Indication: Allergy and Oncology
ASLAN004 is a best-in-class monoclonal antibody with the potential to improve lung function and reduce exacerbations in moderate or severe asthma. The antibody has been found to neutralise both interleukin 4 (IL-4) and interleukin 13 (IL-13) by binding to the IL-13Rα1. 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 eosinophilia and increases in allergen specific circulating IgE.
ASLAN is exploring therapeutic application of ASLAN004 in other inflammatory diseases as well as IL4/IL13 driven tumours.
ASLAN is working with Selexis in Switzerland to establish manufacturing cell lines for ASLAN004. ASLAN has also established a strong relationship with JHL in Taiwan for process development and scale-up of ASLAN004 for GLP toxicology and clinical development. ASLAN has also initiated collaborations in Singapore and the USA to characterise the efficacy of ASLAN004 in specific tumour types.
ASLAN has global rights to all indications from CSL.
ASLAN004 is a fully human therapeutic monoclonal antibody.
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.
CSL Limited (ASX:CSL) is a global biopharmaceutical company that develops, manufactures and markets biotherapies to prevent and treat rare and serious human diseases. CSL owns major facilities in Australia, Germany, Switzerland and the US, and employs over 13,000 people in more than 27 countries. CSL operates two subsidiary businesses, CSL Behring and bio CSL, which are underpinned by a significant Research and Development effort. To learn more about CSL, please visit www.csl.com.au.