Aprea Therapeutics, Inc.

Aprea Therapeutics, Inc. is a clinical-stage precision medicine oncology company focused on the discovery and development of targeted therapies for patients with biomarker-defined cancers, utilizing a synthetic lethality approach to selectively kill cancer cells while sparing normal cells ¹. The company's core business model involves developing small molecule inhibitors that exploit genetic mutations in cancer to widen the therapeutic window, aiming for more effective treatments with minimized side effects ¹. Aprea Therapeutics generates revenue primarily through grants from government and non-government organizations, recognizing this revenue as research and development services occur, qualifying expenses are incurred, or grant conditions are met ². The company has not generated any commercial revenue to date from sales of any drugs and does not expect to generate such revenue for several years, if at all ³.

The company's pipeline includes two lead clinical-stage programs: APR-1051, a WEE1 inhibitor, and ATRN-119 (Mosipasertib), an ATR inhibitor, both discovered internally ¹. Additionally, Aprea Therapeutics has an early-stage preclinical program, APR-1602, a macrocyclic DYRK1A/B inhibitor, which is expected to be ready for IND-enabling studies in the fourth quarter of 2026 ⁴. The company previously engaged in the clinical development of cancer therapeutics related to the mutant p53 tumor suppressor protein, but currently has no ongoing clinical trials involving its p53 reactivator, APR-246 (eprenetapopt), having shifted its primary focus to DNA Damage Response (DDR) pathway targeting ⁵.

APR-1051, a WEE1 inhibitor, is currently in a Phase 1 dose escalation study (ACESOT-1051) with 9 cohorts planned to evaluate doses from 10 mg to 300 mg once daily ⁶. As of March 2, 2026, the company is enrolling cohort 8 at a dose of 220 mg once daily ⁷. Preliminary results have shown early clinical proof-of-concept, including a potential dose-response trend and two unconfirmed partial responses (uPR) in patients with PPP2R1A-mutated uterine serous carcinoma and endometrial cancer at 150 mg and 220 mg dose levels, respectively ⁸. The first uPR patient achieved a 50% reduction in target lesion size and a marked reduction in CA-125 levels from 732 to 70 U/mL ⁹. The second uPR patient also achieved a 50% reduction in target lesion size and a decline in CA-125 from 362 to 47 U/mL ¹⁰. The study indicates APR-1051 has been safe and well-tolerated, supporting a development strategy for a potentially improved therapeutic index ¹¹.

ATRN-119 (Mosipasertib), an ATR inhibitor, is the company's second clinical-stage synthetic lethality product candidate ¹. On October 15, 2025, the recommended Phase 2 dose (RP2D) of 1,100 mg once daily for ATRN-119 monotherapy was determined in the ABOYA-119 Phase 1/2a dose-escalation study ¹². Following dose escalation, the company is exploring ATRN-119 in combination approaches, pausing further enrollment in monotherapy dosing arms of ABOYA-119 and winding down associated clinical trial site activities ¹³. Preclinical data for ATRN-119 demonstrated high selectivity for ATR over related PIKK family kinases, with an IC50 of approximately 4 nM for ATR, and significantly higher IC50 values for ATM (>600-fold), DNA-PK (>2000-fold), and mTOR (>2000-fold) ¹⁴. In a CDX mouse model, ATRN-119 showed statistically significant tumor growth inhibition compared to vehicle control and smaller tumor volume than a competitor ATR inhibitor, with negligible body weight loss ¹⁵.

For the fiscal year ended December 31, 2025, Aprea Therapeutics reported a net loss of $12.6 million ¹⁶, compared to a net loss of $13.0 million for the year ended December 31, 2024 ¹⁷. The accumulated deficit as of December 31, 2025, was $333.6 million ¹⁸. As of December 31, 2025, the company had cash and cash equivalents of $14.6 million ¹⁹. The filing does not provide specific figures for total revenue, gross profit, gross margin percentage, operating income, operating margin, basic and diluted EPS, free cash flow, total debt, or net debt for the reported fiscal period.

The company's net loss decreased from $13.0 million in 2024 to $12.6 million in 2025 [16, 17]. The filing does not provide specific year-over-year comparisons for revenue growth by segment, margin expansion or contraction, or notable shifts in business mix.

