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)

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]

Oncology Development - The company is focused on precision oncology through synthetic lethality, aiming to establish a pipeline of clinical and preclinical programs for cancer treatment [88]. - The lead product candidate, APR-1051, received FDA clearance for its IND application in March 2024, with the first patient enrolled in a Phase 1 study in Q2 2024 [90]. - The second product candidate, ATRN-119, is an oral small molecule inhibitor currently in a Phase 1/2a clinical trial, with safety and efficacy data expected in the second half of 2025 [91]. - The company is exploring combination therapies with other agents, such as PARP inhibitors, to enhance the therapeutic impact of its product candidates [92]. - The company has a preclinical research program in lead optimization for an undisclosed DDR target, focusing on synthetic lethality in oncology [93]. Financial Performance - Grant revenue for the three months ended March 31, 2025 was approximately $0.2 million, a decrease of 47.4% compared to $0.4 million for the same period in 2024 [125]. - Total operating expenses increased to $4.25 million for the three months ended March 31, 2025, up 20.4% from $3.53 million in the same period in 2024 [124]. - Research and development expenses rose to approximately $2.48 million for the three months ended March 31, 2025, an increase of 55.1% from $1.6 million in 2024 [126]. - Net loss for the three months ended March 31, 2025 was $3.93 million, compared to a net loss of $2.81 million for the same period in 2024, reflecting an increase of 40% [130]. - Cash and cash equivalents as of March 31, 2025 were $19.3 million, with substantial doubt about the ability to fund operations for the next twelve months [143]. - Net cash used in operating activities was $3.63 million for the three months ended March 31, 2025, a decrease of 7.7% from $3.94 million in 2024 [137]. - Foreign currency loss for the three months ended March 31, 2025 was $51,803, compared to a gain of $56,176 in 2024, indicating a change of $107,979 [128]. Future Outlook - The company anticipates completing dose escalation for APR-1051 in the first half of 2026 and determining the Recommended Phase 2 Dose for ATRN-119 in the same timeframe [90][91]. - The company expects to incur significant expenses and increasing operating losses for at least the next several years due to ongoing development activities [130]. - The company plans to seek marketing approvals for product candidates that successfully complete clinical trials and establish a commercialization infrastructure [145]. - The company requires additional financing to support ongoing operations and may rely on public or private equity, debt financings, or collaborations [147]. - There is uncertainty regarding the timing and amount of increased expenses, and the company may not achieve or maintain profitability [148]. - Developing drug products is a lengthy and costly process, and the company may not generate necessary data for marketing approval [149]. - The company currently has no committed external source of funds and may face dilution of ownership interests if additional capital is raised through equity sales [150]. - Collaborations or licensing arrangements may require the company to relinquish valuable rights to technology or future revenue streams [151]. - The company anticipates costs related to patent applications, headcount growth, and operating as a public company [152]. Risk Factors - The company is exposed to interest rate risk, but historical fluctuations in interest income have not been significant [158]. - Foreign currency exchange rate changes may affect the revenues and expenses of the company's foreign subsidiaries [159]. - The company does not currently have significant direct foreign exchange risk and has not used derivative financial instruments for hedging [160]. - Inflation has not materially affected the company's business or financial condition in the recent quarter [161].

Financial Performance - Aprea reported cash and cash equivalents of $19.3 million, down from $22.8 million as of December 31, 2024, providing runway into early Q2 2026[15]. - The company incurred an operating loss of $4.1 million for Q1 2025, compared to an operating loss of $3.1 million in Q1 2024[15]. - Aprea reported a net loss of $3.9 million ($0.66 per basic share) for Q1 2025, compared to a net loss of $2.8 million ($0.67 per basic share) in Q1 2024[15]. - Total current assets decreased to $19.8 million as of March 31, 2025, from $23.6 million as of December 31, 2024[19]. - Total stockholders' equity decreased to $15.5 million as of March 31, 2025, from $19.3 million as of December 31, 2024[19]. - Grant revenue for Q1 2025 was $162,463, a decrease of 57.4% compared to $380,569 in Q1 2024[20]. - Total operating expenses increased to $4,248,045 in Q1 2025, up 20.3% from $3,530,239 in Q1 2024[20]. - Net loss for Q1 2025 was $3,932,659, representing an increase of 40% from a net loss of $2,810,091 in Q1 2024[20]. - Net loss per share attributable to common stockholders was $0.66 in Q1 2025, slightly improved from $0.67 in Q1 2024[20]. - Weighted-average common shares outstanding increased to 5,993,866 in Q1 2025, compared to 4,198,326 in Q1 2024[20]. - Total other income decreased to $152,923 in Q1 2025, down 55% from $339,579 in Q1 2024[20]. - Interest income, net, was $204,726 in Q1 2025, a decrease of 27.7% from $283,403 in Q1 2024[20]. - The comprehensive loss for Q1 2025 was $3,932,016, compared to a comprehensive loss of $2,825,174 in Q1 2024[20]. Research and Development - Research and Development (R&D) expenses increased to $2.5 million in Q1 2025 from $1.6 million in Q1 2024, primarily due to the initiation of clinical trials for APR-1051 and ATRN-119[15]. - Aprea's ATR inhibitor, ATRN-119, showed early evidence of anti-tumor activity with tumor shrinkage of 7%, 14%, and 21% in three patients at the 550 mg twice daily dose level[2]. - The ongoing ACESOT-1051 trial for the WEE1 inhibitor APR-1051 is advancing, with patients now being dosed at 100 mg once daily, and preliminary efficacy data is expected in the second half of 2025[3]. - The recommended Phase 2 dose (RP2D) for ATRN-119 is expected to be identified in the first half of 2026, with preliminary safety and efficacy data anticipated in the second half of 2025[6]. - Aprea entered into a Material Transfer Agreement with MD Anderson Cancer Center to support preclinical research on APR-1051 for treating head and neck squamous cell carcinoma[9].

