Focused, goal-oriented research is a rarity in the US National Institutes of Health's (NIH) grant portfolio. But with a $52 million budget until 2005, the NIH's Unconventional Innovations Program (UIP) is showing that it is possible to hold investigators to an aggressive development schedule that turns high-risk science into high-reward commercial products. UIP's use of a unique contracting mechanism, instead of grants, is both driving state-of-the-art science rapidly toward the clinic and spawning the birth of several new companies.

Hollow nanoparticles can be filled with any number of imaging agents or anticancer drugs. Credit: Paul Trombley, Center for Biologic Nanotechnology, University of Michigan

UIP was created in 1998 and administered by the National Cancer Institute (NCI; Bethesda, MD, USA) in an attempt to capitalize on the potential of new technology to radically improve cancer diagnostics, imaging and treatment. Review committees allocate an average of $500,000 for three years, renewable—three projects have already received additional funding.

Of the 12 groups that have received UIP contracts, a majority are in nanotechnologies and at least three of those are nearing human clinical trials. For example, Greg Lanza and Sam Wickline of Washington University (St. Louis, MO, USA) have UIP funding to put together a group of researchers from their home institution, biotech company Kereos (St. Louis, MO, USA), Dow Chemical (Freeport, TX, USA) and Phillips Medical Systems (Andover, MA, USA) to create targeted perfluorocarbon-based nanoparticles that are capable of imaging tumors as small as 2 millimeter. Kereos, which has licensed the technology, hopes to file an Investigational New Drug application within a year or so.

What's most remarkable about UIP, say academic researchers and corporate officials alike, is that the program is pushing a lot of good work into the commercial realm. Yet, these projects would have never even come close to being funded by the traditional NIH grant process. "Without UIP funding, this technology would be sitting in the lab, years from commercialization," says Prasad Sunkara, chief executive of Molecular Therapeutics (Ann Arbor, MI, USA).

The company partnered with Raoul Kopelman at the University of Michigan who, together with biophysicist Brian Ross and neurotoxicologist Martin Philbert, developed so-called nanopebbles—50 nanometer spheres of polyacrylamide—that act as both magnetic resonance imaging agents and delivery vessels for anticancer drugs (see picture). Now, Molecular Therapeutics is gearing up to submit an application for an investigational new drug status to the US Food and Drug Administration (Rockville, MD, USA) for their product.

According to NCI's Ed Monachino, who manages UIP, the program owes its success to its use of contracts rather than grants, similar to the approach that the US military's research arm, the Defense Advanced Research Projects Agency (DARPA; Arlington, VA, USA), uses to foster the development of high-risk research. Contracts, as opposed to grants, set specific milestones to ensure that research is staying on track; contractors must meet on a quarterly basis to continue receiving funds. "It's very time consuming from the program managers part and very demanding on the researchers," says Monachino, who adds that this approach doesn't suit everyone in academia.

But for those who can buy into the method, the benefits are legion. "When you're going at breakneck speed to take something from the lab to the clinic, you need some kind of review and someone external to enforce scientific discipline, to think about what you're doing and what you need to accomplish," says Baker.

The payoff, says Garry Kiefer, research leader in the Pharmaceutical Technology Group at Dow Chemical and one of Lanza's collaborators, is that "[this program] enables companies to invest in high-risk technology with a reasonable investment of resources."

And given the dearth of venture capital available today to fund companies doing high-risk, high-reward work, UIP is filling a much needed role for small biotech companies, too. "UIP is bridging a critical gap in funding these days," says Robert Beardsley, chief executive of Kereos.

More information on UIP funding opportunities is available on the NCI website.