During the reported period, Aprea Therapeutics enrolled the first patient into ACESOT-1051, its Phase 1 dose escalation study for APR-1051, in the second quarter of 2024, following the IND application going into effect in March 2024 ²⁰. On October 15, 2025, the recommended Phase 2 dose (RP2D) of 1,100 mg once daily for ATRN-119 was determined in the ABOYA-119 Phase 1/2a dose-escalation study ¹². Subsequently, the company paused further enrollment in both once daily and twice daily monotherapy dosing arms of ABOYA-119 and initiated an orderly wind-down of certain clinical trial site activities to explore combination approaches for ATRN-119 ¹³. In October 2025, the company issued 20,000, 5,000, and 2,500 shares of common stock to three consultants for services rendered ²¹.

Aprea Therapeutics anticipates additional open-label safety/efficacy data for APR-1051 to be available in the second quarter of 2026 ²². The company expects to complete the dose-escalation part of the ACESOT-1051 study in the third quarter of 2026 ²³. For ATRN-119, following the determination of the recommended Phase 2 dose, the company is considering further development in combination approaches that could expand its therapeutic potential ¹. Aprea Therapeutics is currently in discussions with leading academic centers to explore combining ATRN-119 with radiation in patients with HPV+ head and neck cancer, and additional investigator-led studies evaluating ATRN-119 in combination with an I/O agent and ADCs are also being explored ²⁴.

The company's strategy includes continuing to efficiently develop APR-1051, an orally bioavailable small molecule inhibitor of WEE1, in a Phase 1 clinical trial evaluating patients with biomarkers that may predict sensitivity to WEE1 inhibition ²⁵. The primary objectives of this Phase 1 study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and recommended Phase 2 dose (RP2D) ²⁶. Secondary objectives include evaluating pharmacokinetics and preliminary efficacy, with pharmacodynamic parameters as exploratory objectives ²⁷. Aprea Therapeutics also plans to continue efficiently developing ATRN-119, an orally bioavailable small molecule inhibitor of ATR, in combination approaches ²⁸. The company aims to identify opportunities for combination therapy regimens that may enhance synthetic lethality and increase benefit to genetically defined cancer patient populations ²⁹. Furthermore, Aprea Therapeutics intends to maximize the commercial opportunity of its product candidates across global markets, retaining worldwide development and commercialization rights, and may selectively evaluate strategic partnership opportunities ³⁰.

Aprea Therapeutics expects its expenses to increase substantially as it initiates and conducts clinical trials and additional preclinical research for its product candidates, seeks to identify and develop additional product candidates, pursues marketing approvals, establishes commercial infrastructure, manufactures larger quantities of product candidates, maintains and expands its intellectual property portfolio, acquires or in-licenses other drugs and technologies, defends against intellectual property claims, hires additional personnel, builds out facilities, and continues to operate as a public company ³¹. The company anticipates that if marketing approval is obtained for any product candidates, it will incur significant commercialization expenses related to product manufacturing, marketing, sales, and distribution ³².

Aprea Therapeutics believes that its existing cash and cash equivalents of $14.6 million as of December 31, 2025, and the gross proceeds of approximately $5.6 million from its January 2026 private placement, before deducting placement agent fees and offering costs of approximately $0.4 million, will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the first quarter of 2027 ³³. The company intends to finance its operations through a combination of public or private equity or debt financings or other sources, including collaborations with third parties and grants ³⁴.

The company has identified conditions and events that raise substantial doubt regarding its ability to continue as a going concern within one year after the date of the filing of this Annual Report, due to incurred net losses, utilized cash in operations since inception, and insufficient cash and cash equivalents as of December 31, 2025 ³⁵. The ability to continue as a going concern is dependent upon securing additional funding through collaborations, strategic alliances, license agreements, and/or debt or equity financings, and achieving profitable operations at an indeterminate future time ³⁶.

