First-in-Class IL-4Rα/ST2 Bispecific Antibody AK139 Advances to Clinical Development for Inflammatory Diseases

Key Insights

• Akeso's AK139, the world's first IL-4Rα/ST2 bispecific antibody, receives IND acceptance from China's NMPA for respiratory and skin diseases.
• The novel dual-targeting mechanism simultaneously blocks IL-4/IL-13 and IL-33/ST2 inflammatory pathways, showing superior efficacy compared to single-target therapies in preclinical studies.
• Preclinical data demonstrates AK139's strong dual-specific binding activity, promising pharmacological effects, and favorable safety profile, positioning it as a potential breakthrough therapy.

Akeso, Inc. has achieved a significant milestone with the China National Medical Products Administration (NMPA) accepting the Investigational New Drug (IND) application for AK139, marking a pioneering advancement in inflammatory disease treatment. This first-in-class bispecific antibody uniquely targets both IL-4Rα and ST2, representing Akeso's initial venture into non-oncology bispecific antibodies.

Innovative Dual-Targeting Mechanism

AK139's breakthrough design simultaneously inhibits two critical inflammatory pathways: the IL-4/IL-13 axis through IL-4Rα binding and the IL-33/ST2-mediated inflammation cascade. This dual-targeting approach addresses the complex inflammatory processes underlying various respiratory and dermatological conditions more comprehensively than existing single-target therapies.

The antibody's mechanism of action focuses on the IL-4Rα pathway, which mediates T-helper 2 (Th2) cell responses through IL-4 and IL-13 signaling, while simultaneously blocking the IL-33/ST2 pathway, which acts as a key inflammatory alarm signal in multiple biological systems.

Compelling Preclinical Evidence

Preclinical studies have demonstrated AK139's exceptional potential, with data showing:

• Superior efficacy in inhibiting inflammatory cytokine release compared to single-target antibodies
• Significant reduction in inflammatory cell tissue infiltration
• Strong dual-specific antigen-binding activity
• Favorable safety profile in toxicology studies

Clinical Development Prospects

As Akeso's seventh bispecific antibody to enter clinical development, AK139 represents a significant therapeutic advancement for patients with inadequate responses to current treatments. The drug shows particular promise for:

• Respiratory diseases including asthma and COPD
• Various dermatological conditions
• Other inflammatory disorders where IL-4/IL-13 and IL-33/ST2 pathways play crucial roles

The development of AK139 marks the beginning of a "dual-target era" in inflammatory disease treatment, potentially offering enhanced therapeutic options for patients who have not achieved optimal results with existing therapies.