When Robert J. Alpern, M.D., dean of the School of Medicine, was asked recently to prepare a brief overview of the current state of drug discovery for a symposium at Yale’s West Campus, a familiar phrase came quickly to mind: “It was the best of times, it was the worst of times ...”

It’s an apt description. On the one hand, we live in what some call the “post-Gleevec era,” a time when basic research conducted over decades is bearing fruit in the form of remarkably effective, targeted drugs. But the cost of drug development has risen exponentially as clinical trials and regulations have grown more complex. The average total cost to develop a single approved drug is now pegged at a staggering $1.3 billion, a 60 percent increase since 2005.

Early-stage research carried out by academic scientists in settings like the School of Medicine is unveiling more potential drug targets than ever. But research grants are not designed to sustain the many additional steps involved in drug discovery, and academic researchers lack resources to explore these targets further. The expense and complexity of bringing drugs to the marketplace have understandably made pharmaceutical companies risk-averse and selective about which targets to pursue. The resulting gap between academia and industry has become known as the Valley of Death: only a miniscule number of promising discoveries manage to traverse this chasm, and even fewer result in drugs approved for clinical use.

To begin to bend this troubling curve, some pharmaceutical companies have been building scientific alliances with universities, a trend that has picked up steam during the past few years. In March, President Richard C. Levin announced that Yale University had forged a multi-year research alliance with Gilead Sciences, Inc., a biopharmaceutical company based in Foster City, Calif., to accelerate the discovery and development of new drugs to treat cancer.

Gilead will provide up to $40 million to support cancer research at the School of Medicine over four years, and a total of up to $100 million—the largest corporate commitment in Yale’s history—for the full 10 years outlined in the agreement. Yale maintains ownership of all intellectual property generated by medical school research, and Gilead will have the first option to develop any compound it deems promising.

“The collaboration brings together one of the world’s top research universities and a biopharmaceutical company dedicated to addressing unmet medical needs, with the goal of finding new treatments for cancer,” Levin said. “This truly is transformative support that leverages Yale Cancer Center’s top scientists, our West Campus technology investments, and the resources of the new Smilow Cancer Hospital. I can’t think of a better partner to have in this collaboration than Gilead.”

The project will be governed by a six-member Joint Steering Committee chaired by Joseph “Yossi” Schlessinger, Ph.D., chair and William H. Prusoff Professor of Pharmacology at the School of Medicine. The committee will also include medical school scientists Richard P. Lifton, M.D., Ph.D., chair and Sterling Professor of Genetics and Howard Hughes Medical Institute investigator, and Thomas J. Lynch Jr., M.D., the Richard Sackler and Jonathan Sackler Professor of Medicine, director of Yale Cancer Center, and physician-in-chief at Smilow Cancer Hospital. They will be joined by Gilead scientists Howard Jaffe, M.D., a 1982 alumnus of the School of Medicine and president and chairman of the board of the Gilead Foundation; William A. Lee, Ph.D., senior vice president, research; and Linda Slanec Higgins, Ph.D., vice president, biology.

“Yale’s faculty in this partnership bring critical, complementary skills to form an optimal team,” says Alpern. “Tom Lynch brings experience in clinical trials, Rick Lifton has been a leading innovator in genetics and genomics, and Yossi Schlessinger has unparalleled success in cancer drug development.”

Gilead’s Chief Scientific Officer, Norbert W. Bischofberger, Ph.D., executive vice president, research and development, says that pairing with Yale dovetails well with the company’s current focus on oncology. “Based on the strong track record of the Yale cancer research team, I am confident this collaboration will lead to important advances in the understanding of the genetic basis of cancer as we collectively seek to develop novel targeted therapies for patients in areas of unmet medical need.”

Jaffe says that the collaboration was inspired because “Yale had succeeded in bringing together a critical mass of fantastic talent” in genomics, drug development, clinical trials, and personalized medicine. He agrees with Alpern that Schlessinger is an ideal leader for the initiative, because of his role in the development of two of the most significant targeted cancer therapies of recent years: Sutent, a treatment for stomach and kidney cancers, and PLX-4032, a compound that has had unprecedented success in the treatment of malignant melanoma, one of the deadliest and most intractable cancers. (PLX-4032 is expected to receive FDA approval in the coming months.) “Dr. Schlessinger has a pedigree that is unique,” says Jaffe. “He’s been intimately involved in the creation of two transformative medications.”

In the collaboration, tumor samples will be analyzed to identify gene mutations that disrupt normal cellular functions and promote the uncontrolled cell growth and metastasis seen in cancer. Mutations are believed to underlie the development of drug resistance in cancer, and the team will explore this phenomenon as well. Next, the painstaking process of crystallizing the mutated protein to discern its structure begins, with the aim of revealing sites where drug molecules or antibodies can block cells’ aberrant behavior. After a compound is refined for maximum effectiveness, it can be tested in animals, and finally in humans. Genomics may then enter the picture again to determine the profile of each patient’s tumors to create personalized therapies.

“When we find cancer targets that are new, we will work with Gilead on designing drugs, which they can then test in the clinic,” Schlessinger says. “This is a tremendous opportunity for Yale and Gilead.”