From IMiDs to CELMoDs: Pioneering next generation treatments for blood cancer

Imagine a disease that is inherently complex, shifting and evolving with each individual. That’s the reality of blood cancers like multiple myeloma and non-Hodgkin lymphoma. No two patients are alike, their journeys shaped by a complex interplay of disease stage, prior treatments and individual patient characteristics. As their needs evolve, so too must the range of therapeutic options. For decades, Bristol Myers Squibb (BMS) has stood at the forefront of scientific innovation, and now, building on our deep expertise in targeted protein degradation (TPD), we are pioneering a new era and developing novel CELMoD^™ agents – a powerful class of treatments designed to help close critical treatment gaps in multiple diseases. 
 

The scientific rationale: Building on a legacy of success
 

There has been remarkable progress in the treatment of blood cancers, much of it driven by the groundbreaking science of immunomodulatory drugs (IMiDs) which work by boosting the body’s immune response to destroy cancer cells. These agents, pioneered by BMS, revolutionized the treatment landscape for diseases like multiple myeloma, significantly extending patient survival and improving quality of life. The underlying mechanism of action of the IMiDs, referred to as protein degradation, facilitates the removal of disease-causing proteins from the body. Our expertise in the field, particularly cereblon-mediated degradation, is fueling the next wave of innovation: the development of novel CELMoD agents.

CELMoD agents are not merely incremental improvements; they are purposefully designed as next-generation, biochemically distinct compounds. Leveraging our deep understanding of protein-binding properties, these agents demonstrate improved potency and function, offering superior immune stimulation and more precise protein degradation, compared to their IMiD predecessors. This scientific evolution positions CELMoD agents as a powerful new tool, building directly on the proven success of IMiDs with the goal of achieving even greater therapeutic impact for more patients.

Addressing urgent unmet needs: The potential of CELMoD agents

Despite the significant advances brought by IMiDs and other therapies, the reality for patients battling multiple myeloma and non-Hodgkin lymphoma remains challenging. Multiple myeloma, for instance, is an incurable disease, often presenting in older patients with high-risk features and comorbidities that severely limit tolerable treatment options. This burden is amplified for African Americans, who are diagnosed at twice the rate of white patients. Similarly, in aggressive large B-cell lymphoma, one-third of patients fail to achieve a cure after initial treatment, and with each subsequent relapse, the number of available options diminish.

The potential of CELMoD agents to address these critical gaps is an area with great promise. Their enhanced profile and combinability with existing therapies may enable less aggressive treatment regimens for higher-risk, older patients or patients with comorbidities. The combinability allows for intensification of therapy; for example, in large B-cell lymphoma, oral CELMoD agents added to standard-of-care therapy holds the promise of moving into front-line treatment settings, potentially increasing initial cure rates. For indolent lymphoma, CELMoD agents could become the backbone for chemotherapy-free regimens, offering long-term, tolerable options for patients requiring extended treatment.

The future is now: CELMoD agents and the broader targeted protein degradation platform
 

The excitement surrounding CELMoD agents extends beyond their immediate clinical potential; they represent a cornerstone of BMS’s broader commitment to TPD. Our two decades of scientific expertise and leadership in protein degradation, which began with the foundational work on IMiDs, are now propelling a robust development program.

Our robust TPD research platform encompasses three distinct modalities: molecular glues (which include CELMoD agents), ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This multi-pronged approach allows us to precisely match the right therapeutic modality to a molecular mechanism of action, effectively modulating disease targets. Researchers are actively enhancing the optimization of novel CELMoD agents and other protein degraders, leveraging cutting-edge technologies like AI and machine learning. These technologies accelerate the design and identification of molecules with the precise degradation specificity needed to advance clinical development across oncology and hematology, where our AR ligand degrader is entering late-stage studies.

At BMS, our legacy in protein degradation has laid the groundwork for delivering a new class of innovative therapies. We are committed to advancing CELMoD agents as foundational therapeutic options, poised to significantly improve patient outcomes across broad settings of care and for diverse patient populations.