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Close-up: Stanley Crooke

Isis uses antisense technology to target more effective drugs

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Drug development is risky business. In the biotech industry, 999 out of 1,000 drugs targeted for development will fail, according to Dr. Stanley Crooke, CEO of Isis Pharmaceuticals.

The Carlsbad-based company's successes, including its development of antisense technology and its progress in infectious disease diagnosis, represent a boon for the company and the entire industry.

For the rest of us, these advancements could result in easier, longer and healthier lives.

Here's the general idea: Cancer and many cardiovascular, metabolic and inflammatory diseases occur due to overproduction or abnormal production of proteins. Isis developed antisense technology to target specific areas and to disrupt the body's process in creating these undesired proteins.

Stanley Crooke

"Drug discovery and development is about making patients better, effecting cures and altering the course of chronic diseases," said Crooke, who co-founded Isis (Nasdaq: ISIS) in 1989. "That's what I've done with my life, and (antisense technology) is simply a totally novel approach."

After 18 years and about $2 billion spent, Crooke and his colleagues have revolutionized the industry.

"The key difference is that you create a new class of drugs, designing them to bind to a class of targets that have never been targeted by drugs before: messenger RNA," said Crooke. "And you use genetic information to make a precise ZIP code to specifically attack one, and only one, messenger RNA."

This specificity means rapid diagnosis, faster healing and less side effects. Essentially, the technology goes straight to the source of the problem, tackles it and prevents growth of the disease while promoting healing.

"Drugs are just tools that we put in the body to do a particular job," said Crooke. "As a general rule, the more specific a drug is, the better it is, the safer it is, and the more effective it is." Crooke's interest in antisense technology sparked while helping to establish Bristol-Meyer's anticancer drug discovery and development program. Prior to founding Isis, he also served as president of research and development for SmithKline Beckman Corp., where he coordinated the company's R&D activities in instruments, diagnostics, animal health and clinical labs. With the backing of a number of venture capitalists, Crooke created Isis to pursue the dream of "creating a new platform for drug discovery that will enhance productivity and make better drugs," he said.

The platform has since supported 17 drugs in development and one drug on the market to treat a wide range of diseases. Isis, on a per capita basis, is the most prolific innovator of any company in drug development history, according to Crooke. The Isis team has issued 1,600 patents and has 3,500 patent applications in process.

"Every year when patent roundups are considered, we rank along with the IBMs, the Xeroxes and the like," Crooke said. "What that reflects is the level of innovation in the company and our commitment to tackling big ideas and staying the course."

Through its wholly owned subsidiary Ibis Biosciences Inc., Isis created a second technology called the Ibis T5000 that the company believes will radically change infectious disease diagnosis, making it more efficient.

"It's estimated that if the T5000 had been up and running at time of SARS," Crooke said, "it would have taken us two patients and two days to learn that it was a viral disease, that it was different than anything that had been seen, and that the last time something like it was seen was in China two years earlier."

The biosensor system enables rapid identification of bacterial, viral, fungal and other infectious organisms, as well as analysis of human DNA. Isis plans to eventually spin off the technology, and Ibis Biosciences is a candidate for merger or acquisition, Crooke said.

The company also announced in September that it had been awarded $4.2 million in government contracts to Ibis for biodefense applications.

"We are pleased with the ongoing government support and the opportunity to continue to advance our technology and applications in the biodefense arena," said Michael Treble, president of Ibis and vice president of Isis, in a press release. "These contracts support the Ibis business model to commercialize the Ibis T5000 in multiple business sectors, including government biodefense and infectious disease surveillance, health care-associated infection control, infectious disease research and, in the future, in vitro diagnostics."

Isis' products and technology have made it one of the most sought-out biotech companies in its field. In July, Isis announced it would receive $26.5 million from Cambridge, Mass.-based Alnylam Pharmaceuticals under a patent licensing agreement. The company most recently received $5 million to begin Phase 1 of a study with Johnson & Johnson (NYSE: JNJ) on ISIS 325568, a diabetes drug candidate.

"We're being sought out actively because we have products that are unique and technology that is profoundly revolutionary," Crooke said. "And the evidence for that is the deals that we've done this year."

Isis acquired Symphony Genesis for $120 million in late September and received part of a $1.2 million National Institutes of Health (NIH) grant to use the Ibis T5000 in influenza surveillance research.

"There are companies that have aligned with us that we've provided selective access to our patents, but our goal has been -- and we've succeeded in this -- to be in control of the platforms," Crooke said. "We've created quite a number of partnerships with larger companies."

Isis has also granted technology to smaller companies to focus on specific elements, therapeutic areas or technology that would be complementary to Isis projects. "This brings the greatest value to our shareholders and the greatest value to the widest range of patients," Crooke said.

The company has received positive results from its Phase 2 clinical trial of its cholesterol-lowering drug candidate ISIS 301012, recently given the generic name of mipomersen sodium. Drugs that lower cholesterol -- such as Pfizer's (NYSE: PFE) Lipitor, which reaped $13 billion in sales in 2006 -- tend to be the most profitable for pharmaceutical companies. If successful, mipomersen sodium could lead Isis into profitability. The company reported a loss of $68.1 million in 2006.

Still, Isis' stock performance in recent years may reflect investors' confidence in its drug pipeline and recognition of what the company has accomplished. The stock hovered around $3 a share two years ago and trades at about $17 today.

"This makes the ability to acquire capital from the public market much easier," he said. "The financial market is beginning to recognize the potential value of the drugs and the technology that we've created."

The company, Crooke said, has achieved success through the intensity, work efforts and commitment of team members. Isis has had extraordinarily low turnover, he added, not because the road has been easy, but because of the quality of the dream.

"No one ever claimed that working at Isis was easy. It's demanding, but I do think it's rewarding, and most people stay because it's an environment where intelligence and innovation are rewarded," he said.

"And what we're trying to do has great merit."

Klam is a San Diego-based freelance writer.

Related Link: www.isispharm.com

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