The company’s long history in protein degradation began more than 20 years ago, with Celgene’s (now BMS’) development of the first IMiD® compounds to treat blood cancers. Researchers had been looking into these drugs for decades, but no one had any idea how and why they worked — the evidence was in the clinical outcomes. In the 2010s, scientists made several discoveries that offered stunning clarity and advanced the whole field forward. Today, with targeted protein degradation, researchers are harnessing the cell’s own machinery, for example ubiquitin ligase (E3) enzymes, to degrade disease-causing proteins that were previously considered “undruggable.”
Science Firsthand is a new storytelling platform from Bristol Myers Squibb that celebrates the countless moments along the path from drug discovery through development – unique moments that have the potential to lead to major scientific breakthroughs that ultimately transform the lives of patients. The first episode focuses on the company’s storied history in protein degradation, shining a light on the moment that our team opened the doors of possibility to intentionally designed protein degraders.
The discovery moment – a culmination of hope, of hard work, of complex teamwork – is quite hard to describe, says Bristol Myers Squibb’s Mark Rolfe, PhD, senior vice president, Oncogenesis Thematic Research Center. But the moment that you realize the potential of a compound? It’s those moments that keep our R&D team coming back to work.
Our unique approach to drug discovery and development
This team takes a unique approach to the path of drug development — scientists pursue broad research approaches, where they glean insights on disease targets and their potential effect on human biology and implement those learnings into drug discovery research in the lab, efficiently. The basis for this approach lies in Bristol Myers Squibb’s long-standing expertise in the intricacies of causal human biology, the foundation of our nuanced approach to precision R&D — selecting the right pathways and targets for specific patient populations, matching modalities to mechanisms of disease, and determining novel combinations and sequences to deliver maximum therapeutic benefit. Decades of success and expertise at the disease and molecular levels has given Bristol Myers Squibb unmatched clinical data to determine scientific paths forward.
Bristol Myers Squibb’s legacy and scientific expertise in protein degradation is a prime case study of how the company has created an R&D environment that channels inspiration into exploration where, driven by curiosity, multi-disciplinary R&D teams seek to answer some of science’s toughest questions. Protein degradation is a core approach for the company, through which researchers can harness the body’s natural ability to target and remove unnecessary or harmful disease-causing proteins to maintain equilibrium.
Research teams — including those focused on protein degradation — are driven by scientists and experts who are living nearly a decade in the future and start each day wondering: What does the future look like for patients? What will the treatment landscape look like? How will the standard of care have changed from now to then? Bringing together the brightest minds in discovery and development, the R&D team puts these questions into practice at thematic research centers (TRCs) strategically placed in the liveliest life science innovation hubs . Within these TRCs, Bristol Myers Squibb has a world-class biology, computational, and translational team, giving scientists in-house capabilities to build expertise from some of the largest data sets in the world. These learnings can be shared with academic institutions or with partner organizations to better inform research and potential clinical trials.
The drug development path doesn’t stop once medicines make their way bedside — teams at Bristol Myers Squibb are focused on a continual information circuit back into the lab. Insights across the drug discovery and development continuum are shared with internal experts, who analyze these data and bring insights back to the biologists and chemists in the lab to improve research methods and future hypotheses.
Pioneering our path forward in protein degradation
Bristol Myers Squibb remains the only company that has successfully developed and commercialized protein degrader agents.
Researchers are now pursuing multiple paths to the discovery and development of protein degraders, providing more opportunities for breakthroughs and therapeutic strategies. We are leveraging two different methods of protein degradation: molecular glues (CELMoD™ agents) and heterobifunctional agents (also called ligand-directed degraders, or LDDs). These novel degraders are being designed with precision, agility and intention to target highly biologically validated and novel disease targets.
Advancing toward the future
Protein degraders are just one example of how endless curiosity can make an impact for patients. Our scientists work tirelessly every day aiming to uncover insights that may lead to better treatments for patients in need. As the landscape evolves, so do they — utilizing novel technologies that will help shape the future of drug discovery and development, including AI and machine learning techniques, in everything from analyzing data to completing components of clinical and regulatory documents, all of which will help get medicines to patients in need faster.
While these technologies have accelerated timelines and allowed research and development to become more efficient, it's important to recall the storied history of discovery, and to seek inspiration and deeper understanding from these breakthroughs to propel science and medicine into the future.