Bristol Myers Squibb Highlights Targeted Protein Degradation Advances, Including CELMoD Agents and BCL6 Ligand-Directed Degrader, at EHA 2025 in Milan, Italy
Bristol Myers Squibb today revealed new and updated data from its growing portfolio of targeted protein degradation programs during the 2025 European Hematology Association (EHA) Annual Congress, which is currently underway from June 12-15 in Milan, Italy. The presentations highlight the ongoing progress and growing promise of the company’s innovative therapeutic platform, featuring its investigational oral CELMoD™ (Cereblon E3 Ligase Modulating Drugs) agents mezigdomide, iberdomide, and golcadomide, alongside its first-in-class, oral BCL6 (B-Cell lymphoma 6) ligand-directed degrader (LDD) BMS-986458.
Together, these data reflect a significant step forward in the treatment of hematologic malignancies — a group of aggressive, complex disorders for which many patients still face limited treatment options and poor outcomes — and demonstrate the potential for these novel mechanisms of action to make a profound difference in patient care.
Expanding Targeted Protein Degradation in Hematologic Malignancies
Targeted protein degradation is a powerful therapeutic approach designed to destroy disease-driving proteins within cells, thereby inhibiting their ability to contribute to disease progression. This stands in contrast to traditional small-molecule inhibitors, which typically aim to block a protein’s activity or binding. Degraders enable complete removal of the disease-related protein, offering a way to address resistance mechanisms and target previously undruggable proteins.
Bristol Myers Squibb’s platform includes a range of small-molecule degraders, which exploit the cell’s own disposal mechanisms — typically by sending the target protein to the proteasome for destruction. This approach holds tremendous promise for improving outcomes in patients with hematologic malignancies — disorders that arise from abnormalities in blood-forming cells — and many other disease settings.
Evidence of Clinical Benefit from CELMoD Agents in Multiple Myeloma
The data presented at EHA 2025 further illuminate the potential for CELMoD agents to make a measurable improvement in the lives of patients battling multiple myeloma — a plasma cell malignancy that often relapses after standard treatments and is challenging to control. The updated clinical results from mezigdomide and iberdomide show deepening responses and a tolerable safety profile when used in combination with standard care.
This growing body of data underscores the ability of CELMoD compounds to enable potent and selective degradation of disease-relevant proteins, adding a powerful new tool to aid hematologists in their quest for more durable remissions.
Golcadomide Shows Promise in Non-Hodgkin Lymphoma
Bristol Myers Squibb also presented new data for golcadomide, another CELMoD agent under investigation for non-Hodgkin lymphoma (NHL). This disease comprises a group of diverse hematologic malignancies — including diffuse large B-cell lymphoma (DLBCL) — where there is a significant need for innovative treatment options.
The new data highlight golcadomide’s ability to promote the degradation of Ikaros and Aiolos — two key transcription factors frequently involved in NHL pathophysiology — thereby inhibiting their activity and arresting the growth of tumor cells. The ongoing study shows a favorable safety profile alongside signals of clinical activity, strengthening the case for further investigation in larger, pivotal trials.
BMS-986458: First-in-Class, Oral BCL6 Ligand-Directed Degrader
One of the most significant innovations presented at EHA 2025 by Bristol Myers Squibb was the first clinical data for its BCL6 Ligand-Directed Degrader, BMS-986458, in non-Hodgkin lymphoma. This novel, first-in-class, oral small molecule is designed to target and destroy BCL6, a key driver of B-cell transformation and resistance to standard treatments.
BMS-986458 utilizes a unique, small-molecule motif to enable the degradation of BCL6, adding a powerful new approach to interrupting its signaling and affecting the growth and survival of lymphoma cells. The initial data presented at EHA show a manageable safety profile alongside signals of clinical activity, offering hope for patients with limited treatment options in relapsed or refractory NHL.
Continuing Clinical Development and Commitment to Innovation
Bristol Myers Squibb’s data at EHA 2025 reflect the growing momentum of its targeted protein degradation platform and its potential to transform the treatment landscape for hematologic malignancies. The company’s pipeline includes additional CELMoD compounds, LDDs, and Degrader Antibody Conjugates (DACs) currently in development for both hematologic disorders and solid tumors.
“As a leader in the field of targeted protein degradation, we are passionate about applying our decades of expertise and extensive knowledge to bring forward these new and potentially game-changing therapeutic options for patients,” said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology, and Cell Therapy for Bristol Myers Squibb. “The efficacy signals and tolerability profiles we’re seeing, and which we’re sharing at EHA, collectively reinforce the potential for these medicines to make a dramatic difference in the lives of patients. Our team is looking forward to advancing pivotal trials for each of these compounds in the year ahead and hopefully delivering new treatment options for patients battling these difficult-to-treat hematologic malignancies.”
Bristol Myers Squibb is a leading global biopharmaceutical company whose mission is to discover, develop, and deliver innovative medicines that help patients prevail over serious diseases. The company’s extensive portfolio includes a range of treatments for oncology, hematologic disorders, cardiovascular disease, and many other health conditions. Through its strong pipeline and ongoing collaborations, Bristol Myers Squibb strives to make a meaningful, positive impact on the health of patients across the world.
