Undisclosed AKT1 E17K inhibitor / Rezo Therapeutics - LARVOL DELTA

Discovery of ALTA-2618, the first allosteric, mutant-selective targeted therapy for AKT1 E17K driven cancers (AACR 2024) - "ALTA-2618 is a potent, highly mutant-selective AKT1 E17K inhibitor that demonstrates favorable PK and tolerability with oral once-daily dosing that enables prolonged tumor regressions in multiple AKT1 E17K-mutant PDX models. These data support a mid-2024 IND submission to investigate ALTA-2618 in patients with AKT1 E17K mutant cancers."

Late-breaking abstract • Breast Cancer • Endometrial Cancer • Gynecologic Cancers • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • AKT2 • HER-2

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