Ex Vivo Functional Assays: Capturing the Clinical and Immune Complexity of Lupus for More Predictive Drug Development
Understanding the Challenge of Translating Lupus Therapies
Systemic lupus erythematosus (SLE) is one of the most complex autoimmune diseases to model. It involves the activation of autoreactive lymphocytes, cytokine dysregulation, and multi-organ inflammation that vary widely among patients. This biological heterogeneity has made lupus one of the most challenging areas for drug development, with a likelihood of approval for Phase I candidates of only about 4.6 percent.
Many promising compounds fail in clinical trials because preclinical systems cannot reproduce either the immune complexity or the clinical variability that define lupus. Animal models and immortalized cell lines capture isolated mechanisms but lack the integrated immune and molecular context that drives human disease. Bridging this translational gap requires models that are both human-based and clinically informed.
Preserving Immune Interactions in Their Native Context
Ex vivo functional assays overcome these limitations by testing compounds directly in primary samples from lupus patients, maintaining the native immune microenvironment where T cells, B cells, dendritic cells, and monocytes interact as they do in vivo.
These assays allow researchers to observe how new therapies modulate immune responses, restore tolerance, or rebalance cytokine networks in a physiologic environment. Because they preserve cell-to-cell communication and soluble signaling factors, ex vivo systems reveal multidimensional pharmacologic effects that are not accessible in traditional in vitro models.
Integrating Clinical Data for Translational Relevance
A defining advantage of Vivia Biotech’s ex vivo platform is the use of clinically annotated patient samples. Each sample is linked to complete clinical data, including disease subtype, treatment history, response to prior therapies, and molecular characteristics.
This integration allows researchers to analyze drug activity in treatment-naïve and treatment-experienced samples, uncovering how previous exposure to biologics or small molecules influences pharmacologic response. By connecting functional immune data with detailed clinical metadata, scientists can interpret efficacy and safety findings in a true patient context and identify patterns that support rational trial design.
Exploring Mechanisms with New Therapeutic Classes
The current lupus pipeline includes diverse therapeutic modalities, from monoclonal antibodies targeting interferon pathways to JAK and BTK inhibitors that modulate intracellular signaling. Ex vivo assays provide an ideal platform to explore their mechanisms of action directly in human immune systems.
By quantifying cytokine modulation, cell survival, or pathway inhibition in patient-derived immune cells, researchers gain early mechanistic insight into how these agents restore immune balance. Such data help distinguish between compounds with similar molecular targets but different immune outcomes, supporting more informed selection of candidates with higher translational potential.
Improving Safety and Immune Profiling
Because immune dysregulation in lupus can manifest as both hyperactivation and immunodeficiency, understanding safety margins is essential. Ex vivo assays enable early evaluation of cytokine release, immune activation, and off-target effects in human immune cells. This provides valuable information about potential immune-related toxicities, helping guide go or no-go decisions and refine dosing strategies before animal or clinical studies.