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Volume 88 Issue 15 | pp. 47-50
Issue Date: April 12, 2010

Working For A Biotech Start-Up

Fledgling firms offer rewards that sometimes outweigh the risks of conducting high-stakes research on a fast track
Department: Career & Employment, Business
Keywords: Biotech, Biopharma
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BLUE SKY
Working in Pacific Biosciences surface chemistry group, Cicero (left) and Sebra enjoy freedom to do independent research.
Credit: Dana Underwood
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BLUE SKY
Working in Pacific Biosciences surface chemistry group, Cicero (left) and Sebra enjoy freedom to do independent research.
Credit: Dana Underwood

"If you like excitement, really hard work, and a swashbuckling wild ride, and if you like to feel that everything you do every single day impacts the vitality and viability of your company, then you are going to fit in at a biotech firm," says Gregory L. Verdine, a professor of chemistry and chemical biology at Harvard University and a founder of seven biotech start-ups. "Within these companies, every single person is essential. That's really different from the way it is in big pharma."

In the midst of big pharma's massive layoffs, the environment Verdine describes may have fresh appeal for chemists who otherwise might not have considered working for a biotech start-up company. "The risk of working for a biotech firm is not much different from the risk of working for a large drug company," says Peter L. Toogood, vice president of chemistry at Lycera, a Cambridge, Mass., biopharmaceutical company founded in 2006 to focus on the discovery and development of small-molecule immunomodulators. "These days, nobody in big pharma really knows whether his or her job will be there a year from now," he says.

Employment prospects for chemical scientists in biotech start-ups are also iffy. For Lycera, the sheer number of accomplished scientists laid off by big pharma has made it a lot easier to attract top talent, says Toogood, who came from a senior research role in discovery at Pfizer. However, not all biotech firms have been able to expand. Glen Giovannetti, who oversees consulting firm Ernst & Young's biotechnology practice, says some start-ups are constrained in part by "the current investment climate, which has raised the bar considerably for start-ups seeking funding."

"Chemists, along with members of all scientific disciplines, may see a difficult hiring environment at early-stage companies, at least through the remainder of this year as access to financing continues to be tight," Giovannetti adds.

With lean staffing the norm, biotech start-ups need every employee to take on multiple roles, Verdine says. A chemist in a start-up biotech firm might be expected to do their own molecular modeling, conduct some molecular pharmacology research, or manage outsourcing efforts. In comparison, someone in a similar position in a big company might pass that work to groups dedicated to those tasks, Verdine says.

Verdine
Credit: Stu Rosner/Stu Rosner Photography
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Verdine
Credit: Stu Rosner/Stu Rosner Photography

At Enanta Pharmaceuticals, a Watertown, Mass., biopharma company creating small-molecule anti-infectives, chemists often need to write their own patents, says Verdine, who founded the company in 1998. In contrast, a chemist in a big drug company might rely on the services of an attorney to get that done, he says.

Scientists are also asked to wear many hats at Portola Pharmaceuticals, a South San Francisco-based biopharmaceutical company founded in 2003 to develop cardiovascular and inflammation drugs, according to Anjali Pandey, the company's vice president of chemistry. After making a compound, Portola's synthetic organic chemists do their own purification, analysis, characterization, scale-up, and, sometimes, even solubility, microsomal stability, and formulation work for in vivo studies, she says.

In screening potential hires, Pandey looks for scientists who are flexible. "Things change really fast in small companies, because we have limited management layers," she says. "When a top-level decision is made, people across every department have to stop what they are doing and shift gears. We are not driving a slow car here; we're in a NASCAR race."

Although working at a biotech firm is challenging, it can also be empowering and exhilarating. In a start-up like Portola, chemists routinely interact with biologists, as well as experts in drug metabolism, pharmacokinetics, and animal pharmacology, Pandey says. "Everyone is involved in looking at the data and quickly deciding what the next step in the research should be."

Portola's scientists also benefit from being able to communicate directly with senior management, asking technical questions or gaining insight about the company's goals directly from the top, Pandey says. Those interactions allow chemists and other scientists—regardless of their level—to "see the big picture," she says.

Given their direct involvement in so many aspects of a company's research, scientists in small start-ups frequently enjoy a higher level of visibility than may be possible in a big drug company. "At Portola, even junior scientists play a high-profile role, often being named in patents and listed as coauthors on publications," Pandey says. If all goes as planned, Portola scientists "will be putting their name on best-in-class antithrombotic and anticoagulant drugs aimed at unmet medical needs," she adds.

