November 10, 2025 — Leads & Copy —
Seattle, WA — Aptevo Therapeutics (Nasdaq:APVO), a clinical-stage biotechnology company, has announced the 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 presentation was led by Michelle H. Nelson, PhD, Director of Immunobiology, and Hieu Nguyen, BS, Senior Scientist, both of Aptevo.
APVO451 is designed to address challenges in treating solid tumor types, including urothelial, breast, and pancreatic cancers, where the tumor microenvironment often suppresses the immune system’s ability to fight cancer. The molecule uses Aptevo’s CRIS-7-derived CD3 binding domain, also utilized in the company’s lead clinical drug, mipletamig, which has demonstrated clinical activity with limited safety challenges and no cytokine release syndrome (CRS) in frontline AML patients to date.
Dr. Michelle H. Nelson explained that solid tumors are difficult to treat because the immune system within the tumor is often switched off. APVO451 aims to reactivate the intratumoral immune system, enabling it to target and kill tumor cells more effectively.
The molecule binds to nectin-4, a protein found on numerous solid tumors, guiding the drug to the tumor site and ensuring local immune activation. It uses the CRIS-7-derived CD3 binding domain to activate T cells, triggering tumor-killing activity without inducing CRS. APVO451 also binds to CD40, restoring the inflammatory function of antigen-presenting cells (APCs) and enhancing the immune response. These signals are designed to reactivate anti-tumor immunity suppressed by the tumor, which is a key limitation of many existing immunotherapies.
Key findings from the presentation included:
- 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.
Dr. Nelson stated that these findings reinforce Aptevo’s belief that redirecting T cells is important but may not be enough for solid tumors, requiring the drug to also address intratumoral immune suppression.
APVO451 is undergoing preclinical studies to support IND-enabling work and future clinical development in nectin-4-expressing solid tumors.
APVO451 is a trispecific ADAPTIR-FLEX™ therapeutic candidate designed to target nectin-4 while engaging CD3 and CD40 to orchestrate coordinated T-cell activation and APC costimulation in the tumor microenvironment, designed to restore productive immune engagement in suppressive solid tumors while minimizing off-tumor immune activation.
Aptevo Therapeutics Inc. (Nasdaq: APVO) is focused on developing novel bispecific and trispecific immunotherapies for cancer. Mipletamig is being evaluated in the RAINIER Phase 1b/2 trial for frontline AML treatment in combination with venetoclax + azacitidine and has orphan status for AML. ALG.APV-527, a bispecific conditional 4-1BB agonist co-developed with Alligator Bioscience, is in a Phase 1 trial for solid tumors expressing 5T4. Aptevo has six pre-clinical candidates using ADAPTIR™ and ADAPTIR-FLEX™ platforms.
Aptevo’s mission is to improve treatment outcomes and transform the lives of cancer patients.
Miriam Weber Miller
Aptevo Therapeutics
IR@apvo.com or millerm@apvo.com
+1 (206) 859 6629
Source: Aptevo Therapeutics
