Core Viewpoint - Aprea Therapeutics has initiated the ACESOT-1051 Phase 1 clinical trial for APR-1051, a selective oral WEE1 inhibitor, targeting advanced solid tumors with significant unmet medical needs [1][3]. Company Overview - Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company based in Doylestown, Pennsylvania, focusing on precision oncology through synthetic lethality [7]. Product Details - APR-1051 is a potent and selective small molecule designed to minimize off-target toxicity, potentially offering good safety and tolerability [2]. - The drug targets WEE1 kinase, an enzyme involved in the DNA damage response pathway, and aims to address limitations seen in other WEE1 inhibitors [2]. Clinical Trial Information - The ACESOT-1051 study is a biomarker-driven trial focusing on advanced/metastatic solid tumors with specific gene alterations, including CCNE1/CCNE2 amplification and mutations in FBXW7 or PPP2R1A [3]. - The trial consists of two parts: Part 1 involves dose escalation with up to 39 patients, while Part 2 focuses on dose optimization with an additional 40 patients [5][6]. - The primary objectives include measuring safety, dose-limiting toxicities, and determining the maximum tolerated dose, while secondary objectives assess pharmacokinetics and preliminary efficacy [6]. Milestones and Future Plans - The dosing of the first patient marks a significant milestone in the APR-1051 development program, with plans to provide a clinical update by the end of 2024 and preliminary efficacy data in 2025 [3][4].

Core Insights - ATRN-119 is the first and only macrocyclic ATR inhibitor in clinical trials, showing best-in-class potential [1] - The ongoing ABOYA-119 clinical trial is on track to complete dose escalation and potentially generate initial human efficacy data in the second half of 2024 [1][4] - Safety Review Committee has approved the commencement of dosing at 800 mg once daily for Cohort 6, following positive safety and pharmacokinetic data from Cohort 5 [2][3] Clinical Trial Progress - A total of 17 patients have been enrolled across the first five cohorts with doses ranging from 50 mg to 550 mg once daily [3] - Preliminary signs of clinical benefit have been observed, with two patients achieving stable disease at different dose levels [3] - The Phase 1 dose escalation is expected to be completed by the fourth quarter of 2024, with the recommended Phase 2 dose anticipated in the first quarter of 2025 [4] Drug Characteristics - ATRN-119 is designed for patients with mutations in DNA damage response (DDR) pathways, addressing a high unmet medical need in oncology [4] - The drug has demonstrated a differentiated selectivity and toxicity profile compared to other ATR inhibitors [2][4] - Pharmacokinetic data indicate that systemic exposure increases with each dose level, with therapeutic plasma concentrations observed at doses of 550 mg and above [2][5]

