A bold blueprint for transforming outcomes in lupus

Lupus is an incredibly complex disease that manifests in a variety of ways, and we have seen this reflected in lupus research and development (R&D). Lupus can affect almost any organ system and is thought to be caused by a combination of genetic, environmental and hormonal factors.

Systemic lupus erythematosus (SLE) is the most common type of lupus and can affect almost any organ system, including the skin and joints. Diagnosis can also be difficult, and lupus can be challenging to treat, often with patients not adequately responding to treatment.

Despite many new investigational treatments for lupus being tested over the past 20 years, only a few have been approved. However, recent scientific progress and new approaches have brought fresh hope to the field as researchers develop innovative treatments that could meaningfully change patients’ lives.

At Bristol Myers Squibb, we are committed to elevating our understanding of lupus and improving clinical trials. Our goal is to go beyond small improvements and bring potentially life-changing therapies to patients with immune-mediated diseases.

Driving breakthroughs in lupus with bold thinking

Bristol Myers Squibb is advancing pathbreaking science to push the boundaries of what’s possible in lupus research, building upon more than two decades of success in modulating the body’s immune response to immune-mediated diseases. These efforts are grounded in our R&D principles, which guide our pursuit of bold science. Specifically, if we select the right targets based on causal human biology (the association of a potential therapeutic target in humans to disease onset and progression), match the right kind of therapy to the disease mechanism and provide early evidence that an idea is working, we can increase the chance of success and speed up delivery of transformational medicines to more patients.

Understanding causal human biology is the first and foundational pillar within our R&D principles and is critical to our efforts in immune-mediated disease, including lupus. We believe that a precision-based approach, where treatment can be tailored based on individual’s disease characteristics, is key to offering paradigm-shifting treatment. To do so, we focus on three overarching mechanistic goals that make up our sequential immunotherapy framework:

1. Controlling inflammation through targeted immune inhibition
2. Resetting the immune system by eliminating pathogenic immune memory
3. Promoting immune homeostasis and tissue repair via immune regulatory agents

Together, these goals may offer the foundation for effectively treating immune-mediated diseases, like lupus. This includes the continued development of medicines that control inflammation, which are currently approved for non-rheumatic conditions, exploring these treatments in lupus and other rheumatic diseases. Looking to the future, our scientists are focused on exploring immune reset and tissue repair strategies to address the root cause of disease and restoring immune balance.

Targeting multiple pathways to transform patient outcomes

Our research approaches to lupus treatment mirror the condition's complexity. For example, we are investigating a variety of pathways and mechanisms within the sequential immunotherapy framework so that we can offer tailored approaches, scientifically informed sequencing strategies and complementary combinations for the treatment of SLE. Investigational treatments target key pathways implicated in the disease, including:

• Tyrosine kinase 2 (TYK2) is an enzyme that plays a role in several immune-mediated diseases, including lupus. TYK2 facilitates the signaling of key inflammatory cytokines involved in the development of lupus.
• 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 produce self-targeting antibodies called "autoantibodies,” which also play a role in the aberrant immune response of underlying immune-mediated diseases, such as lupus. Targeting CD19 may reduce pathogenic B cells in lupus through different modalities, including T cell engagers and chimeric antigen receptor (CAR) T cells.

Several additional pathways, including tissue repair mechanisms, are also being investigated in early research across immune-mediated diseases.

By having a variety of approaches for patients with lupus, we aim to treat all patients regardless of where they are in their disease course in order to improve their quality of life.

Key considerations in development

As we advance this research through clinical trials and evaluate potential new treatments, our goal is to address the challenges that have historically impeded progress in lupus, often because of the significant variability observed from patient to patient. We are taking several steps to improve the success of clinical programs:

• Complex clinical trial endpoints to capture the disease's heterogeneity.
• Carefully assessing participants’ disease activity scores at each visit to ensure accurate and consistent data.
• Having a dedicated group within clinical development review study data on an ongoing basis to accurately assess changes in disease activity.

Our continued commitment to patients

A strong dedication to patients drives our R&D efforts and motivates our researchers. Our vision at Bristol Myers Squibb is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases — and that especially rings true in lupus. We envision a future where all patients can achieve long-lasting remissions, free from the daily burden of this life-altering chronic condition.

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