Aptevo Debuts First Trispecific Antibody Candidate, APVO451, with Preclinical Data Demonstrating Immune Activation in Hard-to-Treat Solid Tumors

First data on Aptevo's new molecule presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting

SEATTLE, WASHINGTON / ACCESS Newswire / November 10, 2025 / Aptevo Therapeutics ("Aptevo" or the "Company") (Nasdaq:APVO), a clinical-stage biotechnology company advancing differentiated immunotherapies, announced the first presentation of preclinical data for its new trispecific antibody, APVO451, at the Society for Immunotherapy of Cancer (SITC) 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 {such as urothelial, breast and pancreatic cancers}: 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 (CRS) in frontline AML patients to date.

"Solid tumors are often difficult to treat because the immune system within the tumor gets switched off," said Michelle H. Nelson, PhD, Director of Immunobiology at Aptevo. "APVO451 is designed to wake up the intratumoral immune system so it can more effectively target and kill tumor cells."

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 (APCs), 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.