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]

Core Insights - Aprea Therapeutics is focused on developing innovative cancer treatments that target specific vulnerabilities in cancer cells while minimizing harm to healthy cells [1][4] - The company emphasizes the importance of its strong patent portfolio in advancing its oncology treatments and protecting its intellectual property [2] Patent Portfolio - Aprea's ATR inhibitor program includes four granted U.S. patents, one pending U.S. application, and one pending provisional application, with 19 granted non-U.S. patents and 16 pending non-U.S. applications [2] - The granted patents for the ATR inhibitor program will expire between 2035 and 2037, with potential extensions of exclusivity into 2044 if pending applications are granted [2] - The WEE1 kinase inhibitor program has one pending U.S. patent application and 12 pending non-U.S. patent applications, with potential expiration in 2043 [3] Clinical Development - The lead ATR inhibitor, ATRN-119, is currently in the ABOYA-119 clinical trial for patients with advanced solid tumors having specific mutations in DNA damage response-related genes [2] - The lead WEE1 inhibitor, APR-1051, is being evaluated in the ACESOT-1051 Phase 1 clinical trial for advanced/metastatic solid tumors with certain gene alterations [3] Company Overview - Aprea is pioneering a treatment approach that targets cancer cell mutations while reducing toxicity to normal cells, applicable across various cancer types including ovarian, colorectal, prostate, and breast cancers [4]

Core Insights - Aprea Therapeutics has initiated a Phase 1/2a clinical trial for its experimental drug ATRN-119, with the first patient dosed at a new twice-daily regimen of 550 mg [1][2] - The trial aims to evaluate ATRN-119 as a monotherapy for patients with advanced solid tumors that have mutations in DNA damage response-related genes [2][5] - The twice-daily dosing is expected to enhance the drug's efficacy and optimize therapeutic levels, potentially leading to better clinical outcomes and a faster path to regulatory approval [3][4] Company Overview - Aprea Therapeutics is focused on developing innovative therapies for cancers with specific genetic alterations, aiming to minimize damage to healthy cells [1][5] - ATRN-119 is a first-in-class macrocyclic ATR inhibitor designed for patients with mutations in DNA damage response-related genes, addressing a significant unmet medical need [5][7] - The company is committed to refining its clinical approach based on scientific evidence, which may enhance shareholder value and create partnership opportunities for commercialization [4][6] Clinical Trial Details - The ABOYA-119 trial has been amended to allow for twice-daily dosing, which is expected to improve the drug's pharmacokinetics and pharmacodynamics [2][3] - The primary endpoint of the trial is to assess the tolerability and pharmacokinetics of ATRN-119, with results anticipated in the second half of 2025 [4][3] - The trial will continue to explore both once-daily and twice-daily dosing schedules independently [4]

Core Viewpoint - Aprea Therapeutics, Inc. (APRE) has experienced a decline of 11.1% in its stock price over the past week, but the formation of a hammer chart pattern suggests a potential trend reversal due to increased buying interest and analyst support for earnings estimates [1][3] Group 1: Technical Analysis - The hammer chart pattern indicates that the stock may have found support, suggesting a possible end to the selling pressure and a trend reversal [1] - A hammer pattern forms when there is a small candle body with a long lower wick, signaling that bears may be losing control during a downtrend [2] - This pattern can occur across various timeframes and is used by both short-term and long-term investors, although it should be combined with other bullish indicators for confirmation [2] Group 2: Fundamental Analysis - Recent upward revisions in earnings estimates for APRE are viewed as a bullish indicator, with a 6.6% increase in the consensus EPS estimate over the last 30 days [3] - APRE holds a Zacks Rank of 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks, which typically outperform the market [3] - The Zacks Rank serves as a timing indicator, suggesting that the company's prospects are improving, further supporting the case for a potential turnaround [3]

Financial Position - As of September 30, 2024, the company expects cash and cash equivalents to be approximately $26.2 million, down from approximately $28.7 million as of June 30, 2024, representing a decrease of about 8.7%[4] - The preliminary cash and cash equivalents figure is subject to completion and may vary from the actual financial position as of September 30, 2024[5] Management Changes - The company announced the engagement of Dr. Phillipe Pultar as Senior Medical Advisor, while Dr. Nadeem Mirza will step down as Chief Medical Officer effective October 9, 2024[6]

