Financial Performance - The company incurred significant net losses of $112.7 million, $37.1 million, and $53.5 million for the years ended December 31, 2022, 2021, and 2020, respectively, with an accumulated deficit of $293.8 million as of December 31, 2022[192]. - The company anticipates continued significant expenses and increasing operating losses for the foreseeable future[192]. - The company believes existing cash and cash equivalents, along with net proceeds from a public offering in February 2023, will fund operations into the third quarter of 2024[199]. - The company may need substantial additional funding, which may not be available on acceptable terms, potentially delaying or reducing research and development programs[197]. Product Development and Clinical Trials - The lead product candidate, ATRN-119, is currently in clinical development, with expectations that it will take several years before any product candidates are ready for commercialization[192]. - The company has not completed any clinical trials to date, which limits the ability to assess its capability to develop and commercialize product candidates[222]. - Patient enrollment is a significant factor in the timing of clinical trials, and difficulties in enrollment may delay necessary marketing approvals[224]. - The company may face increased development costs and potential abandonment of clinical trials due to insufficient patient enrollment[226]. - The company is investing a majority of its efforts and financial resources in the research and development of ATRN-119, which is in clinical development[214]. - The company has filed an IND for ATRN-119 but may face delays in filing INDs for other product candidates, which could hinder clinical trials and commercialization efforts[220]. Regulatory and Compliance Risks - Regulatory authorities retain broad discretion in evaluating clinical trial results, which may affect the approval of product candidates[239]. - The company may face significant regulatory challenges if any product candidates receive marketing approval but later show undesirable side effects[252]. - The company must comply with extensive regulatory requirements post-approval, which could impair its ability to generate revenue[370]. - Non-compliance with ongoing regulatory requirements could lead to severe penalties, including suspension of regulatory approval[374]. - The FDA imposes stringent restrictions on off-label marketing, with potential consequences including investigations and allegations of healthcare fraud[379]. Intellectual Property Challenges - The company faces risks related to intellectual property, including the potential for patents to be challenged or found invalid[189]. - The company does not own any composition of matter patents for eprenetapopt, limiting its ability to prevent competitors from using the same compound[304]. - The patent portfolio for eprenetapopt consists of method-of-use and formulation claims, which may not effectively prevent off-label use by competitors[312]. - The company may struggle to acquire or in-license necessary third-party proprietary rights, which could hinder the development of its product candidates[322]. - The company may face challenges regarding the inventorship of its patents and other intellectual property, which could lead to litigation and potential loss of valuable rights[318]. Market and Competitive Landscape - The pharmaceutical and biotechnology industries are highly competitive, with many companies having greater financial resources and expertise[256]. - Market acceptance of the company's product candidates is uncertain, and they may not generate significant revenues if they do not achieve adequate acceptance[254]. - The company is developing ATRN-119, which targets ATR protein in the DNA damage response pathway, competing with other candidates in clinical development[259]. - If the FDA approves generic versions of the company's product candidates, sales could be adversely affected due to competition from lower-priced alternatives[267]. Operational and Economic Factors - The ongoing military conflict between Russia and Ukraine has led to significant volatility in global markets, impacting the company's operations and financial condition[205]. - The company is currently operating in a period of economic uncertainty, which could adversely affect its financial condition and results of operations[204]. - The company is monitoring inflation and geopolitical tensions, assessing their potential impacts on business operations and capital markets[206]. - The impact of COVID-19 on manufacturing facilities and supply lines remains a concern, potentially affecting the timely delivery of clinical supplies[298]. Funding and Financial Strategy - Future capital requirements will depend on various factors, including the scope and costs of clinical trials, regulatory review outcomes, and commercialization activities[200]. - The company expects expenses to increase due to planned operations and may finance cash needs through equity offerings, debt financings, collaborations, and licensing arrangements[202]. - The company may need to relinquish valuable rights to technology or product candidates if it raises additional funds through collaborations or licensing arrangements[203]. Sales and Marketing Challenges - The company currently lacks a sales or marketing infrastructure and has no experience in selling or marketing pharmaceutical drugs[264]. - Establishing a sales and marketing organization is expensive and time-consuming, which could delay the commercial launch of product candidates[265]. - The company may face significant delays in obtaining reimbursement for newly approved drugs, which could adversely impact operating results and financial condition[276].

