Using technology licensed from the U.S. Centers for Disease Control and Prevention, Inviragen LLC is advancing preclinical programs for dengue fever, West Nile virus, smallpox, plague and avian influenza.

Biotech executive Dan Stinchcomb co-founded Inviragen in 2003 with University of Wisconsin vaccine researcher Jorge Osorio. The two put up their own money to seed virtual operations until 2005, when they learned about a dengue vaccine in development at the CDC. The vaccine had generated good preclinical data and was "essentially sitting on the shelf . . . waiting for someone to take it into clinical trials," Stinchcomb said.

So Inviragen prepared to do just that, obtaining an exclusive license to the technology in 2006.

The CDC's dengue vaccine was based on an attenuated DEN-2 virus backbone that had been well-tolerated and generated immune responses in Phase I trials. But dengue fever can be caused by any one of four possible virus strains, so the CDC researchers modified their DEN-2 backbone to create vaccines against DEN-1, DEN-3 and DEN-4. Inviragen then combined the DEN-2 parent vaccine with all three chimeras to create a tetravalent vaccine.

In preclinical studies, the tetravalent vaccine generated neutralizing antibody responses to all four dengue serotypes in both mice and non-human primates. Stinchcomb said the vaccine should enter clinical trials in the second half of 2008.

Inviragen also used the DEN-2 backbone to engineer a vaccine against West Nile virus, and Stinchcomb said the approach potentially could be applied to create vaccines against other flaviviruses such as Japanese encephalitis and tick-borne encephalitis. The West Nile vaccine has generated antibody responses in mice and is slated to begin non-human primate studies next year.

Earlier in its pipeline, Inviragen is working on an attenuated vaccinia virus backbone for plague, smallpox and avian influenza vaccines. The company expects to identify lead candidates in those programs in 2008.

Thus far, Inviragen's funding has come predominantly from grants. Earlier this month, the Fort Collins, Colo.-based company announced that it received an undisclosed amount of funding from the Pediatric Dengue Vaccine Initiative for manufacturing of its dengue vaccine as well as a two-year, $600,000 Small Business Technology Transfer award from the National Institutes of Health for its avian flu program. Last year, Inviragen received a four-year, $2.8 million NIH grant for its dengue program, and it previously received other government grants as well as a small amount of seed funding from individual investors.

Stinchcomb said the funding raised thus far totals about $4.4 million and the company is hoping to raise $6 million in a Series A round by the end of the year.

To make its money last as long as possible, Inviragen plans to conduct clinical work in developing countries. It also has contracted manufacturing to Shantha Biotechnics, of Hyderabad, India.

Still, Stinchcomb told BioWorld Today, he sees a significant market opportunity for the dengue vaccine - one that could top $1 billion. In addition to the military market and traveler's market, Stinchcomb said developing countries present a "tremendous growth opportunity," both through public health programs and through a private market driven by an emerging middle class.

That market has attracted increasing biotech and pharma interest in public health vaccines. In the dengue field, GlaxoSmithKline plc has an attenuated tetravalent vaccine in Phase II, and earlier-stage programs are in the works at AVI BioPharma Inc., Immunotope Inc., Bavarian Nordic and others. In West Nile, Acambis plc signed an $80 million deal with Sanofi Pasteur earlier this month for a Phase II vaccine, and other clinical contenders include Vical Inc., Crucell NV and Hemispherx Biopharma Inc. (See BioWorld Today, Nov. 14, 2007.)

Stinchcomb said Inviragen's dengue backbone is its main differentiator and may prove to have better safety and efficacy in clinical trials. He also noted that the company is interested in potential partnerships with other vaccine developers.