On 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, reported 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 (Press release, Aptevo Therapeutics, JUN 20, 2025, View Source [SID1234654025]).
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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."
Mr. White continued, "Ultimately, this design choice has yielded a compelling safety profile in the clinic, as seen with mipletamig, and supports broader application across indications where tolerability remains a barrier to effective T-cell engagement."
About APVO455: Advancing Nectin-4 T-cell Targeting in Solid Tumors
APVO455 is a preclinical Nectin-4 x CD3 bispecific T-cell engager designed for tumors such as bladder, breast, NSCLC, and head and neck cancers, where Nectin-4 is highly expressed. Unlike other approaches that restrict activity to acidic tumor environments or rely on activated T-cells, APVO455 is designed to avoid binding to or triggering T-cell activation in the periphery and do so only in the presence of Nectin-4 positive tumor cells, offering the potential for a broader therapeutic window and more consistent immune activation.
Looking Ahead
APVO455 represents the third CD3 bispecific in Aptevo’s portfolio and the sixth overall drug candidate in active development. The Company anticipates further expanding its CD3 suite in the future.