Aprea Reports Anti-Proliferative Results and Promising Early-Stage Clinical Data for Next-Generation WEE1 Inhibitor, APR-1051, in HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) in Collaboration with MD Anderson Cancer Center

Core Insights - Aprea Therapeutics announced promising preclinical data and an initial clinical update for APR-1051, a next-generation oral WEE1 inhibitor targeting HPV+ head and neck squamous cell carcinoma (HNSCC) [1][2] - The findings suggest that APR-1051 may provide significant differentiation in oncology, both as a single agent and in combination with checkpoint inhibitors [2] Preclinical Data - Preclinical studies conducted in collaboration with MD Anderson Cancer Center demonstrated robust antiproliferative effects of APR-1051 across various human and murine head and neck cancer cell lines, with IC₅₀ values ranging from 8.9 to 230 nM [6] - Significant anti-tumor synergy was observed when combining APR-1051 with anti–PD-1 therapies in HPV+ HNSCC models, indicating its potential for combination-based clinical trials [6] - Mechanistically, APR-1051 activates cGAS/STING-mediated immunogenic cell death and exploits the HPV E6-driven G2 checkpoint dependency in HPV+ tumors, highlighting a biomarker-driven strategy for patient selection [6] Clinical Update - In the Phase 1 ACESOT-1051 trial, a 62-year-old male patient with advanced HPV-positive oropharyngeal squamous cell carcinoma showed stable disease and a 5% tumor reduction after treatment with a subtherapeutic 70 mg oral dose of APR-1051 [7] - The patient tolerated the therapy well, with no dose-limiting toxicities reported [7] Future Development - Experts from MD Anderson Cancer Center expressed optimism regarding APR-1051 as a promising addition to the treatment portfolio for HPV-associated head and neck cancers, supported by robust preclinical data [8] - Aprea is committed to advancing APR-1051 as a precision oncology agent, leveraging biomarker insights to optimize patient outcomes [8][9] - Enrollment in the ACESOT-1051 trial is ongoing, with plans to evaluate APR-1051 in combination with checkpoint inhibitors for distinct patient populations [12]