Dr. Trevor Sherwood, Discovery and Development Sciences, Oncology Chemistry, Bristol Myers Squibb
Title: Discovery of BMS-986526, an EP4 agonist for the treatment of IBD using direct-to-biology cellular evaluation
Abstract: The EP4 receptor is a GPCR expressed in multiple tissues. In the intestines, the activation of EP4
is linked to restitution of the intestinal epithelial barrier and anti-inflammatory effects on immune cells, making it a target of interest for IBD. However, EP4 expression in other tissues complicates the utility of EP4 agonists. For instance, EP4 agonism in systemic circulation has been shown to result in changes in heart rate and blood pressure. We set out to identify selective EP4 agonists with minimal systemic exposure outside of the gastrointestinal tract. Our campaign began with a high throughput screen which identified a triazine chemotype that was elaborated into a lead compound which demonstrated high circulating exposure. To identify compounds with lower exposure, a direct-to-biology campaign leveraging a nanosynthesis platform was undertaken, enabling us to rapidly explore novel chemical space and identify BMS-986526, a lead that was subsequently nominated as a development candidate. This presentation will describe SAR of our lead chemotype, the execution of our nanosynthesis and direct-to-biology campaign, and the full in vivo profile and synthesis of BMS-986526 and other related leads.
Biosketch: Trevor grew up in New Hampshire and earned his B.S. in chemistry at Rensselaer Polytechnic
Institute in upstate New York in 2008 working with Prof. Robert J. Linhardt on the synthesis of carbohydrates. He then traveled south to New York City where he earned his Ph.D. in 2013 in the laboratory of Prof. Scott A. Snyder at Columbia University, where he completed multiple total syntheses of alkaloid and polyphenolic natural products. In 2013, Trevor joined the Bristol Myers Squibb Discovery Chemistry group in Princeton, NJ, where he has performed research on a variety of different target classes for the treatment of autoimmune disorders and cancers and has led multiple drug discovery programs. Trevor also researches applications for photoredox catalysis in medicinal chemistry with a particular focus on cross-coupling chemistry. He is passionate about LGBTQ representation in chemistry and co-organized a session at the 2024 Spring ACS National Meeting featuring presentations from LGBTQ medicinal chemists. He is now Senior Principal Scientist in Oncology Chemistry as BMS.
Honors and Awards:
American Chemical Society Division of Organic Chemistry Early Career Investigator Award,
2021
Bristol Myers Squibb Research Leveraging Technology Innovation Award, 2019
Bristol Myers Squibb Immunology Chemistry Innovation Award, 2016 and 2023