Rethinking Asthma Preclinical Models: Matching Mouse Models to Drug Mechanism Across Asthma Phenotypes

Asthma is a chronic inflammatory disease of the airways that affects more than 300 million people worldwide. In the era of precision medicine, the development of dupilumab—a biologic agent targeting the IL-4/IL-13 pathway—marked a significant breakthrough, demonstrating near-optimal efficacy in preclinical studies using the house dust mite (HDM)-induced asthma model. However, this exceptional benchmark poses a growing challenge for drug developers aiming to create next-generation asthma therapies: few novel candidates can surpass dupilumab’s preclinical performance within the same HDM model.

Notably, dupilumab and HDM-induced asthma models primarily target eosinophilic inflammation. Clinically, a considerable proportion of asthma patients present with neutrophilic or mixed granulocytic phenotypes, which often respond poorly to existing targeted treatments. To determine whether new asthma drugs can truly exceed current standards and achieve broader therapeutic coverage, it is essential to adopt novel animal models that faithfully recapitulate these refractory phenotypes.

To address this need, GemPharmatech has developed and validated a series of induced mouse models of asthma, including an eosinophil-dominant asthma model, mixed-type asthma model, and a neutrophil-dominant asthma model. These models support a range of preclinical applications aimed at matching drug mechanisms of action (MoA) with appropriate disease phenotypes.

Key topics include:

• Overview of the pathogenesis underlying different asthma phenotypes

• Key characteristics of commonly used asthma animal models

• Application Strategies of selecting asthma models matching drug MoA