Pulse
Pharmaceutical Pipeline
The U makes a push to move drugs from the lab to the pharmacy.
By Trout Lowen
The process of drug discovery and development is most often characterized as a pipeline that starts in the laboratory and ends with commercial production. What is less often talked about outside of the pharmaceutical industry is the decidedly uphill route that pipeline takes.
Thousands of compounds must be screened to find a few hundred that show promise. Of those, maybe five will make it to human clinical trials, and one will get to market. “It’s an uphill battle,” says Jay Schrankler, director of the Office for Technology Commercialization (OTC) at the University of Minnesota. The OTC assists university researchers in translating their discoveries into new products and services. Development of a commercially successful drug can take 10 years or more and cost around $1.8 billion.
Despite that steep trajectory, over the past five years university officials have been quietly assembling a network of industry scientists and academic researchers to advance the university’s research along that pipeline, beginning in 2007 with the hiring Gunda Georg, Ph.D., and the creation of the Institute for Therapeutics Discovery and Development (ITDD). The ITDD has a number of missions: to enable drug discovery and development at the university, to expose students and Ph.D. researchers to industry best practices and project management techniques, and to earn revenue for the university by licensing promising new compounds to Big Pharma. “While we will never be able to market drugs, we will be able to help take these basic discoveries people make in the laboratory and bring them to the level where there is the potential to hand them over to industry,” Georg, the ITDD’s director, says.
Assembling the Experts
The university hired Georg away from the University of Kansas, where she ran an NIH-funded collaboration to develop experimental cancer drugs. Although impressed by her scientific achievements, university officials also were interested in Georg’s experience in the commercial realm. She was co-founder of Proquest Pharmaceuticals and co-inventor of the anesthesia drug Luserda. She had also helped develop a male contraceptive that is now moving toward human trials.
George, who is also chair of the department of medicinal chemistry in the College of Pharmacy, hand-picked five of the directors of the ITDD’s six core units. (The Pharmacology and Biomarkers unit is currently seeking a new director.) All are from industry.
Michael A. Walters, Ph.D., a former Pfizer chemist who heads the ITDD’s Lead and Probe Discovery unit, says he and his colleagues from industry can offer researchers valuable insight into the drug development process. “Drug discovery and development requires knowledge of how industry does that process,” he says. “It’s not that we want to recreate a pharmaceutical company in academia, but we know how things are done in industry, and we can adopt some of their best practices.” For example, the ITDD runs a large-scale lab on the St. Paul campus that operates under good manufacturing practices rules. It also does assay development, high-throughput screening, medicinal chemistry, and disease biomarker development, and it has the capacity to scale up production for clinical trials.
The ITDD is just one component of the university’s focus on drug development. Others include the Center for Translational Medicine, the Biotechnology Resource Center, the Clinical and Translational Science Institute, and the OTC, which has added a number of drug industry professionals to its staff including Reggie Bowerman, a former executive at MGI Pharma and Aventis.
A Nationwide Trend
Minnesota isn’t the only university investing in drug development. A recent survey found approximately 80 small- molecule drug discovery centers located within U.S. universities or nonprofit centers, and that didn’t include the ITDD, Walters notes.
A couple of factors are driving that trend. Pharmaceutical companies are cutting back on basic research, viewing it as too costly and too risky. And, increasingly, the National Institutes of Health, the biggest source of public grant funding for drug research, is expecting researchers to show how their work will translate into actual therapy. “So a lot of institutions are saying we need a drug discovery development unit like this, or we need to partner with one,” Walters says.
And then there is the potential for a big payoff. Since 1999, the anti-HIV drug Ziagen, the most successful drug to be developed at the university, has generated close to $300 million, some of which has been used to fund the ITDD. But Ziagen’s patents are expiring and the university stands to lose millions as a result. That’s giving those driving the assembly of a commercialization pipeline a greater sense of urgency.
Although the chances of discovering the next Ziagen anytime soon are slim, the university continues to generate revenue by spinning off startup companies and concluding license agreements, and it’s always on the lookout for marketable tools or medical devices that might result from researcher discoveries.
The university also hopes having the ITDD will help researchers land more federal grants. But that will require them to develop a new mindset about basic research, says Douglas Yee, M.D., director of the university’s Masonic Cancer Center. “For many years, basic scientists worked on basic problems and didn’t have that much interest in translation,” he says. “I think in the past 10 or 15 years the idea that translation of their findings into something that changes human disease has become an important criterion.” Federal funders such as the National Cancer Institute also want to see multidisciplinary collaboration when recognizing comprehensive cancer centers. “We have to show we have outstanding science and that we work together,” Yee says. To foster collaboration, the university has created formal units called “Corridors of Discovery” to bring people working in the same therapeutic areas together to share information and ideas. The corridors correlate to five general research areas: diabetes, infectious diseases, brain science, cancer, and cardiovascular disorders.
One of the most highly publicized products of these efforts so far is Minnelide, a new treatment for pancreatic cancer. Working in the lab, Ashok Saluja, Ph.D, vice chair of research in the department of surgery, identified several promising compounds that could destroy pancreatic cancer cells including triptolide, a plant substance used to treat arthritis in China. But he needed assistance to take the project farther. Pharmaceutical companies weren’t interested, says Georg, because they couldn’t patent an old natural remedy and, thus, had no incentive to develop a drug.
Triptolide also wasn’t particularly water soluble, which made it difficult to administer. The ITDD stepped in to help. Georg and her research staff at the College of Pharmacy altered the chemical makeup of triptolide to produce a new more drug-like compound, Minnelide. The Center for Translational Medicine is now having Minnelide scaled up for a Phase 1 clinical trial that will probably begin later this year or in early 2012.
It’s a team process, Georg says, with the ITDD acting like the coach or the captain. “I think we were sort of a catalyst,” she explains. “Without us there would be no Minnelide.”
Stewardship
One of the ITDD’s other roles is as a repository of information on all the university’s drug-related research. Two years ago, the ITDD surveyed the university to identify who was working on what drug-related research and at what stage of development it was at, Walters says. The idea was to identify which projects might benefit from collaboration or from additional funding.
As a result of that analysis, the ITDD now plans to focus more closely on diabetes research, an underrepresented area of drug discovery and development at the university. Last October, the university announced a 10-year partnership with Mayo Clinic aimed at curing diabetes. The ITDD expects to play a role in that effort. “The hope is that we bring new drugs to market for diseases where there was no good treatment before,” Georg says. In the long term, the university would like to have another Ziagen-sized commercial success, which could provide an endowment for the ITDD and its other drug-related research efforts. “That’s certainly the hope,” Georg says. “But are we going to succeed or not? We don’t know.”