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
Aprea Therapeutics (NASDAQ:APRE) has announced promising preclinical and early clinical data for APR-1051, its next-generation oral WEE1 inhibitor, in treating HPV+ head and neck squamous cell carcinoma (HNSCC). The drug demonstrated potent antiproliferative effects with IC₅₀ values between 8.9-230 nM in preclinical studies.
In collaboration with MD Anderson Cancer Center, research showed significant anti-tumor synergy when combining APR-1051 with anti-PD-1 therapies. In the Phase 1 ACESOT-1051 trial, a 62-year-old male patient with advanced HPV+ cancer showed stable disease with 5% tumor reduction at first assessment, with no dose-limiting toxicities reported.
Aprea Therapeutics (NASDAQ:APRE) ha annunciato dati promettenti preclinici e clinici precoci per APR-1051, il suo inibitore orale di nuova generazione di WEE1, nel trattamento del carcinoma squamoso della testa e del collo HPV+. Il farmaco ha mostrato forti effetti antiproliferativi con valori di IC₅₀ compresi tra 8,9 e 230 nM negli studi preclinici.
In collaborazione con il MD Anderson Cancer Center, la ricerca ha evidenziato una significativa sinergia antitumorale combinando APR-1051 con terapie anti-PD-1. Nel trial di Fase 1 ACESOT-1051, un paziente maschio di 62 anni con cancro HPV+ avanzato ha mostrato malattia stabile con una riduzione del tumore del 5% alla prima valutazione, senza tossicità dose-limitanti riportate.
Aprea Therapeutics (NASDAQ:APRE) ha anunciado datos prometedores preclínicos y clínicos tempranos para APR-1051, su inhibidor oral de WEE1 de próxima generación, en el tratamiento del carcinoma de células escamosas de cabeza y cuello positivo para HPV (HNSCC). El medicamento demostró potentes efectos antiproliferativos con valores de IC₅₀ entre 8.9 y 230 nM en estudios preclínicos.
En colaboración con el MD Anderson Cancer Center, la investigación mostró una sinergia antitumoral significativa al combinar APR-1051 con terapias anti-PD-1. En el ensayo de Fase 1 ACESOT-1051, un paciente masculino de 62 años con cáncer avanzado positivo para HPV mostró enfermedad estable con una reducción tumoral del 5% en la primera evaluación, sin toxicidades limitantes de dosis reportadas.
Aprea Therapeutics (NASDAQ:APRE)는 차세대 경구용 WEE1 억제제인 APR-1051의 HPV 양성 두경부 편평세포암(HNSCC) 치료에 대한 유망한 전임상 및 초기 임상 데이터를 발표했습니다. 이 약물은 전임상 연구에서 IC₅₀ 값이 8.9-230 nM 범위 내에서 강력한 항증식 효과를 보였습니다.
MD Anderson Cancer Center와의 협력 연구에서 APR-1051과 항-PD-1 치료제 병용 시 유의미한 항종양 상승효과가 확인되었습니다. 1상 ACESOT-1051 임상시험에서 62세 남성 진행성 HPV 양성 암 환자는 첫 평가에서 5% 종양 감소와 함께 안정된 질병 상태를 보였으며, 용량 제한 독성은 보고되지 않았습니다.
Aprea Therapeutics (NASDAQ:APRE) a annoncé des données précliniques et cliniques précoces prometteuses pour APR-1051, son inhibiteur oral de WEE1 de nouvelle génération, dans le traitement du carcinome épidermoïde de la tête et du cou HPV+. Le médicament a démontré des effets antiprolifératifs puissants avec des valeurs d’IC₅₀ comprises entre 8,9 et 230 nM lors des études précliniques.
En collaboration avec le MD Anderson Cancer Center, la recherche a montré une synergie antitumorale significative en combinant APR-1051 avec des thérapies anti-PD-1. Lors de l’essai de phase 1 ACESOT-1051, un patient masculin de 62 ans atteint d’un cancer avancé HPV+ a présenté une maladie stable avec une réduction tumorale de 5 % lors de la première évaluation, sans toxicités limitant la dose rapportées.
Aprea Therapeutics (NASDAQ:APRE) hat vielversprechende präklinische und frühe klinische Daten für APR-1051, seinen oralen WEE1-Inhibitor der nächsten Generation, bei der Behandlung von HPV-positivem Kopf- und Hals-Plattenepithelkarzinom (HNSCC) bekannt gegeben. Das Medikament zeigte in präklinischen Studien starke antiproliferative Effekte mit IC₅₀-Werten zwischen 8,9 und 230 nM.