Company Focus and Strategy - The company shifted its primary focus to the assets acquired from Atrin Pharmaceuticals, particularly the ATRN-119 and ATRN-W1051 programs, following the failure of its Phase 3 trial for APR-246[76] - The acquisition of Atrin was evaluated as a strategic option to create long-term value for stockholders[76] - Aprea acquired Atrin on May 16, 2022, with the transaction structured as a merger, resulting in Atrin becoming a wholly owned subsidiary[103] - The company utilizes integrated discovery technologies, including Repli-Biom, ATRIZE™, and SCET™, to enhance its drug development pipeline[82] - The focus on synthetic lethality in targeting DDR pathways represents an emerging strategy to treat various cancers lacking effective treatments[79] Clinical Development - ATRN-119 is currently undergoing a Phase 1 clinical trial for cancer patients with specific genetic mutations, with plans to open 1-2 additional sites[90] - ATRN-W1051, a selective WEE1 inhibitor, is in preclinical development, with IND-enabling studies anticipated to commence in Q4 2022[92] - Eprenetapopt (APR-246) has received Orphan Drug and Fast Track designations from the FDA for myelodysplastic syndromes and acute myeloid leukemia[93] - The company is planning new Phase 1 dose-optimization clinical trials for eprenetapopt in relapsed/refractory MDS/AML and Richter's transformed NHL[94] Financial Performance - Aprea reported net losses of $4.0 million and $110.2 million for the three and nine months ended September 30, 2022, respectively, compared to $9.5 million and $29.4 million for the same periods in 2021[106] - The accumulated deficit as of September 30, 2022, was $291.4 million, primarily due to research and development costs and general administrative expenses[106] - Total operating expenses for the nine months ended September 30, 2022, were $110.7 million, an increase of $81.1 million from $29.6 million in the same period of 2021[149] - The company incurred a net loss of $80.8 million for the nine months ended September 30, 2022, largely due to acquired IPR&D associated with the Atrin acquisition of $76.0 million[158] Cash and Funding - The company has received net proceeds of approximately $226.2 million from sales of preferred and common stock through September 30, 2022[102] - As of September 30, 2022, Aprea had cash and cash equivalents of $33.1 million, expected to fund operations through the end of 2023[111] - The company has no committed external source of funds and may face challenges in raising additional capital on acceptable terms[165] - Net cash provided by financing activities was $0.6 million for the nine months ended September 30, 2022, compared to $0.1 million for the same period in 2021[159] Expenses and Cost Management - General and administrative expenses for the nine months ended September 30, 2022, were $18.9 million, an increase of $8.7 million from $10.2 million in the same period of 2021[150] - Research and development expenses for Q3 2022 were $1.1 million, down from $6.0 million in Q3 2021, a decrease of $4.9 million[145] - General and administrative expenses for Q3 2022 were $3.1 million, compared to $3.4 million in Q3 2021, a decrease of $0.3 million[146] - Acquired in-process research and development expense from the Atrin acquisition was recorded as an expense at the acquisition date, with no additional IPR&D expense expected in future periods[125] Revenue Expectations - The company has not generated any revenue from product sales and does not expect to do so in the near future[117] - The company does not expect to generate revenue from product sales for several years, if at all, as it has not yet commercialized any product candidates[156] - The company anticipates significant increases in expenses related to ongoing and planned development activities, including clinical trials and establishing a sales and marketing infrastructure[162] Other Financial Metrics - Interest expense for Q3 2022 was $151,123, compared to a negligible amount in Q3 2021, reflecting a significant increase[142] - Foreign currency gain for Q3 2022 was $24,353, compared to a loss of $21,907 in Q3 2021, a change of $46,260[147] - Total other income for the nine months ended September 30, 2022, was $520,715, an increase of $275,160 from $245,555 in the same period of 2021[149] - For the nine months ended September 30, 2022, net cash used in operating activities was $21.0 million, a decrease of $6.5 million compared to $27.5 million for the same period in 2021[158]