Financial Performance - Aprea Therapeutics reported cash and cash equivalents of $32.4 million as of March 31, 2024, up from $21.6 million at December 31, 2023[6]. - The company experienced an operating loss of $3.1 million for Q1 2024, an improvement from an operating loss of $4.6 million in the same period in 2023[6]. - Grant revenue for the three months ended March 31, 2024, was $380,569, compared to $0 in the same period last year[13]. - Total operating expenses decreased to $3.53 million in Q1 2024 from $4.62 million in Q1 2023, a reduction of about 23.5%[13]. - Net loss narrowed to $2.81 million for the three months ended March 31, 2024, compared to a net loss of $4.38 million in the same period last year, reflecting an improvement of approximately 35.9%[13]. - Net loss per share attributable to common stockholders improved to $(0.67) in Q1 2024 from $(1.34) in Q1 2023[13]. Research and Development - Research and Development (R&D) expenses increased to $1.6 million in Q1 2024, compared to $1.3 million in Q1 2023, primarily due to IND enabling studies for APR-1051[6]. - Aprea plans to initiate the Phase 1 ACESOT-1051 clinical trial for APR-1051 in June 2024, following FDA clearance of the IND[2][3]. - The ATRN-119 clinical trial (ABOYA-119) is on track to complete dose escalation by the end of 2024, with initial efficacy data expected in 2H 2024[2][4]. - As of March 12, 2024, 16 patients were enrolled in the dose escalation stage of the ABOYA-119 trial, with preliminary signs of clinical benefit observed in two patients[2]. - A lead candidate for a third synthetic lethality program is expected to be selected in Q3 2024, potentially providing new treatment options for cancer patients[4]. Administrative Expenses - General and Administrative (G&A) expenses decreased to $1.9 million in Q1 2024, down from $3.4 million in Q1 2023, mainly due to reduced personnel costs[6]. - General and administrative expenses decreased significantly to $1.93 million in Q1 2024 from $3.37 million in Q1 2023, a decline of approximately 42.5%[13]. Assets and Liabilities - Total assets increased to $33.20 million as of March 31, 2024, up from $22.65 million at December 31, 2023, representing a growth of approximately 46.5%[11]. - Total current liabilities decreased to $2.97 million as of March 31, 2024, down from $4.39 million at December 31, 2023, a reduction of about 32.2%[11]. - Cash and cash equivalents increased to $32.37 million as of March 31, 2024, compared to $21.61 million at December 31, 2023, representing a growth of approximately 49.9%[11]. Leadership Changes - Nadeem Q. Mirza, M.D., M.P.H. was appointed as Chief Medical Officer effective May 1, 2024, to lead the company's expanding clinical pipeline[5]. Shareholder Information - Weighted-average common shares outstanding increased to 4,198,326 in Q1 2024 from 3,260,484 in Q1 2023, reflecting an increase of approximately 28.7%[13].

Oncology Focus - Aprea Therapeutics is focused on precision oncology through synthetic lethality, with a pipeline enriched by novel targets in cancer treatment[65] - The company is exploring combination therapies with other agents, such as PARP inhibitors, to enhance synthetic lethality[71] - Aprea Therapeutics has no ongoing preclinical studies or clinical trials involving reactivators of mutant p53, focusing instead on DDR pathways[66] Clinical Trials - The lead product candidate, ATRN-119, is currently in a Phase 1/2a clinical trial, with readout expected in Q1 2025[68] - The first four dose cohorts of the ATRN-119 trial have been completed, with ongoing enrollment for additional cohorts[68] - The FDA cleared the IND application for APR-1051, with patient enrollment anticipated in Q2 2024 and safety/efficacy data expected in Q2 2025[69] Financial Performance - Grant revenue for Q1 2024 was approximately $0.4 million, a significant increase of $380,569 compared to no grant revenue in Q1 2023[95] - Total operating expenses decreased to $3.5 million in Q1 2024 from $4.6 million in Q1 2023, a reduction of $1.1 million[96] - Research and development expenses increased to approximately $1.6 million in Q1 2024 from $1.3 million in Q1 2023, an increase of $0.3 million[97] - General and administrative expenses decreased to approximately $1.9 million in Q1 2024 from $3.4 million in Q1 2023, a decrease of $1.4 million[98] - Net loss for Q1 2024 was $2.8 million, compared to a net loss of $4.4 million in Q1 2023, reflecting an improvement of $1.6 million[101] - Cash and cash equivalents as of March 31, 2024, were $32.4 million, expected to fund operations into Q3 2025[100] Funding and Capital - Net cash provided by financing activities was $14.7 million in Q1 2024, significantly higher than $5.1 million in Q1 2023[105][106] - A total of $350 million was registered for issuance under the 2020 Shelf Registration Statement, which expired on November 30, 2023[117] - In February 2023, the company raised approximately $4.9 million by issuing 1,050,000 shares at a public offering price of $5.25 per share[118] - A new shelf registration statement for $150 million was filed on January 26, 2024, including a prospectus for the sale of $1 million of common stock[119] - The company entered into an At the Market Offering Agreement allowing for the sale of up to $2 million of common stock, but no sales have been made under this agreement to date[120] - A private placement offering on March 11, 2024, resulted in gross proceeds of approximately $16 million from the sale of 1,687,712 shares at $7.29 per share[121] - The company has no committed external source of funds and may face dilution of ownership interests if additional capital is raised through equity or convertible debt securities[114] Expenses and Deficits - Research and development expenses are expected to increase as clinical trials for ATRN-119 and APR-1051 are initiated[77] - General and administrative expenses are projected to rise due to increased headcount and activities related to potential commercialization[81] - The company anticipates increased expenses related to ongoing and planned development activities, including clinical trials and product commercialization[107][109] - The accumulated deficit as of March 31, 2024, was $310.9 million, primarily due to research and development costs and general administrative expenses[101] Market Risks - Interest income sensitivity is the primary exposure to market risk, with no significant historical fluctuations noted[124] - Inflation has not materially affected the company's business or financial condition during the three months ended March 31, 2024[126] - Developing drug products is a lengthy and costly process, with no guarantee of obtaining marketing approval or generating revenue[113] Team and Expertise - Aprea Therapeutics has assembled a team with extensive experience in oncology drug development to support its mission[71]