Aprea Therapeutics faces substantial risks, including significant losses since inception and the expectation of continued losses, raising substantial doubt about its ability to continue as a going concern ³⁷. The company will need substantial additional funding, which may not be available on acceptable terms or at all, potentially forcing delays, reductions, or elimination of research and development programs or future commercialization efforts ³⁸. Adverse developments in the financial services industry, such as liquidity concerns or defaults by financial institutions, could impair access to funding sources ³⁹. The company is highly dependent on the success of its clinical-stage product candidates, APR-1051 and ATRN-119, and their clinical trials may not be successful, leading to delays or inability to obtain approval and commercialize them ⁴⁰. The early-stage nature of these trials means preclinical and early clinical results may not predict future success, and initial clinical trial success may not be indicative of final or later-stage results ⁴¹. There is a risk of difficulty enrolling patients in clinical trials, which could delay or prevent necessary marketing approvals ⁴². Serious adverse or unacceptable side effects, or limited efficacy, identified during development could lead to abandonment or limitation of product candidate development ⁴³. The company relies on third parties to conduct clinical trials and some research, and their unsatisfactory performance or non-compliance could cause delays ⁴⁴. If Aprea Therapeutics is unable to obtain and maintain intellectual property protection for its product candidates, competitors could develop similar products, adversely affecting commercialization ⁴⁵. Issued patents may be narrowed, invalidated, or found unenforceable if challenged, and the chemical structure of eprenetapopt is in the public domain, limiting composition-of-matter patent protection ⁴⁶. The company has never obtained marketing approval for a product candidate, and the approval process is expensive, time-consuming, and uncertain, potentially preventing or delaying commercialization ⁴⁷. Regulatory policies may change, and additional government regulations could prevent, limit, or delay approvals ⁴⁸. Post-approval, products remain subject to ongoing regulatory requirements, and failure to comply or discovery of new problems could lead to withdrawal of approval or suspension of sales ⁴⁹. Unfavorable pricing regulations, third-party coverage, and reimbursement policies, or healthcare reform initiatives could harm the business ⁵⁰. Product liability lawsuits could result in substantial liabilities, and current insurance coverage of up to $5.0 million may be inadequate ⁵¹. The reactivation of p53 is a novel and unproven therapeutic approach, and eprenetapopt may never become a marketable product ⁵². The company is dependent on a single third-party manufacturer for active pharmaceutical ingredients, increasing supply risk ⁵³. Cybersecurity threats, IT system failures, or data breaches could compromise sensitive information, leading to liability and reputational harm ⁵⁴.

Management emphasizes Aprea Therapeutics' focus as a clinical-stage precision medicine oncology company, dedicated to the discovery and development of targeted therapies for biomarker-defined cancers through synthetic lethality ¹. The company's strategic priorities include the efficient development of its clinical-stage product candidate, APR-1051, an orally bioavailable small molecule inhibitor of WEE1, currently in a Phase 1 clinical trial ²⁵. Management anticipates additional open-label safety/efficacy data for APR-1051 in the second quarter of 2026 and expects to complete dose-escalation in the third quarter of 2026 [22, 23]. A second key priority is the efficient development of ATRN-119, an orally bioavailable small molecule inhibitor of ATR, with the recommended Phase 2 dose of 1,100 mg once daily having been determined [12, 28]. Management is actively exploring ATRN-119 development in combination approaches, including discussions with leading academic centers for combinations with radiation in HPV+ head and neck cancer, and investigator-led studies with I/O agents and ADCs ²⁴. The company also highlights its early-stage DYRK1A/B inhibitor, APR-1602, expected to be ready for IND-enabling studies in the fourth quarter of 2026 ⁴. Management acknowledges the significant losses incurred since inception, with a net loss of $12.6 million for the year ended December 31, 2025, and an accumulated deficit of $333.6 million [16, 18]. They believe that existing cash and cash equivalents of $14.6 million as of December 31, 2025, combined with approximately $5.6 million in gross proceeds from a January 2026 private placement (before deducting fees and costs of approximately $0.4 million), will fund operations into the first quarter of 2027 ³³. However, management has concluded that substantial doubt exists about the company's ability to continue as a going concern within one year from the financial statement issuance date, underscoring the critical need for additional financing through collaborations, strategic alliances, or debt/equity financings [35, 36].