Last March, an agreement designed to generate new drug candidates for Alzheimer’s disease was announced. One of the partners was AstraZeneca, the global pharmaceutical firm. The other was Penn, specifically the Center for Neurodegenerative Disease Research (CNDR). A press release from Penn Medicine noted that the CNDR “will provide rapid access to unique state-of-the-art drug compound screening assays and knowledge of the biology of tau,” while AstraZeneca’s scientists will supply “basic research with access to the technologies and skills required to discover and develop new drug molecules.”

Each party has a lot to offer the other in the way of skills and resources. If successful drugs emerge and become financially successful, both parties will benefit in terms of royalties and milestone payments. More important, patients will benefit.

“I really think this is one of the models for the future,” says Virginia Lee, “particularly in view of the reduced funding from the government and for academic research.”

Which isn’t to say there won’t be any raised eyebrows at the notion of a prestigious private university partnering with Big Pharma.

“If I had the cure for Alzheimer’s in my pocket right now, it would go nowhere,” John Trojanowski responds. “I don’t have the resources to take that forward and carry it through all the steps required for FDA approval, so it can be a drug made available to clinicians. We have to form partnerships to succeed in the mission of finding cures. That can be done in an ethically correct way, with integrity, and to the benefit of the public.”

The agreement with AstraZeneca was one of the things envisioned back in 2004 when the Marian S. Ware Alzheimer Program was launched at Penn Medicine, sparked by a $6 million gift from Marian S. Ware, a longtime supporter of the University and advocate for medical research and Alzheimer’s treatment. The three-pronged program, which also involved the School of Nursing, focused on drug discovery, clinical research, and care management for Alzheimer’s patients.

In the past, the model worked like this: a university would do the basic research, which mostly involved identifying specific molecules to be targeted, explains Lee. “And very quickly academia would hand that over to a biotech company, generally funded by venture capital. They would then develop an assay. They do drug discovery [and] drug development.

“Often, once the biotech reaches a certain size, and if they have some really good product, they would be bought by a pharmaceutical company,” or the two would form a partnership, she adds. “They would then complete the later-stage clinical trial, and then lead to FDA approval.”

But in the last 10 years or so, for a variety of reasons, the number of biotech companies has shrunk, and the pipeline for developing drugs has dried up alarmingly. The result was what researchers call the Valley of Death for drug development. And lo, into that valley comes the research university.

“We’ve expanded to fill this void and do all the drug discovery, and also to do the preclinical studies,” says Lee. “And I think it’s fair to say that we can actually extend all the way and interact with pharmas as well.”

Kurt Brunden, the scientific director of the Ware Alzheimer’s and Benaroya Parkinson’s Disease Drug Discovery programs at Penn, began his career at the University of Mississippi Medical Center, then moved to Gliatech, a startup biotech company (whose board of advisors included Virginia Lee), becoming vice president of research. From there he went to Athersys, a clinical-stage biopharmaceutical company.

But by 2007, “pharmaceutical output and productivity were very low,” he says, partly because of a more cautious approach to drug approval by the FDA, and also because of various “productivity issues within the companies.” Waves of mergers and reorganizations didn’t help; neither did the financial crisis. The bottom line is that US-based pharmaceutical companies have laid off more than 100,000 people in the last few years.

When he heard about the Ware program, Brunden found himself “quite intrigued by this concept of, in essence, starting what could be thought of as an academic biotech company here at Penn”—even though, historically, drug discovery “is not what academics have done,” mainly because of the multiple disciplines involved and the need for a large “critical mass” of scientists and financial resources. As a result, “it’s only the more prestigious centers that have the kind of infrastructure and the ability to draw these types of funds that are going to succeed.

“But I do think that there is a place for academic drug discovery, particularly given the current trends in the industry,” he adds. “The idea is not to compete with Big Pharma, because that would be suicide for a group our size. It’s to complement Big Pharma’s efforts, and hopefully facilitate some of the things they’re trying to do.”

“Ware enabled us to get our drug-discovery program launched,” says Lee. “Without that we would never be able to be where we are right now.”

Having developed molecular targets and developed assays, she adds, “we want to move some of the preclinical studies further along so we can partner with a pharmaceutical company, which will have much larger resources, to get this into clinical trial.”

Over the past 20 years, the CNDR has developed “a vertical integration for drug discovery,” she says, which includes “all the models and assays we have developed—mouse models, cell-based models.” The drug-discovery program can draw on all that to “identify small molecules that may be the first generation of therapeutics for the treatment of Alzheimer’s disease.

“Drug development is really very, very expensive,” Lee adds. “And what we have that is unique is the collective knowledge and resources—in terms of human brain samples and all the knowledge we gain from genomics and from biomarkers, from pathology, from patient information—as well as all the things that we do in the laboratory. They are all interconnected. And all of this information is fed into our drug-discovery program”—at a fraction of the cost that would be incurred by a pharmaceutical or biotech company.

The important thing is that “everything has to be done aboveboard,” she adds. “All of the deals, like the AstraZeneca deal, go through the Center for Technology Transfer, and then the money is handled by the University.

“So these are important experiments that we are doing now,” she adds. “We’re really pioneers in developing this type of structure, in collaboration and partnership with pharmaceutical companies. And I think that it’s absolutely essential to do that if we want to treat diseases.”—S.H.

 


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COVER STORY: Untangling Alzheimer's By Samuel Hughes
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The Ethics of Alzheimer’s

Crossing the Valley of Death with Big Pharma

Genetic Dragnet


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