2019 Grantee: Nicholas Cosford, PhD
Sanford Burnham Prebys Medical Discovery Institute
Research Project: Pre-clinical Development of a ULK1/2 Inhibitor for Pancreatic Cancer
Award: 2019 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2019 – June 30, 2021
Dr. Cosford received his BSc and PhD degrees in chemistry from the University of Bath and pursued postdoctoral studies at Emory University. He has 20 years’ experience leading small-molecule drug discovery projects in biotech and big pharma, and more recently in the non-profit sector at Sanford Burnham Prebys Medical Discovery Institute.
Dr. Cosford’s research is broadly structured around the chemical biology of diseases and involves the investigation of small molecule interactions with therapeutically important proteins and cellular signaling pathways. One aspect of his research is focused on studying cellular pathways that regulate tumor cell metabolism, apoptosis and autophagy.
Therapeutically, he is interested in the discovery and optimization of compounds that have the potential to treat cancer, central nervous system diseases and infectious diseases. He is also interested in the application of microfluidic technology to chemical and biological problems.
Cancer cells undergoing rapid division rely on a cellular recycling process called autophagy, which removes damaged cellular components and supplies required nutrients for growth. Pancreatic cancer has been shown to be particularly reliant on autophagy and is sensitive to its disruption. Dr. Cosford and his research team’s efforts are directed toward the development of selective compounds that can interfere with autophagy and the advancement of these compounds into clinical trials.
The investigators have identified a series of compounds that inhibit a key activator of the autophagy pathway, a protein called ULK1. Their lead ULK1 inhibitor drug kills pancreatic tumor cells grown in a dish, reduces pancreatic tumor size in animal models, is orally available and is well tolerated in mice.
To prepare their candidate drug for trials in pancreatic cancer patients, Dr. Cosford and colleagues propose to conduct a series of preclinical studies. They will produce large quantities of their drug for animal testing and optimize how the drug is prepared in order to meet the exacting standards required by the Food and Drug Administration (FDA) for human trials. They will then assess the effectiveness of the lead drug and whether it has the expected effect using genetic models of pancreatic cancer as well as mouse models derived from patient tumors. They will also examine the drug-like properties of their compound using established criteria for safety and potency. Performing these studies will allow the team to obtain the critical data required to move this new therapeutic into the clinic.