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> Insights > Asthma Targeted Therapy: The Breakthrough Strategy for the Billion-Dollar Market 
Asthma is a heterogeneous chronic inflammatory disease centered around airway immune imbalance. The Lancet illustrates that approximately 339 million people worldwide are affected by asthma. While conventional therapies like inhaled corticosteroids and β-agonists provide symptomatic relief, they fail to address the underlying pathogenic mechanisms or modify disease trajectory. The advent of endotype-driven classification (Th2-high vs. Th2-low/non-Th2) has revolutionized asthma management:
• Th2-type inflammation, driven by eosinophils, TSLP, IgE, IL-4/IL-13, and IL-5, affects 50%-70% of patients, with targeted therapies now reaching clinical maturity.
• Non-Th2-type inflammation, accounting for 30%-50% of cases, involves mechanisms such as neutrophils, IL-6, and IL-17.
Mechanisms and characteristic pathological features of asthma immunopathology
We have developed a range of products targeting core mechanisms in asthma pathology, including recombinant proteins, cell lines, and inhibitor screening kits of TSLP/TSLPR, IL-4/IL-4R, IL-5/IL-5R, IL-13/IL-13R, IL-6/IL-6R, IL-8, IL-17/IL-17R, IL-33, and IgE Fc, to comprehensively support the development of targeted asthma drugs and therapies.
TSLP: the master regulator of the Inflammatory Cascade
TSLP, released by airway epithelial cells upon inflammatory stimuli, activates dendritic cells, drives Th2 immune polarization, and triggers the IL-4/IL-5/IL-13 cytokine cascade, culminating in a self-amplifying "inflammatory storm." Tezepelumab (Amgen/AstraZeneca): by blocking TSLP signaling, this monoclonal antibody demonstrated a 72% reduction in annualized asthma exacerbation rates in severe asthma patients. SHR-1905 (Hengrui): targeting asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), this candidate has advanced into Phase II clinical trials. CM326 (Keymed Biosciences): featuring epitope-optimized design (3-fold enhanced affinity), it is undergoing combination therapy trials with omalizumab, with regulatory submission anticipated by 2025.
With expanding indications into atopic dermatitis and eosinophilic esophagitis, the global TSLP inhibitor market is projected to exceed $8 billion by 2030, positioning these agents as the first-line therapeutic strategy for intercepting type 2 inflammation.
The role of TSLP in driving asthma disease mechanisms via different inflammatory pathways
IL-4/IL-13: the synergistic duo in dual-target therapeutics
IL-4 drives IgE production and Th2 polarization, while IL-13 induces mucus hypersecretion and fibrotic remodeling. Dual blockade of these cytokines achieves comprehensive suppression of type 2 inflammation by disrupting complementary pathogenic pathways. Dupilumab (Sanofi): as the first-in-class IL-4Rα antagonist, it generated $14.179 billion in 2024 sales (23% YoY growth), solidifying its dominance as the top-selling inflammatory disease therapy. AK139 (Consonance Biologics): a bispecific antibody targeting IL-4/IL-13 (via IL-4Rα blockade) and ST2 pathway activation, achieving triple-action (IL-4/IL-13/ST2 inhibition) to address both dupilumab-responsive and refractory conditions like hypereosinophilic syndrome (HES). This mechanism positions AK139 as a potential paradigm-shifting therapy for complex type 2 inflammatory diseases, overcoming limitations of single-pathway inhibitors.
Dual blockade of IL-4 and IL-13 with dupilumab
IL-5/IL-5RA: a triple-targeted strike against eosinophilic pathogenesis
IL-5 and its receptor IL-5RA constitute a central signaling axis for eosinophil survival, differentiation, and activation, driving eosinophil-mediated inflammation and tissue damage in conditions such as severe asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and HES. Mepolizumab (GSK): as the first anti-IL-5 mAb, it blocks IL-5/IL-5RA interaction, it reduces eosinophil counts in severe asthma/EGPA. Benralizumab (AstraZeneca): anti-IL-5RA mAb inducing antibody-dependent cellular cytotoxicity (ADCC) for rapid eosinophil depletion in asthma/CRSwNP. Reslizumab (Teva): neutralizes circulating IL-5, approved for refractory eosinophilic asthma with elevated eosinophils.