Company Focus and Acquisitions - The company shifted its primary focus to the assets acquired from Atrin Pharmaceuticals, particularly the ATRN-119 and ATRN-W1051 programs, following the failure of its pivotal Phase 3 trial for APR-246[76]. - The acquisition of Atrin was evaluated as a strategic option to create long-term value for stockholders[76]. - Aprea acquired Atrin on May 16, 2022, with the transaction structured as a merger, resulting in Atrin becoming a wholly owned subsidiary[103]. - At the closing of the merger, Aprea issued 1,117,394 shares of common stock and 2,949,630 shares of Series A Preferred Stock, convertible into 10 shares of common stock[104]. Clinical Development - ATRN-119, an orally bioavailable small molecule inhibitor of ATR, has received FDA IND approval for a first-in-human clinical trial expected to begin in Q3 2022[90]. - ATRN-W1051, a selective WEE1 inhibitor, is currently in preclinical development with IND-enabling studies anticipated to commence in the second half of 2022[92]. - The company is planning to study ATRN-119 as both a monotherapy and in combination with standard care in Phase 1/2 clinical trials for solid tumor malignancies[90]. - The company has no ongoing clinical trials for eprenetapopt but has received clearance from the FDA to proceed with new Phase 1 dose-optimization trials in relapsed/refractory MDS/AML[93]. - Eprenetapopt (APR-246) has received Orphan Drug and Fast Track designations from the FDA for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)[93]. - The company believes that the selectivity and toxicology profiles of ATRN-119 may differentiate it from other ATR inhibitors currently in development[90]. Financial Performance - Aprea reported net losses of $98.3 million and $106.2 million for the three and six months ended June 30, 2022, respectively, with an accumulated deficit of $287.3 million as of the same date[105]. - The net loss for Q2 2022 was $(98.3) million, compared to a net loss of $(10.3) million in Q2 2021, reflecting an increase in losses of $(88.0) million[140]. - The net loss for the six months ended June 30, 2022 was $(106.2) million, compared to $(19.9) million in the same period of 2021, indicating an increase in losses of $(86.3) million[145]. - The company incurred a net loss of $86.3 million, primarily due to acquired IPR&D associated with the Atrin acquisition[154]. Expenses and Cash Flow - The company anticipates significant increases in expenses due to planned clinical trials, research and development of product candidates, and establishing a commercialization infrastructure[106]. - General and administrative expenses are expected to increase due to costs associated with the merger and expansion of operations[122]. - Research and development expenses for Q2 2022 were $6.8 million, a slight increase of $0.1 million from $6.7 million in Q2 2021[143]. - General and administrative expenses for Q2 2022 were $15.6 million, up $12.3 million from $3.3 million in Q2 2021, primarily due to a $12.2 million increase in non-cash stock-based compensation[143]. - Total operating expenses for Q2 2022 reached $98.5 million, a significant increase of $88.5 million compared to $10.0 million in Q2 2021[140]. - For the six months ended June 30, 2022, research and development expenses totaled $10.9 million, down $2.5 million from $13.4 million in the same period of 2021[146]. - General and administrative expenses for the six months ended June 30, 2022 were $19.6 million, an increase of $12.8 million from $6.8 million in the same period of 2021[146]. - Total operating expenses for the six months ended June 30, 2022 were $106.5 million, up $86.4 million from $20.2 million in the same period of 2021[145]. - As of June 30, 2022, Aprea had cash and cash equivalents of $39.1 million, projected to fund operations through the end of 2023[110]. - For the six months ended June 30, 2022, net cash used in operating activities was $14.4 million, a decrease of $4.9 million compared to $19.3 million for the same period in 2021[154]. - The company has raised a total of $225.6 million from the sale of preferred and common stock since inception[151]. Future Outlook and Financing - Aprea expects to require additional financing to support operations until significant revenue from product sales is generated[109]. - The company expects expenses to increase significantly as it initiates clinical trials and seeks marketing approvals for product candidates[157]. - The company has no committed external sources of funds and may face dilution if additional capital is raised through equity sales[162]. - The company has filed a universal shelf registration statement for the issuance of securities up to an aggregate of $350 million[165]. Miscellaneous - The COVID-19 pandemic has not materially affected Aprea's financial results for the three and six months ended June 30, 2022, but uncertainties remain regarding its future impact[112]. - The company remains classified as an emerging growth company (EGC) and a smaller reporting company, with market value held by non-affiliates below $700 million and annual revenue below $100 million[138]. - The company does not currently have any significant direct foreign exchange risk and has not used derivative financial instruments to hedge such risk[169]. - There have been no changes in internal control over financial reporting that materially affected the company's financial reporting[172].

