Smith, Charles D. PhD
At one point in my career, I worked for a major pharmaceutical company and I then returned to academics in a variety of institutions. I am now at the Medical University of South Carolina (MUSC) in Charleston, but I also am involved in 2 startup companies: one I founded in Pennsylvania while I was at Pennsylvania State University, called Apogee Biotechnology Corporation, and a new one founded at MUSC in 2009, called Vortex Biotechnology Corporation. In this paper, I will share my perspective on what it is like to be a faculty entrepreneur and some things to think about if you are considering forming a company and starting down this route toward commercialization.
THE TECHNOLOGY TRANSFER OFFICE OPERATIONS
To begin this discussion, it is important to consider the goals of academic technology transfer. The Association for University Technology Managers1 has listed 4 major reasons for academic technology transfer: (1) to facilitate the commercialization of research results for the public good; (2) to reward, retain, and recruit faculty; (3) to induce closer ties to industry; and (4) to generate income and promote economic growth.
The first reason, facilitating commercialization of research for public benefit, is the main driver because there is a need to translate discoveries and basic research into therapeutically useful products. With the obvious potential for financial rewards, this also could be a significant incentive for academics to become involved in these activities and can thus be used as a mechanism to reward, retain, and recruit faculty. Technology transfer promotes closer ties to industry which may in turn help the university's development goals. Finally, technology transfer can generate income for the university and often to promote economic growth within the university's state.
To facilitate these goals, a research-oriented university typically will have a technology transfer office (TTO) that serves several purposes. Most offices are charged with identifying innovations-that is, faculty research projects that have potential commercial value. Because this identification often depends on reporting by inventors about their discoveries, most TTOs are proactive and have their staff going out and talking to investigators to try to find out about the research in their laboratories. Frequently, the TTOs become involved once you, the researcher, file a disclosure document identifying the invention that you believe you have created in your laboratory. As employees of the university, we are typically legally bound to disclose any inventions that result from our research to the institution because that intellectual property belongs to the institution and not to the individual investigator(s).
Once these disclosures are filed and evaluated, the next major component of the TTO's role is to start the patenting process which protects the intellectual property rights to those inventions. Later, for commercialization, the university also acts as a marketing entity to try to move these intellectual property packages out into the corporate sector. The TTO will lead the negotiation of licensing arrangements.
A common scenario in an academic laboratory is that a research project is progressing well, and the investigator makes discovery which she or he then discloses to the university TTO, as required. The TTO then evaluates the commercial potential of the discovery, and the intellectual property position around the particular invention, to decide whether it is worthwhile to file a provisional patent application. It is important to realize that clock starts ticking on the filing date of that provisional patent which is called the patent's priority date. When the patent is issued, the owners have certain rights for 20 years from the patent's priority date. Thus, once you file a provisional patent, you need to move forward as quickly as possible because the value of the technology is typically in its end stage. Early on when you are still developing it, the technology has little or no commercial value. Later-stage products with the concomitant reduction in risk for failure are of much greater commercial value. Thus, you need to move as quickly as possible through the development process to preserve as much of the patent protection for the end stage.
Once you have a provisional patent, the TTO then acts as a marketing entity and will search for companies to license the technology. The challenge here is that early on, the academic invention is usually at such a nascent stage that it is difficult to someone to license that technology as is. So, for example, if you come up with a compound or a series of compounds, you may have to file a provisional patent that carves out some proprietary chemical space around those compounds because those compounds are unlikely to be the end drug. Licensing that patent to a major pharmaceutical company at that stage is very difficult.
If the TTO fails to find a company to pick up this license, the technology can die in terms of its commercialization potential. You can still follow through with your research endeavors around this technology, but it is unlikely that this patent will be converted to a product because universities are reluctant to go forward with converting patents and putting substantial money into intellectual property expenses if no obvious licensor has been found.
FORMING A SPINOUT COMPANY
Another approach to moving discoveries forward is for the faculty member(s) to form a company around the technology and thus to take ownership of the discoveries, develop them, and sell the products. A faculty spinout company is just that: a new company formed by one or more faculty members, often also with outside advisers, to develop a specific technology related to an invention that was made by one of those faculty members. The rest of this paper will focus on academic spinout companies.
It is important to think carefully before you decide to enter this area because creating a spinout company is time consuming and also can be expensive. So before you decide to move into developing a new faculty spinout company, you will want to consider several important issues. First, what is the mindset at your university with regard to involvement in a spinout company? Most universities are becoming more proactive regarding faculty involvement in spinouts and commercialization because of both the mandate from the National Institutes of Health (NIH) to move technology forward and because of the potential upside for the university should their discoveries be commercialized and then provide revenue back to the institution. That said, not everyone is fully supportive of faculty members starting a company because there are a number of issues that need to be considered. As a faculty member contemplating involvement in a spinout, it is helpful to consider the experiences of other faculty members at your university that may have done this before you. Did the others meet with internal resistance? Was the university supportive and willing to help with this type of commercial endeavor? This can differ widely among different universities.
