What would possess someone to leave the safety and security of a stable company or academic life for the twists, turns and perils of a start-up company? How about the opportunity to build something from the ground up and the chance to demonstrate their entrepreneurial spirit. These factors, among others, led Greg Baxter (Aegen Biosciences), Charles Hart (Galileo Labs) and Marty Haslanger (Amphora) to make the leap into start-ups. They each described their experiences in this SBS News e-roundtable discussion.

What does your current company do and what's your role in the company?

G. Baxter: Our company, Aegen Biosciences, commercializes cell-based microfluidic devices for drug discovery and predictive toxicology applications. I am a founder and currently acting as president and CEO of the company.

M. Haslanger: Amphora is a multi-dimensional drug discovery company based on a chemical genomics approach utilizing microfluidics and other technologies. My current role is president and CEO.

C. Hart: I am director of discovery technologies at Galileo Laboratories in Santa Clara, California. Galileo is a drug discovery and development company focused on diseases involving the interrelated pathophysiologies of ischemia and inflammation. Our primary focus is on the discovery of therapeutics for acute cerebral stroke, but we are also exploring the utility of our lead compounds for other important clinical indications involving redox signaling pathologies. We have a powerful discovery platform based on proprietary mammalian cells that can accurately identify lead compounds, a robust set of relevant preclinical animal models, and a nice pipeline of leads and clinical candidates. I am focused on identifying the specific molecular targets of our leads and elucidating their mechanisms of action.

How does this position/company compare to prior positions/companies?

G. Baxter: Prior to starting Aegen, I was a scientist at Cornell University. Prior to my Cornell appointment, I was a research scientist for several small biotechnology companies. The positions may seem very different, but it is more of a continuum. In academia my focus was basic research, turning a concept into a viable technology. Now my focus is taking that technology and developing commercially viable products.

M. Haslanger: Prior to launching Amphora, I was president of Sphinx Labs and executive director research technologies, Lilly Research Labs, Eli Lilly and Company. I was responsible for the Sphinx site in RTP, NC, and research technologies-chemistry group in Indianapolis, IN. My current job is smaller in terms of the people and resources managed but greater in terms of scope.

C. Hart: I spent 10 years at Affymax, the last five of which we were part of GlaxoWellcome. However, when given another opportunity to join a start-up I was keen to again experience the excitement of a new enterprise. I then spent two years at Signature Bioscience, helping set up the biology side of the company, and now have been at Galileo Labs for a bit over a year.

With strong management and a bit of esprit de corps, the environment of a start-up is like a college fraternity or a close-knit extended family. It harbors a bit of a swagger from the confidence that you are part of something bigger than yourself, with the feeling of being a key member of the group. It is marked by shared experiences and a feeling that the path you're on is the right one for the discovery of new medicines for important diseases.

When GW bought Affymax, a number of scientists were concerned about losing the entrepreneurial/start-up spirit and mindset we had enjoyed for so many years. GW was also concerned with that and worked hard to keep the environment and way of thinking intact. In spite of this, a few did not relish working within big pharma and departed. I on the other hand greatly benefited from GW's stewardship of Affymax. I forged collaborations with a number of GW sites and got a close-to-inside-view of the workings of big pharma—how programs were progressed (or cut), decisions made and drugs discovered.

Was it necessary to take a certain "leap of faith" to make this transition?

G. Baxter: A leap of faith is necessary to make any career change that involves a substantial amount of risk. In my case, I left a very secure and scientifically rewarding career, uprooted my family and moved across country, to start a company in the worst economic climate in recent history knowing full well that even in the best of times most start-up companies fail.

M. Haslanger: "Leap of faith" implies that this has been a religious experience—which indeed it has. Moving from a large corporation to the entrepreneurial world requires recalibration on expectations.

What are some of the defining features of working in a start-up?

C. Hart: Although it depends, of course, on the focus and the breadth of approach, a key feature of many start-ups is the opportunity to be an integral part of multidisciplinary research and development teams. Although one may be part of a strict disciplinary or functional group, oftentimes you can find yourself part of a drug discovery or technology development team comprised of biologists, chemists, informaticians and often engineers. Not surprisingly, this arrangement can be a source of unique synergistic productivity and learning in realms outside of your own. (Of course, depending on how managed and organized, it can be a frustrating situation because of the different frames of reference and experience.)

The fact that everyone in the company (from the CEO down to the entry-level positions) shares in the equity of the company in the form of stock options can be a motivating factor and is a common thread that runs through the company. (Of course the current state of biotech stock valuations has of course changed part of the feeling about this!) But following the recovery of our sector, this feature will again be a key team builder and motivator.

Another key feature of a start-up can be an active and engaged scientific advisory board. Oftentimes the scientific founders or early advisors of a company will be from the faculty of local universities. The opportunity to interact closely with them and their labs can complement the interaction with colleagues in your company. Of course the amount of interest and input and the synergy between the corresponding corporate and the academic labs will vary significantly. And one does have to be aware and careful about potential conflicts of interest and confidentiality issues.

