ASLAN004 is a fully human therapeutic monoclonal antibody that neutralises both interleukin 4 (IL-4) and interleukin 13 (IL-13) by binding to the IL-13Rα1 (Company Pipeline, ASLAN Pharmaceuticals, MAY 31, 2016, View Source [SID:1234512886]). The IL-13Rα1 is a key component of the type II receptor dimer that is expressed in epithelial cells, airway smooth muscle, alternatively activated (M2) macrophages, NKT cells, mast cells, eosinophils and basophils. In allergic diseases such as asthma and atopic eczema, IL-4 and IL-13 play a pivotal role in causing airway hyperresponsiveness, pulmonary inflammation, mucus hypersecretion, lung oeosinophilia and increases in allergen specific circulating IgE.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
In oncology, IL-13 signaling is emerging as a key driver of proliferation in cutaneous T-cell lymphoma. More generally in oncology, agonsim of IL-13Rα1 via IL-13 is recognised as a key driver in a shift from an M1 (proinflammatory) to M2 (regulatory/repair) macrophage phenotype that is used by tumour cells to evade killing via host immune surveillance. IL-13Rα1 is a specific marker for the M2 macrophage and mouse studies demonstrate that bone marrow cells from IL-13Rα1 knockout mice preferentially differentiate to an M1 macrophage phenotype. Similarly, knockout of IL-13 or knockdown of IL-13Rα1 via miRNA-155 triggers a switch to an M1 macrophage phenotype (Dhakal et al, 2014, Martinez-Nunez et al, 2011). Consequently, inhibition of IL-13 signalling is emerging as an immune checkpoint for tumour evasion of host immune surveillance and hence an important mechanism for enhancing the immune infiltrate in the tumour microenvironment.
ASLAN004 is the only therapeutic antibody that targets IL-13Rα1, and is progressing into a range of allergic disorders and oncology indications as both monotherapy and in combination with existing immunotherapies.