APVO · Aptevo Therapeutics Inc.

Aptevo Therapeutics reported compelling interim data from the RAINIER frontline AML Phase 1b dose-optimization trial, demonstrating mipletamig in combination with venetoclax and azacitidine achieved an 87% clinical benefit rate and 81% CR/CRi remission rate across 31 evaluable patients, substantially exceeding the 66.4% CR/CRi benchmark from the Phase 3 VIALE-A trial. The complete remission rate of 65% further outperforms the 37% VIALE-A standard, with notable efficacy in high-risk subgroups including 36% TP53-mutated patients who typically have poor prognosis. Safety remains favorable with no cytokine release syndrome observed, a key differentiator enabled by mipletamig's CRIS-7-derived CD3 pathway design. The trial has progressed through Cohort 5, covering all prior dose levels, and now enters its final stage with Cohort 6 enrollment nearly complete, plus Cohort 7 and two expansion groups of six patients each at select doses. This positions Aptevo to select the recommended Phase 2 dose (RP2D) this year and engage regulators for the subsequent Phase 2 trial mirroring the combination regimen. CEO Jeff Lamothe emphasized the consistent data strength and defined path forward, while CMO Dirk Huebner highlighted the focus on a well-characterized dataset for dose selection. These results underscore mipletamig's potential to enhance frontline AML outcomes in older/unfit patients without added toxicity, supporting Aptevo's bispecific immunotherapy platform.