Next, also consider the time and financial commitments required for commercializing a technology, and in doing this, you need realistic expectations about the process. What are the time lines and the funding requirements? If you are thinking that you are going to form a company and work on the compound for a year or so, then license it to a large pharmaceutical company, and make $1 billion, you do not have realistic expectations. The process takes a lot of money and effort to move inventions forward, and you must be prepared to put time and effort into this endeavor.
Another decision is to determine how involved you want to be in the development of this technology. There are some inventors who just want the technology to be licensed out to somebody else who can develop it because they see the commercialization process as a time sink and a potential emotional drain. If you have that mindset, clearly it would not be a good idea to start a spinout company. However, if you want to be a proponent of the technology and be active in pushing its development and following it through (hopefully) to the clinic, then you should consider moving forward with a spinout company.
KEYS TO COMPANY SUCCESS
As a scientist/researcher, you also need to consider your knowledge base. Although you have been through college, graduate school, postdoctoral fellowship(s), and perhaps other research training, this does not typically include business education. However, if you want to be an entrepreneur and be actively involved in forming a company, you need to acquire a new skill set. You need to learn something about accounting, marketing, and other business topics. Basically, you need to participate in the business aspects, not just the scientific aspects, of the company. The scientific aspects are familiar to academic researchers, but also thinking about how the company will be developed, how it will to be financed, and how it is going to progress are more business-type decisions. These require a little bit of a different mindset.
For success, a spinout company will need 3 key ingredients. The first is quality technology: if you are trying to develop something that ultimately is going to provide a poor product, the project is doomed to fail. Second, you need the right personnel: if you do not have the correct people on board for both the business and scientific activities, the company is unlikely to successfully develop. Third, you need adequate funding: the cost to develop a new drug ranges in the hundreds of millions of dollars. Most small biotechnology companies do not expect to take their product's development all the way through approval by the Food and Drug Administration and may be expecting to out-license the technology after phase 2 clinical trials, for example. However, even getting to that point will likely cost tens of millions of dollars. Therefore, you have to be aware of what funding mechanisms are available and appropriate for the different stages of company development.
Finally, you must consider whether you can put the company's needs before your own. If an academic investigator is a scientific founder of a company, there comes a point where she or he will probably need to step aside and allow business people to take over the company's development. A common problem occurs when the scientific founder has such an emotional commitment to the company that he or she is reluctant to allow business experts to take over. This reluctance can hurt the company's development because there comes a time when the company becomes a commercially focused entity instead of a scientific endeavor. At that point, you need to be willing to give control to people who can successfully drive your company through those business development processes.
RAMIFICATIONS OF STARTING A COMPANY
When considering the ramifications of starting a faculty spinout company, you need to know your institution's conflict-of-interest policies. This is critical because these standards will define how you interact with the university in your company capacity. They also will determine what is allowable in terms of resource use, time spent, and so on. These standards vary markedly from university to university, although the current trend is that these policies are becoming more stringent in their regulations.
One issue to consider is your use of time during the day, that is, is there a conflict of commitment? If you are going to maintain your academic position and also to be involved in the development of the company, the company-related effort will take time from your academic career. Most universities permit some level of effort that can be devoted to outside activities such as companies or consulting, and in many universities, this outside effort is on the order of 20% (ie, approximately 1 day per week). Therefore, if your level of commitment to the company is going to exceed that amount (or whatever you university allows), you will need to make arrangements to be less than a full-time faculty member.
If you are considering a spinout company, be sure you consider your long-range plans. If you are not tenured, it may not be a good idea to be thinking about starting a company because there can be ramifications in the tenure and promotion processes. At some institutions, starting a company could be viewed as taking away from your academic life, although at others, commercialization activities are being viewed as legitimate forms of scholarship, and patents count in evaluating the scientific productivity of a faculty member. For example, at MUSC, we explicitly look at commercialization activity in promotion and tenure reviews. That said, you do want to check with your own university to see what the policies are and whether these activities are likely to have a positive or a negative impact on your scientific and academic career.
