C&EN Talks With Kevin Sweeney

It’s said that in every election, a campaign takes on the personality of its candidate. The same can be said for philanthropic efforts, says Kevin Sweeney, coordinator of the Rosenberg Alzheimer’s Project, an 11-month-old organization that supports alternative ideas for developing Alzheimer’s disease drugs. Sweeney ought to know. Before joining the project, he played leading roles in presidential campaigns and held senior environmental posts in the Clinton Administration.

As Sweeney explains, the Rosenberg Project bears the mark of its founder, California philanthropist Douglas C. Rosenberg. In a three-year period, Rosenberg lost his father and both of his stepparents to Alzheimer’s and felt compelled to do something. He built a foundation the way he built his real estate development firm—around the idea that facilitating dialogue between different stakeholders helps speed solutions. In this case, rather than community leaders, the parties involved are labs pursuing novel Alzheimer’s therapies.

The hypothesis behind most Alzheimer’s therapies in drug development is that plaques made from the amyloid-β peptide are the problem. But one lab with funding from the Rosenberg Project, led by Dale Bredesen of Buck Institute for Research on Aging, has amassed evidence that instead suggests Alzheimer’s is the result of a signaling imbalance. The precursor protein to amyloid-β can be cleaved to produce different peptides, and according to Bredesen’s work, the balance between those cleavage products underpins remembering and forgetting. Bredesen’s lab is part of a research network that has discovered a small molecule, F03, that shifts the balance toward remembering. The Rosenberg Project is providing support for a Phase IIa clinical trial of F03 in Australia.

The foundation will also fund a company, PharmatrophiX, that is developing drug candidates that activate the p75 neurotrophin receptor, a receptor most abundant in neurons vulnerable to Alzheimer’s disease. The company’s cofounder, Frank M. Longo of Stanford University School of Medicine, is developing an agent for positron emission tomography in mice that could accelerate testing of a portfolio of p75-targeted compounds, including PharmatrophiX’ lead candidate, LM11A-31.

“We believe Alzheimer’s is a massive systems disease with multiple mechanisms involved,” Sweeney says. Much of the clinical-stage activity in Alzheimer’s focuses on a small number of ideas, and Rosenberg, frustrated by this, wanted to pursue other paths, Sweeney adds. “We can look for more of the same, or we can look for things that are different in fundamental ways.”

A main focus for Sweeney, a management consultant who is also a lecturer at the University of California, Berkeley, Haas School of Business, is making sure Rosenberg’s vision becomes a reality. In other words, he finds ways to get conversations going among Alz­heimer’s researchers.

“A lot of the work I’ve done is about transparency and engagement,” including developing a report that helped shift Nike’s approach to labor rights, Sweeney says. But tensions that occur during development of a new scientific idea can hamper communication, he explains. It’s tough to secure intellectual property while also speaking and publishing to help an idea gain traction in the scientific community, he says.

To make researchers’ development journey less of an internal struggle, the Rosenberg Project has adopted rules of engagement that, according to Sweeney, keep intellectual property secure while also ensuring proposals are scientifically sound. As a condition of Rosenberg Project funding, researchers must participate in collaborative discussions with experts from other labs. All labs sign nondisclosure agreements, as do external parties that help vet the science. “They critique each other, and they help each other,” he says.

The Rosenberg Project also provides intellectual property counsel, Sweeney says. “It helps labs prioritize the work.

“The academic pace has served us well for generations,” Sweeney says. “But it’s a pace that doesn’t work for drug development in 2012, if we’re going to solve Alzheimer’s in 13 years as the Obama Administration is asking us to do” through the National Plan to Address Alzheimer’s Disease. That blueprint outlines goals such as developing effective treatments by 2025.

Those goals may seem unrealistic to the research community, given several recent high-profile failures of potential Alzheimer’s treatments in late-stage clinical trials, including bapineuzumab and semagacestat, he notes. “We know there’s fatigue in the area. That’s why we want to make the ground more fertile for new ideas,” Sweeney says.

A Phase III failure “is a really expensive mistake,” he says. The foundation’s mission is to ensure that problems get discovered at less costly phases of drug development. “How do we speed up the learning, without compromising the science, so we can finally get a success?” he asks.

“If it’s a good idea, let’s move it and find out if it works,” he says. “A quick failure is a good thing.

“Churning through ideas—that’s the way to innovation.”