Core Insights - Aprea Therapeutics, Inc. has provided an update on the Phase 1 ACESOT-1051 study, showing promising results for its WEE1 inhibitor, APR-1051, in patients with advanced solid tumors [1][2][5] Study Results - At the 100 mg dose level of APR-1051, 3 out of 4 patients achieved stable disease according to RECIST v1.1 criteria [1][5][6] - Disease stabilization was observed in patients with tumors harboring mutations relevant to WEE1 kinase inhibition, specifically FBXW7, CCNE1, KRAS, and TP53 [5][6][11] - The trial is currently progressing to a higher dose level of 150 mg following successful results from the 100 mg cohort [5][6] Presentation and Data - Preliminary results from the ACESOT-1051 trial will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics [2][5] - The poster presentation will summarize updated data with a cutoff date of September 17, 2025 [2] Company Overview - Aprea Therapeutics focuses on developing innovative cancer therapies that target specific vulnerabilities in cancer cells while minimizing damage to healthy cells [7] - The company's clinical programs include APR-1051, an oral small-molecule inhibitor of WEE1 kinase, and ATRN-119, a macrocyclic small molecule ATR inhibitor [7]

Core Insights - Aprea Therapeutics has identified the recommended Phase 2 dose of 1,100 mg once daily for ATRN-119, an oral ATR inhibitor, in the ongoing ABOYA-119 Phase 1/2a study for patients with advanced solid tumors [1][6] ATR Program - Aprea is considering further development of ATRN-119 in combination with DNA-damaging agents, radiation therapy, antibody-drug conjugates, and immune checkpoint inhibitors, based on preclinical data suggesting synergistic anti-tumor effects [2][4] - The company is pausing further enrollment in monotherapy dosing arms of ABOYA-119 while ensuring current patients continue to receive therapy without interruption [3] Clinical Data - Preliminary Phase 1 monotherapy data indicate that ATRN-119 has a favorable tolerability profile with manageable adverse events at the RP2D of 1,100 mg once daily, and shows durable disease stabilization in heavily pretreated patients across multiple tumor types [8] - The company plans to present updated data from the ABOYA-119 trial at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on October 24, 2025 [6] WEE1 Program - Aprea is advancing its lead program, the WEE1 kinase inhibitor APR-1051, with ongoing Phase 1 studies actively enrolling patients [7][9] - Early signals of clinical benefit have been observed in patients treated with APR-1051, supporting continued dose escalation and further clinical evaluation [9] Company Overview - Aprea Therapeutics focuses on developing novel cancer therapies that target cancer cells while minimizing damage to healthy cells, aiming to reduce toxicity associated with conventional treatments [10]

Core Insights - Aprea Therapeutics, Inc. announced the acceptance of two abstracts for poster presentations at the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics, scheduled for October 22 - 26, 2025 [1] Group 1: Clinical Programs - The first abstract focuses on APR-1051, a novel WEE1 inhibitor, detailing early safety and efficacy data from the ACESOT-1051 phase 1 trial [2] - The second abstract presents updated data from the ABOYA-119 trial, which involves ATRN-119, a macrocyclic ATR inhibitor, in patients with advanced solid tumors [2] Group 2: Company Mission and Approach - Aprea's mission is to develop innovative cancer therapies that specifically target cancer cells while minimizing damage to healthy cells, aiming to reduce toxicity associated with conventional treatments [3] - The company is currently developing APR-1051 and ATRN-119 for solid tumor indications, utilizing unique vulnerabilities in cancer cell mutations [3]

Aprea Therapeutics FY Conference Summary Company Overview - **Company**: Aprea Therapeutics (NasdaqCM: APRE) - **Industry**: Biopharmaceuticals, focusing on cancer treatment through small molecule inhibitors targeting genetic mutations [1][2] Core Points and Arguments - **Focus on Precision Medicine**: Aprea Therapeutics operates at the intersection of precision medicine and synthetic lethality, emphasizing a targeted approach to cancer treatment [2] - **Pipeline Overview**: The company is developing multiple programs, including: - ATR inhibitor - WE-one inhibitor (APR 1051) - Legacy p53 reactivator - An undisclosed target to be revealed later for intellectual property (IP) reasons [3][4] - **Clinical Trials**: - The WE-one inhibitor has progressed with the first patient enrolled and an open-label study ongoing. Data will be shared at an upcoming conference [4][5] - The ATR program has seen a shift from a once-daily (QD) to a twice-daily (BID) regimen due to pharmacokinetic properties, which has shown positive results [5][6] - **Dosing and Safety**: Initial maximum tolerated dose (MTD) was projected at 150 mg, but increased to 220 mg and 300 mg based on positive safety data, enhancing the therapeutic index [7][8] - **Early Clinical Data**: - Early signs of activity observed in the 70 mg cohort and stable disease in the 100 mg cohort, indicating potential efficacy as doses increase [9][10] - A case study of an 86-year-old patient showed improved response and stability after multiple lines of treatment, supporting the drug's potential [12][13] - **Biomarker-Driven Approach**: All programs are biomarker-driven, focusing on matching mutations with appropriate therapies, which is a key aspect of their personalized medicine strategy [15][16] Additional Important Information - **Collaboration with MD Anderson**: Aprea has a strong collaboration with MD Anderson for HPV positive head and neck cancer, generating promising preclinical data [14][15] - **Combination Therapy Potential**: Preclinical models indicate strong potential for both single-agent activity and combination therapies, with minimal side effects observed [17][19] - **Financial Position**: The company reported $16.5 million in cash, indicating a solid financial foundation to support ongoing and future programs [24] - **Investment Opportunity**: Aprea believes there is a good entry opportunity for investors, with upcoming catalysts expected to drive progress in their clinical programs [25] Conclusion Aprea Therapeutics is positioned as a promising player in the biopharmaceutical industry, focusing on innovative cancer treatments through a precision medicine approach. The ongoing clinical trials and strong financial backing present potential investment opportunities as the company continues to advance its pipeline.

Core Insights - Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing innovative cancer treatments that target specific vulnerabilities in cancer cells while minimizing damage to healthy cells [1][2] Presentation Details - Aprea will present at the H.C. Wainwright 27th Annual Global Investment Conference on September 9, 2025, at 3:30 PM ET, located at the Lotte New York Palace Hotel [2] - A webcast of the presentation will be available for 90 days on the Aprea Investors page [2] Company Overview - Aprea's mission is to create novel cancer therapies that directly target cancer cells, reducing toxicity risks associated with conventional treatments [2] - The company's lead programs include APR-1051, an oral small-molecule inhibitor of WEE1 kinase, and ATRN-119, a macrocyclic small molecule ATR inhibitor, both in clinical development for solid tumor indications [2]

PART I: FINANCIAL INFORMATION [Financial Statements](index=6&type=section&id=Item%201.%20Financial%20Statements) Unaudited condensed consolidated financial statements are presented, highlighting a **$16.5 million** cash balance and going concern doubt Condensed Consolidated Balance Sheet Data (Unaudited) | Indicator | June 30, 2025 (USD) | December 31, 2024 (USD) | | :--- | :--- | :--- | | Cash and cash equivalents | $16,532,199 | $22,849,885 | | Total current assets | $16,927,210 | $23,576,139 | | Total assets | $17,309,710 | $23,979,493 | | Total current liabilities | $3,167,668 | $3,360,975 | | Total stockholders' equity | $13,414,681 | $19,307,455 | Condensed Consolidated Statements of Operations (Unaudited) | Indicator | Three Months Ended June 30, 2025 (USD) | Three Months Ended June 30, 2024 (USD) | Six Months Ended June 30, 2025 (USD) | Six Months Ended June 30, 2024 (USD) | | :--- | :--- | :--- | :--- | :--- | | Grant revenue | $118,111 | $561,574 | $280,574 | $942,143 | | Research and development | $1,912,213 | $2,557,679 | $4,395,279 | $4,158,052 | | General and administrative | $1,593,671 | $1,850,819 | $3,358,650 | $3,780,685 | | Net loss | $(3,238,870) | $(3,470,052) | $(7,171,529) | $(6,280,143) | | Net loss per share | $(0.53) | $(0.58) | $(1.19) | $(1.24) | Condensed Consolidated Statements of Cash Flows (Unaudited, Six Months Ended June 30) | Indicator | 2025 (USD) | 2024 (USD) | | :--- | :--- | :--- | | Net cash used in operating