‘Translation is a Team Sport’

The Learning Collaborative, a partnership between the Leukemia & Lymphoma Society (LLS), University of Kansas Cancer Center, and the National Center for Advancing Translational Sciences (NCATS) at NIH, is attempting to break the traditional drug discovery and development paradigm by bringing together blood cancer, drug discovery, and development expertise across several organizations. The Collaborative was formed with the goal of targeting repurposed drugs as well as novel, new drugs for the treatment of rare blood cancers.

Last week at a TRAIN (The Research Acceleration and Innovation Network) Webinar, the leaders of this unique effort shared what they’ve learned since they signed the Cooperative Research and Development Agreement (CRADA) in 2010. CRADA defined the resources and expertise each collaborator brought to the effort.

The three partner organizations bring complementary strengths to this collaborative. LLS has ample experience working with industry partners, an established network of experts, about 400 active research projects to contribute, and the sense of urgency that patient-driven foundations uniquely bring to the table. The University of Kansas Cancer Center excels in “bench to bedside” translation in drug repurposing, leadership in chemistry, and pharmaceutical experience. NIH’s NCATS brings a focus on rare diseases, industrial scale capabilities, and pharmaceutical experience.

“While some progress has been made in combating these cancers – half of the FDA-approved drugs of the last decade were approved for use in blood cancers – 50 percent of those newly diagnosed will die from their disease within five years,” said Louis DeGennaro, PhD, chief mission officer of the Leukemia & Lymphoma Society.

Scott J. Weir, PharmD, PhD, director, Institute for Advancing Medical Innovation, University of Kansas Cancer Center, gave a snapshot of the first Learning Collaborative effort, the auranofin project, and shared key insights:

• Keeping the patient in mind will accelerate the process and ensure their needs are front and center in the research agenda.
• Defining the collaboration, setting collective objectives, and managing expectations are fundamental.
• Project management is critical, both to manage across organizations and to maximize appeal to industry.
• Tech transfer must be integrated into teams to optimize the leverage of the data.
• Regulatory science issues that will impact their chances of success need to be addressed in the course of the research.
• Defining exclusivity paths and reimbursement strategies from the earliest stages is central to the effort. The group is working on what they call a “ValueMaP” (Value Maximization Path) to help define the value proposition for drug repurposing.

Currently, there are four active projects, two of them involving repurposing rheumatoid arthritis drugs for use in rare blood cancers (the other two are in earlier stages). The goal is to advance projects to clinical proof of concept within 14 months and to engage industry partners along the way.

This model, said Christopher P. Austin, MD, director, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, can be applied to other organizations, and other diseases. “Translation is a team sport. It needs to be approached that way, and very consciously and deliberately managed that way.”

Documents critical to the Collaborative formation will be made available on FasterCures’ TRAIN Central Station soon.

Resources for Medical Research – We’re Gonna Need a Bigger Boat

By Margaret Anderson, Executive Director, FasterCures

It’s appropriations season in Washington, DC, and we are having an early spring. Why does that make me think of Jaws (the movie)? Because I love the beach and sometimes have nagging anxiety about what swims beneath me when I swim in the ocean? Perhaps. (And yes, I know that sharks attack rarely and they are minding their own business.) More so because I think we have allowed ourselves to forget what the real issue is out there lurking in the water. Resources and the future.

Yesterday, the House Appropriations subcommittee on labor, health and human services, and education chaired by Rep. Denny Rehberg (R-Mont.) convened a distinguished panel that focused on investments at the National Institutes of Health (NIH) and the newly created National Center for Advancing Translational Sciences (NCATS). A lot of the discussion centered on NCATS’ value proposition. And some discussion was about the pros and cons of the NCATS approach. (Let’s remember that NCATS is exactly 2 and a half months old now.)

NIH Director Francis Collins reiterated that NIH support for basic research remains consistent and strong at about 54 percent of the agency’s budget. He said he does not expect that percentage to change. He also emphasized that 98 percent the $575 million funding for NCATS comes from preexisting NIH programs. “We believe we could do a lot with modest resources at this point simply by putting the focus on bottlenecks in the drug development pipeline,” said Collins. Threading the needle? That sounds pretty rational.

Acting NCATS Director Thomas Insel has emphasized that NCATS was created to “complement—not compete with—the private sector.” NCATS pools together existing NIH resources and capacity in translational research to foster greater efficiency. It does not develop drugs; instead, it streamlines and improves processes to increase the odds of getting to therapies faster.

Todd Sherer, CEO of Michael J. Fox Foundation for Parkinson’s Research (MJFF), also providing testimony, noted that in pursuit of a Parkinson's cure, MJFF has funded more than $285 million in research since inception, of which 90 percent has gone straight to translational research. "Based on my experience of what can happen when substantive investments are made in translation, the total contributions NCATS can make to drug development may well be greater than the sum of the parts," he said.

At FasterCures, we support NIH’s efforts to create NCATS. Solutions can be tough to develop, and tougher to implement. Groups like MJFF and other outcomes-driven medical research foundations that are part of our TRAIN network, have demonstrated that innovative approaches to disease research are critical to speeding the R&D process. We must try new, promising avenues. NCATS is one tangible way to get moving. So what about the bigger picture?

We should not forget the larger menace on the horizon, the one that should cause the famous John Williams tune from Jaws to be playing in your head now. And that is the need to continue to keep our eye on the overall NIH budget, and the implications of flat or negative funding for NIH, as well as the threat of sequestration in January 2013. 

NCATS, new and important as it is, only accounts for a very thin slice of the NIH budget. Our national investment at the 27 institutes and centers at the NIH have yielded great scientific discoveries that have and will continue to improve health.

NIH also plays an essential role in sustaining our economy. A report released yesterday by United for Medical Research found that in 2011, the NIH directly and indirectly supported 432,094 jobs around the country. While significant, this is actually 55,000 fewer jobs than in 2010 – which, according to the report, “demonstrates that the lack of sustained investment in the agency is beginning to have an impact.”

The ripple effects of a constrained NIH budget go far and wide. Should sequestration (mandatory budget cuts should Congress not reach a budget agreement) happen, the NIH will lose 7.8 percent of its budget – $2.5 billion. Collins said that this means that “2,300 grants we had planned to give in fiscal year 2013 would not be able to be awarded. It would be devastating.”

Do we need to keep innovating our research system? Of course, but we also need resources. Resources feed that important basic science part of the continuum. Resources keep our young investigators in the field.

As the appropriations season unfolds, we urge all members of Congress and the medical research community to keep our eyes on the prize: a strong NIH will not only protect and sustain nearly half a million high quality jobs. This agency is also our biggest chance of having more “shots on goal” in the search for treatments and cures.

This is about resources. This is also about patients – patients today and tomorrow. This is also about the future. Let’s get our priorities straight. There are big fish – maybe even some really big ones – out there we need to be focused on, and as Roy Scheider who played Amity Police Chief Brody told us in Jaws, “We’re gonna need a bigger boat.”