[AACR 2025 Abstract] Enhanced Efficacy of a Tri-Specific Fusion Protein Compared to PD-1/VEGF Bispecific Antibody in Immune Checkpoint Inhibitor-Resistant Tumor Models

Mustbio announced that it will present preclinical data on its novel PD-1/VEGF/IL-2v tri-specific fusion protein at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025, which will be held from April 25 to 30 in Chicago, USA.

The PD-1/VEGF/IL-2v tri-specific fusion protein is currently at the candidate selection stage, with cell line development planned for the second half of this year. The company aims to initiate GLP-compliant toxicology studies in 2026.

In recent years, bispecific antibodies targeting PD-(L)1 and VEGF have drawn attention as a new therapeutic class, showing improved efficacy over anti-PD-1 monotherapy. Summit Therapeutics helped lead this trend by reporting that its PD-1xVEGF bispecific antibody, ivonescimab, extended progression-free survival (PFS) compared to Keytruda in a Phase 3 non-small cell lung cancer trial. Other players in the field include BioNTech and Merck (MSD).

Maengsub Kim, CEO of Mustbio, stated, “Although multiple PD-(L)1xVEGF bispecific antibodies are under development globally, their dual mechanism alone may not be sufficient to overcome immune checkpoint inhibitor resistance. We believe a tri-specific approach incorporating an IL-2 variant (IL-2v), which robustly expands activated immune cells, could offer a novel solution with significant clinical potential.

Mustbio’s tri-specific fusion protein is designed to simultaneously:

        • activate T cells via PD-1 blockade,

      • increase tumor-infiltrating lymphocytes (TILs) through VEGF inhibition, and

      • enhance the proliferation of effector T cells via IL-2v signaling.