Zapaq Inc. was the first company to receive seed money to develop drugs for Alzheimer's disease from the Institute for the Study of Aging under the institute's Founders Program.

Zapaq is a start-up company that initially is focusing on developing drugs for Alzheimer's disease based on inhibiting an enzyme involved in the production of beta-amyloid, a protein that is considered a key factor in Alzheimer's.

"The company received its first financing in January," Zapaq President and CEO James Jenson said. "That's when we really got going."

While the New York-based institute awarded Zapaq $500,000, the remainder of the total $1.1 million in seed money came from the Oklahoma Life Sciences Fund, Jenson said. Jenson worked previously at F. Hoffmann-La Roche Ltd., of Basel, Switzerland, and Triton Biosciences Inc., where he was chairman of the scientific advisory board, among other companies. Jenson divides his time between Oklahoma and Waltham, Mass., where the company's business office and clinical team are located.

Zapaq was incorporated in June 2001 and signed the key technology licenses from the Oklahoma Medical Research Foundation and the University of Illinois in November. Zapaq's research and development activities will be located in Oklahoma City. It also will be home base for Jordan Tang, a scientific co-founder of Zapaq and the person who has played a role in the molecular structure of aspartic proteases.

Tang also pioneered a drug design element, the transition state analogue, that is in all marketed HIV-protease drugs used in AIDS treatment today, the institute said.

The second scientific co-founder is Arun Ghosh, who Jenson said is a leading synthetic, organic and medicinal chemist, and a professor of chemistry at the University of Illinois. Ghosh received his training at Harvard and worked at Merck & Co., of Whitehouse Station, N.J., for six years, Jenson said.

"It's really the power of those two guys that make us the best at what we do," Jenson said, adding that many companies now are pursuing the avenue of targeting the enzyme involved in the production of beta-amyloid.

"It's a very hot target right now," he said. "Alzheimer's disease is becoming one of the better-understood diseases at the molecular level. At the moment, this target is at or near the top of the wish list, so as you can imagine, there are many pharmaceutical companies working on this."

The competitive environment also has required Zapaq to get on the fast track. Jenson said the company is nearing the end of an effort to raise $14 million.

"It's a jump-start for a start-up in a couple of ways," Jenson said. "We have very aggressive objectives with this $14 million. We will have a clinical candidate for Alzheimer's disease in year one, and an investigational new drug filing, and we'll be in the clinic by year two."

The Series A round will allow about half of the expected staff to come on board full time, which will include about a dozen people from both Oklahoma and the University of Illinois.

Jenson said that there are a couple of reasons why he thinks his company is in the lead.

Aspartic proteases, he explained, which are widely distributed in nature, are very difficult to find hits or leads for with high-throughput screening, at least in the experience of developing HIV aspartic proteases.

"Five on the market were designed, not screened for," he said. "So what you have to do is structure-based drug design, and that's where a small company like ours comes in to play."

For example, a company needs to be able to manufacture the protein as a drug target in large quantities to use as a drug discovery tool. It also needs to be able to develop crystal structures of it bound to inhibitors, and it needs to do this iteratively to evaluate new synthetic inhibitors. Then, a company needs to know how to make the new inhibitor in synthetic chemistry.

"You want to step your way into an optimal drug through iterative co-crystallization," Jenson said. "If you do not succeed in any of those four steps, you fail."

Alzheimer's disease isn't Zapaq's only focus.

"Our second target will likely be in infectious disease," Jenson said.