DOYLESTOWN, Pa., May 02, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (NASDAQ:APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced the appointment of Nadeem Q. Mirza, M.D., M.P.H. as Chief Medical Officer (CMO) of the Company, effective May 1, 2024. Dr. Mirza has been an integral part of the Company's senior team as a consultant since February, 2023 and will now assume a more central role in leading the ...

Pre-clinical findings underscore the potential of APR-1051, a next-generation WEE1 kinase inhibitor, to be a well-tolerated and effective treatment for Cyclin E-overexpressing cancers IND for APR-1051 has been cleared; details on planned Phase 1 first in human trial (ACESOT-1051) presented ATRN-119, a novel macrocyclic ATR inhibitor, continues to appear safe and well tolerated with no Dose Limiting Toxicities observed in ongoing Phase 1/2a study; preliminary signs of clinical benefit reported; enrollment in ...

Financial Performance - Aprea Therapeutics reported cash and cash equivalents of $21.6 million as of December 31, 2023[8]. - The company experienced an operating loss of $3.7 million for Q4 2023, compared to an operating loss of $2.7 million in Q4 2022, reflecting a 37% increase in losses[8]. - For the full year 2023, Aprea reported an operating loss of $15.5 million, a substantial decrease from $113.4 million in 2022, primarily due to reduced R&D expenses[9]. - Net loss for the three months ended December 31, 2023, was $(3,443,254), compared to $(2,442,142) for the same period in 2022[14]. - Total operating expenses for the year ended December 31, 2023, were $113,392,228, an increase from $16,055,194 in 2022[14]. - Cash and cash equivalents decreased to $21,606,820 as of December 31, 2023, from $28,786,647 in 2022[15]. - Total current liabilities increased to $4,385,605 as of December 31, 2023, from $3,201,086 in 2022[15]. - Accumulated deficit rose to $(308,083,161) as of December 31, 2023, compared to $(293,796,405) in 2022[15]. - Total assets decreased to $22,650,174 as of December 31, 2023, from $30,155,827 in 2022[15]. Research and Development - Research and Development (R&D) expenses for Q4 2023 were $2.0 million, up from $0.5 million in Q4 2022, indicating a significant increase in clinical trial activities[8]. - The company’s R&D expenses for the year ended December 31, 2023, were $7.6 million, down from $16.4 million in 2022, reflecting the completion of previous clinical trials[9]. - Research and development expenses for the year ended December 31, 2023, totaled $16,402,273, up from $531,406 in 2022[14]. - Aprea plans to initiate the Phase 1 ACESOT-1051 clinical trial for APR-1051 in H1 2024 following FDA clearance of its IND[5]. - The ATRN-119 trial is on track to complete dose escalation by the end of 2024, with initial efficacy data expected in H2 2024[3]. Administrative Expenses - General and Administrative (G&A) expenses for Q4 2023 were $1.6 million, a decrease from $2.1 million in Q4 2022, due to lower personnel costs[8]. - General and administrative expenses for the year ended December 31, 2023, were $20,969,771, compared to $2,120,222 in 2022[14]. Financing and Cash Position - Aprea raised approximately $16 million in a private placement financing in March 2024 to support its clinical programs[1]. - The company anticipates that its current cash position, combined with the recent financing, will be sufficient to meet operating expenses into Q3 2025[9]. Revenue - Grant revenue for the three months ended December 31, 2023, was $14,075, compared to $0 for the same period in 2022[14]. - Interest income for the three months ended December 31, 2023, was $310,287, an increase from $243,082 in the same period of 2022[14].

