China Securities released a research report stating that the heterogeneity of asthma and COPD determines that precise stratification of the type 2 inflammatory pathway and biomarker-driven individualized treatment are prerequisites for realizing the value of biologics. The industry is showing a trend of technological iteration towards "single-target long-acting" therapies and "multi-target synergy," while COPD heterogeneity has fostered a dual-track landscape with both PDE3/4 inhalers and biologics advancing in parallel. The firm believes that Chinese pharmaceutical companies' leading and in-depth pipeline development targeting IL-4Rα, TSLP, PDE3/4, IL-5, and their combinations, coupled with their engineering advantages in long-acting technologies, position them to transition from followers to leaders. It is recommended to focus on leading companies with long-acting technology capabilities and deep pipeline development based on biological research for novel targets and target combinations. Key points from China Securities are as follows.

Asthma and COPD share the type 2 inflammatory pathway, but asthma is primarily driven by Th2 allergy with reversible airflow limitation, while COPD presents a mixed inflammation of Th1/Th17 and Th2 with irreversible airway remodeling. Pathological heterogeneity necessitates treatment based on precise stratification using biomarkers like blood eosinophil counts and FeNO. The synergy and compensatory mechanisms between upstream alarmins and downstream cytokines form the foundational logic for biologic drug development.

In asthma, biologics are undergoing a paradigm shift, moving treatment earlier from severe to moderate cases. Following the validation of IL-4Rα targeting by Dupilumab for dual-pathway blockade, this has become a major focus for domestic competitors. Technological iteration is clearly directed towards long-acting formulations and multi-specific antibodies. GSK's Depemokimab achieves dosing once every six months, while Sanofi's TSLP/IL-13 bispecific antibodies demonstrate superior control of FeNO and eosinophils compared to single-target agents by combining upstream alarmin blockade with downstream effector inhibition. Additionally, TSLP monoclonal antibodies, with their coverage of non-type 2 inflammation, stand as the only phenotype-agnostic biologics. The ST2/IL-33 target is still exploring clinical value in T2-low populations. Overall, the trend is upgrading from "stepwise therapy" towards "precise early intervention."

COPD treatment has entered an era of dual-track advancement with "precision biologics" and "novel mechanism inhalers." Dupilumab, as the first approved biologic for COPD, validated the value of IL-4Rα targeting in the eosinophilic phenotype. The limited efficacy of IL-5 inhibitors and Phase III failures of IL-5R therapies highlight the necessity for strict patient stratification. IL-33 and TSLP targets are attempting to break the non-type 2 inflammation barrier by lowering eosinophil thresholds or covering smoking populations. Bispecific and multi-specific antibodies targeting combinations like TSLP/IL-13 have entered Phase II/III trials to address disease heterogeneity. Concurrently, the PDE3/4 dual inhibitor Ensifentrine, with its dual mechanism of bronchodilation and anti-inflammatory action, addresses the treatment gap for the approximately 70% of patients with non-type 2 inflammation.

Regarding investment advice, the firm believes that Chinese pharmaceutical companies' leading and in-depth pipeline development targeting IL-4Rα, TSLP, PDE3/4, IL-5, and their combinations, coupled with their engineering advantages in long-acting technologies, position them to transition from followers to leaders. It is recommended to focus on leading companies with long-acting technology capabilities, deep pipeline development based on biological research for novel targets and target combinations, and those possessing high-barrier inhaled formulation technologies. Related companies include Hengrui Pharmaceuticals, Innovent Biologics, Jiankang Yuan, Sino Biopharmaceutical, Haisco Pharmaceutical Group, Akeso, KeyMed Biosciences, Mabwell Biotech, and Huahai Pharmaceutical.

Risk warnings include potential delays in regulatory review and approval, industry policy risks, research and development setbacks, lower-than-expected sales, and intensifying market competition.