HX009: A Comprehensive Clinical and Scientific Monograph on a First-in-Class Anti-PD-1/CD47 Bispecific Antibody

Executive Summary

Overview

HX009 is a first-in-class, recombinant humanized bispecific antibody (BsAb) fusion protein under clinical investigation for the treatment of advanced malignancies. It is engineered to concurrently target two distinct and complementary immune checkpoints: the programmed cell death protein 1 (PD-1) on T-cells, a cornerstone of the adaptive immune system, and the cell surface antigen CD47 on tumor cells, a key regulator of the innate immune system's phagocytic response.[1] This dual-targeting strategy is designed to orchestrate a multi-pronged anti-tumor immune attack by simultaneously reactivating exhausted T-cells and disabling the primary "don't eat me" signal used by cancer cells to evade macrophage-mediated destruction.

Core Scientific Innovation

The central innovation of HX009 lies in its rational molecular design, which aims to optimize the therapeutic index by overcoming the principal limitation of prior CD47-targeted therapies: on-target, off-tumor hematological toxicity. The molecule is engineered with a high-affinity binding domain for PD-1 and a deliberately weakened binding affinity for CD47.[3] This design leverages the localization of PD-1-expressing T-cells within the tumor microenvironment (TME) to selectively "hone" the therapeutic agent to the site of the tumor. This localized concentration is intended to facilitate effective engagement with CD47 on adjacent cancer cells while minimizing systemic binding to CD47 expressed on healthy hematopoietic cells, thereby mitigating the risk of severe anemia and thrombocytopenia that has challenged the development of other agents in this class.[3]

Clinical Development Synopsis