Abstract 5539: The anti-tumor activity of BB-202, a novel anti-PD-1/anti-VEGF bispecific antibody

Abstract Background: Immune checkpoint blockade targeting PD-1/PD-L1 and VEGF inhibition each modulates the tumor microenvironment, and their combination has shown synergistic anti-tumor effects in preclinical models. Clinically, combining anti-PD-1/PD-L1 antibodies with anti-angiogenic agents has improved outcomes across multiple cancers and led to several regulatory approvals. Bispecific antibodies that co-target PD-1 and VEGF within a single molecule represent a promising strategy to further enhance this synergy. While the anti-PD-1/anti-VEGF bispecific antibody ivonescimab (AK112) has demonstrated clinical benefit, we developed BB-202, a novel bispecific antibody with a distinct structure designed to improve potency and stability. Methods: BB-202 was engineered using pembrolizumab-derived Fab regions and anti-VEGF VHH fragments fused to a human IgG1 Fc. PD-1 binding affinity was characterized using whole-cell binding assays. PD-1 and VEGFA blockade were assessed using cell-based reporter assays, and PD-1 functional blockade was further evaluated in mixed lymphocyte reaction (MLR) assays. In vivo efficacy and safety were examined in multiple mouse xenograft models, including PBMC-humanized mouse models. Results: BB-202 demonstrated high PD-1 binding affinity equivalent to pembrolizumab. In PD-1/PD-L1 blockade assays, BB-202 showed potency similar to pembrolizumab and substantially greater than AK112 and LM-299. BB-202 also blocked VEGFA activity with potency comparable to bevacizumab (Avastin), AK112, and LM-299. In MLR assays, BB-202 induced robust human T-cell activation, exhibiting approximately 38-fold greater potency than AK112. The molecule also showed excellent accelerated and serum stability.In vivo, BB-202 demonstrated strong anti-tumor activity. In an NCI-H1975 PBMC-humanized mouse model, BB-202 achieved significantly greater tumor growth inhibition than an equimolar dose of pembrolizumab. Consistent results were observed in the NCI-HCC827 xenograft model, where BB-202 again outperformed pembrolizumab. No weight loss or observable toxicities were detected. Conclusion: BB-202 is a potent, stable, and well-tolerated anti-PD-1/anti-VEGF bispecific antibody. Its superior in vitro potency and robust in vivo efficacy, together with a favorable developability profile, position BB-202 as a promising best-in-class therapeutic candidate among PD-1/VEGF-targeting bispecific antibodies. Citation Format: Hongyan Zhong, Daniel Guo, Phuong Nguyen, Daniel Li, Ming Yang, . The anti-tumor activity of BB-202, a novel anti-PD-1/anti-VEGF bispecific antibody abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5539.