Aptevo Highlights APVO603: A Novel Bispecific Antibody Targeting 4-1BB and OX40 for Enhanced Solid Tumor Immunotherapy

Continues focus on development of bispecific anti-cancer agents with differentiated mechanisms of action

SEATTLE, WASHINGTON / ACCESS Newswire / March 18, 2025 / Aptevo Therapeutics (NASDAQ:APVO), a leader in the development of novel bispecific antibodies for cancer treatment, based on its proprietary ADAPTIR® and ADAPTIR-FLEX® platform technologies provided an overview of solid tumor anti-cancer compound APVO603, currently in preclinical development for the treatment of solid tumors. APVO603 is a novel bispecific antibody designed to enhance anti-tumor immune responses through dual targeting of 4-1BB (CD137) and OX40 (CD134), two key co-stimulatory receptors involved in T cell and NK cell activation.

APVO603 is part of Aptevo's solid tumor anti-cancer pipeline and represents a significant step forward in leveraging the company's proprietary ADAPTIR® platform to develop safer and more effective immuno-oncology therapies.

Targeted Immune Activation for Solid Tumors

APVO603 is designed to activate the costimulatory 4-1BB and OX40 pathways in the tumor microenvironment, leading to enhanced T cell expansion, survival, and cytotoxic function while avoiding systemic toxicity. This targeted immune activation could overcome immune suppression in solid tumors, a major challenge in cancer immunotherapy.

Preclinical studies have shown that APVO603:

• Enhances T cell and NK cell proliferation and tumor lysis, while maintaining a favorable safety profile and inhibiting immune exhaustion
• Induces a robust anti-tumor response in preclinical tumor models, suggesting strong therapeutic potential

"We are excited about the potential of APVO603 to enhance the potency of T cells and NK cells while addressing the limitations of current therapies for solid tumors," said Michelle Nelson, PhD, Director of Immunobiology at Aptevo. "Our preclinical findings support APVO603's ability to deliver 4-1BB and OX40 synergistically resulting in targeted immune stimulation with reduced toxicity risks, differentiating it from existing immunotherapies."

Aptevo's Advancing Immuno-Oncology Pipeline

APVO603 is one of three promising preclinical candidates in Aptevo's bispecific antibody pipeline, alongside APVO711, a bispecific + checkpoint inhibitor, and APVO442, a T-cell engager targeting prostate cancer. These programs build on Aptevo's expertise in bispecific antibody engineering and reinforce the company's commitment to developing novel immunotherapies that improve outcomes for cancer patients.

Clinical Programs

Lead Candidate Mipletamig for Acute Myeloid Leukemia (AML): Mipletamig, Aptevo's lead bispecific antibody, is currently in a frontline Phase 1b/2 combination trial, RAINIER, following positive results from earlier studies.

RAINIER results reported to date include:

• 100% of patients in Cohort 1 of the trial achieved remission within 30 days
• One patient experienced complete remission with minimal residual disease (MRD)-negative status (100% elimination of cancer cells)
• Favorable safety profile consistent with prior trials, showing no incidences of cytokine release syndrome (CRS) in the current trial to date, a common and often dose limiting side effect seen in similar therapies

ALG.APV-527: ALG.APV-527 is being evaluated in a Phase 1 trial for solid tumors likely to express the tumor antigen 5T4. Tumor types treated to date include breast, colon, pancreatic and non-small cell lung cancer. Positive preliminary data from the study were presented at the European Society of Medical Oncology Congress in September and at the Society for Immunotherapy of Cancer conference in 2024. These results showed that ALG.APV-527 demonstrated positive safety and tolerability across all cohorts, ten of 17 evaluable patients (59%) achieved stable disease (SD), and biomarker analysis confirmed immune activation in the tumor microenvironment.

This drug has the potential to advance treatment in hard-to-treat solid tumors, demonstrating the versatility of Aptevo's technology across a wide range of cancer types.

About Aptevo Therapeutics

Aptevo Therapeutics Inc. (Nasdaq:APVO) is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. The company has two clinical candidates. Mipletamig is currently being evaluated in RAINIER, a Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard of care venetoclax + azacitidine. Mipletamig has orphan status for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and is being evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has three pre-clinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIR® and ADAPTIR-FLEX®. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com.