On December 10, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, reported that the first patient has been dosed in the Phase I PERFORM trial of ATG-031 for the treatment of patients with advanced solid tumors or B-cell non-Hodgkin’s lymphoma (B-NHL), at The University of Texas MD Anderson Cancer Center, the lead center of the study that also includes three other clinical trial centers across the U.S (Press release, Antengene, DEC 10, 2023, View Source [SID1234638385]).
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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.
"We are delighted that the PERFORM trial has successfully dosed its first patient in the U.S. CD24 is a target with great potential in regulating macrophage activities in tumor environment. Supported by the striking preclinical efficacy demonstrated by blocking CD24 in preclinical studies and a promising preclinical safety profile based on CD24’s limited expression in normal tissue, Antengene has quickly initiated the PERFORM study in the U.S. to further assess the safety and tolerability of ATG-031 in late stage cancer patients," said Dr. Amily Zhang, Antengene’s Chief Medical Officer. "Moving forward, we will continue to work closely with investigators at MD Anderson and three other clinical trial centers in the U.S. to bring clinical benefit to more patients as soon as possible."
"With the joint persistent efforts from Antengene’s internal teams, we have made great strides to the development of ATG-031, a first-in-class anti-CD24 monoclonal antibody targeting the novel ‘don’t eat me’ pathway, while making rapid progress with the clinical development of other core assets. To date, we have established close collaboration with more than 100 clinical trial centers in the U.S., Australia, and the Mainland of China," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. "Remaining committed to our global innovation strategies and steadily expediting our clinical programs, we will focus on next generation novel treatments to address broad unmet medical needs post the current immune checkpoint inhibitors."
About 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 (AACR) (Free AACR Whitepaper) 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-031 induces efficient phagocytosis with a picomolar EC50 and stimulates the pro-inflammatory cytokines production by macrophages.