activities | $(6,761,917) | $(7,577,512) | | Net cash provided by financing activities | $440,728 | $14,688,645 | - The company has concluded that its cash balance of approximately **$16.5 million** as of June 30, 2025, is not sufficient to fund operations for at least twelve months, raising substantial doubt about its ability to continue as a going concern[33](index=33&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=19&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Analysis of financial condition and operations, noting a **$16.5 million** cash position insufficient for twelve months and raising going concern issues [Overview](index=19&type=section&id=Overview) Aprea focuses on precision oncology with lead candidates APR-1051 and ATRN-119 in Phase 1 trials, anticipating initial data in H2 2025 - The company's primary focus is on its two clinical-stage synthetic lethality product candidates: **APR-1051** (WEE1 inhibitor) and **ATRN-119** (ATR inhibitor)[83](index=83&type=chunk)[85](index=85&type=chunk)[86](index=86&type=chunk) - Key clinical milestones include the enrollment of the first patient in the ACESOT-1051 (**APR-1051**) Phase 1 study in **Q2 2024** and ongoing enrollment in the ABOYA-119 (**ATRN-119**) Phase 1/2a trial[85](index=85&type=chunk)[86](index=86&type=chunk) - Aprea anticipates releasing open-label safety/efficacy data for both **APR-1051** and **ATRN-119** in the **second half of 2025** and determining the Recommended Phase 2 Dose (RP2D) for both in the **first half of 2026**[85](index=85&type=chunk)[86](index=86&type=chunk) [Results of Operations](index=28&type=section&id=Results%20of%20Operations) Net loss decreased to **$3.2 million** for Q2 2025 but increased to **$7.2 million** for the six-month period, due to lower grant revenue and higher R&D Comparison of Operations (Three Months Ended June 30) | Indicator | 2025 (USD) | 2024 (USD) | Change (USD) | | :--- | :--- | :--- | :--- | | Grant revenue | $118,111 | $561,574 | $(443,463) | | Research and development | $1,912,213 | $2,557,679 | $(645,466) | | General and administrative | $1,593,671 | $1,850,819 | $(257,148) | | Net loss | $(3,238,870) | $(3,470,052) | $231,182 | Comparison of Operations (Six Months Ended June 30) | Indicator | 2025 (USD) | 2024 (USD) | Change (USD) | | :--- | :--- | :--- | :--- | | Grant revenue | $280,574 | $942,143 | $(661,569) | | Research and development | $4,395,279 | $4,158,052 | $237,227 | | General and administrative | $3,358,650 | $3,780,685 | $(422,035) | | Net loss | $(7,171,529) | $(6,280,143) | $(891,386) | - The **$0.2 million** increase in R&D expenses for the six months ended June 30, 2025, was primarily driven by a **$0.5 million** increase in costs for the ABOYA-119 clinical trial for **ATRN-119**, partially offset by a decrease in non-program consulting expenses[121](index=121&type=chunk) [Liquidity and Capital Resources](index=32&type=section&id=Liquidity%20and%20Capital%20Resources) The company holds **$16.5 million** in cash, insufficient for twelve months, raising going concern doubts, despite recent capital raises - The company's cash and cash equivalents were **$16.5 million** as of June 30, 2025, which is not sufficient to fund operations for at least the next twelve months[124](index=124&type=chunk)[136](index=136&type=chunk) - In March 2024, the company raised approximately **$16.0 million** in gross proceeds through a securities purchase agreement involving common stock and warrants[126](index=126&type=chunk) - During the six months ended June 30, 2025, the company sold **243,139 shares** of common stock under its At the Market (ATM) agreement, resulting in net proceeds of approximately **$0.4 million**[129](index=129&type=chunk)[134](index=134&type=chunk) - Net cash used in operating activities decreased to **$6.8 million** for the first six months of 2025, compared to **$7.6 million** for the same period in 2024, primarily due to changes in operating assets and liabilities[131](index=131&type=chunk)[132](index=132&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) Market risks include interest rate sensitivity on cash and foreign currency exposure from its Swedish subsidiary, with no derivative use or material inflation impact - The primary market risk is interest income sensitivity on cash and cash equivalents, affected by U.S. interest rate changes[151](index=151&type=chunk) - The company faces foreign currency exchange rate risk from its Swedish subsidiary, Aprea