Akeso Announces IND Acceptance for AK139, a Bispecific Antibody Targeting IL-4Rα and ST2 for Respiratory and Skin Diseases

HONG KONG, Feb. 13, 2025 /PRNewswire/ -- Akeso, Inc. (9926. HK) ("Akeso" or the "Company") is pleased to announce the acceptance of its Investigational New Drug (IND) application by the China National Medical Products Administration (NMPA) for AK139, a bispecific antibody targeting IL-4Rα and ST2. AK139 is under investigation for a number of indications, including respiratory and skin diseases.

AK139 is Akeso's first innovative bispecific antibody outside the field of oncology to enter clinical development.  It is also Akeso's seventh bispecific antibody to enter clinical development. As the world's first IL-4Rα/ST2 bispecific antibody to enter the clinic, AK139 simultaneously targets and blocks both the IL-4/IL-13 pathway (by binding to the IL-4Rα subunit shared by both IL-4 and IL-13 receptor complexes) and the IL-33/ST2-mediated inflammation pathway. Preclinical studies have demonstrated robust synergistic therapeutic effects between these targets. In preclinical studies, AK139 shows clinical potential compared to existing monotherapy drugs targeting these pathways.  AK139 is expected to advance the treatment of respiratory diseases, dermatological conditions, and other disorders where these inflammatory pathways play a critical role in disease pathogenesis. This first in class therapy is set to introduce a "dual-target era" in the treatment of these conditions, providing enhanced therapeutic options for patients with inadequate responses to current treatments.

Innovative Dual-Target Mechanism for Improved Therapeutic Potential

The IL-4, IL-13, and IL-33/ST2 pathways play a central role in the inflammatory processes underlying asthma, COPD, and other related conditions. AK139, as the first bispecific antibody targeting both IL-4Rα and ST2, offers a targeted approach to modulate these pathways. By binding to both IL-4Rα and ST2, AK139 blocks the key signals associated with IL-4, IL-13, and IL-33, addressing the complex inflammation signaling pathways in these related diseases.

• IL-4Rα Pathway: IL-4 and IL-13 are primarily involved in immune responses mediated by T-helper 2 (Th2) cells. The Th2-mediated inflammatory pathways play a critical role in the pathogenesis and progression of respiratory diseases, skin conditions, and other related diseases. Research has shown that IL-4 and IL-13 share a common receptor, IL-4Rα. AK139 is highly specific in binding to IL-4Rα, blocking the interaction between IL-4Rα and IL-4 or IL-13, as well as inhibiting the downstream signaling pathways mediated by these interactions, and thus exerting therapeutic effects on these diseases.
• IL-33/ST2 Pathway: Interleukin-33 (IL-33), acting as an alarm signal, binds to its specific receptor ST2, activating downstream signaling pathways that lead to inflammation in multiple human biological systems, including the respiratory, cardiovascular, and musculoskeletal systems. IL-33 plays a key role in both type 2 and non-type 2 inflammatory responses. Studies have shown that the expression levels of IL-33 and its receptor ST2 are significantly elevated in inflammatory diseases such as respiratory and skin conditions, where they serve as important mediators of disease response. AK139 specifically binds to ST2, inhibiting the inflammatory response mediated by IL-33.

Preclinical studies have demonstrated that AK139 showcases strong dual-specific antigen-binding activity and promising pharmacological effects in both in-vitro and in-vivo. The antibody has shown remarkable synergy between the targets, significantly outperforming single-target antibodies targeting IL-4 or ST2 in key measures.  These key measures include the inhibition of inflammatory cytokine release and the reduction of tissue infiltration by inflammatory cells. Additionally, preclinical toxicology studies showed that AK139 presents a favorable safety profile.

Based on the pre-clinical data so far, AK139 has the potential to become a breakthrough therapy for respiratory and dermatological diseases.

SOURCE Akeso, Inc.