Abstract 638: Discovery of HX016-7, a novel PD-L1 x VEGF BsAb, as a new candidate treatment of solid tumors

Abstract A first-in-class PD-L1xVEGF bispecific antibody (BsAb), BNT327/PM8002, has demonstrated promising efficacy in treating TNBC and NSCLC cancers in advance stage of clinical development, which prompted us to engineer a novel and potentially best-in-class (BIC) PD-L1xVEGF BsAb by using a validated anti-PD-L1 and a novel anti-VEGF (HX006, a novel VEGF mAb with more favor activity over Avastin) mAb sequences. HX016-7 has 2+2 IgG1 symmetric structure constructed by grafting the PD-L1 binding domain of PD-L1 mAb onto the N-terminus of HX006. HX016-7 binds with similarly affinity to PD-L1 recombinant protein with EC50 of 0.27nM (vs. 0.36nM by BNT327/PM8002) and to VEGF recombinant protein with EC50 of 0.094nM (vs. 0.063 by BNT327) in ELISA assay. It also binds similarly to the PD-L1 positive cell line as BNT327/PM8002 with comparable affinity. Reporter-based bioassay for PD1/PD-L1 blockade function demonstrated that HX016-7 has EC50 of 4.85 nM (vs. 5.13nM for BNT327/PM8002), while reporter-based bioassay for VEGF function demonstrated that HX016-7 has EC50 of 11.7nM (vs. 15.8nM for BNT327/PM8002). In a MC38-hPD-L1-hVEGF colorectal cancer syngeneic model implanted in hPD-1 humanized mice, HX016-7 was shown to have comparable anti-tumor activity as BNT327/PM8002, but stronger activity over HX006, which can be attributed to both PD-L1- and VEGF-targeting. In a subcutaneous A549 non-small-cell lung cancer (NSCLC) cell-derived xenograft model in immunocompromised mice, HX016-7 also showed slightly stronger anti-tumor activity over BNT327/PM8002, which can be attributed to anti-VEGF function. We believe these preclinical data warrants the candidacy of HX016-7 to be further developed for the treatment of solid tumors. Citation Format: Hang Ke, Tao Yang, Feiyu Peng, Jialing Li, Cen Chen, Stephen Xiong, Lei Zhang, Faming Zhang, Henry Qixiang Li. Discovery of HX016-7, a novel PD-L1 x VEGF BsAb, as a new candidate treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 638.