Akeso moves first-in-class IL-4Rα/ST2 BsAb into Phase II for respiratory, autoimmune diseases

Edited by Robert McTiernan··2 min read

China-based Akeso Inc., (9926.HK) announced clearance from China’s National Medical Products Administration (NMPA) to initiate seven Phase II studies for its first-in-class bispecific antibody (BsAb) AK139, which targets IL-4Rα and ST2 to address multiple respiratory and autoimmune conditions.

Akeso is approved to initiate Phase II trials evaluating AK139 in chronic obstructive pulmonary disease (COPD), severe bronchial asthma, chronic spontaneous urticaria, allergic rhinitis, chronic rhinosinusitis with nasal polyps, moderate-to-severe atopic dermatitis, and prurigo nodularis.

AK139 simultaneously blocks the IL-4/IL-13 axis by binding IL-4Rα and inhibits IL-33/ST2-mediated inflammatory signaling. Early preclinical data indicate that this dual-target approach delivers stronger anti-inflammatory effects compared with antibodies against a single target, along with a favorable safety profile.

As the first antibody drug engineered to co-target both IL-4Rα and ST2 to enter clinical trials, AK139 leverages Akeso’s AI-enabled discovery platform and expands the company’s bispecific portfolio beyond oncology into chronic inflammatory and autoimmune diseases.

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Research context

IL‑4Rα blockade suppresses downstream, amplifying type‑2 effector biology by inhibiting both IL‑4 and IL‑13 signaling. The pathway is central to IgE class switching, mucus/goblet metaplasia, airway hyperreactivity, barrier dysfunction, and alternative macrophage programs. The evidence base for the target is mature and broad in allergic respiratory/skin disease, led by Sanofi’s IL-4alpha-targeted Dupixent (dupilumab).

ST2 (IL‑33 receptor) blockade targets a more upstream “alarmin” axis (IL‑33→ST2) that can rapidly activate ILC2, mast cells, basophils, and Th2 cells—often viewed as an epithelial danger signal pathway that initiates/exacerbates T2 inflammation and can contribute to steroid resistance/recurrence in barrier tissues. The combination of IL‑33/ST2 with IL‑4/IL‑13 via IL‑4Rα in one molecule is therefore aimed at driving suppressing both the triggering and the maintenance/amplification of T2 inflammation.

While Akeso’s AK139 is the first IL-4Rα/ST2-targeted BsAb to reach the clinic, Zai Lab previously presented preclinical data for ZW1528, a similarly targeted BsAb, at the American Thoracic Society (ATS) International Conference held in 2025. Companies are also developing BsAbs that combine TSLP and IL-4Rα targeting, for example Tavotek Biotherapeutics’ preclinical stage Tavo105.