RISK-TAKERS
Marshall (left) collaborates with chemist Uyen Tran, an associate scientist at miRagen.
Credit: Tammy Egan/miRagen
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RISK-TAKERS
Marshall (left) collaborates with chemist Uyen Tran, an associate scientist at miRagen.
Credit: Tammy Egan/miRagen

Some scientists at start-ups exercise much more autonomy than their counterparts in most big drug companies. "There's very little bureaucracy here, so people are free to do science without a lot of impediments," says Gary D. Glick, founder and chief scientific officer of Lycera and a professor of chemistry at the University of Michigan, Ann Arbor. "We have a structure that enables people to take advantage of their scientific talents—something people seem to be really looking for these days."

A company with a similar philosophy is Menlo Park, Calif.-based Pacific Biosciences (PacBio), which is poised to launch its first product, a next-generation DNA-sequencing instrument. "We try to hire the best and the brightest, set a direction, and then give our scientists and engineers the freedom to do what they are trained and paid to do," says Ron Cicero, senior manager of the surface chemistry group at PacBio, which was founded in 2004.

Although PacBio's culture encourages employees—in fields ranging from enzymology to synthetic chemistry to optics engineering—to share information and collaborate, they are able to pursue their own ideas more freely as individuals than they might in a large drug company. "We've found that if you try to stifle the creativity of the very bright, capable scientists and engineers we have here by giving them marching orders, you are going to lose out," Cicero says.

The opportunity to do "creative, cutting-edge science and apply it toward the goal of going public" is what spurred Robert Sebra to join PacBio after completing a Ph.D. in biochemical engineering. Although he had been seeking an academic position, Sebra discovered the company during his job search and became fascinated with its goal of sequencing a genome using its transformative detection platform. Through real-time monitoring of biological processes at single-molecule resolution, the technology enables rapid genome sequencing at low cost. "I knew I would never get bored. That is what drew me here and keeps me here to this day," says Sebra, who is a senior scientist in the company's surface chemistry group.

Glick
Credit: U of Michigan
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Glick
Credit: U of Michigan

At PacBio for three years, Sebra feels he is thriving in a small company that "allows him to foster his individuality both as a scientist and as a person." Describing himself as someone with a "weird fashion sense," he says he feels comfortable wearing "really crazy clothing to work" on days when he is not involved in special meetings. "People here accept you for who you are while still focusing on your scientific contributions, which makes me feel great about coming to work," he says.

As part of its effort to help employees feel comfortable and valued, PacBio also hosts social events such as its annual Lobsterfest, during which all employees enjoy lobsters purchased by firm's chief executive officer.

Social interactions among staff members are also important to the growth and development of Boulder, Colo.-based miRagen Therapeutics, President and CEO William Marshall says. The company, which was established in 2007 to develop microRNA-based drugs for cardiovascular and muscle disease, hosts events such as chili cook-offs and periodic "Friday afternoon clubs," which may include a game of volleyball or an outing to a local brewery.

These events allow employees to "kick back, relax a bit from the intense focus on generating data, and celebrate great research outcomes," he says. "There is a strong sense of urgency in the start-up environment, and it is important to provide a balance that recharges people's batteries." The events also allow the company's biologists and chemists to forge relationships that help them better collaborate in the lab, something Marshall believes helps in "driving projects forward."

In another effort to help motivate employees to pull together and support company growth, some companies issue stock or stock options to them. Start-ups reason that people are often "willing to give more of themselves to a company if they own a larger fraction of it," Verdine says. That's important because "at the end of the day, we are looking for passionate, hard-working people who take their ownership in their company seriously," he says.

As co-owners, employees at Gloucester Pharmaceuticals "went all out for five years to get a drug approved, and they ended up being rewarded for all that hard work" when the company was sold to Celgene for $640 million early this year, says Verdine, who founded the Cambridge, Mass., firm focused on developing new therapies for the treatment of cancer. However, "it does not always work out that way."

The probability that an employee will benefit from a major payout from stock options is relatively low because of the many risks inherent in building a successful start-up company, "but employee ownership provides unparalleled incentive because of the real success stories in the industry," miRagen's Marshall says. "For us, there are unknowns around every corner as we try to identify new synthetic derivatives that can address a novel drug targeting modality," he continues.

"Biotechnology is a risky business," Portola's Pandey says. "Our scientists face the challenge of trying to make a molecule that is better than our competitors. You never know what will be successful and what will fail." Given all the risks of this kind of research, she says, "I don't think there is anything like stability anywhere in this industry anymore."