Clinical Programs - Aprea Therapeutics has two clinical programs: ATRN-119, an oral macrocyclic ATR inhibitor, and APR-1051, a next-generation oral WEE1 kinase inhibitor[72][73]. - ATRN-119 is currently in a Phase 1/2a clinical trial, with preliminary data indicating it is safe and well-tolerated, and potential efficacy data expected in the second half of 2025[72]. - APR-1051 has received FDA clearance for its IND application, with the first patient enrolled in the ACESOT-1051 trial, and preliminary results show it is safe with no hematologic toxicity[73]. - Aprea Therapeutics is focusing on synthetic lethality as a treatment strategy for various cancer types, aiming to establish a leadership position in this emerging field[71]. - The company is exploring combination therapy opportunities for its product candidates, supported by a Phase II SBIR grant from the National Cancer Institute[75]. Financial Performance - The company has not generated any revenue from product sales and does not expect to do so in the near future, relying primarily on grant revenue[78][79]. - Grant revenue for the three months ended September 30, 2024, was approximately $354,621, an increase of $35,153 compared to $319,468 for the same period in 2023[105]. - For the nine months ended September 30, 2024, grant revenue was approximately $1.3 million, an increase of $727,608 from $569,156 in the same period in 2023[110]. - Net loss for the three months ended September 30, 2024, was $3,783,769, compared to a net loss of $3,204,515 for the same period in 2023, reflecting an increase of $579,254[105]. - The accumulated deficit as of September 30, 2024, was $318.1 million, with net losses of $10.1 million for the nine months ended September 30, 2024[115]. Expenses - Research and development expenses are expected to increase as clinical trials for ATRN-119 and APR-1051 are initiated, reflecting the higher costs associated with later-stage clinical development[84]. - Research and development expenses for the three months ended September 30, 2024, were approximately $2.8 million, up $723,796 from $2.1 million in the same period in 2023[106]. - Total research and development expenses for the nine months ended September 30, 2024, were approximately $7.0 million, an increase of $1,422,649 from $5.6 million in the same period in 2023[111]. - General and administrative expenses are anticipated to rise due to increased headcount and activities related to potential commercialization of product candidates[89]. - General and administrative expenses for the three months ended September 30, 2024, were approximately $1.6 million, a decrease of $114,477 from $1.7 million in the same period in 2023[108]. - General and administrative expenses for the nine months ended September 30, 2024, were approximately $5.4 million, a decrease of $1,398,465 from $6.8 million in the same period in 2023[112]. Cash Flow and Financing - As of September 30, 2024, the company had cash and cash equivalents of $26.2 million, expected to fund operating expenses for at least the next twelve months[114]. - Net cash used in operating activities was $10.0 million for the nine months ended September 30, 2024, compared to $8.4 million for the same period in 2023, reflecting an increase of $1.6 million primarily due to changes in operating assets and liabilities[116]. - Cash used in investing activities was $15,478 for the nine months ended September 30, 2024, primarily for the purchase of property and equipment, with no cash used in investing activities for the same period in 2023[117]. - Net cash provided by financing activities was $14.7 million for the nine months ended September 30, 2024, from the sale of 1,687,712 shares of common stock and various warrants, after deducting approximately $1.3 million in expenses[118]. - The company raised approximately $4.9 million from the sale of 1,050,000 shares of common stock in February 2023, after deducting underwriting discounts and offering expenses[130]. - The company entered into a securities purchase agreement in March 2024, resulting in gross proceeds of approximately $16.0 million from the issuance of common stock and warrants[134]. Future Outlook - The company expects to continue incurring significant expenses and increasing operating losses for at least the next several years[115]. - The company anticipates increased expenses related to clinical trials, product development, and operating as a public company, necessitating additional financing[120]. - Future capital requirements will depend on various factors, including the scope and progress of clinical trials and potential commercialization activities[122]. - The company has no committed external sources of funds and may face challenges in raising additional capital on favorable terms[126]. Market and Economic Risks - The company does not currently have any significant direct foreign exchange risk and has not used derivative financial instruments to hedge such exposure[139]. - Inflation has not had a material effect on the company's business, financial condition, or results of operations during the nine months ended September 30, 2024[140]. - The primary exposure to market risk is interest income sensitivity, which is affected by changes in the general level of U.S. interest rates[136]. - Historical fluctuations in interest income have not been significant for the company[137]. - The company faces market risk from changes in foreign currency exchange rates affecting its non-U.S. dollar functional currency foreign subsidiaries[138]. - The financial position of subsidiary Aprea AB is measured using the local currency as the functional currency[138]. - Cash accounts holding U.S. dollars at Aprea AB are remeasured based on the exchange rate at the date of remeasurement[138].

