A Model For Life Sciences Research Funding

By Wayne Koberstein

Ever wonder where the money goes when you donate to a large “Fight This Cancer” campaign? How does such a donation translate into productive research? What are the chances it will help yield a breakthrough treatment or “cure,” which many campaigns proclaim as their goal?

Similarly, if you run a life sciences company or plan to start one, do you know for certain that the vast sums raised by megacampaigns are distributed to researchers in a rational way? Do the funding organizations systematically ensure meaningful results? And do they present a clear route by which companies can obtain access to the funded research for commercialization into products that benefit patients?

One funder that can arguably answer yes to all of those questions is the Prostate Cancer Foundation (PCF). It not only does an effective job of research funding and coordination in prostate cancer, but also inspires emulation outside its immediate sphere. With its strong science-driven focus, tight research timelines, and unique role as a community of academic and industry researchers, the foundation stands as a new model for other funding agencies in the life sciences.

OFFERING MORE EFFICIENCY AND PRODUCTIVITY IN RESEARCH
The PCF approach may seem like an implicit criticism of the larger charity drives or “megafunds” such as Susan G. Komen for the Cure, but more accurately it is an alternative. Rather than covering every possible base with a vast universe of fundraisers, donors, scientists, marketers, and administrators, the PCF model assumes that a smaller-scale, more hands-on organization, run by physician scientists, offers more efficiency and productivity in research. Its commitment to fast decision making and effective funding also promotes quicker outcomes and analysis of funded research and, therefore, course corrections. Greater coordination and targeting of research may result.

In an era when pharmaceutical companies admit throwing money at research is no guarantee of positive results, it is appropriate to assess the nonprofit funds not just by how much they invest in research but how and where they invest it.

“Philanthropy is more than giving out money; you have to show results,” says Howard Soule, the PCF’s chief science officer. Soule emphasizes that “every one of our awards is science-based, selected to help patients in the short term.”

Did the PCF founders see such accountability lacking in other, traditional funds and intentionally design it into the organization? “There are two answers to that question,” PCF president Jonathan Simons replies, “Yes, and hell yes!”

Like other funds such as the American Heart Association, says Simons, the entire PCF board consists of people who have been touched in one way or another by the targeted disease. Chief founder Mike Milken also brought business principles to the plan, setting up what is essentially a nonprofit venture fund “laser focused” on bringing down prostate cancer morbidity and mortality rates in the shortest possible time frame. “Venture philanthropy” is now a new player in the VC-starved world of the life sciences industry.

Virtually no effective research in treating prostate cancer was taking place when the PCF started up in 1993. Thus, the group has directly pushed almost all significant advances against the disease since then, including five novel drugs approved by FDA in the past three years — a feat no other nonprofit funder can claim. (See “Real Results.”) Meanwhile, prostate cancer rates fell much faster than most other solid-tumor cancer tumors. All that is related to PCF efforts to “create an exchange or marketplace for extremely good vetting and evaluation,” according to Simons.

Although it is not a patient-support organization of a Komen’s scale and variety, the PCF supports research into better prevention, detection, and the range of early to late treatment, with related programs in nutrition, genetics, disease mechanisms, tumor metastases, and diagnostics. All are superficially similar to the research areas of Komen and other cancer groups, were it not for the much tighter timelines and coordination of the PCF system.

“Looking at small companies and start-ups, and at how innovations get to the patient, we are very interested in what we can do as a nonprofit,” says Simons. “We never put a philanthropic dollar into a company, but we often put a lot of money into university science that can open up or amplify a technology for companies. So, we are constantly curious about where the best research ideas are in government, in universities, nonprofits, and for-profits. And, we are constantly talking to companies, trying to introduce them to the scientists who have those ideas.”

The PCF’s first purpose is not to be an economic development force, but it does help companies by funding preclinical studies, “de-risking” technologies prior to commercialization and by personal diplomacy and networking — it bridges between academia and industry. It also aids companies directly with services that support product development, from funding trials to expert guidance, according to Simons. “We can assemble a scientific advisory board for any company in about a week, on almost any topic, with experts from around the world.”

TWO WAYS TO GET THE PCF’s ATTENTION
A researcher enters the PCF community in one of two ways — by writing a tight paragraph stating the purpose and value of the research to be funded or by receiving a tap on the shoulder from PCF scientists on the hunt for programs that fit its goals and the “human capital” they contain.

“If you can say, in four sentences or less on a piece of paper, how a relationship with us can get science to the patient and then how the patient could benefit, it presents an easy value proposition for us to be involved in,” Simons explains. Most other organizations use an NIH-like application procedure that may start with a summary letter but ultimately requires all the bureaucratic skills of a good grant writer.

Plenty of examples abound of the “shoulder-tap” route into the PCF family. Two investigators who answered the foundation’s call and have since become leaders in the group are James Allison, Ph.D., chair of the Sloan-Kettering Institute, and Matthew Smith, M.D., Ph.D., at Massachusetts General Hospital.

