Undisclosed AKT1 E17K inhibitor / Rezo Therapeutics - LARVOL DELTA

Discovery and characterization of AKT1-E17K mutant-selective inhibitors for the treatment of AKT1-E17K mutant cancers (AACR-NCI-EORTC 2025) - "In an AKT1-E17K-expressing ER+ BC CDX model (CRISPR MCF7-AKT1-E17K), VVD-4009 (30 mg/kg QD) combined with fulvestrant achieved tumor regression without inducing hyperglycemia, a dose-limiting toxicity observed with the capivasertib/fulvestrant combination...In contrast to alpelisib, MK-2206, and capivasertib, VVD-4009 preserved skin barrier integrity...In summary, we have developed potent and highly selective AKT1-E17K inhibitors that demonstrate superior in vivo efficacy in AKT1-E17K-driven models compared to capivasertib. These findings underscore the value of high mutant selectivity combined with optimized PK for effectively treating aggressive, refractory AKT1-E17K mutant cancers."

Gynecologic Cancers • Oncology • Triple Negative Breast Cancer • AKT1 • AKT2 • ER • PAK2