Selection of Lead Candidate
Background
Client developed a JAK3 inhibitor and wanted to select a lead candidate to take into a first in man study. In addition, they wished to obtain a provisional indication of efficacy in a panel of autoimmune diseases.
Prototrial Strategy
Synexa utilized a series of functional flow cytometry assays to assess the impact of the JAK3 inhibitor on the activation of Th1, Th2, Th17, Treg, DC and NK cell subsets. Initial studies utilized samples from healthy volunteers which were stimulated with a range of cytokines, mitogens and antibodies specific for the immune cell subset of interest. Assay readouts included cell activation markers and intracytoplasmic cytokines. The efficacy of the JAK3 inhibitor was benchmarked against Tofacitinib.
Analytical Strategy
Synexa utilized a series of functional flow cytometry assays to assess the impact of the JAK3 inhibitor on the activation of Th1, Th2, Th17, Treg, DC and NK cell subsets. Initial studies utilized samples from healthy volunteers which were stimulated with a range of cytokines, mitogens and antibodies specific for the immune cell subset of interest. Assay readouts included cell activation markers and intracytoplasmic cytokines. The efficacy of the JAK3 inhibitor was benchmarked against Tofacitinib.
Outcomes
We identified the lead candidate with greatest anti-inflammatory efficacy and confirmed its biological activity in samples taken from patients with rheumatoid arthritis and SLE. The work also identified anti-inflammatory effects.
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