Core Insights - Aprea Therapeutics has initiated dosing of the first patient with HPV+ head and neck squamous cell carcinoma in the ACESOT-1051 clinical trial evaluating APR-1051, marking a significant milestone in the study [1][4] - The ACESOT-1051 trial aims to assess the safety and efficacy of APR-1051, a WEE1 inhibitor, in patients with advanced solid tumors, particularly those with specific gene alterations [3][5] Company Overview - Aprea Therapeutics is focused on developing innovative cancer treatments that target specific vulnerabilities in cancer cells while minimizing harm to healthy cells [1][7] - The company's lead product, APR-1051, is a small molecule designed to address tolerability issues associated with the WEE1 class of inhibitors [3][7] Clinical Trial Details - The ACESOT-1051 trial is a Phase 1 study that will evaluate APR-1051's safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in advanced solid tumors [5][6] - The trial consists of two parts: Part 1 focuses on dose escalation with an expected enrollment of up to 39 patients, while Part 2 aims for dose optimization with up to 40 patients [5][6] HPV+ Cancer Context - HPV+ head and neck squamous cell carcinoma is characterized by defects in the DNA damage response pathway, making it a potential target for WEE1 inhibition [2] - Approximately 70% of the 20,000 annual cases of oropharyngeal squamous cell carcinoma in the U.S. are linked to HPV [2]

