Aprea Therapeutics, Inc. announced that the first patient has been dosed in the ACESOT-1051 Phase 1 study evaluating daily oral WEE1 inhibitor APR-1051 as monotherapy in advanced solid tumor patients with unmet medical need. APR-1051 was discovered and preclinically evaluated by Aprea?s team of chemists and scientists. APR-1051 is a potent and highly selective small molecule designed to limit off-target toxicity that may provide good safety and tolerability and has shown a potentially favorable drug exposure in pre-clinical models.

APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, the company believes APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted.

ACESOT-1051 is a focused biomarker-driven study with advanced/metastatic solid tumors harboring the following cancer-associated gene alterations: Amplification/overexpression of CCNE1 or CCNE2 regardless of tumor type, or Deleterious mutations in FBXW7 or PPP2R1A regardless of tumor type, or Colorectal cancer with KRAS-GLY12 and TP53 co-mutation, or Uterine serous carcinoma regardless of biomarker status. The first patient was enrolled at NEXT Oncology, San Antonio, Texas. Additional centers, including The University of Texas MD Anderson Cancer Center, are expected to participate.