美国知名癌症中心将牵头开展抗CD24单抗ATG-031的I期临床研究

PERFORM研究是一项在晚期实体瘤或B-NHL患者中开展的首次人体、多中心、开放性I期剂量索求试验。该研究的首要目的为评估ATG-031单药的平安性和耐受性，并确定II期研究的使用剂量。该研究的次要目的为确定ATG-031的药理特征和免疫原性，评估该药物的初步疗效。

ATG-031是一款可按捺 “别吃我” 旌旗并强化由巨噬细胞介导的肿瘤细胞吞噬的全球首创（first-in-class）人源化抗CD24单克隆抗体。肿瘤细胞经由过度表达让其免于被巨噬细胞发现和吞噬的“别吃我”细胞外观卵白逃脱来自人体免疫系统的监测。CD24（分化抗原簇24）是一个首要的 “别吃我” 旌旗，它经由按捺由巨噬细胞介导的肿瘤细胞吞噬，在肿瘤免疫逃逸中起着要害感化。与另一个“别吃我”靶点CD47比拟，CD24具有更局限的健康组织分布和更高的肿瘤组织表达，而且不在人红细胞上表达，这使得CD24靶向疗法降低了在靶脱瘤毒性，具有更大的平安窗。

作为一个新型固有免疫搜检点，CD24经由与表达于肿瘤相关巨噬细胞（TAM）上的按捺受体Siglec-10（唾液酸连系性免疫球卵白样凝集素10）的互相感化，实现肿瘤细胞的免疫逃逸。在2023年美国癌症研究协会年会（AACR 2023）上发布的临床前数据显露，ATG-031能够纳摩尔级别亲和力与CD24特异性连系并阻断CD24与Siglec-10的互动。此外，ATG-031可诱导皮摩尔EC50水平的高效吞噬感化，并促进巨噬细胞排泄促炎细胞因子。

德琪医药有限公司（简称“德琪医药”，香港生意所股票代码：6996.HK）是一家以研发为驱动，并已进入贸易化阶段的生物制药领先企业，以“医者无疆，立异永续”为愿景，德琪医药专注于血液及实体肿瘤范畴的同类首款和同类最优疗法的早期研发、临床研究、药物生产及贸易化，致力于经由供应冲破性疗法，改善全球患者生活质量。

自2017年以来，德琪医药现已竖立起一条拥有9款从临床延展至贸易化阶段的肿瘤药物资产研发管线，个中，6款产物具有全球权益，3款产物具有亚太权益。公司已在美国及多个亚太市场获得29个临床批件（IND），并递交了10个新药上市申请（NDA）。今朝，希维奥^®（塞利尼索片）已获得中国大陆、中国..、中国香港、韩国、新加坡和澳大利亚的新药上市核准。

Antengene Announces Phase I Study of Anti-CD24 Monoclonal Antibody ATG-031 

-   The Phase I “PERFORM” study will evaluate the safety and tolerability, pharmacology, immunogenicity, and preliminary efficacy of ATG-031 in patients with advanced solid tumors or B-cell non-Hodgkin’s lymphoma (B-NHL).

-   ATG-031,discovered and developed in-house by Antengene,is the world's first anti-CD24 antibody to advance to the clinic in oncology and Antengene’s third drug candidate to enter clinical studies in the U.S.

Shanghai and Hong Kong, PRC, September 21, 2023 — Antengene Corporation Limited (“Antengene” SEHK: 6996.HK), a leading commercial-stage innovative, global biopharmaceutical company dedicated to discovering, developing, and commercializing first-in-class and/or best-in-class medicines for hematology and oncology, today 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.

Dr. Amily Zhang, Antengene’s Chief Medical Officer said,“We are excited about the progress being made with ATG-031. We look forward to further characterizing the safety, tolerability, and preliminary efficacy of ATG-031. We will begin enrolling patients for the study as soon as possible and plan to release the first batch of preliminary data from the study in 2024.”

“Through committed work and unrelenting innovation, our R&D organization successfully advanced the ATG-031 program to the clinical stage in just three years, an achievement that has truly made us proud,” said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. “Based on the robust preclinical data of ATG-031, we are confident that the drug will continue to demonstrate its therapeutic potential in clinical studies. Moving forward, Antengene will press ahead the clinical development of its global rights programs with the aim of serving a broader population of patients.”

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.

Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of “Treating Patients Beyond Borders”.

Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 29 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 10 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO^® (selinexor) already approved in Mainland of China, Taiwan China, Hong Kong China, South Korea, Singapore and Australia.