ASLAN Pharmaceuticals announced the presentation of new translational eblasakimab data at the 51st Annual European Society for Dermatological Research (ESDR) Meeting. Two posters are being presented as e-posters throughout the duration of the congress from September 28 to October 1, 2022, in Amsterdam, Netherlands. AD is a chronic inflammatory skin disease that is associated with significant pruritus (itch)1. It is the most burdensome symptom reported by AD patients.

The IL-4/IL-13 receptor system serves as a clinically validated therapeutic target for AD and consists of the Type 1 (IL-14Ra1 and the common ? chain) and Type 2 (composed of IL-4Ra1 and IL-13Ra1) receptors2. The poster shows results from an analysis of the expression pattern of IL-13Ra1 in skin derived from AD patients and compared to healthy controls in a study designed to better understand the role of IL-13Ra1 in AD using spatial localization with immunohistochemistry (IHC) and to delineate the function of the Type 1 and 2 receptors using comparative transcriptomics.

The data showed a significant increase of IL-13Ra1 expression in lesional (L) (P<0.001) and non-lesional (NL) (P=0.45) AD skin compared to matched healthy controls. In addition, IL-13Ra1 expression on mast cells and eosinophils was significantly increased in L (P=0.034 and P=0.024, respectively) and NL (P=0.031 and P=0.046, respectively) AD skin compared to matched controls. Inhibition of the Type 1 receptor with anti-common ?

chain antibody resulted in increased expression of MMP9 (P<0.001), which is a collagenase that is elevated in AD patients and may exacerbate inflammation-promoting tissue edema3,4. Inhibition of the Type 2 receptor by eblasakimab induced suppression of genes including XBP1 (P<0.001), which is required for leptin-mediated Type 2 survival and cytokine production5, and CXCL8 (P=0.046), levels of which correlate with AD severity. IL-4 and IL-13 have distinct effects on itch pathways and neuronal excitability that can be inhibited by targeting IL-13Ra17,8. Eblasakimab binds to the human Type 2 receptor subunit IL-13Ra1 with high affinity, preventing signaling of IL-4 and IL-13 through the Type 2 receptor expressed on a range of immune and non-immune cells, including sensory neurons7,9. Sensitization of sensory neurons forms the cellular and molecular basis for multiple somatosensory disorders such as chronic itch, neurogenic inflammation, and forms of painful dysfunction10. The poster shows the results from a study to determine neuronal responses of human dorsal root ganglia (hDRG) neurons to itch signalling induced by pruritogens under various conditions.

The effects of IL-4 and IL-13 on spontaneous neuronal activity (SA) in hDRG neurons induced by inflammatory soup (IS), which contains bradykinin and prostaglandin, were measured with and without eblasakimab as a model for hypersensitization of sensory neurons.