AB, whose functional currency is the Swedish Krona[152](index=152&type=chunk) - The company does not believe that inflation has had a material effect on its business during the six months ended June 30, 2025[154](index=154&type=chunk) [Controls and Procedures](index=40&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls and procedures were effective as of June 30, 2025, with no material changes in internal control over financial reporting - Based on an evaluation as of June 30, 2025, the CEO and CFO concluded that the company's disclosure controls and procedures were effective[156](index=156&type=chunk) - There were no changes in internal control over financial reporting during the most recent fiscal quarter that materially affected, or are reasonably likely to materially affect, internal controls[157](index=157&type=chunk) PART II: OTHER INFORMATION [Legal Proceedings](index=40&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently subject to any material legal proceedings - As of the reporting date, Aprea Therapeutics is not a party to any material legal proceedings[159](index=159&type=chunk) [Risk Factors](index=40&type=section&id=Item%201A.%20Risk%20Factors) Significant risks include financial instability, high development risks for lead candidates, reliance on third parties, IP challenges, regulatory uncertainty, and stock volatility [Risks Related to Financial Position and Need for Additional Capital](index=46&type=section&id=Risks%20related%20to%20our%20financial%20position%20and%20the%20need%20for%20additional%20capital) Ongoing significant net losses, no commercial revenue, and insufficient cash raise going concern doubts, necessitating substantial additional funding - The company has incurred significant losses since inception, with a net loss of **$7.2 million** for the six months ended June 30, 2025, and an accumulated deficit of **$328.2 million**[172](index=172&type=chunk) - Management has identified conditions that raise substantial doubt about the company's ability to continue as a going concern, as its cash of **$16.5 million** is insufficient to fund operations for the next year[176](index=176&type=chunk)[178](index=178&type=chunk) - The company will need substantial additional funding to continue operations, and if unable to raise capital, it may be forced to delay, reduce, or eliminate its drug development programs[185](index=185&type=chunk)[187](index=187&type=chunk) [Risks Related to Discovery, Development, and Commercialization](index=58&type=section&id=Risks%20related%20to%20the%20discovery%2C%20development%20and%20commercialization%20of%20our%20product%20candidates) Success depends on lead candidates ATRN-119 and APR-1051, facing high development risks, unpredictable trial outcomes, patient enrollment challenges, and intense competition - The company's future success is substantially dependent on its ability to obtain marketing approval for and commercialize its two lead product candidates, **ATRN-119** and **APR-1051**[212](index=212&type=chunk) - There is a high risk of failure, as results from early-stage clinical trials may not be predictive of future results in later, larger studies[216](index=216&type=chunk)[232](index=232&type=chunk) - The company faces substantial competition from major pharmaceutical and biotechnology companies with greater financial resources and expertise in developing and marketing cancer treatments[260](index=260&type=chunk)[261](index=261&type=chunk) [Risks Related to Dependence on Third Parties](index=85&type=section&id=Risks%20related%20to%20our%20dependence%20on%20third%20parties) Aprea relies on third-party CROs for clinical trials and a single manufacturer for API, increasing supply chain risk and reducing direct control - The company relies on third parties like CROs and medical institutions to conduct its clinical trials, which reduces its control over these activities but does not relieve it of its regulatory responsibilities[289](index=289&type=chunk)[290](index=290&type=chunk) - The company is dependent on a single contract manufacturer for the API and drug product for its product candidates and does not currently have redundant supply arrangements in place[298](index=298&type=chunk)[299](index=299&type=chunk) [Risks Related to Intellectual Property](index=90&type=section&id=Risks%20related%20to%20our%20intellectual%20property) IP risks include limited patent protection for eprenetapopt and the potential for current DDR inhibitor