Clinical Development - The FDA cleared the IND application for APR-1051 in March 2024, with the first patient enrolled in the Phase 1 study in Q2 2024 [84]. - The recommended Phase 2 dose for ATRN-119 is 1,100 mg once daily, determined on October 15, 2025, during the ongoing Phase 1/2a study [86]. - The company has paused further enrollment in both monotherapy dosing arms of ATRN-119 to explore combination approaches with other therapies [86]. - The company is evaluating combination opportunities for its product candidates, including ATRN-119 and APR-1051, supported by a grant from the National Cancer Institute [88]. - The company has an early preclinical research program for an undisclosed DDR target, currently in the lead optimization stage [90]. Financial Performance - The company has not generated any revenue from product sales and does not expect to do so in the near future [94]. - Grant revenue for the three months ended September 30, 2025, was $1,848, a decrease of $352,773 from $354,621 in 2024 [116]. - Total operating expenses for the three months ended September 30, 2025, were $3,119,236, down from $4,451,637 in 2024, representing a decrease of $1,332,401 [116]. - Research and development expenses for the three months ended September 30, 2025, were approximately $1.6 million, a decrease of $1.2 million from approximately $2.8 million in 2024 [118]. - General and administrative expenses for the three months ended September 30, 2025, were approximately $1.5 million, down from approximately $1.6 million in 2024, a decrease of $124,919 [119]. - Net loss for the three months ended September 30, 2025, was $2,972,410, compared to a net loss of $3,783,769 in 2024, an improvement of $811,359 [116]. - Grant revenue for the nine months ended September 30, 2025, was approximately $0.3 million, a decrease of $1,014,342 from $1.3 million in 2024 [123]. - Total operating expenses for the nine months ended September 30, 2025, were $10,873,165, down from $12,390,374 in 2024, a decrease of $1,517,209 [122]. - Net cash used in operating activities for the nine months ended September 30, 2025, was $9,933,147, compared to $10,045,814 in 2024, a decrease of $112,667 [135]. - The accumulated deficit as of September 30, 2025, was $331.2 million, with significant losses primarily from research and development activities [129]. Cash and Financing - As of September 30, 2025, the company had cash and cash equivalents of $13.7 million, which is insufficient to fund operating expenses for the next twelve months [128]. - Net cash provided by financing activities was $0.8 million for the nine months ended September 30, 2025, after deducting approximately $36,000 in issuance costs from sales of common stock [138]. - For the nine months ended September 30, 2024, net cash provided by financing activities was $14.7 million, after deducting approximately $1.3 million in underwriting discounts and offering expenses [139]. - The company anticipates a substantial increase in expenses related to ongoing and planned development activities, including clinical trials and preclinical research [141]. - Additional financing will be required to support continuing operations, with potential sources including public or private equity, debt financings, and collaborations [144]. - The company may face significant delays or reductions in product development if it fails to raise necessary capital [149]. - The company has no committed external source of funds and may experience dilution of ownership interests if additional capital is raised through equity sales [147]. Risk Factors - The company is exposed to interest rate risk, with cash equivalents primarily in bank deposits and money market accounts [155]. - Inflation has not had a material effect on the company's business or financial condition during the nine months ended September 30, 2025 [158]. - The company does not currently have significant direct foreign exchange risk and has not used derivative financial instruments to hedge such exposure [157]. Company Status - The company qualifies as a "smaller reporting company," with a market value of common stock held by non-affiliates below $700 million [114]. - The company has not recorded any income tax expense or benefits due to uncertainty in realizing benefits from net losses [109].

