Cultivating Cures: Biotech Industry Turns to Plant-Bred Drugs

Source from:  San Mateo County (CA) Times by Nicholas Yulico 04/26/2004

ROWS OF GENETICALLY altered tobacco plants fill a Hayward greenhouse, but they're not intended for cigarettes or cigars. Instead, they carry human antibodies that may one day help ward off tooth decay and the common cold., BUSINESS WR The plants are being developed by Planet Biotechnology of Hayward, one of a new breed of biotech companies that are taking a green approach to developing new drugs. If successful, they could lead to faster and less costly production of antibodies and proteins to treat anything from tooth decay to cancer, and give what many consider a deadly weed a new role in helping save lives. While several companies are using genetically modified food such as rice and corn to create drugs, Planet Biotechnology and others have found tobacco to be the best crop to grow plant-produced drugs, largely because it's not a food product. Nobody has gotten a plant-produced drug on the market yet, but several are making their way through clinical trials, which means a plant-made drug could be on the market in the next two to three years, experts say. "There is a lot of stuff in development and all the signals we've seen so far have been very positive," said Val Giddings, vice president of food and agriculture at the Biotechnology Industry Organization, or BIO. Antibodies and other proteins are produced in limited, sometimes insufficient, quantities by the human immune system. To make them in large quantities involves using the cells of animals or plants. Today, antibody and protein-based treatments are produced by the likes of local leaders Genentech of South San Francisco and Emeryville-based Chiron using animal hosts. But the benefits of using plants -- lower costs and greater quantities of the resulting drugs -- have prompted companies like Planet Biotechnology and Large Scale Biology of Vacaville to pursue the leafy course. A major benefit of using plants is that they radically reduce the cost of production of drugs. They also eliminate the need to use transgenic animals, a process that animal rights groups have protested. Genentech produces its drugs, including its popular cancer-fighting Herceptin, using genetically engineered Chinese hamster cells that are replicated in giant stainless-steel fermenting tanks at the company's Vacaville facility, which cost $250 million to build. To handle additional demand for drugs, Genentech recently broke ground on an expansion, set to open in 2009, which will cost $600 million. In a plant-based process, the DNA of plants cells is altered to enable them to produce therapeutic proteins, and the plants themselves become the factories for creating drugs. To get the drugs extracted from the plants and eventually purified is an additional, costly step. If companies turned to a plant-based system, a doubling in demand for a drug could simply mean doubling a crop, which costs substantially less than building a new manufacturing facility, Giddings said. Giddings didn't name names, but did say that "it is true that a number of companies are very interested in plant-based production." Officials at Genentech would not comment on whether the biotech pioneer is looking at the option. However, major pharmaceutical companies still need to see more proof that a plant-based system works on a large scale before they take the risk of investing in such a process, said Roger Wyse, a managing director at Burrill & Co, a San Francisco-based merchant bank and venture capital firm that invests broadly in life science companies. Planet Biotechnology's two lead products are antibodies that fight tooth decay and the common cold -- two of the most widespread infections in humans. Both drugs have yet to be approved by the U.S. Food and Drug Administration, but "CaroRX" -- the tooth-decay fighter -- has received European approval and could launch in 2005, said Elliott Fineman, chief executive officer of Planet Biotechnology. The private company uses plants because the antibodies that fight the common cold and tooth decay cannot be produced in the cells of mammals, Fineman said. Planet Biotechnology and other companies say they chose tobacco -- rather than corn, rice or other plants used in the process -- because a lot is known about its genetics. Plus, it is not a food product. "We felt that could be a plus in that there is some concern about the integrity of food production and the impact of genetic modification of crops," Fineman said. That controversy came to the forefront in early April when the U.S. Department of Agriculture denied Sacramento-based Ventria Bioscience's request to plant a genetically modified rice crop containing two human proteins that fight infections in infants. The company would have been the first to plant such a crop in California. Opponents, which include environmental groups and rice growers, maintained that the move would have endangered the food supply. "Anybody growing (genetically modified) corn or rice should be a little worried right now," said Daniel Tus, vice president of business development at Large Scale Biology, a Vacaville-based company that is also using tobacco to make drugs. U.S. clinical trials for Planet Biotechnology's CaroRX are currently under way at the University of California, San Francisco School of Dentistry. "RhinoRX," the company's antibody that aims to prevent the common cold (rhinovirus), will begin clinical trials by the end of the year at the University of Virginia. Sales of CaroRX are expected to total anywhere from $250 million to $2 billion annually in each of the U.S. and European markets, Fineman said. The product could be the first plant-made drug to hit the market. "If the Planet folks are saying they can perhaps get out there in 2005, that's to my knowledge the quickest thing going out there," Tus said. Founded 10 years ago, Planet Biotechnology began its antibody research in 1997. The company hopes to raise an additional $8 million in financing this year, which will help fund the commercialization of CaroRX and add more employees to manage the expansion of the company. Thus far, operations have been funded through $750,000 in venture capital money in 1999, $5 million in small business innovative research grants, and stock options and equity invested by employees and founders of the company. "What the future of the company will be, whether it's a public company or remains private, will depend on the nature of the financing that we get and what is the nature of the return investors are looking for," Fineman said. At Planet Biotechnology's Hayward facility, which consists of lab space and a greenhouse in back, the production of antibodies begins with the cutting of a tobacco leaf into small sections. Genes from a human antibody are introduced into the sections. Eventually, genetically altered plants are formed, which produce seeds that can further propagate other plants, which are chopped up and turned into juice, from which the antibodies are extracted and purified. Fineman estimates that using his company's plant-based system would cost $25 million to $40 million to produce 100 kilograms of drugs. The same amount of drugs produced in Genentech's fermenting tanks costs "ten times that," Fineman said. But even if the production costs are reduced it does not necessarily mean that consumers would end up paying less money for plant-made drugs, because research and development expenses for drugs are so high. "The bottom line is that usually the cost of manufacturing a drug is the smallest component of the cost of developing a drug," said Wyse of Burrill & Co. Bringing a drug to the market typically runs around $800 million, and the manufacturing cost represents from 10 to 20 percent, with purification costs totaling 50 percent of that, Wyse said. In the end, using plants might cut the production cost in half, but that still remains a small portion of the total cost, he added. As Wyse puts it, even if the manufacturing cost of a drug were zero, drugs would still be very expensive for consumers. However, using a plant-based manufacturing system does have other benefits, as many proponents attest to. It allows companies to create large volumes of drugs in markets where the margins are not high, such as herpes treatments or vaccines for diseases in Third World countries, the theory goes. The system also may provide a cheaper way for companies to move drugs through clinical trials, which would help lower development costs. Wyse pointed to one company that spent $100 million on a fermenting facility to produce a drug that later failed in Phase III trials. "They spent $120 million for nothing," Wyse said. By spending less on initial capital costs, plant-based drugmakers can focus on drugs that have widespread uses and lesser costs, proponents say. But could Genentech produce its drugs in a plant-based system? "In theory, any protein you can make in a fermenter, like Genentech (does), could be made in plants," said Tus of Large Scale Biology. But there is a caveat, he added. "In some cases, proteins for pharmaceuticals contain certain types of sugars, and plant sugars can be a little different from animal sugars," Tus said. That could lead to a different immune system response in humans, he explained. Several experts agreed with Tus's account, and Fineman said that intensive research is being done to address the issue. Enditem