Venture Philanthropy Strategies to Support Translational Research: Workshop Summary (2009)

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2 Models for Building a Translational Research Program In session two, the hypothetical voluntary health organi- zation, the Colten Foundation, has decided to go for- ward with a translational research program and is interested in hearing about models of organization and leadership structure. How can a program be organized to ensure appropriate expertise and leadership are available? What financial models are effective and effi- cient? Workshop participants offered insight and pro- vided details of some model for addressing these questions. After the decision has been made to utilize venture philanthropy strategies to support a translational research program, an organization naturally begins to consider looking at structural models that have worked in the past for other, similar organizations. Questions about how best to recruit leadership, attract bright investigators into your disease space, and fund sustainable research arise, and much can be gleaned from the experiences and best practices of other voluntary health organi- zations. APPROACHING SCIENTIFIC DISCOVERY Jonathan Simons, president and chief executive officer of the Pros- tate Cancer Foundation, put forth two different models for thinking about how to approach scientific discovery that might be applied to voluntary 21 

22 VENTURE PHILANTHROPY STRATEGIES health organizations that are just starting to set up their translational re- search program. In the “Lewis and Clark expedition” model for scientific discoveries, there is a very clear objective. Drawing from the Lewis and Clark expedition, President Jefferson issued a mandate to explore, map, and document the Missouri River and move westward, discovering the most useful waterways from which to engage in commerce from ocean to ocean. There was no time line. The expedition reported back both suc- cesses and failures. It had the latest state-of-the-art tools, as well as the funding and support needed not just to test a given hypothesis (that a par- ticular path of navigation was viable) but to engage in pure exploration, both generating and testing hypotheses as it progressed. Applying this expeditionary model to a translational research program would imply a diverse, well-funded, flexible, and independent effort. As an alternative to this expeditionary model, Simons outlined the “NASA” model. NASA’s Gemini and Mercury programs were con- cerned primarily with testing and retesting every system and every pro- cedure required to meet the long-term goal before actually mounting the Apollo missions and moving on to the eventual moon landing. Each as- pect of the long-term mission was broken down into individual missions, each conducted independently. Rather than invest in broad, sweeping research and letting each incremental discovery redefine the mission, the NASA approach breaks the problem down into discrete units and ex- plores them independently, increasing the likelihood of making the final “moon shot” successful. Simons sees value in such an approach for trans- lational research. “[It would be better to have] 20 Gemini missions in Parkinson’s disease where you learn an enormous amount than it would be to have three failed, large-scale, basically phase 3 trials.” LEADERSHIP In every successful grand challenge, there is always someone in charge who has not only the knowledge and vision to guide a program, but also the leadership abilities to get things done, explained Linda Van Eldik, professor in the Department of Cell and Molecular Biology at Northwestern University Feinberg School of Medicine. Leadership must include people who can be active participants in that vision. One of the biggest leadership challenges for many translational research programs is cultural—specifically, knowing how to navigate the differences in aca- demic and corporate leadership culture. 

BUILDING A TRANSLATIONAL RESEARCH PROGRAM 23 Traditionally, the leadership model has been that academia and aca- demic advisers drive the agenda, but workshop participants believe this model is changing. Cynthia Joyce of the Spinal Muscular Atrophy Foun- dation explained that for a patient advocacy organization, soliciting ad- vice and guidance from academia and thought leaders and driving research programs is not unusual. What has become increasingly clear, but sometimes less obvious, is that there is no one paid to spend 100 per- cent of his or her time following a problem from start to finish. This cre- ates a leadership gap, where foundations need to step in and act as the focal point for the research, said Joyce. This is especially true of rare dis- eases, where the volume of work is relatively small, she added. Increas- ingly, voluntary health organizations are doing more than just writing checks by presenting research results at scientific meetings if they be- lieve they have the scientific expertise and the broad, constant-attention view that the research needs. Becoming more involved and actively lead- ing the scientific process is an important role for a voluntary health or- ganization. This, of course, amplifies the importance of having a strong, active scientific advisory board, according to Joyce. Hosting scientific meetings is another way that voluntary health or- ganizations are establishing themselves as experts in many fields of en- deavor. They are the conveners and information brokers and can provide an overview of the research landscape. Katie Hood of The Michael J. Fox Foundation for Parkinson’s Research agreed and shared that increas- ingly the foundation receives inquiries from investors, companies, and researchers who want to know who they can talk to or should be talking to in this space. They are often confused about or do not know how to navigate the different players and rapid information flow, and what they want to know is if there is a go-to person who can help point them in the right direction. Increasingly, this “person” is the foundation, she said. Future Leaders: Addressing the Pipeline Issue Richard Nakamura, deputy director of the National Institute of Men- tal Health, believes that there is a desperate need to attract more indi- viduals into research to create not just a year’s worth of research, but a sustained effort that could ensure the pipeline is full. “There’s no doubt that the science right now is great,” he commented, “but our ability to train new scientists and keep them in science has been dropping precipi- tously. We’re losing a whole generation.” Rae Silver, professor of natu- 