Financial Performance - The company incurred significant net losses of $14.3 million, $112.7 million, and $37.1 million for the years ended December 31, 2023, 2022, and 2021, respectively, with an accumulated deficit of $308.1 million as of December 31, 2023[214]. - The company has not generated any commercial revenue to date and expects to continue incurring significant expenses and increasing operating losses for the foreseeable future[214]. - The company received approximately $16.0 million in gross proceeds from a private placement of common stock and warrants in March 2024, which is expected to fund operations into the third quarter of 2025[221]. Product Development and Clinical Trials - The lead product candidate, ATRN-119, is currently in clinical development, and it may take several years before any product candidates are ready for commercialization[214]. - The company is in the early stages of clinical trials for ATRN-119, and initial success may not predict future results in later studies[242][243]. - The company has not tested APR-1051 in clinical trials, and the results of preclinical studies may not be indicative of future clinical trial outcomes[242][243]. - The company may not be able to file INDs or commence additional clinical trials on expected timelines, and the FDA may not permit proceeding with trials[244]. - The company has filed INDs for ATRN-119 and APR-1051, but may face delays in filing INDs for other product candidates due to manufacturing or study delays[245]. - Delays in patient enrollment for clinical trials could significantly impact the timeline for obtaining necessary marketing approvals[248]. - The company may struggle to enroll a sufficient number of eligible patients, which is critical for timely clinical trial completion[250]. - Adverse events in clinical trials could lead to increased regulatory scrutiny and impact the perception of the company's product candidates[251]. - The outcome of preclinical studies and early clinical trials may not predict success in later trials, leading to potential setbacks[267]. - The company may need to conduct additional clinical trials if initial results are inconclusive, requiring substantial additional funds[265]. - Clinical drug development is lengthy and expensive, with uncertain outcomes that could lead to additional costs and delays[266]. - Clinical trials may face delays due to various factors, including regulatory authorization and patient recruitment challenges[268]. Regulatory and Compliance Risks - The company has never obtained marketing approval for any product candidate, and the approval process is expensive, time-consuming, and uncertain[211]. - Regulatory authorities retain broad discretion in evaluating clinical trial results, which may affect the approval process for product candidates[264]. - The FDA and comparable foreign regulatory authorities may refuse to accept or approve new drug applications (NDAs) or marketing authorization applications (MAAs), potentially delaying the approval process by several years[376]. - Any delay in obtaining marketing approvals could prevent the company from commercializing product candidates, generating revenues, and achieving profitability[377]. - The research, testing, and approval processes for drugs are subject to extensive regulation, and the company has limited experience in managing clinical trials necessary for obtaining marketing approvals[379]. - The FDA and EMA require compliance with Good Clinical Practice (GCP) standards, and failure to comply could result in unreliable clinical data and delays in marketing approvals[317]. - The company may encounter unfavorable pricing regulations and reimbursement policies that could harm its business[300]. - Delays in obtaining reimbursement for newly approved drugs could adversely affect the company's financial condition and operating results[303]. Funding and Financial Needs - Future capital requirements will depend on various factors, including the costs of clinical trials, regulatory reviews, and commercialization activities for ATRN-119 and other product candidates[222]. - The company may need substantial additional funding, which may not be available on acceptable terms, potentially delaying or reducing research and drug development programs[219]. - The company has incurred and expects to incur additional costs associated with operating as a public company, which may impact future funding needs[220]. - The