PLANNING YOUR BUSINESS
In practice, to develop a spinout company, you need a realistic plan, which considers both the scientific aspects of the drug development process and the business components of the company. It is difficult for a purely scientific and academic individual to perform all of the needed functions of a company, so it is common to partner with somebody who has business experience in the area of technology that you intend to develop. As you plan, you need to define your milestones and your expectations for project development, both short- and long-term. It is important to develop short-term goals to keep you on schedule because the patent clock is ticking, and you need to get through the development process as quickly as possible.
To start, you will need a "business plan" which is basically a written document much like a grant application that communicates the essential aspects of the core business and how you aregoing to develop the product. The business plan differs from a typical grant application in that it is a dynamic document. You need to be able to adjust your business plan based on any new findings, new market opportunities, or the realities of your funding. You want your business plan to be as concise and as specific as possible, and for a biotechnology business, there are a number of required considerations.
The first is the matter of intellectual property. As discussed earlier, as a faculty researcher, you must disclose your discoveries to the university so that the TTO can file a provisional patent application and, you hope, convert that to a filing with the US Patent and Trademark Office or a Patent Cooperation Treaty filing. For your company to have a product to develop, you need to license that technology from your university through a licensing agreement.
Second, you must manage any conflicts of interest. As mentioned earlier, having your university's rules well defined and clearly denoting your roles in both your academic and your commercial activities are critical. In doing this, you also should discuss with your university any additional institutional resources that your company may require. For example, you will likely need wet laboratory space. Many universities have biotechnology incubator facilities associated within the institution or within the same city. Addressing these issues before you begin is critical because you need to clearly dissociate company-related activities from your academic laboratory activities. You do not want to be working on company projects within your academic laboratory because that could result in a conflict of interest and lead to problems in determining ownership of further inventions.
Next, one must consider infrastructure needs. Instrumentation and specialized facilities costs can pose difficulties for a small company, but universities typically have much of the needed infrastructure. For instrumentation needs, one option is to arrange for use of instruments at the university on fee-for-service basis. Most universities offer these services. Similarly, if you are developing a product that requires animal testing, your company will probably not build its own animal facility. Again, the university can typically provide assistance by providing access to animal resources on a fee-for-service basis. In this type of arrangement, the University's Institutional Animal Care and Use Committee will manage the research protocols for the commercial experimentation.
Fourth, you need qualified employees, including business people as well as scientists and various ancillary professional services, such as legal services and accounting. You need to contract with a law firm that has experience with early-stage biotechnology companies. This is generally not a problem in larger cities but may not be available in smaller towns. In that case, you will be working with a firm that is offsite.
Finally, to move your company's project forward, obviously you need funding. At this point, your commercialization project is usually not fundable under the typical NIH RO1 grant mechanism because it is no longer basic research but is commercial product development. There are, however, a variety of sources of funding available for biomedical companies.
FUNDING THE PROCESS
First, when discussing potential sources of capital for an early-stage company, people often mention family, friends, and fools. These sources are typically very limited but may be sufficient for initially forming the business and getting it up and running.
Obtaining a loan (and thus accruing debt) for early-stage development is difficult for a small company, and especially in the current economic environment, this is probably not a viable plan for obtaining any significant funding for a company. Therefore, you need to consider alternative funding sources.
"Angel Investors" are wealthy individuals, usually with interest in a particular commercial area, who want to be involved in early-stage companies. In many cities, organized networks of Angel Investors seek investment opportunities, and these investors typically invest from $100,000 to $500,000. These individuals, if interested, are generally more flexible than are institutional investors or venture capital firms.
A number of venture capital firms focus on biomedical companies. Although some do invest in early-stage companies, most are seeking later-stage companies with a relatively short time to an exit point, that is, an event that will allow them to cash out their position.
Corporate investors, such as pharmaceutical companies, also generally look to partner the later stages of product development, but this varies widely depending on the company, the technology and the development time line. If you are successful in partnering with a pharmaceutical company early in the process, you may be able to not only receive research and development funding but also access the larger company's commercialization expertise.
Other funding options to consider are grants, specifically the Small Business Innovation Research (SBIR) and the Small Business Technology Transfer (STTR) grant programs.2 As detailed at www.sbir.gov, these are federally mandated programs with set-aside funding for US small-business concerns to support research and development with the potential for commercialization. Several government agency receiving funding from Health and Human Sciences, for example, the NIH, Department of Defense, National Science Foundation, and so on, must use 2.5% of its extramural budget for the SBIR program.3 The STTR program is a parallel program, albeit with smaller budget (0.3% of the agency's extramural budget).3 Currently, the SBIR and STTR programs are awarding $2 billion to small high-tech businesses.2 These are very useful programs for a new start-up company because the funding is nondiluting, that is, does not require a transfer of equity in the company to the funding agency.
