Antengene Corporation Limited announced that a Phase I study of the best-in-class anti-CD24 antibody, ATG-031, has been approved by the Institutional Review Board (IRB) of The University of Texas MD Anderson Cancer Center in Houston, Texas, the United States. This clinical study, codenamed the PERFORM trial and led by MD Anderson, will be conducted in patients with advanced solid tumors or B-NHL. The PERFORM trial is a first-in-human, multi-center, open-label, Phase I dose-finding study of ATG-031 in patients with advanced solid tumors or B-NHL.

The study's primary objective is to evaluate the safety and tolerability of ATG-031 as a monotherapy, and determine the appropriate dose for Phase II studies. The secondary objective is to characterize the pharmacology, evaluate the immunogenicity, and assess the preliminary efficacy of ATG-031. ATG-031 is a first-in-class humanized CD24 monoclonal antibody which inhibits the "don't eat me" signal and enhances macrophage-mediated phagocytosis of cancer cells.

Tumor cells evade the surveillance of the human immune system by over-expressing "don't eat me" surface proteins that signal macrophages to prevent the detection and phagocytosis of cancer cells. CD24 (cluster of differentiation 24) is a prominent "don't eat me" signal that plays a significant role in tumor immune evasion by suppressing macrophage-mediated phagocytosis. Compared to CD47, another well-known "don't eat me" target, CD24 has a more restricted distribution in normal tissue and higher expression in cancerous tissue.

In addition,unlike CD47,CD24 is not expressed on human red blood cells,allowing for a wider therapeutic window and minimal on-target-off-tumor toxicity as a CD24-targeted therapy. As a novel innate immune checkpoint, CD24 orchestrates immune evasion through its interaction with the inhibitory receptor Siglec-10 (sialic-acid-binding Ig-like lectin 10) expresses on tumor-associated macrophages (TAMs). Preclinical data presented in 2023 at the American Association for Cancer Research Annual Meeting (AACR 2023) demonstrated that ATG-031 can specifically bind to CD24 with nM affinity and block the interaction of CD24 and Siglec-10.

Furthermore, ATG-31 induces efficient phagocytosis with a picomolar EC50 and stimulates the pro-inflammatory cytokines production by macrophages.