In Zusammenarbeit mit dem MD Anderson Cancer Center zeigte die Forschung eine signifikante antitumorale Synergie bei der Kombination von APR-1051 mit Anti-PD-1-Therapien. In der Phase-1-Studie ACESOT-1051 zeigte ein 62-jähriger männlicher Patient mit fortgeschrittenem HPV-positivem Krebs stabile Erkrankung mit 5 % Tumorreduktion bei der ersten Bewertung, ohne berichtete dosislimitierende Toxizitäten.
- None.
- Initial clinical data limited to only one patient
- Current dosing at subtherapeutic 70mg level
- Still in early Phase 1 stage of development
Insights
Aprea's APR-1051 shows promising early results in HPV+ head and neck cancer with both single-agent activity and immunotherapy synergy potential.
Aprea's preclinical and early clinical data for their WEE1 inhibitor APR-1051 represents a meaningful development in the targeted therapy landscape for HPV-positive head and neck squamous cell carcinoma (HNSCC). The preclinical results demonstrate potent anti-proliferative activity with IC₅₀ values between 8.9 to 230 nM across various HNSCC cell lines, indicating strong single-agent potential.
What's particularly significant is the mechanistic rationale—APR-1051 exploits a specific vulnerability in HPV+ tumors. The HPV E6 oncoprotein disrupts p53 function, making these cancer cells heavily dependent on the G2/M checkpoint regulated by WEE1 kinase. This creates a synthetic lethality opportunity that APR-1051 targets. Additionally, the activation of cGAS/STING-mediated immunogenic cell death explains the observed synergy with anti-PD-1 therapy in preclinical models.
The early clinical data, while limited to a single patient, offers an encouraging signal. A 5% tumor reduction and disease stabilization in a heavily pre-treated patient (after three lines of platinum therapy) at a subtherapeutic 70 mg dose suggests meaningful biological activity. The absence of dose-limiting toxicities at this level is also promising for the therapeutic window.
These results position APR-1051 as potentially differentiated in the competitive WEE1 inhibitor landscape, with a clear biomarker strategy (HPV status) for patient selection that could enhance clinical success probability in subsequent trials. The collaboration with MD Anderson adds credibility to these findings, though larger patient cohorts at therapeutic doses will be necessary to validate these early signals.
Preclinical data demonstrate potent single-agent and combination effects in head and neck squamous cell carcinoma (HNSCC) models, including synergy with anti–PD-1 therapy
Initial Phase 1 clinical update shows early disease control in first HPV+ patient treated with APR-1051
DOYLESTOWN, Pa., June 25, 2025 (GLOBE NEWSWIRE) -- 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, today announced 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).
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.
The chart below shows how APR-1051 potentiatiated the immune response to checkpoint inhibitors in an HPV+ HNSCC model.
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.
About Aprea
Aprea is pioneering a new approach to treat cancer by exploiting vulnerabilities associated with cancer cell mutations. This approach was developed to kill tumors but to minimize the effect on normal, healthy cells, decreasing the risk of toxicity that is frequently associated with chemotherapy and other treatments. Aprea’s technology has potential applications across multiple cancer types, enabling it to target a range of tumors, including ovarian, colorectal, prostate, and breast cancers. The company’s lead programs are APR-1051, an oral, small-molecule inhibitor of WEE1 kinase, and ATRN-119, a small molecule ATR inhibitor, both in clinical development for solid tumor indications. For more information, please visit the company website at www.aprea.com
The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.
Forward-Looking Statement
Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, our ability to continue as a going concern, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law.
Investor Contact:
Mike Moyer
LifeSci Advisors
mmoyer@lifesciadvisors.com
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/d8dcbce3-58cc-4c7f-af86-00f1440e02b4
FAQ
What are the key findings from Aprea's (APRE) APR-1051 clinical trial in HPV+ cancer?
How effective is APR-1051 in preclinical studies for head and neck cancer?
What is the mechanism of action for Aprea's (APRE) APR-1051 drug?
What are the next steps for Aprea's (APRE) APR-1051 development?
How did the market react to Aprea's (APRE) APR-1051 clinical data announcement?
