On June 25, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported new preclinical data and a clinical update on APR-1051, the Company’s next-generation oral WEE1 inhibitor, in human papillomavirus–positive (HPV+) head and neck squamous cell carcinoma (HNSCC) (Press release, Aprea, JUN 25, 2025, View Source [SID1234654106]).

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These findings result from an ongoing translational research collaboration with renowned oncology leader MD Anderson Cancer Center and support the potential of APR-1051 both as a single agent and in rational immunotherapy combinations for biomarker-driven treatment of HPV+ HNSCC. "We are excited by the preclinical data generated by independent researchers, and the early clinical signal of APR-1051 in an HPV-positive cancer patient," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea Therapeutics. "We believe that APR-1051 could offer significant differentiation in the competitive oncology landscape, as a single agent, as well as in combination with checkpoint inhibitors."

Preclinical Highlights from MD Anderson Collaboration:

Potent single-agent activity: APR-1051 demonstrated robust antiproliferative effects across a broad panel of human and murine head and neck cancer cell lines, including HPV+ subtypes, with IC₅₀ values ranging from 8.9 to 230 nM.
Enhanced combination synergy: Significant anti-tumor synergy was observed with APR-1051 and anti–PD-1 therapies in HPV+ HNSCC models, positioning APR-1051 as a candidate for combination-based clinical trials.
Mechanistic rationale: APR-1051 was shown to activate cGAS/STING-mediated immunogenic cell death and to exploit the HPV E6-driven G2 checkpoint dependency in HPV+ tumors. Given WEE1’s central role in regulating the G2/M checkpoint, HPV+ tumor cells appear highly reliant on WEE1 signaling for survival. This provides a biomarker driven strategy for targeted patient selection and optimized clinical outcomes.

Clinical Update from Phase 1 ACESOT‑1051 Trial:

In a 62-year-old male with advanced HPV-positive oropharyngeal squamous cell carcinoma who had progressed after three prior lines of platinum-based therapy, once-daily administration of a subtherapeutic 70 mg oral dose of APR-1051 resulted in stable disease with a 5% tumor reduction at the first radiographic assessment.
The patient tolerated therapy well, with no dose-limiting toxicities reported.
Next Steps and Future Development:

Enrollment in the ACESOT-1051 trial is ongoing and progressing, with dose escalation into higher levels and the continued inclusion of HPV+ patients.
Pending additional data, future trial arms may evaluate APR-1051 in combination with checkpoint inhibitors to address unmet medical needs across distinct patient populations.
Drs. Abdullah Osman and Jeffrey Myers from The University of Texas MD Anderson Cancer Center commented, "We are very encouraged by these early findings and see APR-1051 as a potentially promising addition to the therapeutic portfolio for treating HPV-associated head and neck cancers. The mechanistic rationale and robust preclinical data strongly support the potential for enhanced patient outcomes when APR-1051 is administrated as a single agent or in combination with existing immunotherapies."

Aprea remains committed to advancing APR-1051 as a next-generation precision oncology agent in molecularly defined tumors, leveraging biomarker insights to optimize patient outcomes.

About APR-1051

APR-1051 is an oral, highly selective WEE1 inhibitor designed to minimize off-target activity and optimize pharmacologic selectivity. APR-1051 is currently being evaluated in the ACESOT-1051 Phase 1 clinical trial (NCT06260514) in patients with advanced solid tumors harboring DNA damage response (DDR) alterations.