PharmAthene (www.pharmathene.com), founded in 2001 before 9/11, focused on biodefense from day one, recalls David Wright, president and CEO. At the moment, the company is working to commercialize some of its defense projects. “The idea of dual use emerged when we tried to build a business. It’s not a new model,” Wright says. “There are hundreds of examples of commercial technologies that began as defense projects.”
Protexia®, developed for the U.S. Department of Defense to prevent morbidity and mortality from chemical weapons, also shows promise in protecting against heroin, cocaine, and pesticide exposure and may be useful in the ICU when patients are brought out of sedation. There’s even a potential use in Alzheimer’s treatment, Wright notes.
Likewise, GenPhar (www.genphar.com) is working with the U.S. Army to develop countermeasures against two subtypes of Ebola and three subtypes of Marburg virus. “In tests at 1,000 times the lethal dose, prototypes showed 100 percent protection,” John Dong, M.D., Ph.D., president and CEO, says. The compounds provide broad-spectrum protection by targeting up to eight subtypes of virus simultaneously. Importantly, “the Army tested these compounds at their cost,” he adds.
Flexibility is the key to biodefense work, Dr. Dong explains. Although these compounds have only one potential limited market, the platform is being leveraged to treat hepatitis C, HIV, and pandemic influenza.
Most companies involved in biodefense work, however, focused initially on commercial applications. Chimerix (www.chimerix-inc.com) touts its ProLipTag technology, which was used to develop a broad-spectrum cidofovir mimetic without kidney toxicity to treat smallpox, according to George Painter, Ph.D., president and CEO. The technology was developed to allow known drugs to be modified to improve dosing parameters, broaden therapeutic applications, and decrease the risk of adverse reactions.
ProLipTag can be used for commercial spin-offs to treat viral infections in organ transplants and as a topical application for genital warts. The approach appears to work for herpes, pox, adeno, papilloma, and polynoma viruses, Dr. Painter says, although the mechanism of action isn’t fully elucidated.
Chimerix received a $37.1 million grant from the NIAID, before Bioshield was passed in 2004, that financed the high-risk development period, which allowed the company to raise venture capital later. “It would have been difficult otherwise to raise money for a drug with no commercial market,” Dr. Painter says.
Advanced Life Sciences (ALS; www.advancedlifesciences.com) is another firm banking on dual use. It is developing cethromycin as a treatment for anthrax and other bioagents, but it also effectively treats community-acquired pneumonia and other respiratory tract infections. Animal studies of the drug show 100% protection against lethal doses of inhaled anthrax, according to ALS. The company began working with NIAID this summer to continue evaluating cethromycin against high-priority biodefense agents. Because cethromycin has a dual binding site, it can overcome resistance from many pathogens, explains Patrick Flavin, chief legal counsel.
“We’re not a biodefense company,” Flavin emphasizes. “We’re developing cathromycin for respiratory tract infections, and we’re working with the government to leverage safety and efficacy data to develop other applications.” The benefit, he says, is in the development funds provided by the government, which let the company conserve money for commercial development programs.
U.S. government work isn’t confined to U.S. companies. British firm deltaDOT (www.deltadot.com) is working with a U.S. consortium in a DARPA-funded project to accelerate vaccine production. The benefit for deltaDOT is twofold. It gains funds to advance its Peregrine HPCE and Osprey protein stability-technology platforms and also gains visibility, according to Richard Lingard, vp of sales.
The Peregrine HPCE analysis system is used for on-site bioreactor monitoring, product purification, and final product optimization, replacing a process that typically took two days with one that delivers accurate results in about 20 minutes, according to the company. Importantly, Peregrine uses label-free intrinsic imaging, so unlabeled proteins can be monitored directly, in real time, and cost effectively, Lingard notes.
Headquartered in Brisbane, Australia, with a second office in Seattle, Implicit Bioscience (www.implicitbioscience.com) is tapping into biodefense money as a virtual company. It’s in late-stage development work with a broad-spectrum immunologic that regulates the host response factor.
“Biodefense isn’t a field for a fully integrated company,” according to Garry Redlich, Implicit’s CEO, explaining the reason for this virtual business model. “Only a handful of labs have the capability to work with high-level threat agents,” so Implicit works with those labs around the world using project-based management methodology. “All of us work on various projects, depending upon expertise,” he explains.
“The government is coming with eyes wide open to see the benefit of working with agents with dual uses,” Redlich says, “and we get work done that otherwise would be paid for by shareholders.” The benefits at the company are seen in toxicology, method of action, delivery options, and pharmacokinetics.