At high-risk firms, employees face the threat of losing their jobs when companies fail or are purchased by a larger company. Although being thrown into unemployment is never comfortable, employees need not worry that being part of a failed start-up will taint their résumé, Pac Bio's Cicero says. Employees aren't held accountable if markets crash or an employer can't raise funding for a potentially stellar idea, he says. Instead, prospective employers expect that those who have been through a failure or acquisition have probably gained from the experience. "They have likely learned how mistakes were made and how to prevent them in the future," he says.

COMPANY PERKS
A Pacific Biosciences employee enjoys a tasty meal during the company's annual Lobsterfest.
Credit: Dana Underwood
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COMPANY PERKS
A Pacific Biosciences employee enjoys a tasty meal during the company's annual Lobsterfest.
Credit: Dana Underwood

Any experience—good or bad—that chemists can garner knowledge from gives them an edge in finding a job in a start-up biotech firm. In particular, start-ups like to hire scientists who have come out of large pharmaceutical companies, which "are very effective at training them—something smaller companies just don't have the infrastructure to do," Verdine says.

When hiring chemists at all levels of training, Lycera prefers candidates who have at least 10 years of pharmaceutical experience in drug discovery, Toogood says. "We need new hires who can make an immediate impact on our programs."

There are exceptions. Postdoctoral students who have worked in the lab of an academic founder of a company often have an edge in getting a job in a start-up, Verdine says. It is not uncommon for them to come in and help transfer the technology from the academic lab, he says.

MiRagen will consider "taking scientists right out of a postdoc or graduate program if their experience is in a sweet spot for us in terms of what we need to do to move projects forward," Marshall says.

PacBio hired Sebra fresh out of graduate school partly because he showed the potential to link his graduate work on surface biochemistry to the company's development of molecular detection technology, Cicero says. And given that single-molecule detection of biomolecules at interfaces is a relatively new field of study, someone with the right skill set may come straight from school, he says.

Chemists who can demonstrate an understanding of other disciplines have a distinct advantage in finding a job in a biotech firm. In particular, these companies "put a greater premium on people who are comfortable navigating the world of biology also," Verdine says.

Lycera seeks top-notch synthetic or medicinal chemists who understand or want to learn about other aspects involved in discovering drugs, such as pharmacokinetics, pharmaceutics, and research informatics, says Toogood. "We want people who are trained broadly and think broadly."

Those who have training "just outside of synthetic chemistry, physical organic chemistry, and spectroscopy and understand molecular recognition and some aspects of biochemistry and chemical biology are going to set themselves apart in a competitive job market," Glick adds.

Verdine strongly advises chemistry graduate students to "step out of their comfort zone" and complete postdoctoral studies in another field before entering the workforce. Young chemists need to consider "the changing landscape of the drug industry, which will place increasing value on being able to do things other than just synthetic organic chemistry," he adds.

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FAST TRACK
Pandey (fourth from left) leads a Portola group that includes synthetic organic, medicinal, and process chemists who are developing small molecules.
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FAST TRACK
Pandey (fourth from left) leads a Portola group that includes synthetic organic, medicinal, and process chemists who are developing small molecules.

Staffed with scientists who can collaborate across disciplines, biotech start-up firms are hopeful that they will be able to continue to expand into drug discovery niches left unexploited by big pharma. "Smaller, more nimble companies are positioning themselves to take on early-stage research that is more amenable to chemists' skills, while larger drug companies are focusing on development," Marshall says. "It makes sense for big drug companies to leverage interactions with small biotech companies that are willing to take on greater risk to discover the next breakthrough concept and then leverage their own formidable experience and resources to drive discoveries from the bench to the bedside."

Start-ups may find increasing opportunities in natural products research, an area largely eschewed by big pharma, Verdine says. With this in mind, just last month, he founded yet another firm—Warp Drive Biosynthetic, a company that will "work very heavily on complex molecules, including natural products," he says.

In addition, smaller companies involved in the development of small molecules are poised for growth, Portola's Pandey says. "Most big pharma companies are now looking to small and mid-sized biopharma companies to obtain small molecules for their pipelines through licensing deals or acquisitions," she says.

Pandey believes "synthetic organic chemists and medicinal chemists will have a lot of opportunities in biotech and biopharma companies going forward—at least in the small-molecules arena, which is where everybody wants to be right now."

 
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