Q&A with Robert Plenge: What is Bristol Myers Squibb’s research strategy and where are we taking it?

Robert Plenge, executive vice president and head of Research at Bristol Myers Squibb (BMS), shares insights about our approach to pharmaceutical discovery and research, key platforms and areas of focus, and what he feels are the most exciting opportunities ahead to innovate for patients. 

Q: Tell us a little about BMS’ Research organization.

A: At BMS, the cornerstone of our Research organization is the strategy — how we approach our research and put the different pieces together — and the extraordinary team that puts this into practice. That’s what sets us apart as a company. Our holistic research and development framework is comprised of five key principles that shape our end-to-end approach: selecting targets with strong causal human biology, matching the right modality to a biological mechanism of action, bridging from research to development with early clinical confidence, accelerating development of transformational medicines, and ensuring global patient access. In Research, we are deeply focused on the first three of these principles, which are core to our scientific approach.

The first is what we call causal human biology, or the application of human data — from BMS clinical trials as well as large-scale datasets from around the world — to understand the relationship between disease development and progression and a potential therapeutic target. We leverage this principle at the outset, when identifying new targets at the beginning of the drug discovery journey — often using AI models to help uncover key insights in complex human datasets.

That’s the first part. The second principle is matching the right therapeutic modality to a molecular mechanism of action. Today, there are many therapeutic options, or modalities, for us to choose from within BMS, based on decades of experience discovering and developing new medicines: small molecules, biotherapeutics, and cell therapies, to name just a few. We have accumulated significant expertise across many different approaches, but with so many options at our fingertips, choosing the right one is crucial. We must understand the appropriate treatment approach based on an understanding of the biological mechanism of disease, harnessing the power of our differentiated research platforms. Increasingly, our scientists are using AI to help us connect biological mechanisms to therapeutic strategies more precisely, supporting our goal of choosing the optimal modality from the start.

We also have to consider the specific patient population and manufacturing needs. Ultimately, we need to be intentional and thoughtful about which modality to apply against a type of disease so that we get the best possible results for patients.

And of course, we must ultimately take these medicines to patients at scale. That’s why the third principle focuses on bridging from research to development with a clear path to clinical proof of concept. We think carefully about showing early evidence that a medicine is working — through targeted patient selection, translational endpoints, and predictive diagnostics — so we can increase the probability of success before clinical development even begins. All of these factors help guide how we advance medicines across the R&D continuum.

These principles set the foundation for a research organization that’s unique. We have capabilities and platforms that are truly differentiating, particularly in the areas of targeted protein degradation, cell therapy and radiopharmaceutical therapeutics (RPTs). We’re also advancing additional innovative modalities, such as antibody-drug conjugates (ADCs), to further expand our impact. Additionally, we have amazing team members from all around the world with a passion to help patients prevail over serious diseases. When you stitch all of these together, we believe these factors will help us deliver transformative and high-quality medicines with an increased probability of success. And while these three principles provide the foundation for our research strategy, they’re part of a broader end-to-end framework, strengthened by technologies like AI that allow us to ask better questions, design better medicines, and get them to patients faster.

Q: The three differentiated platforms you mentioned — targeted protein degradation, cell therapy and RPTs — what is BMS doing in these spaces, and why are they so important?

A: Targeted protein degradation is one of the most promising and versatile platforms in our portfolio, and it encompasses a range of approaches — including CELMoD™ agents (also known as molecular glues), ligand-directed degraders (LDDs), and degrader-antibody conjugates (DACs).

Human cells constantly produce and recycle proteins, but when that process goes awry, it can lead to diseases like cancer or autoimmune conditions. Our protein degradation platform allows us to eliminate disease-driving proteins that were once considered undruggable, using a range of modalities that help target proteins for degradation. Beyond our two commercially available protein degrader medicines, we have multiple assets in registrational trials and early development, as well as a very robust discovery program, aided by computational sciences like artificial intelligence (AI) and machine learning.

For example, for prostate cancer, we have an asset that targets androgen receptors, which regulate the growth and development of the prostate. This is the first asset from our protein degradation platform to be studied in solid tumors, and the Phase 1 data validate the potential that this platform brings for patients beyond currently approved degraders for hematologic malignancies. Patients with metastatic prostate cancer have a five-year survival rate of just 32% — across our Research organization, we’re working to change that.

CAR T cell therapy is a type of treatment where you introduce engineered cells into the patient’s body to help fight a disease. CAR T can use the patient’s own cells (known as autologous) or donated cells (allogeneic), enhancing their ability to fight disease before introducing them or reintroducing them into the body. With this platform, we have a comprehensive strategy to unlock the full potential of CAR T cell therapy to deliver transformative treatments to as many patients as possible. BMS is the only company that has two approved CAR T cell therapies with two distinct targets. We have a wealth of experience in clinical development and manufacturing, and we have additional programs that are in clinical development that we’re really excited about. We have a very robust research program in this area, too, allowing us to explore novel approaches like our dual CAR asset, which targets two antigens at once. We’re also going beyond blood cancers and are particularly excited about the potential of CAR T cell therapy to reset the immune systems in patients with autoimmune diseases like lupus.

RPTs are another exciting platform, representing a new wave of innovation in solid tumors. These medicines latch onto cancer cells and deliver a precise dose of radiation to kill them, even when there are low levels of surface markers that identify the cells as cancerous. We believe it’s an important emerging therapeutic modality, and there’s a lot of excitement here at BMS around adding this technology and expertise to our growing capabilities to deliver new and novel medicines to patients leveraging the latest scientific advances.

Q: What are some trends across the industry that you’re excited about?

A: I’m a very optimistic person. I guess that’s why I’m in the Research part of the organization — it’s fun to think and dream, imagining a better future and then working to make it happen. If you just look at the number of new modalities that are out there, and at the increasing insights we have in human biology, we have so many opportunities. Scientific progress in neuroscience, for example, is leading to new therapeutic approaches for patients and their families — from neuropsychiatric disorders like schizophrenia to neurodegenerative diseases such as Alzheimer’s. It’s incredible to consider the possibilities ahead. I’m likewise energized by the collaboration taking place across the healthcare landscape. I always look forward to industry-wide events where we get to meet with innovators from all over who are bringing forward life-changing science.

Another area that’s really exciting is how AI is changing the way we do research. At its best, AI allows us to ask more complex questions and provide better answers, faster — helping us uncover new biology, generate insights from complex datasets, and accelerate early discovery.

It’s still early days, but we’re already seeing how these tools, when guided by scientific rigor and skilled scientists, can amplify human potential.

Ultimately, we’re all working to solve the greatest unmet medical needs for patients. Working across this ecosystem and putting new insights into practice, leveraging cutting-edge technologies like AI and new therapeutic modalities, and working with the best colleagues I could imagine — that’s what leads to transformational medicines that improve patients’ lives.