Aprea Therapeutics Unveils Early Data on Oral WEE1 Inhibitor APR-1051 at EORTC-NCI-AACR Conference

Aprea Therapeutics, Inc., a clinical-stage biopharmaceutical company centered on precision oncology via synthetic lethality, has announced preliminary safety results for its WEE1 inhibitor, APR-1051. These findings, presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, come from ACESOT-1051, a Phase 1 first-in-human study. This study evaluates the safety, pharmacokinetics, pharmacodynamics, and initial efficacy of APR-1051 as a single-agent treatment in patients with advanced solid tumors featuring cancer-associated gene alterations.

The ACESOT-1051 study, currently in its dose escalation phase, anticipates enrolling up to 39 patients. Oral APR-1051 is administered daily in 28-day cycles, with eight planned cohorts testing doses from 10 mg to 150 mg. So far, patients have been enrolled in three initial cohorts receiving 10 mg, 20 mg, and 30 mg doses, respectively. Preliminary data includes results from two out of three patients, as of October 7, 2024, indicating that APR-1051 is safe and well-tolerated without significant hematologic toxicity.

During the first treatment cycle, hemoglobin, hematocrit, and platelet counts remained stable or increased slightly. No signs of neutropenia were observed, and white blood cells and neutrophils showed an upward trend in the two evaluated patients. All recorded adverse events (AEs) were Grade 1 or 2, with one Grade 1 AE (abdominal distention) possibly related to APR-1051. Importantly, no QT prolongation was detected. Of the three patients dosed, one experienced disease progression after 49 days, another withdrew after 36 days, and the third continues to receive treatment.

Dr. Philippe Pultar, Aprea's Senior Medical Advisor and Lead of WEE1 Clinical Development, expressed optimism about the preliminary data, noting that APR-1051's design aims for selectivity for WEE1 without the off-target effects seen in other similar molecules. The company plans to continue dose escalation to further confirm the drug's safety profile and explore its therapeutic potential, with hopes to generate preliminary efficacy data in 2025.

APR-1051 targets WEE1 kinase, a key player in the DNA damage response pathway. Aprea believes APR-1051's unique molecular structure and selectivity for WEE1, combined with improved pharmacokinetic properties and absence of QT prolongation, may address the shortcomings of other WEE1 inhibitors. Although there have been no direct comparative studies, the company is hopeful about the potential benefits of APR-1051.

Active enrollment for the ACESOT-1051 trial is ongoing at three U.S. sites: NEXT Oncology locations in San Antonio and Dallas, and The University of Texas MD Anderson Cancer Center, with plans to expand to additional sites. Dr. Anthony Tolcher, Founder of NEXT Oncology, highlighted the encouraging minimal toxicity observed in the trial's participants, emphasizing the importance of WEE1 kinase as a therapeutic target for patients with limited treatment options.

The ACESOT-1051 study design includes Part 1, a dose escalation phase expected to enroll up to 39 patients, using accelerated titration followed by Bayesian Optimal Interval (BOIN) design for dose levels. Part 2 will focus on dose optimization with the goal of selecting the Recommended Phase 2 Dose (RP2D), and is expected to include up to 40 patients.

Aprea Therapeutics, headquartered in Doylestown, Pennsylvania, is dedicated to developing precision oncology treatments through synthetic lethality. Their lead program, ATRN-119, is an ATR inhibitor in clinical development for solid tumors, and APR-1051, a WEE1 inhibitor, has recently entered clinical trials. 

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