Aptevo Therapeutics debuts trispecific antibody candidate APVO451

Aptevo Therapeutics (APVO) announced the first presentation of preclinical data for its new trispecific antibody, APVO451, at the Society for Immunotherapy of Cancer Annual Meeting on Saturday, November 8, 2025. The poster was presented by Michelle H. Nelson, PhD, Director of Immunobiology and Hieu Nguyen, BS, Senior Scientist, both of Aptevo. APVO451 is designed to solve a central challenge in the treatment of certain solid tumor types: The tumor microenvironment often shuts down the immune system’s ability to fight cancer. The new molecule leverages Aptevo’s proprietary use of the CRIS-7-derived CD3 binding domain-the same binding domain used in the Company’s lead clinical drug, mipletamig, which has shown strong clinical activity with limited safety challenges and, no cytokine release syndrome in frontline AML patients to date. APVO451 brings two coordinated immune signals together in a single, targeted molecule. First, it binds to nectin-4, a protein commonly found on numerous solid tumors, which guides the drug directly to the tumor site and helps ensure that immune activation happens locally rather than throughout the body. Once there, the molecule uses the Company’s proprietary CRIS-7-derived CD3 binding domain to activate T cells, triggering tumor-killing activity without inducing CRS that can occur with many T-cell engagers. Finally, APVO451 binds to CD40 and restores the inflammatory function of antigen-presenting cells, helping to ramp up the immune response. Working together, these signals are intended to re-activate anti-tumor immunity where it has been suppressed -a key shortcoming for many existing immunotherapies. Key Findings from the Presentation Local Activation in the Tumor: APVO451 triggered T-cell and APC activation only when bound to the target nectin-4, suggesting the potential for strong immune activity without systemic over-activation resulting in a potentially favorable safety profile. Dual Immune Re-Activation: The molecule stimulated the effector functions of T-cells and restored APC function – two arms of the immune system that cause treatments to often fail in solid tumors due to the tumors’ ability to suppress the immune system. Activity Under Suppressive Conditions: In cultured tumor models designed to mimic tumor suppression, APVO451 eliminated nectin-4-positive tumor cells more effectively than a standard CD3 T-cell engager potentially demonstrating the ability of APVO451 to overcome a suppressive tumor microenvironment.