By Mary Welch

EPIcyte Pharmaceutical Inc. sees its future in corn seeds and believes that the plants can be used to mass-produce antibodies for therapeutic benefit.

"Our founders - Mich Hein and Andrew Hiatt - were at the Scripps Research Institute and they were intrigued about the abilities of secretory IgA in drug development," said Robert Leach, chief executive officer for the San Diego-based company. "They were interested in the molecule's ability to bind and transport a drug from the inside of the body to the outside. They were working on Plantibodies in the late '80s and, while everyone was looking at the genetic possibilities of plants for crop improvement, they were thinking about applying it to the production of vaccines and antibodies."

When the two scientists left the institute to start EPIcyte in 1996, they focused on developing medical therapies for diseases that affect the mucous membranes. The company has two core technologies, Plantibodies and Transport Molecules, and is working on the treatment and prevention of specific epithelial diseases such as certain cancers, infections and chronic inflammatory conditions.

The research world has been limited in its ability to use antibodies because of cost and time constraints, Leach said. "Today's use of antibodies are produced in low volumes and are targeted for specific disease states such as cancer and organ transplantation. We envision using antibodies for everyday use. Our targets are areas like sexual diseases, and most intriguingly, developing a prevention instead of a cure."

According to EPIcyte, there are at least 78 antibodies in clinical trials and more than 360 in clinical or preclinical development. In addition, the current cost to scale-up the manufacture of antibodies in fermenters can reach $300 million per facility. Standard fermentation methods make about 10 kilograms or less of antibodies a year, EPIcyte said, while it could produce 10,000 kilograms a year.

"In addition, the cost of transgenic animal products of antibodies is complicated by purificant issues as well as consumers having some ethical issues about genetically modifying animals," Leach said. "We have none of those issues. We can turn plants into antibody factories. And we can do it so much cheaper. The payoff is that we can produce them in the $1 to $2 range."

EPIcyte's technology enables antibodies in green plants to be economically produced on an agricultural scale. In fact, Leach said the technology can produce unlimited quantities of pharmaceutical-grade antibodies and related molecules at prices that are 25 to 100 times less expensive than animal culture cells.

Leach said plants have other benefits as well. Plants are the most efficient bioreactors for the production of complex proteins, such as antibodies, and are the only transgenic system capable of producing secretory antibodies that can protect mucous membranes.

Initially, the company used tobacco leaves; now it uses corn seed. "Corn seed is a stable crop and really is a protein storage vehicle."

The company is using its own Plantibodies technology to produce proprietary antibodies and is developing the antibodies using its other core technology, Transport Molecules, to target drugs specifically to epithelial tissues. Now in preclinical development, EPIcyte has an anti-herpes antibody and an anti-sperm antibody to prevent conception.

"We may be talking about a barrier gel or putting it in the condom," Leach said. "Since women like to take control of their destiny, we're probably looking at a barrier gel that could provide protection for maybe a week."

The company also is working on a class of antibodies that can deliver drugs to diseased tissue linings. "About 80 percent of all antibodies desire to go from the inside to the outside to combat disease on the outside," he said. "They are the first line of defense against invasion by foreign microorganisms. Our Transport Molecules take advantage of the natural transport pathway that these antibodies use to travel to the outside."

The company's initial drug under development would be carried using its Transport Molecules, which are linked to an aminoglycoside to combat severe pulmonary infection, specifically cystic fibrosis. The Transport Molecules are produced using plants employing the Plantibody production methods. EPIcyte plans on combining Transport Molecules with already proven drugs, thus increasing dose concentrations and limiting toxicity.

"It's like a freight train, and it turns out it works," he said. "The drug we're using for the cystic fibrosis indication is very toxic but it releases topically so it works."

Both the topical formulations for herpes prevention and birth control as well as the cystic fibrosis drug system should be ready for Phase I development in 2001, Leach said. Helping spur on the development schedule is a recent $5 million round of venture capital that closed earlier this year. That round included four investor groups: TD Javelin Capital Fund, of Birmingham, Ala.; CMEA Life Sciences, of San Francisco; Viridian Capital Partners, of San Francisco; and Dow Chemical Co., of Midland, Mich. To date the company has raised $6 million and expects to receive between $4 million and $8 million in government funding this year. The money should last until the drugs are in Phase II.

"Of course, we are in talks with licensing partners, said Leach. "That will be the next round of announcements."