Are you dabbling more in the commercial end of things (raising capital, marketing, sales, "deal-making," etc.) and less in the scientific arena?

M. Haslanger: Yes. For me this change of focus is a challenge and a source of stimulation.

G. Baxter: The majority of my time is spent raising capital and marketing the technology. I have had very little time for actual bench work.

Has your "built-in" network in the industry come in handy?

G. Baxter: The numerous contacts I have built over the years through my work in industry and academics have been invaluable. These contacts have led to very rewarding research collaborations both directly and indirectly.

C. Hart: Building, maintaining and growing a network of colleagues in the biotechnology and pharmaceutical businesses is very important, both personally and professionally. But like most important things, you really do have to work at it. The advantages come when you least expect it, when you need some quick information on a molecule or cell line, advice on an experimental design, thoughts on strengths and weaknesses of a technology you are considering, suggestions on how to deal with a tricky situation with a superior, co-worker, or direct report, etc. etc. With nearly every situation that you may face, when you stop and think about it for a minute, you can usually come up with someone who is much more expert, or more experienced, than you. And during career transitions your network will definitely come in handy. Just like friendships and other relationships, professional relationships need to be symbiotic and reciprocal to sustain themselves.

TO WHAT EXTENT (IF ANY), HAVE YOU HAD TO BROADEN YOUR SKILL SET (I.E., GETTING INVOLVED IN "NON-CORE" ADMINISTRATIVE FUNCTIONS, SUCH AS ACCOUNTING, HR POLICIES, BENEFITS ADMINISTRATION, EVEN ISSUES SUCH AS REAL ESTATE, LEASES, SITE SELECTION, ETC.)?

G. Baxter: As a scientist starting a new business I knew I would have to fill numerous roles, above and beyond the scientific aspects. In start-up companies most everyone involved usually has multiple roles. My responsibilities cover everything from dishwasher, to head of HR, to negotiating licenses and everything in between. The benefit to having these roles is that as the company grows I will have an intimate understanding of these positions and be better prepared to select the right individuals to fill these roles and be able to provide better oversight.

M. Haslanger: Finances, particularly as practiced by venture capitalists, is the most important function on the learning curve.

C. Hart: One example I can give was when we needed more lab and office space. I was asked to join the committee to choose the architect and to work with her in designing our new space. This was an excellent and memorable experience, and really forced me to think hard about the efficiencies (and inefficiencies) of drug discovery research. We ended up visiting a number of other company labs to assess the advantages and disadvantages of particular design and layout issues. This was also a situation where we were trying to use the design of the building to facilitate interactions between groups traditionally isolated from each other in their day-to-day activities (chemists, biologists and engineers).

What resources have you relied on to broaden these skills (e.g., seminars, articles, books, etc.)?

M. Haslanger: There's been no time for structured learning, I have "learned by doing" with varying degrees of success.

G. Baxter: To broaden my skills, I initially read articles and books. After gaining enough knowledge to ask intelligent questions, I have relied on the advice of experts such as seasoned business people, accountants and attorneys.

What's been the biggest challenge and the greatest satisfaction?

G. Baxter: The biggest challenge has been raising sufficient capital. The greatest satisfaction has been being able to participate in the growth and evolution of a technology from concept to product.

M. Haslanger: The biggest challenge is communicating with a very diverse audience in the investment community. The greatest satisfaction comes from building a great team of people who are having significant impact on the way drugs are being discovered.

C. Hart: The greatest challenges and the greatest rewards working in a start-up environment are related, and both come with assembling and working in project teams. You get people coming together from different scientific disciplines, different organizational experiences, with different skills. You then get going on a problem where each is contributing what they do best, everyone is clear on the goals and the ultimate purpose of the goals, and the efforts of both the individuals and the group are appreciated and recognized. When this machine gets going, and everyone is clicking, it is a very special thing—productive, creative and rewarding for both the company and the individual.

Well then, what are some of the advantages of working in pharma versus a biotech start-up?

C. Hart: An advantage of being part of big pharma is the wealth of resources at your disposal, if you know where to look. There are experts within the company on nearly every disease, nearly every target type and nearly every analytical platform. Although it may take three phone calls or three e-mails to track down the person with the expertise or information, once they find out you are a 'fellow employee' and have true need for the information, help is usually yours for the asking. Likewise, unlike most biotech companies that have a limited budget for commercial database access, journal subscriptions, industry intelligence reports, etc. etc., the major pharmaceutical companies usually have excellent coverage of these resources as well as experts in using them on staff.

Another key aspect of working in pharma (although this can be true for biotechs as well) is the opportunity to be part of international teams. Working closely with people in other countries is a great way to get a close inside look at different cultures and traditions.

Another advantage of employment in big pharma is that the opportunities for formal personal and professional development training tend to be much greater. Whether the topics are presentation skills, organizational management training, more effective supervision and the like, formal training opportunities are much more common and encouraged. (Yes, I know some see this as a disadvantage!)