Published in UT San Diego, February 3, 2014
Leading the development of a new platform technology for drug discovery, getting a drug approved by the Food and Drug Administration for a chronic illness and serving as chief executive of a company for 25 years are all significant accomplishments. Stanley Crooke, CEO and chairman of the board of Carlsbad-based Isis Pharmaceuticals, has achieved all three.
In 1989, Crooke started Isis to focus on antisense — a new technology that he believed could be used to create better drugs more effectively. At the time, he lived in the Philadelphia area, where he was the head of worldwide R&D at SmithKline Beckman, one of the world’s largest pharmaceutical companies. He said that he located Isis in San Diego because it was one of three life-science centers in the U.S. (Boston and San Francisco were the other two), and he wanted to live here. Twenty-five years later, he is still the CEO of Isis, which has survived some tumultuous times when early research results were disappointing and cash was running low.
The firm has a market capitalization of about $5.5 billion and is trading at all-time highs largely because of the FDA’s approval last year of Kynamro, a drug used to treat HoFH (a rare inherited condition that makes the body unable to remove “bad” cholesterol). The agency’s action validates antisense as a proven, broadly applicable and efficient drug discovery platform. We caught up with Crooke to review the history of Isis.
Q: Why did you want to start a company? Why couldn’t you pursue antisense at SmithKline Beckman?
A: I knew that developing a drug using antisense would take 20 to 25 years. You need a simple, focused agenda, and the agenda has to create a level of desperation. That desperation must be balanced by a commitment to do high-quality experiments. In a big company, 20 years is three CEOs, two mergers and 42 budget crises, so a high-risk long-term vision would eventually lose.
Q: When did you know that antisense would work?
A: It was 18 years and $2 billion before I became convinced that antisense would become a major drug discovery platform … Unless you’re extremely lucky, all big ideas go through five phases — wild enthusiasm, disappointment, it will never work, grudging acceptance, and it was my idea to begin with. At Isis, we went through all of those phases.
Q: How were you able to obtain the $3.8 billion that Isis has raised to date?
A: If you have a big, high-quality dream and you appear to be a person who can realize that dream, it’s possible to sell it and sell it again and weather the storms.
(Crooke has been very savvy about financing. Isis went public in 1991 — very early in its existence — and quickly did secondary offerings when market conditions permitted. Other funding has come from additional equity investment, license fees and royalties. Isis had $625 million in cash at the end of 2013.)
Q: How did you handle the disappointments? (The company had two products that failed in late-stage clinical trials.)
A: The senior people and I looked at the data and said, do we see a path forward? Every time we looked we did see a path, and every step took us closer to a success scenario. At times it wasn’t clear that we would be able to raise the money to continue. There was tremendous depression because of the disappointment and tremendous fear and anxiety in the organization that had to be managed and marshaled to a new enthusiasm. The key to leading through a crisis is to pivot to a new dream that is consistent with the overall dream.
At a major turning point, Crooke turned to his wife, Rosanne Crooke, one of the key scientists at Isis, and asked her to lead the team that developed Kynamro. “We’re best friends and partners. We manage disappointments by looking forward, we try to be upbeat and focus on the positive and learn from our mistakes,” said Rosanne.
Rule No. 218