Summary                      

￭  IPG0521 is a potent, selective, preclinical CCR8 antibody antagonist developed to complement our immuno-oncology pipeline portfolio. As a large-molecule biologic therapeutic, IPG0521 reinforces our leadership position on the validated CCR8 target through a distinct, differentiated mechanism of action.

￭  It is engineered to deliver robust antitumor activity by blocking the function of immunosuppressive regulatory T cells (Tregs), while utilizing mild, controlled ADCC (antibody-dependent cellular cytotoxicity) activity. This innovative design is intended to deliver a superior safety profile compared to competing CCR8 antibodies that rely on non-selective, potent cell depletion strategies.

￭  Furthermore, IPG0521 has served as a critical preclinical research tool, delivering essential in vivo proof-of-concept data for the entire CCR8-targeting program in IgG4-Related Disease, which is being clinically advanced via our small-molecule candidate IPG7236.

IPG0521 in Oncology

Mechanism of Action

￭  Targeted Immunosuppression Blockade: IPG0521 is a potent antibody antagonist that selectively blocks the migration of tumor-infiltrating Tregs and abrogates their immunosuppressive function—a primary barrier to effective endogenous antitumor immunity.

￭   Differentiated Safety-First Design: Critically, its primary mechanism of action is functional inhibition of Tregs, paired with only mild ADCC activity. This stands in stark contrast to competing antibodies that rely on potent ADCC to physically deplete all CCR8-expressing cells non-selectively.

￭   Broad Immune Reactivation: This mechanism has been validated in vivo via RNA sequencing, which confirms that IPG0521 treatment drives significant upregulation of genes associated with antigen presentation, innate immunity, and effector T cell activation.

Key Differentiation

￭  Superior Safety Profile: The mild-ADCC design is intentionally engineered to mitigate the risk of on-target, off-tumor toxicity linked to high-ADCC strategies, which can damage healthy peripheral tissues expressing CCR8.

￭  Synergy with Checkpoint Inhibitors: Preclinical data demonstrate strong synergistic potential with anti-PD-1 therapies, positioning IPG0521 as a promising candidate to overcome resistance to standard-of-care immunotherapies.

￭   Strategic Pipeline Complement: As a large-molecule biologic, IPG0521 diversifies our CCR8 therapeutic franchise, expanding our coverage across modalities and strengthening our intellectual property position.

Current Development Status

￭ IND Approvals for Clinical Trials: The program received IND approvals from both the U.S. FDA and China NMPA in 2025 for the treatment of advanced solid tumors.

In vitro and in vivo Properties

￭ High-Affinity Binding Across Species: IPG0521 binds to CCR8 with high affinity across five species: human, rat, dog, mouse, and cynomolgus monkey.

￭ Potent Dose-Dependent Antitumor Activity: IPG0521 demonstrated significant, dose-dependent tumor growth inhibition in a syngeneic H22 hepatocellular carcinoma mouse model.

IPG0521 in IgG4-Related Disease (IgG4-RD)

Key Differentiation

￭   Program De-Risking: IPG0521 generated the first in vivo proof-of-concept that CCR8 pathway blockade is a viable, highly effective therapeutic strategy for IgG4-RD.

￭   Therapeutic Hypothesis Validation: Studies confirmed that CCR8 blockade effectively attenuates core pathological features of the disease, including tissue inflammation and progressive fibrosis.

In vivo Properties

In a validated mouse model of IgG4-RD, treatment with IPG0521 produced significant, dose-dependent therapeutic effects:

• Reduced Organ Inflammation & Fibrosis: Treatment markedly reduced pancreatic inflammation, evidenced by decreased immune cell infiltration and parenchymal destruction, and dose-dependently attenuated pancreatic fibrosis.

• Downregulated Pathogenic Cytokines: Treatment significantly downregulated the expression of key pro-inflammatory and pro-fibrotic cytokines—including IL-6, IL-1β, IFN-γ, IL-10, and TGF-β—in affected salivary gland tissue.

Current Development & Status

￭ IND Approvals for Clinical Trials: The program has successfully received IND approvals from the FDA and NMPA for IgG4-Related Diseases.

Publications

•Binle Tian, Zhilong Wang, Na Wang, Xuebing Jia, Yuanyuan Zhang, Jingyi Zhou, Wen Zhang, Zheng Li, Junli Xue, JianFei Wang, Guo-Huang Fan, Qi Li. CCR8 antagonistic antibody abolishes immunosuppression of regulatory T cells and modulates antitumor immune micro-environment in Liver Cancer. Cancer Res, in submission