PaxVax Corp. is gearing up for Phase III trials with PXVX-0200, a fast-acting cholera vaccine designed to target both developing countries and the more lucrative travelers' market – exemplifying PaxVax's "double bottom-line" mission, according to the firm's executive vice president and chief operating officer, Nima Farzan.

Existing cholera vaccines are inactivated and require two doses that must be given several weeks apart. PXVX-0200 is a live-attenuated vaccine that requires just one dose, which would be more convenient for travelers preparing to set off for a cholera-endemic area, particularly those needing to travel on short notice. A single dose vaccine also would be more efficient for aid workers trying to ensure that people in developing nations get protection from Vibrio cholerae bacteria, which cause severe diarrhea leading to an estimated 100,000 to 130,000 deaths per year.

The areas in which cholera is endemic often lack the infrastructure and logistics to track patients and make sure they receive both doses of the vaccine, Farzan explained. Further complicating matters, cholera results from ingesting contaminated water or food, so outbreaks often occur in the wake of natural disasters like hurricanes or earthquakes – making follow-up even more challenging.

The FDA accepted PaxVax's investigational new drug application for PXVX-0200, and the biotech plans to start Phase III trials by the end of the year. The vaccine is able to jump into late-stage development because it was previously marketed in a few countries by Berna Biotech AG, which was acquired by Crucell NV (now Johnson & Johnson). Crucell had its own cholera program and removed Berna's product from the market, returning the rights to the University of Maryland. PaxVax was then able to license those rights. (See BioWorld Today, Dec. 7, 2005.)

PXVX-0200 "fit into the mission and values of the company," Farzan said, justifying the asset's acquisition. But the rest of PaxVax's pipeline is based on its adenoviral platform for the creation of low-cost, oral vaccines. The lead program to arise from that platform is an H5N1 vaccine slated to start Phase II trials this year. PaxVax also has anthrax and HIV vaccines heading into Phase I trials this year, as well as rabies and dengue vaccines in preclinical development.

Farzan said PaxVax's adenoviral platform is based on an adenovirus vaccine the military has administered to 10 million recruits over the past 30 years. "We've piggybacked onto this existing vaccine," he explained, but PaxVax developed a proprietary technology allowing it to insert viral proteins targeting various infectious agents. "We can insert any protein we want," Farzan said.

And PaxVax has another trick up its sleeve. The biotech developed an inexpensive, high-yield manufacturing process and has its own GMP manufacturing facility in San Diego. Yet Farzan, who joined PaxVax from the vaccines arm of Novartis AG, said bulk manufacturing for most vaccines is not expensive – it's the formulation, fill and finish process that loads the bulk product into syringes that adds to the cost. Since PaxVax's vaccines are oral, their formulation, fill and finish process involves simple spray-drying and pressing tablets, traditional pharmaceutical technologies that cost just pennies a pill.

The downside of using an adenoviral vector is that the approach has been associated with safety concerns, particularly in the gene therapy field. But Farzan pointed to the vaccine's 30-year history as evidence of its safety. Additionally, there are concerns that vector immunity could make patients who receive one vaccine using the platform less responsive to subsequent vaccines using the same platform, but Farzan said data indicated PaxVax's technology can overcome that issue.

With PXVX-0200 for cholera, PaxVax intends to launch the product first in the U.S. and Europe for the traveler's market, which – while not a blockbuster opportunity – Farzan said should be profitable. The company then hopes to provide the vaccine at-cost to the "GAVI-57," i.e. the 57 countries eligible for support from the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunizations).

PaxVax plans to follow a similar business model with several of its products. Since its founding in 2007 by venture capitalist and serial entrepreneur Kenneth Kelley, PaxVax has been what Farzan referred to as a "double bottom-line company" – one concerned with making money but also with social responsibility. The line between those two goals is not always easy to walk. "There are not a lot of great models to follow," Farzan said, but "we're finding our own way."

The Menlo Park, Calif.-based biotech is unsure how to retain its mission in the face of an eventual future exit – Farzan noted that California is supportive of "flexible-purpose" public companies, while the right big pharma acquirer might also retain PaxVax's policy of forgoing profits in the developing world.

And being a socially responsible firm has its benefits, including access to socially responsible investors. PaxVax has thus far raised $10 million in equity from Ignition Partners, Sterling Stamos and friends and family, as well as $35 million in convertible debt from Ignition and the Wellcome Trust. The biotech also has a $25 million government grant for its anthrax program and is subcontracting on a $5 million HIV grant. It also has a small grant from the Gates Foundation for a polio program.

By the summer, Farzan expects PaxVax to have closed another round of financing, although whether that takes the form of a more traditional venture round, a partnership investment or more money from impact investors such as socially responsible funds remains to be seen.