Core Viewpoint - Aprea Therapeutics, Inc. is actively participating in the Maxim Healthcare Virtual Summit, showcasing its focus on precision oncology through synthetic lethality [1][4]. Group 1: Company Overview - Aprea Therapeutics is a clinical-stage biopharmaceutical company based in Doylestown, Pennsylvania, specializing in precision oncology [4]. - The company's lead program is ATRN-119, a small molecule ATR inhibitor aimed at treating solid tumors [4]. - Aprea has recently initiated clinical development for APR1051, an oral small-molecule WEE1 inhibitor [4]. Group 2: Event Participation - Dr. Oren Gilad, President and CEO of Aprea, will present at two sessions during the Maxim Healthcare Virtual Summit [1]. - The first session is a Precision and Immune Oncology Panel scheduled for October 16, 2024, from 2:00 to 3:00 PM ET [2]. - The second session is a Fireside Chat on October 17, 2024, from 3:30 to 4:00 PM ET [2].

Company Update - Aprea Therapeutics has engaged Dr Philippe Pultar as its senior medical advisor to support the development and advancement of APR-1051, a potential best-in-class WEE1 inhibitor [1] - Dr Pultar brings extensive experience in oncology, including the development of a WEE1 inhibitor (azenosertib) from early to late-stage clinical development [2] - Dr Pultar's prior role at Zentalis Pharmaceuticals involved strategy and execution of the global clinical development of azenosertib, a WEE1 inhibitor [2] Clinical Development - Patient enrollment is ongoing in the Phase 1 ACESOT-1051 study, which assesses the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of APR-1051 in advanced solid tumors with certain cancer-associated gene alterations [3] - Aprea plans to provide an update on the progress of the ACESOT-1051 clinical study by the end of 2024 [3] - The WEE1 program is part of Aprea's portfolio of DDR-targeted therapeutics aimed at delivering precision medicine solutions [3] Leadership and Expertise - Dr Pultar has over 17 years of experience in early and late-stage clinical development, including roles at Zentalis Pharmaceuticals, Novartis Oncology, Agennix AG, and ImClone Systems [5] - Dr Pultar initiated seven Phase 1 and Phase 2 trials with azenosertib as a single agent and in combination with chemotherapy and targeted agents across multiple indications [5] - Dr Pultar's foundational education includes Medical Studies and Residency at Université de Médecine de Poitiers, France [6] Strategic Vision - Dr Pultar believes WEE1 inhibition is a promising therapeutic approach in oncology and is impressed by the progress of APR-1051, which has a differentiated profile and compelling pre-clinical data [4] - Aprea's President and CEO, Dr Oren Gilad, highlights Dr Pultar's track record of successfully leading programs through late-stage development and regulatory approval [4] - Dr Pultar's addition aligns with Aprea's strategy to bring in exceptional talent to advance its programs and maximize the therapeutic potential of APR-1051 [4] Leadership Transition - Dr Nadeem Mirza will step down as Chief Medical Officer effective October 9, 2024, but will remain with the company until no later than December 13, 2024, to ensure a smooth transition [4]

Company Performance - Aprea Therapeutics reported a quarterly loss of $0.58 per share, better than the Zacks Consensus Estimate of a loss of $0.64, and an improvement from a loss of $0.87 per share a year ago, indicating a 33.33% year-over-year improvement [1] - The company achieved a revenue of $0.56 million for the quarter, surpassing the Zacks Consensus Estimate by 462%, compared to $0.25 million in the same quarter last year [1] - Over the last four quarters, Aprea Therapeutics has exceeded consensus EPS estimates three times and topped consensus revenue estimates two times [1] Market Outlook - Aprea Therapeutics shares have declined approximately 28.5% since the beginning of the year, contrasting with the S&P 500's gain of 12% [2] - The current consensus EPS estimate for the upcoming quarter is -$0.65 on revenues of $0.15 million, and for the current fiscal year, it is -$2.57 on revenues of $0.8 million [4] Industry Context - The Medical - Biomedical and Genetics industry, to which Aprea Therapeutics belongs, is currently ranked in the top 30% of over 250 Zacks industries, suggesting a favorable industry outlook [5] - Precigen, Inc., another company in the same industry, is expected to report a quarterly loss of $0.09 per share, reflecting a year-over-year change of -12.5%, with revenues anticipated to be $1.28 million, down 27.7% from the previous year [5][6]