Craig M. Crews


Craig M. Crews, Ph.D. is an American scientist at Yale University. He is the John C. Malone Professor of Molecular, Cellular, and Developmental Biology, and also holds joint appointments in the departments of Chemistry and Pharmacology. Crews is a former Editor of Cell Chemical Biology and the Executive Director of the Yale Center for Molecular Discovery. His research interests focus on Chemical Biology, particularly on controlled proteostasis. Crews has been a pioneer in the field of Targeted Protein Degradation and his lab's research led to the development of the FDA approved anti-cancer drug Carfilzomib.

Education and training

Crews graduated from the University of Virginia in 1986 with a bachelor's degree in Chemistry, after which he performed research at the University of Tübingen as a German Academic Exchange Service Fellow. As a graduate student in the laboratory of Raymond Erikson at Harvard University, Crews purified and cloned the MAP kinase kinase MEK1, a key kinase that controls cell growth. He subsequently worked in the research group of Stuart Schreiber as a Cancer Research Institute Fellow before joining the faculty of Yale University as an assistant professor in Molecular, Cellular, and Developmental Biology.

Research

Crews studies controlled proteostasis, i.e., the pharmacological modulation of protein turnover. In 2001, Crews developed PROTACs, a new technology to induce proteolysis. PROTACs are dimeric molecules that recruit specific intracellular proteins to the cellular quality control machinery in a catalytic manner for subsequent removal by the proteasome. This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer. The excitement around the field has resulted in private and public investment of more than $3.5 billion in therapeutic approaches based on targeted protein degradation. Prior to its work on PROTACs, the Crews lab’s synthesis and mode of action studies of the natural product epoxomicin revealed that it is a potent and selective proteasome inhibitor. Subsequent medicinal chemistry efforts produced the epoxyketone containing proteasome inhibitor YU101, which served as the basis for the multiple myeloma drug Carfilzomib.

[Arvinas]

In 2013, Crews founded New Haven-based Arvinas, which uses the PROTAC protein degradation technology from his lab to develop drugs to treat cancer, neurodegeneration, and other diseases. In 2015, Arvinas partnered with Merck and Genentech to develop PROTAC-based drugs. In 2018, Arvinas signed a $830M plus deal with Pfizer. On 1 Oct 2019, Bayer and Arvinas announced that they had finalized the terms of their agreement to jointly launch a new company, Oerth Bio, with John Dombrosky as its chief executive officer. Oerth Bio leverages Arvinas’ expertise in targeted protein degradation and Bayer’s decades of experience in developing both human therapies and innovative, sustainable agricultural technologies. On 23 October 2019, Arvinas presented initial safety, tolerability, and pharmacokinetic data from the company’s ongoing Phase 1 clinical trials of two orally bioavailable PROTACs, targeting the Androgen Receptor and the Estrogen Receptor. Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed. Further updates are expected at the ASCO Annual Meeting in 2020.

Proteolix

In 2003, Crews co-founded the biotechnology company Proteolix to develop YU101, the next generation proteasome inhibitor from his lab, which ultimately became carfilzomib. Marketed under the trade name Kyprolis, carfilzomib was approved by the FDA on June 20, 2012 for use in patients with multiple myeloma who have received at least two prior therapies and have demonstrated disease progression on or within 60 days of completion of the last therapy. Based on successful Phase II trials of carfilzomib, Onyx Pharmaceuticals acquired Proteolix in 2009 and was itself acquired by Amgen in 2013 for $10.4 billion.

Awards and recognition