the company said in a late-day press release that it "does not expect to receive revenue from an ABX-IL8 commercial collaboration this year and is now less likely to achieve its previously announced revenue target for 2002, although alternative sources of revenue are being explored."

The double-blind, placebo-controlled Phase IIb study randomized 256 patients to placebo, 200 mg or 300 mg of ABX-IL8 at 32 sites in the U.S. Patients were assessed at each visit and observed for up to 24 weeks after the last dose. The study's primary endpoint was the proportion of patients achieving greater than or equal to 75 percent improvement in their Psoriasis Area Severity Index scores at week 15 compared to baseline. Results showed that 3 percent of placebo-treated patients experienced greater than 75 percent PASI score improvement, compared with 2 percent of patients treated with 200 mg ABX-IL8 and 6 percent of patients treated with 300 mg.

The guidance remains the same, however, Abgenix said, for an operating loss (before depreciation and amortization of intangibles) of $105 million to $120 million, achieved by reducing expenses through stoppage of the ABX-IL8 trials and, possibly, reducing staff.

Corvas' stock (NASDAQ:CVAS) closed Tuesday at $2.54, up 4 cents. Abgenix's shares (NASDAQ:ABGX), unaffected by the late-breaking news, ended the day at $15.11, up $1.36.