Summary                      

￭ IPG0521 is a potent, selective CCR8 antagonist antibody with IND clearances from both the U.S. FDA and China NMPA. It is the first and only CCR8 antibody antagonist designed to block CCR8 signaling with mild ADCC activity.

￭  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 design is intended to mitigate the on-target, off-tumor toxicity risk associated with 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 antitumor immunity. 

￭   Differentiated Safety-First Design: Its primary mechanism is functional inhibition of Tregs paired with mild ADCC activity, in contrast to antibody approaches that rely on potent ADCC-mediated depletion of CCR8-expressing cells.

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

Key Differentiation

￭  Safety-Differentiated Design: The mild-ADCC profile is intended to mitigate the risk of on-target, off-tumor toxicity associated with high-ADCC strategies.

￭  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 biologic modality, IPG0521 extends the company's CCR8 franchise through a distinct, differentiated mechanism of action.

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, TGF-β, BAFF, and IL-33—in affected salivary gland tissue.

Current Development & Status

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

Publications

•Tian B, Wang Z, Cao M, Wang N, Jia X, Zhang Y, Zhou J, Liu S, Zhang W, Dong X, Li Z, Xue J, Wang J, Fan G, Li Q. CCR8 antagonist suppresses liver cancer progression via turning tumor-infiltrating Tregs into less immunosuppressive phenotype. J Exp Clin Cancer Res. 2025;44. doi: 10.1186/s13046-025-03286-x. PMID: 40186298.