Summary                      

￭  IPG0521 is a potent and selective, pre-clinical CCR8 antibody antagonist being developed to complement our pipeline in immuno-oncology. As a large-molecule (antibody) therapeutic, IPG0521 extends our leadership on the validated CCR8 target through an alternative and differentiated mechanism of action. 

￭  It is engineered to provide robust antitumor activity by blocking the function of immunosuppressive regulatory T cells (Tregs) while utilizing only mild 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 aggressive cell depletion.

￭  Furthermore, IPG0521 has played a critical role as a pre-clinical surrogate, providing the essential in vivo proof-of-concept for the entire CCR8-targeting program in IgG4-Related Disease, which is being clinically advanced with our small-molecule candidate, IPG7236.

IPG0521 in Oncology

Mechanism of Action

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

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

￭ Broad Immune Reactivation: This mechanism was validated in vivo through RNA-sequencing, which confirmed that IPG0521 treatment leads to a significant up-regulation of genes associated with antigen presentation, innate immunity, and T cell activation.

Key Differentiation

￭ Superior Safety Profile: The mild-ADCC mechanism is specifically designed to avoid the risk of on-target, off-tumor toxicity associated with high-ADCC strategies that can damage healthy tissues expressing CCR8.

￭ Synergy with Checkpoint Inhibitors: Pre-clinical data indicate a strong potential for synergy with anti-PD-1 therapy, positioning IPG0521 as a promising solution for overcoming resistance to current immunotherapies.

￭ Strategic Pipeline Complement: As a large-molecule antibody, IPG0521 diversifies our CCR8 franchise, providing a distinct therapeutic modality and intellectual property position.

Current Development & Status

￭ IND Approvals for Clinical Trials: The program has successfully received IND approval from the FDA and NMPA in 2025 for solid tumors.

In vitro and in vivo Properties

￭ High affinity bounding to CCR8: IPG0521 bound to CCR8 with high affinity from five different species: Human, Rat, Dog, Mouse, and Monkey.

￭ Potent Antitumor Activity: IPG0521 demonstrated significant and dose-dependent inhibition of tumor growth in a syngeneic liver cancer (H22) mouse model.

IPG0521 in IgG4-RD

Key Differentiation

￭ De-risked the IgG4-RD Program: IPG0521 provided the first in vivo evidence that blocking the CCR8 pathway is a viable and highly effective therapeutic strategy for treating IgG4-RD.

￭ Validated the Therapeutic Hypothesis: The study confirmed that CCR8 blockade effectively attenuates the key pathological features of the disease, including inflammation and fibrosis.

In vivo Properties

In a mouse model of IgG4-RD, treatment with IPG0521 resulted in significant and dose-dependent therapeutic effects:

￮ Reduced Organ Inflammation: Markedly reduced pancreatic inflammation, characterized by decreased immune cell infiltration and parenchymal destruction. Significantly attenuated pancreatic fibrosis in a dose-dependent manner.

￮ Downregulated Key Cytokines: Significantly downregulated the expression of key pro-inflammatory and pro-fibrotic cytokines (IL-6, IL-1β, IFN-γ, IL-10, and TGF-β) in affected salivary glands.

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