Assistant

A month after Crucell NV reported positive data from a Phase Ib trial of its monoclonal antibody cocktail in rabies, the Dutch firm landed a potential $113 million deal with vaccine maker Sanofi Pasteur.

The exclusive agreement calls for Crucell's rabies monoclonal antibodies as next-generation rabies biologicals to be used in conjunction with Sanofi's rabies vaccine to prevent viral infection in people exposed to rabies.

Crucell will receive €10 million (US$14.8 million) up front and could get milestones of up to €66.5 million down the road. The firm also will be entitled to an undisclosed royalty percentage on sales of the final product by Sanofi.

News of the deal pushed shares of Crucell (NASDAQ:CRXL) up $2.03, or 12 percent, Thursday to close at $18.74.

For its part, Crucell, of Leiden, the Netherlands, will continue handling the development and manufacturing activities and retains exclusive distribution rights in Europe and co-exclusive distribution rights in China, as well as rights to sell its antibody products to supranational organizations such as UNICEF.

Crucell executives could not be reached for further comment, but so far, the company's antibody cocktail, which consists of two human monoclonal antibodies against rabies, has performed well in early studies, showing in Phase I testing that the product is well tolerated and provides immediate passive neutralizing activity.

Most importantly, data indicated that the antibodies can be given safely in combination with a rabies vaccine without interfering with the vaccine's efficacy, which means that, pending further successful development and marketing approval, Crucell's antibodies could come to replace rabies immunoglobulin (RIG), the current antibody product that is administered with rabies vaccines.

Paris-based Sanofi, which has been the market leader for postexposure prophylaxis treatments against rabies, already offers a rabies vaccine, along with the combined administration of RIG, a treatment that has long been proven 100 percent effective in preventing viral infection in postexposure patients prior to becoming symptomatic.

Both the vaccine and RIG must be given to prevent viral infection, but there's a downside to using RIG (or equine rabies immunoglobulin). Not only does it originate from nonhuman (or equine) serum, which adds certain safety concerns, but RIG also is in short supply. Patients exposed to rabies, most often through the bite of a rabid animal, must get treatment prior to becoming symptomatic. After that point, the infection becomes fatal.

An estimated 40,000 to 70,000 people die of the disease every year, primarily in Asia, where RIG frequently is hard to come by and the prevalence of rabies is high.

Crucell's antibodies are in development as an alternative to RIG. They were generated using its MAbstract technology and can be manufactured readily under serum-free conditions using the firm's PER.C6 technology. The antibody cocktail already gained fast-track designation from the FDA, and the company is gearing up to start Phase II testing in the first half of this year.

Upon approval, Crucell has projected peak sales of the rabies antibody cocktail to exceed $300 million.

In addition to RIG, the product would compete with HyperRAB S/D, a hyperimmune antibody preparation marketed by Research Triangle Park, N.C.-based Talecris Biotherapeutics Holdings Corp. Other companies developing products for rabies include NanoViricides Inc., of West Haven, Conn., which is developing a nanoviricide, a drug candidate designed to attack enveloped virus particles and dismantle them, which has shown promising results in animal studies.

Crucell currently markets seven vaccine products, and though the majority of its pipeline consists of vaccine candidates - aimed at diseases such as yellow fever, malaria, tuberculosis and pandemic flu - it also has branched out into the field of antibodies. In addition to its rabies cocktail, the firm has an antibacterial antibody program in preclinical development.