Aptevo Expands Differentiated CD3 Portfolio with APVO455, Advancing a Suite of Targeted T-cell Engagers

Mipletamig-driven clinical validation of the CRIS-7 derived CD3-binding domain underpins Aptevo's expansion from hematologic to solid tumors

New candidate APVO455 targets Nectin-4+ cancers, joins mipletamig (AML) and APVO442 (prostate) in Aptevo's tumor-directed CD3 suite

SEATTLE, WASHINGTON / ACCESS Newswire / June 20, 2025 / Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (Nasdaq:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, today announced the addition of preclinical candidate APVO455 to its growing portfolio of CD3-directed candidates built on the CRIS-7 derived CD3 binding domain-an approach demonstrating compelling potential across both hematologic and solid tumors.

With this announcement, Aptevo now has a suite of three CD3-engaging molecules in development. All three share the same CRIS-7 derived binding domain with a low cytokine release profile. In addition, APVO455 and APVO442 contain CD3 binding domains that are optimized for targeting solid tumors. All three molecules are designed to drive tumor-specific immune activation while limiting systemic toxicity. The suite includes:

• Mipletamig , a CD123 x CD3 bispecific currently in Phase 1b/2 for frontline AML, where 85% of evaluable frontline patients across two trials have achieved remission in combination with standard of care. No cytokine release syndrome (CRS) has been observed in the first two trial cohorts of the ongoing RAINIER trial

• APVO442 , a PSMA x CD3 candidate targeting prostate cancer, currently in preclinical development

• And now APVO455 , a Nectin-4 x CD3 bispecific developed to address multiple solid tumor types

"With APVO455, we are rounding out a purposefully designed CD3 product suite that reflects both scientific rigor and clinical learning," said Marvin White, President and CEO of Aptevo. "Compelling mipletamig clinical results, where we have treated more than 100 patients across three trials, give us confidence that CRIS-7 is a critical differentiator. Our molecules behave predictably, drive selective activation and are emerging from a shared design strategy grounded in real-world human data."