Drug hunters

CAMBRIDGE, Mass. — Ask Microbia CEO Peter Hecht if drug discovery is an art or science, and he’ll likely tell you that it’s both. Reflecting on the company’s short—yet remarkably productive—history, the former Whitehead postdoc is quick to attribute Microbia’s success to a convergence of science, people, and passion. “Our strong bias is that you need all three legs of the stool,” says Hecht. “Building a pharmaceutical company from scratch is a very challenging problem.”

Since Microbia’s launch in 1998, Hecht and his colleagues at the Cambridge-based company appear to have solved many of the problems that other biotech start-ups find insurmountable. In May, the group’s recent capital round-up netted Microbia an additional $40 million to bankroll a growing portfolio of drug candidates, bringing the total venture capital raised to date to $99 million. Three of Microbia’s drug candidates are expected to enter clinical trials over the next year, the first a novel treatment for Irritable Bowel Syndrome that will begin Phase I clinical studies this fall.

An idea is born

Hecht, along with Brian Cali, Todd Milne, and Eric Summers, joined Whitehead Founding Member Gerry Fink’s lab as postdoctoral researchers to study the regulatory networks that fungi use to sense and respond to their environment. Microbia began when the four saw an opportunity to try something they long had wanted to do: translate basic research into therapies to treat disease.

At the time, Fink’s lab was deeply involved in studying the control switches that turn harmless yeast into pathogens that cause life-threatening fungal infections. The lab discovered that the process by which baker’s yeast, the same ingredient used to make bread and beer, changed from a rounded shape to a filamentous form was similar to how disease-causing fungi like Candida albicans transform to attack a host cell. The discovery suggested that baker’s yeast could serve as a safe and economical model to study fungal infections.

Using the baker’s yeast model, Fink and his research team found that the controls governing how yeast switch from a benign to pathogenic form also control how fungi produce chemicals to defend themselves in their normal environment. These chemicals, called secondary metabolites, are used commercially to make an array of products, including antibiotics, antifungals, immunosuppressants, and the cholesterol-lowering drugs known as statins. The challenge in this process, called biomanufacturing, lies in finding ways to “trick” microbes into producing enough chemicals to meet medicinal and commercial demands. Understanding how to control microbial regulatory networks, the group discovered, could lead to the development of new therapies as well as improvement of the production of microbial products.

The partners saw an opportunity to harness the power of both in a way that would lay the foundation for a productive—and profitable—drug-discovery outfit. By overlapping the search for therapies with a program to improve the production of microbial products, the team of Hecht, Cali, Milne, and Summers knew they could build a revenue stream to help fund the drug-discovery arm of the operation—something every pharmaceutical start-up company dreams of.

“That’s when the light bulb went on that there was a model here: an underlying technology taken from Whitehead science that we could use to build two businesses with a common, underlying foundation,” explains Hecht. “To an extent that I find remarkable, we are doing just that five years later.”

From postdocs to entrepreneurs

Launching Microbia meant more than working out the details of a technology licensing agreement with Whitehead. The group knew that they needed guidance from senior scientists and millions of dollars in venture capital. But before biotech-savvy investors would pony up the cash to establish a new pharmaceutical company, Microbia needed a solid business plan with a definitive seal of scientific approval. The crew knew they needed help. Fortunately, help was just down the hall in Fink’s office.

“Gerry [Fink] supported us completely,” says Cali, Microbia’s vice president for program management. “He didn’t react like we were insane when we told him we wanted to do this. Had he tried to dissuade us, ours might have been a different story.”

Early on, Fink, who serves as the chair of Microbia’s board of advisory scientists, connected the crew with scientific leaders, including former Whitehead Director David Baltimore, who helped evaluate the Microbia plan. Hecht and his partners spent the next several months refining their strategy, gathering financial backing, negotiating technology licensing agreements, and recruiting others to join in the venture.

Much to the group’s surprise, they found encouragement and support at every turn. “Before we had our own space, the fifth floor conference room [in Whitehead’s Nine Cambridge Center facility] was the site of many late-night, formative debates about Microbia’s scientific strategy,” says Milne, now Microbia’s vice president for biology. “People at Whitehead were consistently supportive and helpful from the very beginning.”

In just five years, the Microbia team has succeeded in developing a profitable biomanufacturing process business, called Precision Engineering™, that rapidly improved two microbial manufacturing strains now in commercial use. In 2002, the group recruited Celebrex creator John Talley and pharmaceutical guru Mark Currie to their team—a major coup for a company then barely 3 years old. In addition to their hunt for antifungals based from the founding Whitehead technology, the Microbia team is creating and developing new drugs to treat gastrointestinal disease and cardiovascular disease and non-narcotic medications to treat chronic pain.

Although the Microbia founders earned their scientific independence from Whitehead years ago, the team remains close to the Institute. Hecht, Cali, Milne and Summers are now members of Whitehead’s Board of Associates and Cali recently met with a group of postdocs at the Institute to discuss careers in industry. In addition, Microbia has sponsored programs such as the Whitehead Symposium, and Carolyn Gilson, another Whitehead alum who joined Microbia early on and is Microbia’s manager of administration, has coordinated student participation in the Institute’s high school spring lecture series.

“If we are serious about science making a difference in the world, someone has to translate basic research into product applications,” Hecht says. “Whitehead is in a unique position to promote entrepreneurship and help commercialize great science. We are enormously grateful to Whitehead for enabling us to live our dream of creating important new medicines.”