SBIR AND STTR GRANTS
The SBIR and STTR programs encompass 3 phases of development, not to be confused with the typical phases of clinical trials. Phase 1 SBIR grants are to assess feasibility and for defining a potential product. Phase 1 grants are relatively small grants offering $150,000 in a 6-month period for the SBIR program or $100,000 in a 12-month period in the STTR program (total costs).3 Phase 2 grants are for product development, so they are larger and for longer terms. The budget guidelines for SBIR phase 2 grants allot $1,000,000 over a 2-year award period, whereas the guideline for phase 2 STTR grants is $750,000 over a 2-year award period. These are guidelines, and the average NIH phase 1 award is typically approximately $190,000, and awards for NIH phase 2 projects average approximately $1,200,000.4 Phase 3 is not funded by NIH because this is the commercialization phase. For this, you need to find other sources of monies, for example, from venture capital or through a commercial partnership to conduct the commercialization of the product(s). In some Federal agencies, phase 3 may involve follow-on non-SBIR/STTR funded R&D or production contracts for products, processes, or services intended for use by the U.S. Government.3
One critical difference between the SBIR program and the STTR program relate to the research entities involved. In the SBIR program, the company/small business also is the research entity. You are allowed to partner with a research institution, such as a university, but this partnering is not required. In contrast, for an STTR grant, a partnership between the small business and an academic institution is required. Employment requirements for the Principal Investigator (PI) for the project also are a key difference between the SBIR and STTR programs. Within the SBIR program, the PI must have the small business as his or her primary site of employment, that is, she or he must be more than 50% employed by the company during the award period.3 Thus, the faculty member must reduce his/her effort in an academic position to less than 50% to serve as the PI on an SBIR grant. This is not true for STTR grants, which require only that the PI devote at least 10% effort to the funded project.5 Therefore, the academic investigator can serve as the PI of an STTR project that involves collaboration between a research entity and a small business. The grant is actually submitted by the company; funds are awarded to the company, and the company will subcontract to the university to pay the research expenses at the university.
The general review criteria for SBIR and STTR grant applications are similar to those for a typical NIH RO1 grant, for example, their significance, the extent to which the project meets an unmet need with a market opportunity, how reasonable and feasible the approach is, how innovative the project is, how qualified the investigators are to conduct the research, and the availability of appropriate facilities and resources for conducting the project. However, it is important to remember that the SBIR/STTR programs are designed to support innovative product development-not basic research. For phase 2 projects, which are for product development, reviewers also consider the track record and data acquired during the phase 1 portion of the study. This is important in demonstrating the feasibility of the project. By the end of phase 1, you should have identified what your product will be, and then in phase 2, you outline the processes that you will follow to commercialize that product. In phase 2, the significance, approach, and innovation are all still important, but also weighed heavily is the product development plan. In the phase 2 application, you must be very specific about how you plan to move this product forward and what its commercial use(s) will be. The product development plan is similar to your business plan in that it is concise yet proves that the product has a high degree of commercial potential and that the company's team has the experience to move the product toward commercialization.
The following personal perspective is based on my having served on more than 20 SBIR/STTR study sections, both as a committee member and as the committee Chair for the National Cancer Institute's SBIR and STTR programs. Additionally, both Apogee Biotechnology Corporation and Vortex Biotechnology Corporation have been the recipients of multiple SBIR and/or STTR awards from the NCI and other NIH Institutes. My first observation for successful funding of phase 1 SBIR or STTR grants is to have well-developed preliminary studies. Although preliminary studies are not technically required for a phase 1 SBIR or STTR grant application, I have never seen a successful application that did not have a compelling body of preliminary studies. Second, novel drug targets and cutting-edge technologies (devices, diagnostics, delivery systems, etc) are highly valued in these programs. Conversely, it is difficult to obtain grant funding for a well-explored target for which clinical drugs are already developed.
One fairly common mistake in completing phase 1 applications is to focus too much on the science of the project. It should be kept in mind that the SBIR and STTR programs are not intended for basic inquiry, but rather for identifying and developing a commercial product. A project that has tremendous science but has nothing to do with developing a product will not score well in the SBIR/STTR program. However, applicants with academic backgrounds who have experience successfully writing academic grants often do well in the SBIR/STTR programs because they are familiar with structuring a grant application.
Another requirement for success in the SBIR and STTR programs is having a well-qualified PI. The PI for the project must have the scientific credentials to support him or her acting as a scientific leader for the project. Frequently, with new companies, a postdoctoral fellow or someone associated with the laboratory will be the PI on the SBIR grant, which is acceptable as long as he or she has the scientific background to serve as the investigator.
