Abstract 5541: Characterization and functional evaluation of PF-08634404 (SSGJ-707) a tetravalent PD-1 x VEGF bispecific for the treatment of cancer

Abstract PF-08634404 (formerly known as SSGJ-707) is an investigational anti-PD-1 and anti-VEGF bispecific antibody designed to simultaneously inhibit PD-1-mediated T cell dysfunction and VEGF-A-mediated tumor angiogenesis and immune suppression in the tumor microenvironment. PF-08634404 is a tetravalent 2+2 bispecific leveraging Common Light Chain Linear Fab x2 (CLF2) technology with an IgG4 backbone. The PD-1 and VEGF-A binding arms of PF-08634404 are unique among the PD-1 x VEGF bispecific class. PF-08634404 has demonstrated promising clinical activity in NSCLC and CRC in clinical trials conducted in China. Here we present preclinical data demonstrating binding to and functional inhibition of PD-1 and VEGF-A by PF-08634404 in vitro. PF-08634404 displays nanomolar binding affinities for PD-1 and VEGF-A and can bind both targets simultaneously. The functional inhibition of VEGF by PF-08634404 is increased (∼7.5-fold) compared to relevant benchmarks, and the inhibition of PD-1 is equivalent or superior to relevant benchmarks. Consistent with this class of bispecific molecules, PF-08634400 multimerizes in the presence of dimeric VEGF-A, increasing the avidity for PD-1 (100-fold), driving rapid internalization of PD-1 on T cells, and improving the functional inhibition of PD-1 (10-fold). Collectively, these data characterize core features of the bispecific mechanism and support the ongoing clinical investigation of PF-08634404 proof of concept and pivotal trials in multiple disease settings/tumor types. Citation Format: Ryan A. Heiser, Meghan Zuck, Catalina Sakai, Eliana Moskovitz, Laila Shehata, Markus Carlson, Florian Heinkel, Sherif Abdelhamed, MIchelle Ulrich, Matt Rathgeber, Brian P. O'Connor, Joseph D. Dekker, Haomin Huang, Sharsti Sandall. Characterization and functional evaluation of PF-08634404 (SSGJ-707) a tetravalent PD-1 x VEGF bispecific for the treatment of cancer 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 5541.