Ligufalimab (AK 117): A Comprehensive Profile of a Differentiated, Next-Generation CD47 Inhibitor

Executive Summary

Ligufalimab, also known as AK 117, is an investigational, humanized immunoglobulin G4 (IgG4) monoclonal antibody developed by Akeso Inc. that targets the CD47-SIRPα innate immune checkpoint.[1] This report provides a comprehensive analysis of Ligufalimab, synthesizing available preclinical, clinical, and strategic data to assess its potential as a therapeutic agent in oncology. The central value proposition of Ligufalimab lies in its differentiated safety profile, which has been engineered to mitigate the class-defining hematotoxicity—specifically hemagglutination and severe anemia—that has challenged first-generation CD47 inhibitors.[4] This favorable safety profile, which obviates the need for a risk-mitigating "priming dose," positions Ligufalimab as a potential best-in-class agent.

Akeso is pursuing a sophisticated and ambitious clinical development strategy for Ligufalimab, characterized by its focus on creating proprietary, high-efficacy combination regimens with its other advanced pipeline assets. These include the PD-1/VEGF bispecific antibody Ivonescimab and the PD-1/CTLA-4 bispecific antibody Cadonilimab.[7] This approach aims to create a multi-pronged attack on the tumor microenvironment by simultaneously engaging both innate and adaptive immunity.

The clinical program for Ligufalimab is broad, spanning both hematologic malignancies and a wide array of solid tumors. In hematology, it is being investigated in combination with standard-of-care agents for higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukemia (AML).[3] In solid tumors, Ligufalimab is advancing into late-stage, global, registrational trials, most notably a landmark Phase 3 study in combination with Ivonescimab versus pembrolizumab for the first-line treatment of head and neck squamous cell carcinoma (HNSCC).[8]