Aptevo Therapeutics expands anti-cancer pipeline with APVO452, APVO451

Aptevo Therapeutics (APVO) announced expansion of its anti-cancer pipeline with the filing of two provisional patents for trispecific candidates, APVO452 and APVO451 for prostate cancer and multiple, additional solid tumor types with significant unmet needs. These programs build on the Company’s growing suite of CRIS-7-derived, CD3-directed molecules and are supported by compelling clinical validation from lead candidate, mipletamig, which has demonstrated strong clinical safety and efficacy for the treatment of acute myeloid leukemia. Aptevo’s CD3-engaging portfolio is anchored by mipletamig, a first-in-class CD123 x CD3 bispecific currently being evaluated in RAINIER, a Phase 1b/2 trial for frontline AML. In total, mipletamig has been evaluated in more than 100 patients across three trials, where mipletamig has consistently demonstrated high remission rates and a favorable safety and tolerability profile, with no observed cytokine release syndrome in frontline patients treated to date. Building on this clinical validation, Aptevo previously expanded the suite with tumor-directed bispecifics APVO442 and APVO455. All share the CRIS-7-derived CD3 binding domain, designed to deliver tumor-specific immune activation with a lower risk of systemic toxicity. Expansion into trispecific molecule development represents a potentially profound emerging treatment option with the potential to unlock deeper, more durable anti-tumor responses by simultaneously engaging multiple immune pathways while limiting systemic toxicity. Solid tumors remain difficult to treat because the tumor microenvironment actively suppresses immune responses, limiting the efficacy of current therapies. To address this, Aptevo is advancing a new class of trispecific engagers that unite tumor targeting, T cell activation, and immune costimulation in a single molecule. This design has the potential to be delivered safely while harnessing the body’s own immune system to fight tumors locally in the tumor microenvironment. APVO452 targeting PSMA, CD3, and CD40, is designed to address prostate cancers via PSMA targeting. This molecule works like a three-in-one tool: One-part locks onto the tumor, another part activates the body’s T cells to fight, and the third part reprograms other immune cells that normally protect the tumor. In preclinical studies, this trispecific approach was able to effectively kill tumor cells and, importantly, only switched on the immune system when tumor cells were present APVO451 similarly incorporates trispecific design principles, targeting Nectin-4, CD3, and CD40, and is intended for a broad range of solid tumors. Early data indicate potent, anti-cancer activity that attacks cancer in multiple ways, increasing the opportunity to address critical unmet needs by offering treatment options for multiple solid tumors