Now on the PCF scientific advisory board, Allison was a researcher at UCLA who had not yet focused on prostate cancer until Howard Soule approached him in 1999 regarding his early publication on the potential of anti-CTLA-4 strategies. The PCF subsequently funded Allison’s mouse models and further work that eventually led to the approved immunotherapy ipilimumab and others in development.

“They track interesting things in the literature and try to bring people into the prostate-cancer community. That’s certainly what they did with me,” Allison says. “They took note of my work and helped steer me into prostate cancer, and they stayed with it the whole way — helped fund clinical trials, helped two companies launch two drugs together, and helped me understand the business side. It is not like interacting with a funding agency; it’s more like interacting with a community. It has a common goal.”

PCF applicants receive a funding decision within 60 days, and successful applicants obtain funding within 90 days of applying. From there on, everything is geared for synergy and rapid results. All funded researchers enter a network of collaboration, culminating annually in a retreat where they report on their progress and exchange insights with peers, interact with industry researchers and executives, and plan groupwide priorities and goals for further research.

The invitation-only annual retreat reflects the organization’s overall approach. There it gathers the “best and brightest” in prostate-cancer research worldwide to sit in one big room for presentations with ample discussion. Over the two days, the PCF defines a set of critical research questions, develops the research agenda for the coming year, and then funds the research, either alone or in cooperation with other funders such as the DOD and the NCI (National Cancer Institute).

PCF does not support basic bench science; all funded projects must have the potential to initiate clinical trials within two years. That admittedly difficult timeline, compared to the decade-long vista more common among the megafunds, tends to focus minds and resources on the goal of bringing benefits to patients. At the same time, and along with a suite of special grants to “young researchers,” the foundation often funds an investigator over an entire career, as it has with Allison and Smith. It also funds a handful of institutions to do specific but large “challenge” projects, each designed to answer one of its critical research questions.

A BEST PRACTICE FOR RESEARCH FUNDING
Several good reasons exist to see the PCF model as a best practice for coordinating funding and research. If accountability for the results is important, the model appears designed to ensure it. The PCF emphasizes accountability and transparency in numerous ways, from its lean structure to its concentration on science over marketing and administration. At least two other disease-research campaigns, the Melanoma Research Alliance and the Michael J. Fox Foundation, both founded since the PCF, share many aspects of the same model.

But what about fundraising? The megafunds have set records — Komen alone raised more than $4B last year, with fundraising events in almost every U.S. city and town. The PCF also raises funds from major donors and local events, about $40M last year and $475M since its inception. But PCF revenues go mainly to science, according to Simons. “Of course, we work hard to raise money, but the purpose of fundraising is to drive more human capital into research.”

The PCF also “amplifies” its own grant money by attracting additional private and public investment. The group cites a total of more than $10B in financial capital it has attracted to prostate-cancer research from government, VCs, pharma and biotech companies, academic centers, and others. It also counts among its “results” $100B in “human capital” — supporting more than a thousand new scientists and 9 out of 10 publications in the field — as well as “incalculable social capital” in its overall impact on research and treatment.

A final note: Like global warming looming over the natural world, one eminent and common danger all disease philanthropists face is radical reductions in public research funding, especially by the NIH. Congress seems bent on hitting science on many fronts, but has singled out basic medical research as one of its preferred targets for federal cutbacks — exactly the area least covered by any other funding.

“Severe NIH cutbacks would obviously affect the PCF research enterprise,” says Simons. “We would naturally have to work to fill in the gap as much as possible. Government research needs to be viewed as an investment, not an expense. In the end, it is research and science for patients that creates the real value.”

SIDEBAR
REAL RESULTS
The Prostate Cancer Foundation and its partner, the PCF-Department of Defense Prostate Cancer Clinical Trials Consortium (PCCTC), have supported research leading to five novel FDA-approved treatments for prostate cancer in the past three years—an extraordinary record.

Zytiga (abiraterone)
Approved May 2011 for metastatic, castration-resistant prostate cancer
Abiraterone is a new targeted therapy in the class of androgen production blockers. In total, PCF invested $8.2M in research (PCF Creativity and Challenge Awards 2007-2010) for fast-forwarding treatment science research around abiraterone.

Xgeva (denosumab)
Approved September 2011 for bone loss in non-metastatic prostate cancer
Patients undergoing androgen deprivation therapy (ADT) tend to be at high risk for fractures, including fractures of the spine. Denosumab injections increase bone mass to reduce the risk of such fractures. Since 1997, the PCF has invested more than $1.8M on the work of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center on denosumab and treatment sciences on improving survivorship.

Yervoy (ipilimumab)
Approved March 2011 for melanoma
Research on this CTLA-4 agonist by UCLA’s James Allison, Ph.D., was largely funded by the PCF since 1999 and approved by the FDA in March 2011 for the treatment of melanoma. Phase 3 trials are now underway for ipilimumab in prostate cancer (BMS).

Provenge (sipuleucel-t)
Approved March 2010 for advanced prostate cancer
Sipuleucel-t is a therapeutic vaccine. Since 1993, PCF has invested nearly $2M as venture philanthropy to support dendritic cell vaccines and immunotherapy research including Provenge by Dr. Eric Small at UCSF beginning in 1999.