patents to be challenged or invalidated by competitors - The chemical structure of **eprenetapopt** is in the public domain, meaning the company does not have composition of matter patents and relies on method-of-use and formulation patents, which may not prevent competitors from using the same compound for other uses[310](index=310&type=chunk)[321](index=321&type=chunk)[322](index=322&type=chunk) - The company's patents could be challenged in court or before administrative bodies and be found invalid or unenforceable, which would limit its ability to stop competitors from commercializing similar products[319](index=319&type=chunk)[324](index=324&type=chunk) [Risks Related to Regulatory and Marketing Approval](index=110&type=section&id=Risks%20related%20to%20regulatory%20and%20marketing%20approval%20and%20other%20legal%20compliance%20matters) Significant risks exist in the expensive, lengthy, and uncertain regulatory approval process, with no prior approvals and ongoing compliance challenges post-approval - The company has never obtained marketing approval for a product candidate and has limited experience in conducting the clinical trials necessary to obtain such approvals[362](index=362&type=chunk)[365](index=365&type=chunk) - The marketing approval process is expensive, time-consuming, and uncertain, and regulatory authorities have substantial discretion to delay, limit, or deny approval[364](index=364&type=chunk)[366](index=366&type=chunk) - Even if a product is approved, it will be subject to extensive ongoing regulation, and failure to comply could lead to significant penalties, including withdrawal of the product from the market[276](index=276&type=chunk)[380](index=380&type=chunk) [Risks Related to Common Stock](index=141&type=section&id=Risks%20related%20to%20our%20common%20stock) Stock price volatility is expected, with significant insider ownership influencing decisions, and a risk of Nasdaq delisting impacting liquidity and price - As of June 30, 2025, executive officers, directors, and principal stockholders beneficially owned approximately **50.9%** of the common stock, giving them substantial influence over corporate matters[459](index=459&type=chunk) - The company's stock price has been and is likely to continue to be volatile due to factors such as clinical trial results, regulatory actions, and market conditions[463](index=463&type=chunk) - The company is required to meet Nasdaq's continued listing requirements and may be subject to delisting if it fails to do so, which would negatively affect the stock's price and liquidity[477](index=477&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=149&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered equity sales or repurchases occurred during the quarter or six months ended June 30, 2025, beyond prior 8-K disclosures - There were no sales of unregistered equity securities during the quarter ended June 30, 2025, other than those previously disclosed on Form 8-K[478](index=478&type=chunk) [Defaults Upon Senior Securities](index=149&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is not applicable to the company - Not applicable[480](index=480&type=chunk) [Mine Safety Disclosures](index=149&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[481](index=481&type=chunk) [Other Information](index=149&type=section&id=Item%205.%20Other%20Information) This item is not applicable to the company - Not applicable[482](index=482&type=chunk) [Exhibits](index=150&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with Form 10-Q, including CEO/CFO certifications and Inline XBRL data files - The exhibits filed with this report include certifications from the CEO and CFO under Sections 302 and 906 of the Sarbanes-Oxley Act, as well as XBRL data files[485](index=485&type=chunk)

[Business and Clinical Update](index=1&type=section&id=Business%20and%20Clinical%20Update) Aprea Therapeutics reported positive progress in its two lead clinical programs, APR-1051 and ATRN-119, showing early clinical activity and disease control in Phase 1 trials - CEO Oren Gilad highlighted emerging data from both lead programs (APR-1051 and ATRN-119) showing evidence of clinical activity, strengthening confidence in the company's DDR (DNA Damage Response) assets[2](index=2&type=chunk) [ACESOT-1051: WEE1 inhibitor, APR-1051](index=1&type=section&id=ACESOT-1051%3A%20WEE1%20inhibitor%2C%20APR-1051) The Phase 1 trial for oral WEE1 inhibitor APR-1051 shows early disease