Nick: My team seeks to apply a deep mechanistic understanding of immune and stromal biology within the TME to design and develop novel therapies that have the potential to either combine with or replace existing standard-of-care cancer treatments. We work collaboratively across the discovery, translational and development groups at Bristol Myers Squibb to progress programs from discovery all the way through to proof-of-concept testing in humans. In other words, we see if the drug we designed to modulate a biological pathway in the TME translates to clinical benefit. As a team we are constantly looking to challenge assumptions, particularly where we know there is more to learn related to TME biology, and this is all done with a relentless focus on patient needs.
Q: What excites you about the work Bristol Myers Squibb is doing in the TME?
Nick: As a pioneer in the field of immunotherapy with two of the first approved checkpoint inhibitors, we are in a unique position to leverage patient-level data and tissue samples from past clinical studies. We can analyze this information to understand what TME characteristics predicted response or lack of response to therapy. Using these insights, we can divide a patient population, for example, non-small cell lung cancer, into distinct groups and prioritize which molecules in our emerging pipeline have the potential to overcome therapeutic resistance in those groups. In this way we hope to identify those patients most likely to benefit from our drugs.
Bristol Myers Squibb has four recently created thematic research centers (TRCs) dedicated to the full breadth of oncology research, which allows us to consider a complete repertoire of treatment combinations across modalities, targets and tumor indications. Combined with a remarkable network of collaborations with physicians and academic scientists outside of Bristol Myers Squibb, we are extremely well-positioned to define key problems and deploy our collective knowledge to create innovative next-generation therapies that drive early, deep and durable patient responses to treatment.
Q: What are some of the challenges researchers face in developing treatments to overcome the immunosuppression that takes place in the TME?
Nick: The TME has been a kind of Bermuda Triangle in developing therapies for cancer, particularly for solid tumors. The TME can have unique qualities depending on the type of cancer, the genetics of the cancer and the location of the cancer in the body. It can also be difficult to study exactly what takes place as it cannot be easily replicated outside of the body. Overall, it is extremely complex and dynamic.
We must look at the TME as a whole and explore key interactions that take place within it. Our ultimate goal is to overcome the many hurdles contributing to the immune suppression that allows for cancer cell survival and progression.
To get a better perspective of how to overcome these challenges, our team looks carefully at preclinical research to get a holistic understanding of how the potential therapeutic will act within the TME. From there, we consider that information in the context of different patient groups to get a stronger understanding of how it may work from a broader population standpoint.
Q: What is it about your work that most motivates you?
Nick: On a personal level, I have seen the difference that immunotherapy can make in a cancer patient’s life. The fact that I get to be involved in and contribute to the innovation and advancements that are currently happening is incredibly motivating.