ATN-031 Novel macrophage activator targeting primarily on solid tumors

Summary and Differentiations

• CD24 is a novel "don’t eat me" target not expressed in healthy erythrocytes, thus potentially overcoming the pharmacological issues and red cell toxicity commonly seen with CD47 antibodies
• First-in-class humanized CD24 mAb inhibits the "don’t eat me" signal by blocking CD24-Siglec10 pathway and enhances macrophage-mediated phagocytosis of cancer cells
• CDx antibody successfully developed in-house for patient selection
• Potent single agent in vivo efficacy and synergy with chemotherapy or CPI

"Don’t Eat Me"

• Reduced phagocytosis
• M2-like Tumor Associated Macrophage
• Immunosuppressive Tumor Microenvironment
• Less tumor antigen presentation
• In-activated T and NK cells

"Eat Me"

• Increased phagocytosis
• M1-like Tumor Associated Macrophage
• Pro-inflammatory Tumor Microenvironment
• Enhanced Tumor Antigen presentation
• Activated T and NK cells

CD24 Has Higher Tumor Expression Compared to CD47

Comparison Analysis

• CD24 showed much higher tumor expression (TCGA) and narrower normal tissue distribution (GTEx), with significantly lower normal heart and CNS expression, compared with CD47
• Anti-CD24 potentially has a larger therapeutic window compared with anti-CD47

A 20-hour Time-Lapse Imaging of ATN-031-Induced Phagocytosis

• Phagocytosis occurred within 5 minutes after the addition of ATN-031
• Leukemia cells were completely digested within 10 hours

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