control, with three patients achieving stable disease, expanded enrollment for HPV+ tumors, and further data expected in H2 2025 - **Three patients** achieved stable disease: one in the 70mg cohort and two in the 100mg cohort, including patients with HPV+ head and neck, rectal, and uterine cancers[1](index=1&type=chunk)[2](index=2&type=chunk) - The trial is currently enrolling patients at a **100 mg once-daily dose**, with plans to escalate to 150 mg, following a 2025 revision to optimize the therapeutic window[4](index=4&type=chunk) - Enrollment criteria expanded to include HPV+ tumors after a patient with HPV+ HNSCC showed stable disease with a **5% tumor reduction** at a 70 mg dose[4](index=4&type=chunk) - A collaboration with MD Anderson Cancer Center demonstrated potent single-agent activity of APR-1051 in head and neck cancer cell lines and significant synergy with anti-PD-1 therapies in preclinical models[5](index=5&type=chunk) - Future plans include releasing additional data in **H2 2025**, completing dose-escalation in **H1 2026**, and potentially evaluating APR-1051 in combination with checkpoint inhibitors[8](index=8&type=chunk) [ABOYA-119: ATR inhibitor, ATRN-119](index=2&type=section&id=ABOYA-119%3A%20ATR%20inhibitor%2C%20ATRN-119) The Phase 1/2a trial for ATR inhibitor ATRN-119 shows early activity with seven patients achieving stable disease, and three patients at 550 mg showing tumor shrinkage, leading to a dose reduction to 400 mg due to toxicity - In the ongoing Phase 1/2a trial, **seven patients** with advanced solid tumors demonstrated stable disease[2](index=2&type=chunk)[9](index=9&type=chunk) - **Three patients** in the 550 mg twice-daily cohort showed meaningful tumor shrinkage of **7%, 14%, and 21%**[9](index=9&type=chunk) - Dose-limiting toxicity observed in two patients at the 550 mg level led to a dose reduction to **400 mg twice daily** to optimize the therapeutic profile[9](index=9&type=chunk) - Additional safety and efficacy data are expected in **H2 2025**, with the recommended Phase 2 dose anticipated in **H1 2026**[9](index=9&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) Aprea reported a net loss of **$3.2 million** for Q2 2025, an improvement from Q2 2024, driven by decreased operating expenses, with **$16.5 million** in cash expected to fund operations into Q2 2026 [Financial Performance](index=2&type=section&id=Financial%20Performance) The company's Q2 2025 operating loss narrowed to **$3.4 million** from **$3.8 million** year-over-year, driven by reduced R&D and G&A expenses, with net loss per share improving to **$0.53** Q2 2025 vs. Q2 2024 Statement of Operations | Metric | Q2 2025 | Q2 2024 | Change | | :--- | :--- | :--- | :--- | | Operating Loss | $3.4 million | $3.8 million | Decreased | | Net Loss | $3.2 million | $3.5 million | Decreased | | Net Loss Per Share | $0.53 | $0.58 | Improved | | R&D Expenses | $1.9 million | $2.6 million | Decreased | | G&A Expenses | $1.6 million | $1.9 million | Decreased | - The decrease in R&D expenses was mainly due to higher study start-up costs in 2024 for the ACESOT-1051 trial and lower personnel costs in 2025[9](index=9&type=chunk) - The decrease in G&A expenses was primarily driven by lower professional fees, particularly legal expenses, and a reduction in personnel costs[9](index=9&type=chunk)[10](index=10&type=chunk) [Financial Position and Cash Runway](index=2&type=section&id=Financial%20Position%20and%20Cash%20Runway) As of June 30, 2025, Aprea held **$16.5 million** in cash and cash equivalents, projected to fund operations into Q2 2026 Cash and Cash Equivalents | Date | Amount | | :--- | :--- | | June 30, 2025 | $16.5 million | | December 31, 2024 | $22.8 million | - The company believes its current cash and cash equivalents are sufficient to meet operating and capital expenditure requirements into **Q2 2026**[9](index=9&type=chunk) [Corporate Information and Forward-Looking Statements](index=4&type=section&id=Corporate%20Information%20and%20Forward-Looking%20Statements) Aprea is a clinical-stage biopharmaceutical company focused on cancer treatment through targeted therapies like APR-1051 and ATRN-119, with the report including standard forward-looking statement disclaimers - Aprea's strategy is to develop treatments that exploit vulnerabilities in cancer cell mutations to kill tumors while minimizing effects on healthy cells[11](index=11&type=chunk) - The company's lead programs, **APR-1051** (WEE1 inhibitor) and **ATRN-119** (ATR inhibitor), are in clinical development for solid tumor indications[11](index=11&type=chunk) - The press release contains forward-looking statements concerning clinical trials, regulatory submissions, and financial projections, which are subject to inherent risks and uncertainties, cautioning readers against undue reliance[13](index=13&type=chunk)[14](index=14&type=chunk)