Financial Condition - The company incurred a net loss of $14.3 million for the year ended December 31, 2023, and an accumulated deficit of $321.0 million as of the same date [271]. - The company has not generated any commercial revenue to date and expects to continue incurring significant operating losses for the foreseeable future [271]. - The company has approximately $22.8 million in cash and cash equivalents as of December 31, 2024, raising substantial doubt about its ability to continue as a going concern [276]. - The company has identified conditions that raise substantial doubt regarding its ability to continue as a going concern within one year after the filing of its Annual Report [276]. - The company has incurred significant losses since inception and may never achieve or maintain profitability [271]. - The company expects expenses to increase due to planned operations and will finance cash needs through equity offerings, debt financings, collaborations, and strategic alliances [286]. - Future capital requirements will depend on various factors, including the costs and outcomes of clinical trials and regulatory reviews [285]. - The company may need to seek additional funds sooner than planned due to changing circumstances and potential faster capital consumption [285]. - The company faces risks from global economic uncertainty, including geopolitical conflicts and regulatory changes, which could adversely affect its financial condition [288]. Product Development and Clinical Trials - The company is substantially dependent on the success of its product candidates ATRN-119 and APR-1051, which are currently in clinical development [264]. - The company has never obtained marketing approval for any product candidate and may face challenges in doing so in the future [268]. - The company is in the early stages of testing product candidates ATRN-119 and APR-1051 in Phase 1 clinical trials, with no later phase trials conducted yet [308]. - The company has filed and obtained INDs for ATRN-119 and APR-1051, but may face delays in filing INDs for other candidates due to manufacturing or study delays [309]. - The success of ATRN-119 and APR-1051 will depend on timely patient enrollment and completion of clinical trials, as well as obtaining marketing approvals [306]. - Patient enrollment in clinical trials is critical, and difficulties in enrollment could delay necessary marketing approvals [315]. - Adverse events during clinical trials could lead to interruptions or halts in trials, affecting the approval process by the FDA [321]. - The company has limited experience in conducting clinical trials, which may hinder the ability to complete pivotal trials [312]. - The company may need to conduct additional clinical trials or testing, which could lead to unplanned costs and delays in obtaining marketing approval [335]. - There is a high failure rate for product candidates in clinical trials, and setbacks could materially harm the company's business and financial condition [308]. - Clinical trials are lengthy and costly, with no assurance that they will demonstrate safety and efficacy to the satisfaction of regulatory authorities, potentially leading to additional funding needs [331]. Competition and Market Risks - The company may face substantial competition from larger pharmaceutical and biotechnology companies with greater resources and expertise [347]. - The commercial opportunity could be diminished if competitors develop safer or more effective drugs that gain market approval faster [348]. - Market acceptance of approved products is uncertain and may depend on factors such as efficacy, safety, and the willingness of healthcare providers to prescribe them [344]. - The company may need to develop companion diagnostic tests for its product candidates, which could present additional challenges and delays [339]. - The company is developing ATRN-119, an orally bioavailable small molecule targeting Ataxia ATR protein, which may face significant competition from other late-stage clinical drugs [352]. - APR-1051, another product candidate, is an orally bioavailable small molecule inhibitor of WEE1, with potential competition from various other companies' products in clinical development [353]. Regulatory and Compliance Challenges - The company must comply with stringent regulatory requirements for clinical trials and manufacturing, and failure to do so could result in significant sanctions [390]. - The FDA placed a partial clinical hold on the clinical trials of eprenetapopt in combination with azacitidine, and a clinical hold on trials evaluating eprenetapopt with acalabrutinib or with venetoclax and rituximab [374]. - Regulatory agencies may require extensive additional clinical trials post-approval, which could be expensive and time-consuming, potentially limiting or withdrawing product sales [363]. - The company may be subject to unfavorable pricing regulations and reimbursement policies that could negatively impact revenue generation from approved products [366]. - Coverage and reimbursement from government authorities and private insurers are uncertain, which may affect the demand and pricing of commercialized products [367]. Intellectual Property Risks - The company faces risks related to intellectual property, including potential challenges to the validity and enforceability of its patents, which could adversely affect its business and financial condition [399]. - The patent portfolio for eprenetapopt consists of method-of-use and formulation patent claims, but does not include composition-of-matter patents, which may limit competitive protection [406]. - The company may need to cease development or commercialization of product candidates if it cannot obtain necessary licenses from third parties involved in patent disputes [413]. - The company may face significant harm if it fails to obtain patent term extensions or data exclusivity for its product candidates, which could allow competitors to launch similar products after patent expiration [416]. - The company may incur substantial costs and time in defending its patents against infringement claims, which could distract from its core business operations [424]. Sales and Marketing Challenges - The company lacks a sales and marketing infrastructure and has no experience in selling or marketing pharmaceutical drugs, which may hinder commercialization efforts [357]. - Establishing a sales and marketing organization or outsourcing these functions could incur significant costs and delays in product launches [358]. - The company may face adverse effects on sales if the FDA approves generic versions of its product candidates, as generic drugs typically capture a significant percentage of sales from branded products [361]. - The lengthy approval process and unpredictability of clinical trial results may hinder the marketing approval of ATRN-119, significantly harming the company's business and prospects [451]. Miscellaneous Risks - The company may encounter unforeseen expenses and difficulties as it transitions from a research-focused entity to one capable of supporting commercial activities [282]. - The company may have to relinquish valuable rights to technology or revenue streams if it raises additional funds through collaborations or licensing arrangements [287]. - The company is dependent on a single third-party manufacturer for the active pharmaceutical ingredient, increasing the risk of supply issues [385]. - The company currently holds clinical trial liability insurance coverage for up to $5.0 million, which may not be adequate to cover all potential liabilities [370]. - The consequences of the U.K.'s withdrawal from the EU remain largely unknown, creating uncertainty regarding macro-economic and financial implications [455].

