ZMS-4426 / Simcere - LARVOL DELTA

ZMS-4426, an oral degrader of SMARCA2 shows potent anti-tumor activity, but variant selectivity against SMARCA4 across species (AACR 2026) - "Furthermore, the in vitro synergistic effects were observed when SMARCA4-loss NSCLC cells were treated with ZMS-4426 in combination with docetaxel.ZMS-4426 exhibited good oral availability in mice, rats, and dog...Further, the combination treatment of ZMS-4426 and nab-paclitaxel effectively suppressed tumor growth to a greater extent than either agent alone.However, ZMS-4426 was not tolerated in dog for 7-day treatment at 2 mpk...In a head-to-head comparison with compound A (a reference molecule from WO2025194405, Prelude Therapeutics), treatment of ZMS-4426 and compound A for 4-day at 5 mpk intravenous injection in rats both induced complete degradation of SMARCA4 at 24 hours post-dose, indicating that neither compound preserved its selectivity profile in vivo.In conclusion, our potent and selective SMARCA2 degrader, ZMS-4426 induces strong synthetic lethality in SMARCA4 deficient cells both in vitro and in vivo. However, more studies are needed to elucidate discrepancy..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • SMARCA2 • SMARCA4