Assistant

While it awaits results from a confirmatory trial with hereditary angioedema drug DX-88, Cambridge, Mass.-based Dyax Corp. picked up another partner for its antibody platform, signing Sanofi-Aventis in a potential $500 million deal.

The agreement gives Paris-based Sanofi rights to develop and commercialize DX-2240, a preclinical cancer compound, plus nonexclusive rights to use Dyax's antibody phage display technology to discover and develop additional compounds. Under the terms, Dyax expects to receive at least $25 million this year, and could receive up to $500 million in total up-front and milestone payments upon commercial success of the first five antibody programs, including DX-2240, emerging from the deal. Another five commercial products could follow.

Shares of Dyax (NASDAQ:DYAX) jumped 21 percent on the news Tuesday to close at $4.30, up 74 cents.

The deal "truly validates our technology and truly validates our discovery capability," Dyax Chairman, President and CEO Henry Blair said during a presentation at the BIO CEO conference in New York.

To date, that technology has generated Dyax's internal drug pipeline, which includes more than 10 prospective compounds in early development, and has led to several deals under the company's licensing and funded research program, such as partnerships with the likes of Biogen Idec Inc., Amgen Inc. and ImClone Systems Inc., which has yielded 12 clinical candidates and more than 70 early stage programs.

It also generated DX-2240, a fully human monoclonal antibody that targets the Tie-1 receptor on tumor blood vessels. It's "actually an agonist for Tie-1," Blair said, and though the exact mechanism of action isn't yet known, preclinical data have shown that DX-2240 "significantly inhibits tumor progression in mouse xenograft models" of solid tumors and also appears to inhibit tumor vasculature development.

"It's a very promising drug that we've had excellent results with," particularly in combination with targeted cancer therapies such as Avastin (bevacizumab, Genentech Inc.) and Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp.), Blair added. "That's why we wanted to" partner DX-2240, since a large firm like Sanofi would be better equipped to conduct the more complicated combination therapy trials.

In addition to up-front and milestone fees, the Sanofi agreement entitles Dyax to royalties on any commercial sales of DX-2240 and other antibodies. More importantly, Blair said, the antibody license agreement "also gives us the ability to participate in the compounds that are discovered by Sanofi-Aventis" through co-development and co-promotion options.

"We are truly a company in transition," he said, and the Sanofi agreement "is an indication of that."

Dyax anticipates reaching the market with its first product by the end of this year. DX-88, a recombinant plasma kallikrien inhibitor, previously demonstrated strong efficacy data in a Phase III hereditary angioedema (HAE) trial completed early last year and is in a confirmatory Phase III study under a special protocol assessment with the FDA. Pending positive results, the company expects to file a biologics license application "before midyear," Blair said, "and we are expecting priority review."

DX-88 has orphan designation in the U.S. for HAE, an acute inflammatory condition characterized by episodes of severe swelling affecting the extremities, the gastrointestinal tract and the larynx. At this time, there are no FDA-approved therapies for HAE, though Dyax is one of several companies close to market. Potential competitors include: Lev Pharmaceuticals Inc., which recently got an approvable letter for its C1 inhibitor Cinryze; Jerini AG, which has an April 26 PDUFA date for Icatibant, a synthetic peptidomimetic agent; CSL Behring, which is expected to file for approval this year for its C1 inhibitor Berinert; and Pharming NV, which has a C1 inhibitor derived from the milk of transgenic rabbits that is completing Phase III testing.

Dyax hopes to be able to expand DX-88's use beyond HAE. The company expects to evaluate the compound in idiopathic angioedema and recently completed a Phase I/II study in the prevention of blood loss during on-pump coronary artery bypass graft surgery (CABG). A Phase II study for further development of the drug in on-pump cardiothoracic surgery, including CABG and heart valve replacement or repair, is ongoing.

Much earlier in the pipeline, Dyax has DX-2400, an antibody targeting matrix metalloproteinase 14 (MMP-14), in preclinical development for solid tumors.