Drug Development and Clinical Trials - Aprea Therapeutics is advancing its WEE1 inhibitor, APR-1051, which has shown a 29.4% overall response rate (ORR) in a Phase 2 study for recurrent uterine serous carcinoma[16]. - The company is currently enrolling the fourth cohort in a Phase 1 study for APR-1051, with safety and efficacy data expected in H1 2025[6]. - Aprea's ATR inhibitor, ATRN-119, is in a Phase 1/2a study, with data readout anticipated in H2 2025[6]. - The clinical study for ACESOT-1051 is enrolling up to 79 patients, focusing on advanced solid tumors with specific gene alterations[40]. - The ongoing study for ATRN-119 aims to establish a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) with a total enrollment of up to 132 patients[62]. - The study design for ATRN-119 includes a dose escalation phase with up to 72 patients, followed by a dose expansion phase[62]. - Aprea Therapeutics is conducting ongoing Phase 1/2a clinical studies for ATRN-119, with preliminary signs of clinical benefit observed at low doses[74]. Drug Safety and Efficacy - Aprea's WEE1 inhibitor has demonstrated minimal off-target effects, preserving hematologic safety profiles in clinical trials[6]. - APR-1051 has shown negligible inhibition of hERG channels, suggesting a low risk of QT prolongation at effective doses[29]. - APR-1051 has been reported to be safe and well-tolerated, with no hematologic toxicity observed in preclinical studies[48]. - No serious adverse events (SAE) or Grade 4 adverse events related to ATRN-119 were reported, with the most common adverse events being Grade 1 and Grade 2[71]. - ATRN-119 is potentially differentiated from other ATR inhibitors in selectivity and toxicity profile, providing continuous tumor suppression[74]. Financial Position and Funding - Aprea Therapeutics reported cash and equivalents of approximately $22.8 million as of December 31, 2024[77]. - The company closed a private placement of common stock in March 2024, raising approximately $16.0 million, with potential additional funds of up to $18.0 million from warrant exercises[77]. - Aprea Therapeutics is financed into Q4 2025, with near-term catalysts expected from ongoing clinical trials[81]. Strategic Goals and Market Positioning - The company aims to identify lead candidates for its discovery platform by 2024, focusing on optimizing drug development[6]. - Aprea's clinical pipeline includes multiple anticipated milestones from 2024 to 2026, indicating a robust development strategy[7]. - The company emphasizes the need for highly efficient WEE1 inhibitors with improved safety profiles, addressing significant unmet medical needs in oncology[16]. - The company is focused on expanding its market presence through innovative therapies that address critical gaps in cancer treatment[5]. - Aprea Therapeutics has a strong intellectual property portfolio, including four issued US patents protecting lead molecules and analogs[76]. - The company aims to achieve short-term inflection points and evaluate optimal strategic partnerships in the oncology space[81]. - The company has opportunities in various cancers, including ovarian, colorectal, prostate, and breast cancers, with both single-agent and combination therapies being explored[81]. Drug Characteristics and Performance - APR-1051 demonstrated a Cmax of 1,460 ng/ml at a dose of 10 mg/kg/day, indicating potentially favorable drug exposure compared to competitors[28]. - In preclinical studies, APR-1051 showed a tumor volume reduction in OVCAR-3 xenograft models, with significant suppression of tumor growth[32]. - ATRN-119 exhibits near-dose proportional exposure following oral administration, with a Tmax of approximately 2 hours and a half-life estimated between 4-6 hours[68][74]. - APR-1051 is being developed as a best-in-class WEE1 inhibitor, targeting specific cancer-associated gene alterations[47]. - ATRN-119 is positioned as a potentially best-in-class oral ATR inhibitor, with continuous daily dosing being evaluated[55].

Core Viewpoint - Aprea Therapeutics has entered into a Material Transfer Agreement with MD Anderson Cancer Center to supply its WEE1 kinase inhibitor, APR-1051, for preclinical research on head and neck squamous cell carcinoma (HNSCC) [1][2][3] Group 1: Agreement and Research Goals - The agreement allows MD Anderson to conduct preclinical experiments to generate efficacy and mechanistic data for future clinical trials [2] - The research aims to characterize the therapeutic potential of APR-1051 in treating both HPV+ and HPV- HNSCC tumors [2][3] - The project is overseen by leading experts in head and neck cancers, Professors Jeffrey N. Myers and Abdullah A. Osman [2] Group 2: Clinical Significance and Background - HNSCC, particularly HPV-associated cases, poses significant clinical challenges, with approximately 70% of oropharyngeal squamous cell carcinoma (OPSCC) cases in the US linked to HPV [4] - Previous studies at MD Anderson indicated that HPV+ HNSCC tumor lines are sensitive to WEE1 kinase inhibition, suggesting a promising therapeutic target [4] - The inhibition of WEE1 kinase may enhance the sensitivity of cancer cells to existing treatments, representing a novel therapeutic strategy [3] Group 3: Product Information - APR-1051 is a potent and selective small molecule designed to address tolerability challenges and potentially achieve greater clinical activity than other WEE1 inhibitors [6] - The candidate is currently being evaluated in the ongoing ACESOT-1051 clinical trial for advanced solid tumors with cancer-associated gene alterations [6] - Aprea retains all rights to APR-1051 under the terms of the agreement with MD Anderson [5] Group 4: Company Overview - Aprea Therapeutics focuses on innovative cancer treatments that exploit vulnerabilities in cancer cell mutations while minimizing damage to healthy cells [7] - The company's lead programs include APR-1051 and ATRN-119, both in clinical development for solid tumor indications [7]