Advancing lupus research to address unmet needs

At Bristol Myers Squibb, we strive to go beyond the incremental in our research and development efforts for immune-mediated diseases such as lupus. Hear perspectives from Francisco Ramírez-Valle, MD, PhD, and Alyssa Johnsen, MD, PhD, on how our scientists are advancing lupus research across the disease spectrum.

Ramírez-Valle is senior vice president and head of Immunology & Cardiovascular Thematic Research Center, and Johnsen is senior vice president, head of Clinical Development, Immunology, Cardiovascular and Neuroscience.

Pioneering an innovative approach to lupus research

As proven pioneers in modulating the body’s immune response, Bristol Myers Squibb is pursuing pathbreaking science to push the boundaries of what’s possible in lupus research.

Given the significant unmet need and heterogeneity of lupus, we are cultivating a broad portfolio of investigational products. Informed by causal human biology, we take a strategic research approach to:

• control inflammation through targeted immune inhibition;
• reset the immune system by eliminating pathogenic immune memory;
• promote immune homeostasis via immune regulatory agents and tissue repair.

Targeting multiple pathways

"We are studying a variety of pathways and mechanisms so that we can offer tailored approaches, scientifically informed sequencing strategies and complementary combinations,” says Johnsen. “I’m really excited about the transformation in care that we may be able to bring to patients in the future.”

Bristol Myers Squibb researchers are investigating several potential treatments for lupus, ranging from small molecules and biologics to cell therapies. These investigational treatments are informed by this strategic research framework and target key pathways implicated in the disease including:

• TYK2: Tyrosine kinase 2 (TYK2), a naturally occurring enzyme in the body that has been shown to play a role in several immune-mediated diseases, including lupus. TYK2 facilitates the signaling of key inflammatory cytokines involved in the development of lupus.
• CD19: CD19 is a highly specific antigen found in abundance on the surface of B cells. B cells play a central role in antigen presentation and are precursors to cells that produce self-targeting antibodies called ‘autoantibodies.’ Autoantibodies contribute to autoimmune diseases such as lupus.
• TLR7/8: Toll-like receptors (TLR) 7 and 8 help detect the presence of certain pathogens in the body and initiate and amplify both innate (nonspecific) and adaptive (specialized or specific) immune responses. Overactivation of TLR7/8 contributes to inflammation that occurs in immune-mediated diseases, including lupus.
• IL2: Low levels of IL-2 (a signaling molecule) in systemic lupus erythematosus are associated with decreased activity of Treg cells, an important type of immune regulatory cell that help prevent the body from attacking itself.

Understanding the complexity of lupus

Lupus is an autoimmune disease comprised of several disease types that can affect many organ systems in different ways.

“Despite the fact that there have been many investigational drugs tested in lupus, very few have reached approval, leaving a high unmet need for new treatments,” says Ramírez-Valle. “Lupus looks very different from one patient to the to the next, and so to discover new targets we have to have very sophisticated clinical data from which to inform our understanding of the disease.”

Leveraging the power of precision medicine               

Identifying the appropriate therapeutic mechanisms and modalities for each patient based on individual characteristics, such as biomarkers, disease type, disease drivers, severity, lifestyle and prior treatment exposure is of particular importance in lupus.

“Our goal in lupus, like many chronic immune-mediated diseases, is for patients to achieve remission and, even better, cures,” says Johnsen. “And how do we do that? It is unlikely that there is going to be any one therapy that can provide long-lasting remission for all patients, so we work to find the right drug for the right patient using segmentation strategies. If we can more precisely understand the different manifestations of lupus and what might be driving them, we can then tailor our research to specific populations of patients.”

Prioritizing diversity in research and clinical trials

Lupus disproportionately affects women of African American, Hispanic, Asian and Native American ancestry above others. To ensure our research, development and treatments meet the needs of the patients we seek to serve, Bristol Myers Squibb is committed to increasing clinical trial diversity. We identify and engage clinical trial sites in racially and ethnically diverse geographies in the U.S. while working with our innovative Patient Expert Engagement Resource (PEER) group to ensure that the patient perspective is heard and considered at every step of the drug discovery and development process.

“It is of critical importance to continue to gather data that is representative of the population affected by lupus, so that we can take a holistic approach to drug discovery and development,” says Ramírez-Valle. “We are working to find targets and ways to stratify patients across diverse backgrounds.”

Our commitment to lupus research and community engagement

Expertise in the underlying biology of immune-mediated diseases propels research forward at Bristol Myers Squibb. Our teams are deeply committed to advancing patient care to break efficacy ceilings and create significant and meaningful advances for people living with lupus.

“We are taking a different approach by thinking about lupus as a heterogeneous group of autoimmune conditions,” says Ramírez-Valle. “Our research framework helps us identify the appropriate therapeutic mechanism for each patient based on individual characteristics, an approach we believe will bring forward medicines that can alleviate the burden of this disease.”

“We all have to be looking forward at not just what we have today, and not just what we will have in three to five years, but what we are still going to need in 10 years,” says Johnsen. “We all work together in order to advance medicines for patients with a very forward-looking view.”