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| Stanley Crooke, CEO of Isis Pharmaceuticals |
Dr. Stan Crooke is founder, chairman and chief executive officer of Carlsbad, Calif.-based Isis Pharmaceuticals. In 2006, he was named in Nature Biotechnology as one of biotechnology’s influential individuals. Crooke is currently on the board of Regulus Therapeutics Inc., a company jointly owned by Isis. Prior to founding Isis, Crooke was president of research and development for SmithKline Beckman Corp. (SKB). He also coordinated the research and development activities of SKB including its instruments, diagnostics, animal health and clinical laboratory businesses. Prior to joining SKB, Crooke helped establish the anticancer drug discovery and development program at Bristol-Myers, which succeeded in bringing to market a significant number of drugs. During his career, Crooke has supervised the development of 19 drugs on the market and others in development. He received his master's and doctorate degrees from Baylor College of Medicine and his bachelor's in pharmacy from Butler University.
Q: Share with me a brief history of Isis. How did the company first get started?
A: I founded it 21 years ago to pursue what was a novel idea at the time that had no data, which was the notion of antisense technology. We’ve persevered in that process in what I think has proven to be an important enterprise. When I started the company I said the probability of our success was near zero and that it would be 20 years and at least $2 billion before we really knew, and I think that’s been proven the case.
Q: Tell me what antisense technology means.
A: It’s the only direct route from genomics to drugs that I know of. It’s the use of chemically modified oglionucleotides (short chains of nucleotides made synthetically to replicate the human DNA sequence) to interact with specific messenger or other RNAs to cause their function to be disrupted.
Think of it as the third platform for drug discovery. Small molecules are 120 years old now. Protein therapeutics are really quite old, but monoclonal antibodies are about 35 or 40 years old. We think antisense will take place alongside those as a third platform.
Q: How did you get to the point to where you were discovering and developing drugs that bind to RNA instead of proteins?
A: I’ve always been interested in RNA as a place in drug action. I feel the proposition is simpler. It seemed to me that it was time to evaluate whether one could create oglionucelotides that had good drug properties. And, if we could, then the hope was antisense drugs would be more specific because you can build them to be gene-specific. And the technology would be much more efficient than small molecule or protein-based drug discovery because the basic rules of how the oglionucleotide interacts with the target RNA are understood.
Armed with that information, then it becomes a much more rational process for drug discovery. All of those things, I think, have been borne out as we’ve made progress over the last 20 years.
Q: Talk a little about Isis’ strategy to license drugs in the earlier stages of development. I hear you’ve generated more than $1.6 billion from the successful execution of this partnership strategy?
A: It’s really quite simple. With small molecule and protein therapeutics you never know when you’re going to get another drug.
So, the idea was to invest in innovation tied to a technology that was sufficient enough that we could generate large numbers of drug opportunities per unit of time with a small group of people. And not to build an infrastructure that gets in the way of innovation. Our goal has been to keep the company small. It’s a mantra here at Isis that we intend to stay small, around 300 to 400 people, which is where we are now. And, armed with that technology, we can create five new drugs a year. Today, we have 23 drugs in development. Next year, we’ll have 28. And we will do the discovery, the early development to proof of concept and then let organizations that are geared to the brute force of Phase 3 and marketing and sales do that.
Q: What’s on the immediate horizon for Isis?
A: Mipomersen, our Phase 3 cholesterol-lowering drug being developed with Genzyme, gets filed in the first half of next year, in the U.S. and Europe, for the first group of patients. These are patients who have severe high cholesterol and extreme cardiovascular risk. Then, there will be subsequent filings for an ever-growing volume of patients and long-term safety. It’s going to treat people who have high cholesterol, who can’t get their cholesterol down with existing drugs and who can’t take statins. It’s an exciting drug that’s going to make a big difference in patients’ lives.
Q: When you’re not at work, where else do you spend your time?
A: My wife and I have a home in Sedona, Ariz. so we like hiking in the red rocks. Other than that, I like to read, play chess and generally goof around.
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