Core Insights - Aprea Therapeutics is making progress in its clinical trials, particularly with its WEE1 inhibitor APR-1051, showing early signs of disease control in patients with stable disease [1][3][4] - The company reported financial results for Q2 2025, indicating a decrease in operating loss compared to the same period in 2024, with cash and cash equivalents of $16.5 million as of June 30, 2025 [2][8][11] Clinical Development - The ongoing Phase 1 ACESOT-1051 trial of APR-1051 has shown that three patients achieved stable disease, including one patient with HPV-positive head and neck squamous cell carcinoma [3][7] - Aprea's ATR inhibitor ATRN-119 is also in clinical trials, with seven patients demonstrating stable disease and three showing significant tumor shrinkage at the 550 mg dose [3][11] - The company is expanding enrollment criteria for ACESOT-1051 to include patients with HPV+ tumors, with additional data expected in the second half of 2025 [7][11] Financial Performance - For Q2 2025, Aprea reported an operating loss of $3.4 million, a decrease from $3.8 million in Q2 2024, with R&D expenses at $1.9 million [11][17] - The company’s net loss for the quarter was $3.2 million, or $0.53 per share, compared to a net loss of $3.5 million, or $0.58 per share, in the same quarter of 2024 [11][17] - As of June 30, 2025, Aprea's total assets were $17.3 million, down from $24.0 million at the end of 2024 [14][15] Strategic Collaborations - Aprea has entered into a translational research collaboration with MD Anderson Cancer Center, which has yielded promising preclinical results for APR-1051 [5][9] - The collaboration aims to explore the potential of APR-1051 in combination with anti-PD-1 therapies for HPV+ head and neck cancer [5][9] Future Outlook - Aprea plans to submit an abstract to a major oncology conference and anticipates additional safety and efficacy data from its trials in the near future [7][11] - The company is also considering future arms of its trials to evaluate APR-1051 and ATRN-119 in combination with other therapies to address unmet medical needs [11][12]

Pipeline and Milestones - Aprea Therapeutics' WEE1 inhibitor (APR-1051) ACESOT-1051 Phase 1 study expects safety/efficacy data in H2 2025 and complete dose escalation in H1 2026 [7, 43] - Aprea Therapeutics' ATR inhibitor (ATRN-119) ABOYA-119 Phase 1/2a study expects safety/efficacy data in H2 2025 and Recommended Phase 2 Dose (RP2D) in H1 2026 [8, 68] - Six patients in the ATRN-119 dose escalation cohorts achieved stable disease, with three patients (50%) in the 550mg BID cohort demonstrating measurable tumor shrinkage of 7%, 14%, and 21% [53] APR-1051 (WEE1 Inhibitor) - APR-1051 is a potent WEE1 inhibitor with high selectivity, showing >150-fold, >50-fold, and >600-fold difference in IC50 compared to PLK1, PLK2, and PLK3 inhibition, respectively [31] - Clinical data cutoff on March 4, 2025, for APR-1051 (N=9) showed treatment-related adverse events, including alanine aminotransferase increased (2 patients), aspartate aminotransferase increased (2 patients), and lymphocyte count decreased (1 patient) [26] ATRN-119 (ATR Inhibitor) - ATRN-119 exhibits near-dose proportional exposure following oral administration, with AUC 0-24hr ranging from 180 ng*h/mL at 50mg to 6899 ng*h/mL at 550mg [55] - Clinical data cutoff on May 1, 2025, for ATRN-119 (N=32) showed treatment-related adverse events, including nausea (13 patients), diarrhea (12 patients), and fatigue (10 patients) [57] - ATRN-119 is the first and only macrocyclic ATR inhibitor, potentially offering increased selectivity and improved tolerability compared to first-generation acyclic structures [59, 66] Financials and Capitalization - As of March 31, 2025, Aprea Therapeutics had approximately $19.3 million in cash and equivalents [73] - Aprea Therapeutics has 5,531,373 common stock, 2,701,864 warrants, 782,243 options, and 30,607 restricted stock units outstanding as of May 14, 2025, resulting in 9,061,683 fully diluted equivalents [73]

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]