Barely a year old, it didn't take long for Chimerix Inc. to catch the attention of the U.S government in its search for a smallpox therapeutic.

The San Diego-based company received a $36.1 million grant from the National Institutes of Health to continue development of an oral antiviral drug for smallpox infections and complications resulting from vaccinations. The National Institute of Allergy and Infectious Diseases, a unit of the Bethesda, Md.-based NIH, will pay the award over a four-and-a-half-year period.

"We're pleased to have it and get started," Chimerix President and CEO George Painter told BioWorld Today. "It's part of a bioterrorism partnership program, and it's for direct expenses associated with developing an agent."

At the same time, the company also closed on a second round of financing worth $3.1 million. Its founding investors, San Diego-based Sanderling Ventures and San Francisco-based Asset Management, bought the preferred stock. Since its July 2002 founding, Chimerix has raised $5.6 million in venture capital.

With the smallpox development funds, the company initially plans to choose between one of two compounds - CMX-001 and CMX-002. Both have shown promising activity, but further efficacy testing in the next six months is expected to highlight the stronger antiproliferative candidate.

Both are derivatives of cidofovir, marketed in the U.S. as Vistide by Gilead Sciences Inc. Chimerix is applying its platform technology to the intravenously administered AIDS drug to create an effective, orally available option. Developed by Karl Hostetler at the University of California at San Diego, Chimerix's technology conjugates a dietary lipid to a drug to enhance cell permeability and improve efficacy. He founded the firm, which maintains its base on the West Coast and will expand into research facilities in La Jolla, Calif., but also maintains development operations in Research Triangle Park, N.C.

In vitro studies showed that the resulting compounds were 50- to 200-fold more efficacious than the original formulation of cidofovir, said Painter, who before arriving at Chimerix last October served as the executive vice president of research and development at Triangle Pharmaceuticals Inc. Durham, N.C.-based Triangle merged with Foster City, Calif.-based Gilead last year in a transaction valued at $464 million. (See BioWorld Today, Dec. 5, 2002.)

He added that in vivo studies in mice showed the drugs to be 80 percent to 90 percent bioavailable, compared to less than 3 percent bioavailability of cidofovir unless it is infused intravenously. At the same time, the reformulated compounds avoid cidofovir's dose-limiting toxicity in the kidney. Whole-body radiography scans showed that after absorption, CMX-001 and CMX-002 are concentrated in the liver, spleen and lungs - the primary smallpox infection sites, Painter said.

"All the indications are positive to carry a drug forward," he added, noting that the two candidates differ only by the lipid conjugated to them. "The change in lipids causes a change in the way the drug is moved out of the gut to the target organs, and the rate at which it's built up into those organs."

He said that after Chimerix identifies a candidate to move forward, it would conduct additional toxicology studies in mice. The product then would move into efficacy studies in monkey models, evaluations that will fall on the shoulders of the U.S. Army Medical Research Institute for Infectious Diseases. An eventual Phase I study would test a single escalating dose of the compound for safety, tolerability and its pharmacokinetic profile.

The route toward registration could move along at a quicker clip than that of most development programs, as positive monkey data would be sufficient under animal efficacy rules.

"We need to have a meeting with the FDA to get guidance on the drug," Painter said. "And then we'll need to find out what the FDA wants with regard to more safety."

Beyond the smallpox program, Chimerix is working to apply its technology to improve other bioactive molecules and expand their uses. Painter said the nine-employee company would soon expand to 25, with 15 in California and the remainder in North Carolina.

One program is using the lipid technology to create a derivative of foscarnet, an AIDS drug now off patent approved for the same cytomegalovirus retinitis indication as cidofovir, that will combat resistant HIV. Chimerix also plans to apply the technology to treatments for hepatitis C virus and senile macular degeneration.

"As we've begun to gather data that shows that the technology helps drugs that are otherwise not orally bioavailable become bioavailable," Painter said, "and apply it to drugs that are approved but have limitations that can be overcome, it becomes quite attractive."