Mechanisms of action of biological drugs targeting IL-5 or its receptor
IgE: the upstream orchestrator of allergen-driven hypersensitivity
IgE, the least abundant antibody isotype in human serum, exerts its biological effects via two receptors: the high-affinity receptor FcεRI (expressed on mast cells and basophils) and the low-affinity receptor FcεRII/CD23 (primarily on B cells and eosinophils). Free IgE preferentially binds FcεRI, and upon allergen-mediated crosslinking of receptor-bound IgE, triggers mast cell/basophil degranulation, releasing histamine, leukotrienes, and other inflammatory mediators that drive immediate allergic responses.
Omalizumab (Genentech/Novartis): the first-in-class anti-IgE monoclonal antibody that neutralizes free IgE to prevent FcεRI/FcεRII binding. It remains a cornerstone therapy for moderate-to-severe allergic asthma and chronic spontaneous urticaria (CSU), achieving sustained suppression of IgE-mediated airway inflammation. Ligelizumab (Novartis) & LP-003 (Tiancheng Biologics): high-affinity anti-IgE mAbs in Phase III trials for IgE-dependent disorders. Preclinical data demonstrate superior IgE suppression compared to omalizumab.
The structure of IgE and IgE receptors
IL-33/ST2 axis: an alarm amplifier of tissue damage
The IL-33/ST2 axis serves as a pivotal driver of asthmatic airway inflammation: allergens or tissue injury triggers airway epithelial cells to release IL-33, which activates ILC2s and Th2 cells. These effector cells subsequently secrete mediators including IL-5 and IL-13, leading to eosinophilic infiltration, mucus hypersecretion, and airway hyperresponsiveness - ultimately establishing a pro-inflammatory positive feedback loop. Clinical evidence demonstrates that sputum or serum IL-33 levels correlate with disease severity in asthma patients, while soluble ST2 (sST2) may serve as an indirect biomarker of pathway activation. Etokimab (I-Mab Biopharma), optimized for IL-33 gene polymorphisms prevalent, has completed patient enrollment in its Phase II trial. The strategic combination of IL-33 inhibitors with TSLP-targeted therapies through "dual upstream blockade" may expand therapeutic coverage to broader patient populations.
Airway epithelium–shifted mast cell infiltration regulates asthmatic inflammation via IL-33 signaling
Traditional asthma treatments primarily focus on Th2-type inflammation. However, approximately 50% of patients do not respond well to standard therapies and are referred to as having "refractory asthma." In recent years, studies have found that non-Th2 inflammatory mechanisms (such as Th1, Th17, and neutrophilic inflammation) play significant roles in refractory asthma, potentially offering new directions for overcoming treatment bottlenecks.
Mechanisms of non-T2 asthma, including neutrophilic inflammation and airway hyperresponsiveness
Key cytokines associated with non-Th2 asthma: IL-17, IL-8, and IL-6
• IL-17 stimulates neutrophil recruitment to the airways by activating bronchial epithelial cells to release IL-6 and IL-8 via p38 MAP kinase and ERK phosphorylation cascades. Elevated IL-17 levels in severe asthma patients’ sputum and serum serve as an independent disease risk predictor.
• IL-8, the most potent pulmonary neutrophil chemokine, is secreted by airway epithelial cells, T cells, macrophages, and activated neutrophils. Sputum IL-8 levels are significantly higher in non-eosinophilic asthma patients than in eosinophilic phenotypes and healthy controls, correlating positively with sputum neutrophil proportion and count, indicating its specific role in non-eosinophilic asthma pathology through a positive feedback loop.
• Elevated IL-6 levels are observed in asthma patients’ serum, BAL fluid, and sputum, inversely correlating with lung function. A high-IL-6 phenotype is associated with higher obesity, metabolic complications, mixed granulocytic inflammation, and poorer prognosis, suggesting its potential as a biomarker for asthma endotyping.
We have developed a range of products targeting core mechanisms in asthma pathology, including recombinant proteins, cell lines, and inhibitor screening kits of TSLP/TSLPR, IL-4/IL-4R, IL-5/IL-5R, IL-13/IL-13R, IL-6/IL-6R, IL-8, IL-17/IL-17R, IL-33, and IgE Fc, to comprehensively support the development of targeted asthma drugs and therapies.
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