company expects expenses to increase due to planned operations and will finance cash needs through equity offerings, debt financings, collaborations, and licensing arrangements[224]. Intellectual Property Risks - The company faces risks related to intellectual property protection, which could impact its ability to commercialize product candidates successfully[211]. - The patent portfolio for eprenetapopt consists of method-of-use and formulation claims, but lacks composition-of-matter patents, limiting protection against competitors[330]. - The company faces challenges in maintaining patent protection, as existing patents may be narrowed or invalidated through litigation or administrative proceedings[338]. - The company may need to obtain licenses from third parties if it loses patent rights, which could limit its ability to develop and commercialize product candidates[342]. - The company may become involved in expensive and time-consuming lawsuits to protect its patents, which could distract management and impact financial resources[355]. - The company faces risks of infringement claims from third parties, which could result in substantial damages and impact its ability to market its product candidates[360]. Market and Competitive Landscape - The pharmaceutical industry is highly competitive, with many companies having greater financial resources and expertise[283]. - The market acceptance of approved product candidates will depend on efficacy, safety, and competitive pricing[280]. - Existing cancer treatments may hinder the market penetration of new product candidates, even if approved[284]. - The company is developing ATRN-119 and APR-1051, both of which will face competition from other candidates in clinical development[285][287]. Operational Risks - The company lacks a sales and marketing infrastructure and has no experience in selling or marketing pharmaceutical drugs, which may hinder the commercialization of product candidates[291]. - Establishing a sales and marketing organization or outsourcing these functions could incur significant costs and delays in product launches[292]. - The company faces risks in recruiting and retaining effective sales and marketing personnel, which could impact commercialization efforts[292]. - IT system failures or cybersecurity issues could adversely affect the company's operations and business[288]. External Factors - The ongoing military conflict between Russia and Ukraine, along with geopolitical tensions, has created economic uncertainty that could adversely affect the company's business and financial condition[226][227]. - The company is monitoring inflation and global capital markets, assessing potential impacts on its operations due to geopolitical tensions and market disruptions[227]. - The company may face challenges in obtaining additional funding due to adverse developments in the financial services industry, which could impair its business operations[232][235]. - Ongoing clinical trials may face delays or disruptions due to epidemic or pandemic disease outbreaks, affecting the company's operations and financial condition[309].

Financing led by Sphera Healthcare with participation from new and existing healthcare-focused institutional investors $16.0 million in upfront gross proceeds with the potential to receive up to an additional $18.0 million in potential warrant exercise proceeds for an aggregate of up to $34.0 million in total gross proceeds DOYLESTOWN, Pa., March 11, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (NASDAQ:APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision on ...

Core Insights - Aprea Therapeutics has submitted an Investigational New Drug (IND) application to the FDA for APR-1051, an oral WEE1 kinase inhibitor aimed at precision oncology [1][2] - The company believes APR-1051 has unique characteristics that may differentiate it from other WEE1 inhibitors, including its molecular structure and selectivity [2] - If the IND is cleared, Aprea plans to initiate a Phase 1/2a clinical trial in the first half of 2024 to evaluate APR-1051's safety and efficacy [2] Company Overview - Aprea Therapeutics is a clinical-stage biopharmaceutical company based in Doylestown, Pennsylvania, focusing on precision oncology through synthetic lethality [3] - The company's lead program is ATRN-119, an ATR inhibitor for solid tumor indications, and it has completed all IND enabling studies for APR-1051 [3]