GS002，一种具有靶向细胞毒递送和免疫检查点抑制的新型抗PD-L1 ADC

GS002 (also designated 002mAb-GSLP003) is an investigational anti-PD-L1 antibody-drug conjugate (ADC) with a drug-to-antibody ratio (DAR) of 8. It comprises a high-affinity, Fc-silent IgG1κ antibody engineered to promote endocytosis, site-specifically conjugated via a solubility-enhanced linker to a novel topoisomerase I inhibitor payload. A key distinguishing feature of GS002 is its optimized linker-payload system, which enhances solubility and stability, and incorporates a payload that is superior to DXd, exhibiting potent bystander killing while resisting drug efflux. Preclinically, GS002 demonstrates a dual mechanism of action, combining potent PD-L1-targeted cytotoxicity with immune checkpoint blockade. In vitro, GS002 mediated enhanced endocytosis relative to two competitor ADCs and induced potent cytotoxicity in PD-L1-positive tumor cells, with minimal impact on antigen-presenting cells such as M0 macrophages and myeloid dendritic cells. In vivo, GS002 elicited sustained antitumor activity across multiple cell-derived xenograft models, including EMC-1, KARPAS-299, and H1975, matching or exceeding the efficacy of 002mAb-GGFG-DXd and two competitor ADCs. The solubility-enhanced linker-payload design of GS002 conferred favorable pharmacokinetics in rats following a single 6 mg/kg IV dose, exhibiting closely overlapping plasma concentration-time curves for total and conjugated antibody. GS002 also demonstrated high plasma stability across species, with minimal premature payload release after 21 days at 37°C. Furthermore, its developability profile was comparable to the unconjugated antibody (002mAb), showing similar hydrophobicity and thermostability as evidenced by identical HIC retention times and closely matched Tm and Tagg values. In summary, GS002 represents a highly differentiated PD-L1-targeting ADC candidate with synergistic dual mechanisms, compelling efficacy in vitro and in vivo, a favorable pharmacokinetic profile, and excellent developability properties, supporting its advancement into further IND-enabling development.