New institute gears up to develop better drugs faster

As academic scientists, Giulio Draetta, M.D., Ph.D., and Lynda Chin, M.D., cultivate the patient, long-term research that builds the foundation for understanding and attacking cancer biology. It’s the type of discovery-oriented work published in top scientific journals: Cell, Nature and Science.

As leaders of MD Anderson’s new Institute for Applied Cancer Science (IACS), they’ve built a team of veteran scientists to swiftly and thoroughly evaluate cancer drug target candidates and ruthlessly select likely winners.

This effort is designed to decrease the staggeringly high failure rate of cancer drugs entering clinical trials — today, 19 of 20 drugs entering human testing fail to achieve approval by the U.S. Food and Drug Administration.

“We want to kill a project quickly and early,” says Chin, professor and chair of MD Anderson’s Department of Genomic Medicine, as well as scientific director of the IACS. “Our approach is to conduct a comprehensive analysis on the target at the preclinical stage to validate its essential role in cancer and determine the specific cancer types in which such a target is mission critical.

This knowledge will dramatically increase the probability of success of drugs against that target in the clinical testing stage.”

For the institute, Draetta notes, “Papers in first-rate journals aren’t the true measure of success. New compounds delivered for clinical trial backed by rigorous, comprehensive and reproducible science are the ultimate merit by which we will all be judged.”

Progress in cancer treatment has come via an inefficient process. As noted, only 5% of preclinical candidates become effective, approved drugs. As a result of such a failure rate, developing a new drug takes a long time (on average seven to 12 years), and it may cost more than $1 billion to go from “target” to “drug” to “trial” to “approval.”

Innovation in drug development

Accelerating drug development will require seamless integration of rigorous discovery science spanning genomics, computational science, cancer biology, molecular pathology and more. Equally important, this knowledge must be driven toward clear drug development endpoints through an “applied” engine governed by disciplined timelines and goals.

Giulio Draetta, M.D., Ph.D.

This requires a culture that integrates the scholarly brilliance and creativity of academia and the effective management principles of industry, respectively, Chin says.

The new institute is essentially an agile biotech company embedded in an academic setting. The plan is to:

• exploit the transformative advances in cancer genomics, genetics and biology to identify the best cancer-driving molecular targets,
• execute a research plan designed to elucidate key biology relevant to drug discovery and reach “go/no-go” decisions efficiently and
• develop drugs most likely to succeed by applying industry-level criteria, as well as building a body of biological insights around the drug that will enable its successful clinical development.

“There’s no question that academia is best at the basic discovery science,” says Draetta, professor in the Department of Genomic Medicine and director of IACS. And academia excels with its clinical trials at the end of drug development.

Between those landmarks lies what Chin calls “the valley of death” for candidate drugs, the translational research steps needed to reach Phase I clinical trials.

Bridging that gap requires a goal-oriented culture and seasoned professional scientists with world-class expertise in drug discovery as well as in genomics, computational biology, deep cancer biology and model systems.

Draetta and Chin are former leaders of the Belfer Institute for Applied Cancer Science in Boston. The Belfer Institute was the first iteration of this academic-industry construct launched by Chin and current MD Anderson President Ronald DePinho, M.D.

MD Anderson’s new institute builds on the Belfer Institute’s model, but with internal drug discovery capability and expansion to translational medicine. Draetta and Chin have been joined by 18 scientists from Belfer and plan to have 70 scientists on board by year’s end.

Their industrial experience, coupled with MD Anderson’s research capabilities and clinical excellence present an unprecedented opportunity to improve cancer drug development.