An Antibiotic to the Rescue

How Cubist's Jeff Alder turned a devastating Phase III failure into an approval.

Keith O'Brien
Oct 1, 2007
<figcaption> Credit: © 2007 Leah Fasten</figcaption>
Credit: © 2007 Leah Fasten

The bad news rippled through the well manicured office park in Lexington, Mass., and settled somewhere on Jeff Alder's desk in January 2002. Cubist, a drug development company focusing on creating novel anti-infectives, was cutting short the first Phase III trial of its lead anti-infective compound, an intravenous antibiotic then called Cidecin. The problem was that the drug was not effective in treating community-acquired pneumonia (CAP). The failure took everyone by surprise, and stock prices at the company, which had gone public in 1996, plummeted more than 40%. Cubist, which had lost $70 million in 2001 and was banking on FDA approval of its lead drug candidate, considered the news devastating. "Basically," Alder says, "everything was riding on why we had this failure in the CAP trials."

Cubist was founded in 1992 in Cambridge, and five years later licensed a drug from Eli Lilly called...

"The singular most important quality for a leader is the ability to instill trust, and Jeff has that. People believe him and trust him." --Jake Clement

From Encyclopedia Brittanica to Cubist

As a boy growing up in Toledo, Ohio, Alder spent his days reading volumes of the Encyclopedia Britannica. He recalls reading in particular about virologists, and soon decided that science was the field for him. At first, Alder says, he wanted to become a physician, but at Ohio State University - where he earned a bachelor's degree in microbiology in 1981 and a doctorate in the field in 1987 - Alder nixed the idea of going to medical school in favor of basic science. His research focused on malaria, syphilis, and Lyme disease.

Alder liked life in academia, where he remained until 1990 as a postdoctoral associate in the University of Wisconsin's department of medical microbiology. It was in academia that his first learned the power of animal models and an important lesson that remains with him today: "Mice don't lie." Wanting to focus more on producing effective drugs rather than just publishing papers, Alder joined Abbott Laboratories in August 1990.

There, over the next eight years, Alder evaluated 17 different compounds and helped design a 2,300-square-meter animal testing facility for infectious disease and cancer studies. "He has one of the best grasps of infectious disease of any drug discoverer in the business," says Jake Clement, a former project leader at Abbott who hired Alder and is now senior vice president of science and technology at Vancouver-based Migenix. What impressed Clement just as much was how Alder handled himself under pressure. "The singular most important quality for a leader is the ability to instill trust," Clement says. "And he has that. People believe him and trust him."

On a recent afternoon, meeting with chemists inside the office park in Lexington, Alder, who doesn't spend much time in the lab anymore these days, was right at home among his staff. He laughed and even high-fived employees as they discussed positive test results for a new preclinical drug candidate designed to treat Clostridium difficile-associated disease of the colon, which often results from treatment with other antibiotics that disrupt gut flora. "Excellent," he says to them, as he turned to leave. "We'll be on to success in no time."

From the time Alder joined Cubist in 2000, Thorne says, people there felt at ease among the tall, lanky Midwesterner with his easy smile and quick wit. By January 2002, when the CAP trials showed daptomycin to be less effective than the standard treatment, Alder had been at the company for a few years. Thorne says they quickly learned that Alder wasn't just a good leader, but also a good communicator. "He has the ability to take two binders full of science - in terms of data and complicated studies - and make it into plain English so that people can understand it," says Helen Boucher, an infectious disease specialist at the Tufts New England Medical Center and a consultant to several pharmaceutical companies, including Cubist.

This skill, Boucher recalls, became especially handy when a small team from Cubist, including Alder, went before the FDA's anti-infective drug advisory committee to get approval to use Cubicin in treating infections in the bloodstream. It's been said that the difference between a good scientist and a great scientist is the ability to communicate. Standing before the FDA's committee, under pressure yet again, Alder proved that he was the latter, Boucher says. "We all came to know and love him much more as we came through this experience," she recalls. "He really has grace under pressure and really rose to the occasion in ways that probably exceeded everyone's expectations."

Instead of reading the Encyclopedia Britannica, Alder was now reading management books - such as Death by Meeting: A Leadership Fable ? About the Most Painful Problem in Business - and implementing changes at Cubist. For example, he gave everyone a chance to speak for two minutes in the "rapid round" at weekly drug evaluation update meetings. "Everyone was included in these meetings," Thorne says, "and everyone could speak in the rapid round." Given the troubles that lay ahead for Cubist, Alder's ability to lead, communicate and, above all, develop anti-infectives would become indispensable. Perhaps what impressed colleagues most was his ability to put his head down, work hard, and stay cool under pressure. "He's a marathoner and an iron man," Thorne says, "and he's all those things on the job, too."

<figcaption>Alder with Cubist's Jared Silverman, principal scientist of microbiology research and Grace Thorne, senior director of clinical microbiology. Credit: © 2007 Leah Fasten</figcaption>
Alder with Cubist's Jared Silverman, principal scientist of microbiology research and Grace Thorne, senior director of clinical microbiology. Credit: © 2007 Leah Fasten

Moving past a loss

His approach paid off in the Cubicin successes, but that party was short-lived. Less than six months later, Frank Tally, considered by many to be the father of daptomycin, died of the same sort of infection he had worked so hard to treat: a blood-borne staph infection. "He's kind of been the rock, been here forever," says Alder, still referring to the former chief scientific officer in the present tense. "Unfailing champion and an optimist. You've really got to be optimistic and think you can overcome the hurdles in this business. If you don't think you can solve the problems, you don't belong here."

Now, with Tally gone, Alder is always hammering the importance of optimism into his staff. The company has grown since he got there, and so has his role: From overseeing seven people in three departments, Alder now oversees some 50 people in seven departments. As he moves forward in the wake of Cubicin's success, Alder, 48, says his mission remains the same: treating the sickest people of all.

As such, Alder says, there are new drugs in Cubist's preclinical pipeline: a Gram-negative lipopeptide, a second-generation daptomycin that no longer binds to pulmonary surfactant and has been effective in the lungs during animal trials, and a drug candidate that targets C. difficile-associated disease. And so, even with investors happy with Cubist's growth, Alder isn't resting. Like the marathon runner that he is, he just keeps pushing on.

"People are dying," he says. "They're dying of Gram negative-resistant infections. They're dying of Clostridium difficile in the gut. They're still dying of Staph aureus in the blood. That, to me, alone, is plenty of drive and motivation to develop these things as quickly as we can."