Aprea Therapeutics presents initial clinical data on ATRi, ATRN-119

Aprea Therapeutics announced highlights of two posters presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 14, 2023 in Boston, MA. The data in the posters include first-in-human clinical data from the ongoing Phase 1 dose escalation trial of ATR inhibitor, ATRN-119 LINK to Poster, and pre-clinical data from the WEE1 inhibitor, ATRN-1051 LINK with planned IND submission Q4 2023. ATRN-119 is in an ongoing Phase 1/2a dose escalation trial in solid tumors to determine the recommended Phase 2 dose, with a daily dosing administration over a 56-day cycle. To date, no hematologic or liver function toxicities in these heavily pretreated solid tumor patients have been observed across the first three cohorts at dose levels of 50mg, 100mg, and 200mg NCT04905914. The efficacy findings are still early in the dose escalation portion of the trial and there was one Stable Disease patient at the 50mg low dose cohort determined at end of cycle 1. The company is actively enrolling cohort 4 at 350mg and anticipates dose expansion of the trial in Q2 2024. The second poster presented focused on ATRN-1051, the WEE1 inhibitor, and highlights the selectivity of ATRN-1051 with low off-target activity against PLK1, PLK2 and PLK3, a family of kinases that promote M phase entry, a critical phase in the cell cycle. The selectivity of ATRN-1051 relative to the WEE1 class is also highlighted by its limited effects on red blood cell counts, hERG inhibition, and body weight loss in the pre-clinical data. PLK off-target activity has been a challenge for other WEE1 inhibitors in this class, as this off-target activity substantially counters the effects of WEE1 inhibition.