More than a decade ago, Yale chemist Craig Crews founded a biotechnology company in New Haven based on his pioneering research into PROTACs (or PROteolysis TArgeting Chimera), a technology that treats certain types of cancer and other diseases by degrading the proteins that cause them.
That company, Arvinas, has since developed a PROTAC therapy called vepdegestrant, which is now helping patients living with breast cancer.
Last week, vepdegestrant, which is developed by Arvinas and Pfizer under the brand name Veppanu, became the first PROTAC therapy to be approved by the U.S. Food and Drug Administration.
The once-daily oral therapy will be available as treatment for adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated advanced or metastatic breast cancer. Breast cancer is the most common cancer among women worldwide, with many tumors driven by estrogen receptor signaling.
For Crews, the FDA approval of vepdegestrant as a treatment for breast cancer now has additional personal meaning.
"I'm thrilled that breast cancer patients will have an additional option for treatment," said Crews, who is the John C. Malone Professor of Molecular, Cellular, and Developmental Biology and professor of chemistry in Yale's Faculty of Arts and Sciences and professor of pharmacology at Yale School of Medicine. "My mother was diagnosed last year with breast cancer, and so I know the challenges that patients and their families face with thinking about therapeutic options."
Largely pioneered at Yale, PROTACs have already inspired dozens of other companies that are developing degrader therapies across numerous cancer types.
The FDA approval of vepdegestrant will reinforce that momentum, Crews said.
"PROTACs are a new class of drugs, and this first approval will encourage drug developers to explore the use of PROTACs for other diseases such as neurodegeneration (dementia) and other challenging diseases," Crews said.
For years, Crews has bridged the gap between academia and biotech as a professor and entrepreneur. He has launched several drug development companies, including Arvinas and Halda Therapeutics, which was recently acquired by Johnson & Johnson, a milestone for a company built around a novel therapeutic drug for prostate cancer.
Indeed, Crews's career has been defined by translating research from the lab to the real world. Since 1995, his lab has worked specifically at the interface of chemistry and biology. One early project focused on a small molecule that blocked protein degradation, also known as a proteasome inhibitor. This project ultimately led to the founding of another company, Proteolix, and the development of Kyprolis, a FDA-approved drug for treating multiple myeloma, a blood cancer.
Through this work, Crews became interested in the opposite approach - not blocking protein degradation but inducing protein degradation. At the time, he asked himself: "Could we find a way to drag 'problem proteins' to the natural machinery responsible for recycling proteins inside of cells?"
This led to the development of PROTACs, which were licensed to his second company, Arvinas, in 2013. His lab continued to work with Arvinas through a sponsored research agreement to develop the technology, which led to vepdegestrant's successful approval last week.
Said Crews: "It has been extremely satisfying to take this idea from academic concept to FDA approval over the past 25 years, and demonstrates the continued need for supporting basic research, which is the underlying foundation for most of the exciting new drugs developed these days."