24 VENTURE PHILANTHROPY STRATEGIES ral and physical sciences at Columbia University, echoed his concern and expressed that science careers are becoming increasingly less attractive. “There are so many threats around everything that you do, it’s increas- ingly difficult to get research funding, so scientific careers don’t seem to be that interesting and exciting,” she said. Participants agreed that the best way to attract new researchers to a specific disease or area of interest was to recruit. The term “recruit” is used to refer to several ways that voluntary health organizations are at- tempting to attract high-quality researchers to their disease space. By investing directly in researchers and funding their careers, a voluntary health organization such as the Colten Foundation could ensure a pipe- line of talent for years to come. The Prostate Cancer Foundation, for ex- ample, is directly funding the careers of key researchers, said Simons. Joyce explained that in the case of the Spinal Muscular Atrophy Foundation, the disease is relatively understudied, so it was important to first raise awareness of the disease in order to recruit individuals to work on core research and identify new areas for discovery. The foundation invested in recruiting scientists to the field, and Joyce explained that part of this outreach has been through the contract research organizations conducting its fee-for-service research. By increasing its presence in the contract research organization industry, the foundation has increased awareness of the disease overall and the foundation in particular, which will keep new scientists involved with the disease. Similarly, when The Michael J. Fox Foundation started recruiting scientists to its staff research team, it focused on identifying talented young researchers—frequently senior postdocs—who had not yet fully embarked on an academic career. Hood believes that the decision to hire younger scientists who had not yet committed to a single path of research was essential for the foundation to develop an open-minded approach to the field. FUNDING MODELS Once strong leadership is in place, decisions on how to fund and how involved to be with various programs can be made with the voluntary health organization’s long-term goals in mind. Workshop participants spoke about a balance between an organization’s need for accountability and researchers’ need for freedom. Van Eldik put it this way: 

BUILDING A TRANSLATIONAL RESEARCH PROGRAM 25 Historically, investigators would apply for a grant from a foundation or another funding organization and they’d get the grant, and there would be no oversight, no ac- countability for what happened with that money. All of that is changing. Because now, if you are going to try to develop something further on, especially for drug dis- covery, you need to have a set of milestones that you’re accountable for. There’s a balance between having too restrictive a milestone that doesn’t allow any flexibility in the work to be able to take advantage of some of this serendipity that might come up, and having no account- ability. Funding through a grant is a big incentive for academic investigators, concluded Van Eldik, and often investigators work with foundations be- cause of it, but it is also important to recognize that not every project re- quires the same level of management and interaction. For example, The Michael J. Fox Foundation’s Rapid Response Program for early-stage, hypothesis-driven work is very different from the foundation’s other pro- grams. Funding decisions are made extraordinarily quickly, within 6 weeks of receiving an application. There are no milestones. There are no mandatory deliverables. In effect, there is no management to be done, because the nature of the science does not require it. In other funding programs, The Michael J. Fox Foundation is highly involved in the process. Hood said that in the case of a drug develop- ment, multistage grant, the foundation is significantly involved, sitting at the table during decisions. This level of intense involvement is not al- ways welcome and can in fact be problematic. Hood explained that be- cause of this policy of involvement, the foundation found that some researchers would simply walk away rather than put up with what was seen as intrusive management, especially when, like the Colten Founda- tion, The Michael J. Fox Foundation was new to venture philanthropy. Ultimately, Joyce maintained, the Colten Foundation should seek to be a source of not just capital, but smart capital. This essentially means being direct and proactive about funding decisions, focusing on working within partnerships that are productive and funding the best opportunities. 

26 VENTURE PHILANTHROPY STRATEGIES The Base Model: Program Grants While there is no single model of funding research, the most basic is the simple grant. For example, the Spinal Muscular Atrophy Founda- tion’s program grants can include basic, translational, and clinical re- search. Based on the project at hand, deliverables and milestones are established to ensure that all of the parties involved talk to one another. But these basic grants are themselves changing, and sometimes tradi- tional academic contracts begin to look almost exactly like industry ones, said Joyce. The Alternate Model: Fee-for-Service When there are research needs that simply are not attractive to either academia or industry, a voluntary health organization has an opportunity to bridge this gap by paying for the work to be done on a simple fee-for- service basis. At the Spinal Muscular Atrophy Foundation, one such gap was the development of a viable screen assay, Enzyme-Linked Immu- nosorbent Assay (ELISA) for spinal muscular atrophy, a project that had languished in the academic community. “The best way to do it is with a contract research organization,” said Joyce. Fee-for-service contracts such as the Spinal Muscular Atrophy Foundation ELISA project are one of the most unique ways for a foundation like Colten to make a differ- ence—by directly targeting a “dead zone” in the disease space and apply- ing capital. The discussion provided a good list of major issues covered in ses- sion two; these are summarized below (Box 2-1). BOX 2-1 Key Points: Models for Building a Translational Research Program • Sometimes you need to spend time and energy testing various hypotheses in a methodical way. • Strong leadership with a broad vision and set of goals is essential. • If you have the scientific expertise and a broad view, then do not be afraid to lead the scientific research. • Expand the workforce pipeline by investing in researchers and their careers. • Try to strike a balance between researcher freedom and foundation ac- countability. • Be flexible in how you approach each project⎯not every project needs the same level of interaction and management.