Tiny San Diego startup wants to help develop medicines cheaper and faster Algae will be grown in huge plastic bags

By Penni Crabtree
UNION-TRIBUNE STAFF WRITER

May 20, 2005

Scientists are exploring seemingly bizarre sources to come up with potential new medicines, from anti-cancer substances found in devilfish to compounds isolated from marine fungus.

SCOTT LINNETT / Union-Tribune Rincon Pharmaceuticals is working on a way of producing drugs by introducing the gene sequence responsible for producing a particular human protein into algae. Once there, the algae cells "read" the gene sequence and begin producing the protein.

Now a tiny San Diego biotechnology startup called Rincon Pharmaceuticals has its own unique twist on a therapeutic: Complex monoclonal antibody drugs produced from pond scum.

Rincon chief executive Bruce Steel prefers the more elegant term chlamydomonas reinhardtii, a freshwater green algae that the company has genetically engineered to produce human-like proteins that can be used as medicines.

But he concedes the point, more or less.

"We're not really pond scum. Pond scum grows on the surface of ponds, while this algae grows throughout the entire water column," said Steel, who, after a pause, laughs. "We're more pool scum."

In a pond or in a pool – Rincon plans to grow the stuff in huge plastic bags in greenhouses – the goal is to find a cheaper, faster way to make monoclonal antibody therapies like Massachusetts-based Biogen Idec's top-selling cancer treatment, Rituxan.

Today, Rincon is expected to announce a collaboration with Biogen Idec to explore the use of its algae system in producing monoclonal antibody medicines now in development at Biogen Idec, the nation's third-largest biotech.

"This collaboration is not aimed at a specific product or challenge, but as a leader in biomanufacturing, we're always looking for novel and innovative opportunities to potentially boost productivity and efficiency," said Michael Kowolenko, senior vice-president of pharmaceutical operations and technology at Biogen Idec. "Partnering with smaller companies is a smart way to bring in new ideas and thinking."

SCOTT LINNETT / Union-Tribune Rincon chief scientist Steve Mayfield examined algal strains the company is using to make anti-cancer antibodies. Rincon chief executive Bruce Steel said the company's approach could make it dramatically cheaper to produce cancer drugs.

Traditionally, monoclonal antibodies are made by splicing engineered hamster or mouse cells with human DNA components, which produce human-like antibodies that can be grown in vats and then harvested and purified.

The process is time-consuming and costly: a gram of monoclonal antibody costs about $1,000 to $1,500 to produce, while the manufacturing facilities needed to make them cost as much as $400 million and require years to build and obtain certification from federal regulators, according to industry statistics.

Such huge capital expenditures can be risky, in part because planning and building a biomanufacturing plant takes at least five to six years. And that is usually well before a company actually knows if the experimental drug slated to be manufactured five years down the road will actually work.

For instance, Biogen Idec expects its $380 million biologics manufacturing plant in Oceanside to be completed and fully licensed next year – the end of a six-year process that began in 2000 when Idec Pharmaceuticals first bought the land. Idec later became a part of the merged Massachusetts biotech.

In contrast, the kind of facility needed to produce monoclonal antibodies using Rincon's algae system would cost between $10 million and $20 million, and would take only two to three years to get up and running, said Steel.

SCOTT LINNETT / Union-Tribune Rincon chief executive Bruce Steel said the company's approach could make it dramatically cheaper to produce cancer drugs.

And the algae-based production system, if it ultimately proves successful, could produce antibodies as cheaply as $100 to $150 per gram, Steel said.

"The goal is to increase the number of therapies that make it to market and the number of patients who can get the drug – and decrease the overall cost to society of doing this," said Steel, noting that drug companies charge as much as $20,000 per patient for some protein drugs.

The technology involved in Rincon's algae production system was developed in the laboratory of Stephen Mayfield, a researcher at the Scripps Research Institute, and licensed to the biotech.

"Algae spent millions of years learning to survive on nothing – they pull nutrients from the water and derive energy from the sun," said Mayfield. "It doesn't take much to get these guys to grow, so this stuff is really cheap."

The Rincon system involves introducing the gene sequence responsible for producing a particular human protein into the cells of the algae. Once there, the algae cell "reads" the human gene sequence and begins producing the protein.

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The algae grow and multiply in a petrie dish, and then are transferred and grown in plastic bags of increasing size, all the way up to 25,000 liters. The algae are then harvested, and the human protein is extracted from the plant cells and purified.

Rincon isn't the only company exploring the use of aquatic plants to produce less expensive protein drugs. A North Carolina biotech, Biolex, is doing similar research with lemna, or duckweed.

In February, Biolex started a Phase 1 clinical trial of an hepatitis C treatment that utilizes the duckweed system, and the company has a number of research collaborations with other drug companies.

Both Rincon and Biolex boast that their aquatic plant systems can avoid some of the problems that have plagued other transgenic systems, particularly in the area of containment.

Algae and duckweed can be grown in bags in closed facilities, avoiding some of the concerns about outdoor cross-contamination with traditional field crops that have haunted the industry.

In 2000, Aventis, the maker of StarLink corn, was forced to recall taco shells and other products contaminated by genetically modified animal feed. And in 2002, Texas-based ProdiGene was fined by federal regulators after 500,000 bushels of soybeans were found to be contaminated by corn that was genetically engineered to produce medicine.

Last year, Epicyte, a San Diego biotech that pioneered the notion of altering corn and other plants to produce protein drugs, closed its doors, unable to find investors. Epicyte sold its extensive intellectual property to Biolex.

"Our feeling is that unless you are in some type of plant that is containable, and easy to manipulate and scale up, it's going to be a very tough road to go," said Steel.