In applying to the SBIR or STTR program, one should propose a reasonable budget for the project. This may (and typically does) exceed the guidelines, but the reviewers will carefully consider if the budget is reasonable for the amount of work proposed. The budget does not formally impact the review score, but it does affect the sense of whether or not the applicant appreciates the extent and costs of the efforts required to execute the proposed studies. Additionally, it is necessary to demonstrate that you have access to the required resources, for example, animal facilities and analytical instrumentation, often through fee-for-service agreements with a university. If you cannot show that you have access to resources that you need for your project, the project's feasibility may be questioned.
Regarding funding success rates, I believe that there is a perception that obtaining SBIR and STTR grant funding is easy. Although that may have been the case in the past, it is not borne out by current data. Figure 1 presents the success rates for R01 and R43 (phase 1 SBIR) grant applications in 2009 for all NIH institutes. As indicated there, the success rates for both types of applications are generally similar, typically in the 15% to 25% range. Because the success rates do vary somewhat among institutes, it may be advantageous to the applicant if a proposal is targeted to an institute with a higher success rate. Clearly, funding through the SBIR and STTR programs is not a certainty. Historical data for the success rates for the entire NIH SBIR and STTR programs are presented in Figure 2. The data indicate that the success rates for SBIR grant applications have been quite consistent for the past 6 years. Conversely, the success rates for both phase 1 and phase 2 STTR grant applications substantially decreased from the 2004 levels. Since 2005, the success rates for phase 1 SBIR and STTR grant applications have very similar, near the 20% level. The success rates for phase 2 SBIR and STTR grant applications are universally higher than the corresponding phase 1 success rates. Therefore, there currently is a small statistical advantage to using the SBIR mechanism over the STTR mechanism for project development. More importantly, success in obtaining funding of a phase 1 grant application lays a solid foundation for successful competition for subsequent phase 2 funding.
In conclusion, the NIH has mandated that academic institutions translate their basic science discoveries into new commercial products. This mandate has placed increased emphasis on developing mechanisms for technology transfer, and one viable mechanism is to create a faculty spinout companies. However, in doing this, the investigator needs to be aware of the emotional and professional ramifications of choosing to go down this path. Additionally, options for obtaining funding for the commercialization of the technology will need to be examined early in the life of the company. Several states have early-stage commercialization programs that can be accessed. However, one of the best sources of early-stage funding, are the SBIR and STTR programs of the NIH and other government funding agencies. The SBIR and STTR programs provide substantial funding for product development. These are nondiluting sources of capital for small business and should be accessed as early as possible in the development of the technology.5
QUESTIONS AND ANSWERS
Q: …I am an author for some SBIR and STTR grant applications. I am not sure about NIH, but regarding…the Department of Defense, we fund a bit more in SBIR and STTR, but we fund contracts. That process is a little different than the grant world, with the reporting requirements and things of that nature. NIH also is a contract, too, right? It is not a grant?
A: NIH SBIR and STTR awards can be either grants or contracts, but the large majority are grants.
Q: With the Department of Defense, you accept a contract.…it is important to pursue several phase 2 grants because continual phase 1 funding can be a little detrimental on getting funding…. Is that true with the NIH program too?
A: Yes, it is true for NIH grants also. From that, you can take 2 points. First, because the phase 1 grants are short term, living with just phase 1 grants is unnerving because phase 1 grants are an unstable source of revenue for the company. However, you are correct: it looks bad for a company to be exploring many different areas with numerous phase 1 grants and never following through with phase 2 grants or further commercialization of the product. The reviewers do view that as a negative.
Q: So if I gathered some preliminary data, could go straight to a phase 2 grant?
A: No, you need to obtain phase 1 funding first. Once you have the phase 1 grant, you can apply for the phase 2, but you must describe what you developed under phase 1. Typically, you would finish the phase 1 and then do a phase 2. There is a program called the "Fast Track" through which you can submit a grant proposal that essentially covers both phases 1 and 2. Very specific milestones are set to evaluate the success of the phase 1 component, and the project undergoes an administrative review after phase 1. Program will award the funds for the phase 2 component if the milestones have been met. This accelerates the time line of the project because it does not have to go through peer review at the end of phase 1.
Q: I have secured funding from a state trust fund to develop a new product. Does that affect me positively?
A: Yes. Similar to your situation, some states have programs that will match phase 1 SBIR/STTR grant awards (usually partially and/or capped). It is a positive with the reviewers if you indicate that you are able to leverage the investment from the SBIR or STTR program by acquiring these other sources of revenue to drive the program forward.
The author thanks Carie Lambert for editorial and technical writing assistance in preparing this manuscript for publication.