Aprea Therapeutics Starts Dosing in Phase 1 Trial for Oral WEE1 Inhibitor APR-1051

Aprea Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to precision oncology, has announced a significant milestone in its clinical pipeline. The first patient has been dosed in the ACESOT-1051 Phase 1 study, which is assessing the daily oral WEE1 inhibitor, APR-1051, as a monotherapy in patients with advanced solid tumors who have significant unmet medical needs. This development is a crucial step forward for the company.

APR-1051, discovered and evaluated preclinically by Aprea's team, is a potent and highly selective small molecule. It is designed to limit off-target toxicity, providing good safety and tolerability, and has shown favorable drug exposure in preclinical models. APR-1051 targets the WEE1 kinase, an essential enzyme in the DNA damage response pathway. Preclinical studies suggest that APR-1051 may overcome the limitations of other WEE1 inhibitors due to its unique molecular structure, selectivity for WEE1, improved pharmacokinetic properties, and the absence of QT prolongation at effective doses.

The ACESOT-1051 study focuses on advanced and metastatic solid tumors with specific cancer-associated gene alterations, including:
- Amplification/overexpression of CCNE1 or CCNE2,
- Deleterious mutations in FBXW7 or PPP2R1A,
- Colorectal cancer with KRAS-GLY12 and TP53 co-mutation,
- Uterine serous carcinoma, irrespective of biomarker status.

Dr. Oren Gilad, President and CEO of Aprea, expressed his excitement about this milestone, emphasizing that the first patient dosing represents a significant advancement in their clinical pipeline. He noted that this study is crucial for evaluating the single-agent activity of APR-1051, which will lay the groundwork for future combination treatments. The study aims to confirm the safety profile of APR-1051 and generate data to optimize its use in treating patients. A clinical update is expected by the end of 2024, with preliminary efficacy data anticipated in 2025.

The first patient was enrolled at NEXT Oncology in San Antonio, Texas, with additional centers like The University of Texas MD Anderson Cancer Center expected to join. Dr. Anthony Tolcher, Founder of Next Oncology, highlighted the importance of this trial, noting the high unmet medical need for patients with Cyclin E overexpression, who currently have poor prognosis and no effective therapies. He emphasized that WEE1 kinase is a validated oncology target and expressed his hope for the study's outcomes.

The ACESOT-1051 study is designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of APR-1051 in patients with advanced solid tumors. The study consists of two parts: the first part involves dose escalation and aims to enroll up to 39 patients, while the second part is focused on dose optimization, enrolling up to 40 patients, to determine the Recommended Phase 2 Dose (RP2D).

The study's primary objectives include measuring safety, dose-limiting toxicities, and determining the maximum tolerated or administered dose. Secondary objectives involve evaluating pharmacokinetics and preliminary efficacy according to RECIST or PCWG3 criteria, with pharmacodynamics as an exploratory objective. The University of Texas MD Anderson Cancer Center is the lead site, and the study will be conducted at multiple sites across the U.S.

Overall, this development marks an important step for Aprea Therapeutics as they advance their clinical program with APR-1051, aiming to address the unmet needs of patients with advanced solid tumors.