IL-11 receptor is a novel target for drug development with pharmacological activity in fibro-inflammatory disease

IL-11, a novel target for drug development, has been associated with several fibroinflammatory diseases including thyroid eye disease (TED), where it plays an important role in signaling to stromal cells activating multiple intracellular pathways. In TED patient tissue, IL-11 is elevated and stimulates multiple effects important in disease progression, including the production of proinflammatory cytokines, hyaluronic acid (HA) and fibrotic markers. LASN01, a potent antibody to IL-11 receptor, inhibits these effects and is a potential therapeutic agent for TED. Teprotumumab, an antibody to IGF-1 receptor, inhibits HA production and adipogenesis and is effective in reduction of proptosis. Activation of the IGF-1 and IL-11 pathways in TED tissue induces the expression of fibroinflammatory genes regulated by LASN01 and lipid biosynthetic genes regulated by Teprotumumab. Clinical studies show that LASN01 is well tolerated and in a placebo-controlled phase II trial in TED, LASN01 resulted in a statistically significant resolution of clinical activity score (CAS) in 88% of treated patients (p=0.028), but had lesser effects on proptosis. The data supports the importance of IL-11 biology in fibroinflammatory disease and that IL-11 receptor is a pharmacologically active target for drug development.