Financial Performance - As of September 30, 2025, Aprea reported cash and cash equivalents of $13.7 million, down from $22.8 million as of December 31, 2024, indicating a decrease of approximately 40%[8] - The company reported an operating loss of $3.1 million for Q3 2025, an improvement from an operating loss of $4.1 million in Q3 2024, reflecting a reduction of about 24%[13] - The net loss for Q3 2025 was $3.0 million, or $0.47 per basic share, compared to a net loss of $3.8 million, or $0.64 per basic share, in the same period of 2024, representing a reduction of about 21% in net loss per share[13] - Total operating expenses for Q3 2025 were $3,119,236, down from $4,451,637 in Q3 2024, representing a decrease of approximately 30%[19] - Net loss for Q3 2025 was $(2,972,410), an improvement from $(3,783,769) in Q3 2024, indicating a reduction in losses[19] - Total comprehensive loss for the nine months ended September 30, 2025, was $(10,146,094), compared to $(10,057,386) for the same period in 2024[19] Research and Development - Research and Development (R&D) expenses decreased to $1.6 million in Q3 2025 from $2.8 million in Q3 2024, a decline of approximately 43%[13] - Research and development expenses for the nine months ended September 30, 2025, were $6,034,196, compared to $7,004,451 for the same period in 2024, reflecting a decrease of about 14%[19] - The recommended Phase 2 dose (RP2D) for ATRN-119 was identified as 1,100 mg once daily, following the completion of the dose-escalation study[9] - Aprea is considering combination strategies for ATRN-119 with radiation or checkpoint inhibitors to enhance clinical impact[3] - In the ongoing Phase 1 ACESOT-1051 trial for APR-1051, 3 out of 4 patients (75%) in the 100 mg once daily cohort achieved stable disease[5] Assets and Equity - Aprea's total assets as of September 30, 2025, were reported at $14.3 million, down from $24.0 million as of December 31, 2024, reflecting a decrease of approximately 40%[17] - Total stockholders' equity decreased to $10.9 million as of September 30, 2025, from $19.3 million at the end of 2024, a decline of about 44%[17] Revenue and Income - Grant revenue for Q3 2025 was $1,848, compared to $354,621 in Q3 2024, showing a significant increase[19] - Interest income for Q3 2025 was $150,669, compared to $348,741 in Q3 2024, showing a decline of approximately 57%[19] - Total other income for Q3 2025 was $144,978, down from $313,247 in Q3 2024, indicating a decrease of approximately 54%[19] Shareholder Information - The weighted average common shares outstanding for Q3 2025 were 6,372,938, an increase from 5,939,755 in Q3 2024[19] - The net loss per share attributable to common stockholders for Q3 2025 was $(0.47), an improvement from $(0.64) in Q3 2024[19] Currency Impact - Foreign currency translation resulted in a loss of $(1,117) in Q3 2025, contrasting with a gain of $23,557 in Q3 2024[19] Cash Runway - The company has cash runway projected into the fourth quarter of 2026, indicating sufficient funds to meet operational needs[2]

Core Insights - Aprea Therapeutics, Inc. reported financial results for Q3 2025, highlighting clinical progress in its WEE1 and ATR inhibitor programs, with cash runway extending into Q4 2026 [1][2]. Clinical Development - The ongoing ACESOT-1051 trial for APR-1051 (WEE1 kinase inhibitor) shows promising early signs of anti-tumor activity, with 3 out of 4 patients achieving stable disease at the 100 mg once daily dose [2][4]. - APR-1051 has advanced to the 150 mg once daily cohort as part of the dose escalation strategy [2][4]. - ATRN-119 (ATR kinase inhibitor) has identified a recommended Phase 2 dose of 1,100 mg once daily, with plans to explore combination strategies with radiation or checkpoint inhibitors [2][9]. Financial Performance - As of September 30, 2025, Aprea reported cash and cash equivalents of $13.7 million, down from $22.8 million at the end of 2024 [9][13]. - The company recorded an operating loss of $3.1 million for Q3 2025, an improvement from a $4.1 million loss in Q3 2024 [9][16]. - Research and Development (R&D) expenses decreased to $1.6 million in Q3 2025 from $2.8 million in the same quarter of 2024, primarily due to reduced study startup costs [9][16]. Business Strategy - Aprea is focusing on a differentiated DNA damage response (DDR) approach to treat cancers with specific vulnerabilities, particularly those over-expressing Cyclin E [5][8]. - The company is considering future studies of APR-1051 in combination with checkpoint inhibitors to address unmet medical needs across distinct patient populations [5][9].

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)