Imneskibart (AU-007) IL-2–CD25 “decoy” antibody + low-dose aldesleukin drives tumor shrinkage in CPI-refractory melanoma (early PFS signal)

Imneskibart (AU-007) is an AI-designed anti–IL-2 monoclonal antibody that blocks IL-2 binding to CD25 (trimeric IL-2R) while preserving signaling through CD122/CD132 (dimeric IL-2R), aiming to expand Teff/NK without expanding Tregs; it was tested with low-dose subcutaneous aldesleukin (± nivolumab) in an ongoing Phase 1/2 study in locally advanced/metastatic cutaneous melanoma with confirmed progression after prior anti–PD-1 + anti–CTLA-4 or anti–PD-1 + anti–LAG-3 doublet CPI (n=15 treated; n=14 efficacy-evaluable; NCT05267626). Across imneskibart + aldesleukin, 9/14 had tumor reductions (-1% to -100%), median PFS was 7.6 months (median follow-up 9.3 months), and 6 patients remained on treatment; in the imneskibart + aldesleukin + nivolumab cohort to date, 2/6 efficacy-evaluable achieved PR (33%) with -35% and -31% shrinkage and 67% had disease control at 4 months—numerically above historical single-agent high-dose IV IL-2 ORR ~16% (with substantial toxicity) and notably encouraging for a post–doublet-CPI-refractory population. Pharmacodynamically, treatment decreased peripheral Tregs and increased CD8/Treg ratios (up to 2–3× over baseline), with >2× increases associated with longer time on treatment/PFS/OS; safety looked favorable with Grade 3/4 drug-related AEs in 14% overall and 0% in the +nivolumab subgroup, and no discontinuations for drug-related AEs (subcutaneous low-dose IL-2 schema, not classic inpatient high-dose IL-2).