Clinical Development - The company is focused on developing eprenetapopt, a small molecule p53 reactivator, for hematologic malignancies, including MDS and AML, with orphan drug and fast track designations from the FDA[65] - The Phase 3 trial of eprenetapopt with azacitidine for frontline treatment of TP53 mutant MDS enrolled 154 patients but failed to meet its primary endpoint of complete remission (CR) rate, achieving a 53% higher CR rate compared to the control arm without statistical significance[71] - In a Phase 2 trial for post-transplant maintenance therapy, eprenetapopt showed a 1-year relapse-free survival (RFS) rate of 58% and overall survival (OS) rate of 79% in 33 patients, significantly higher than historical data[72] - The Phase 1/2 AML trial reported a CR rate of 37% and a composite response rate of 53% in 30 evaluable patients, meeting the primary efficacy endpoint[73] - The FDA placed a partial clinical hold on trials of eprenetapopt in combination with azacitidine due to safety and efficacy concerns, affecting ongoing patient enrollment[66][68] - The company plans to share data with the FDA to resolve the partial clinical hold and continue its clinical trials[72][74] - The company is currently conducting multiple clinical trials for eprenetapopt, including a Phase 3 trial in the U.S. for TP53 mutant MDS with azacitidine[99] - The FDA has placed a partial clinical hold on the company's trials of eprenetapopt in combination with azacitidine, which the company intends to resolve[99] Financial Performance - As of September 30, 2021, the company had incurred net losses of $9.5 million and $29.4 million for the three and nine months ended September 30, 2021, respectively, with an accumulated deficit of $173.4 million[81] - The company has not generated any revenue from product sales and does not expect to do so in the near future[92] - The net loss for Q3 2021 was $9.5 million, an improvement of $2.9 million compared to a net loss of $12.3 million in Q3 2020[119] - For the nine months ended September 30, 2021, total operating expenses were $29.6 million, down from $38.6 million in the same period of 2020, a decrease of $8.9 million[125] - Research and development expenses for Q3 2021 were $6.0 million, down from $8.7 million in Q3 2020, a decrease of $2.7 million[119] - Research and development expenses for the nine months ended September 30, 2021, totaled $19.4 million, down from $28.5 million in 2020, a decrease of $9.1 million[125] - The company incurred a foreign currency loss of $21,907 in Q3 2021, significantly reduced from a loss of $74,565 in Q3 2020, an improvement of $52,658[124] - General and administrative expenses for Q3 2021 were $3.4 million, slightly down from $3.5 million in Q3 2020, a decrease of $0.1 million[123] Cash and Funding - The company had cash and cash equivalents of $61.4 million as of September 30, 2021, expected to fund operations into 2023[86] - The company has financed operations through approximately $224.0 million in net proceeds from preferred and common stock sales as of September 30, 2021[80] - Cash and cash equivalents as of September 30, 2021, were $61.4 million, following net proceeds of $224.0 million from stock sales since inception[131] - The company anticipates significant increases in expenses related to ongoing and future clinical trials, requiring additional financing to support operations[82] - Future capital requirements will depend on various factors, including the scope and costs of clinical trials and drug discovery for eprenetapopt and other candidates[140] - The company has filed a universal shelf registration statement for the issuance of securities up to an aggregate of $350.0 million, with an at-the-market offering program for up to $50.0 million of common stock[145] - The company does not currently have any committed external sources of funds and may face dilution of ownership interests if additional capital is raised through equity or convertible debt securities[142] Operational Risks - The company is closely monitoring the impact of the COVID-19 pandemic on its business operations, although it did not materially affect financial results for the three and nine months ended September 30, 2021[89] - The company has assessed its clinical supply chain and observed no disruptions to date, continuing to monitor the potential impact of the pandemic[88] - The company expects to incur increased expenses associated with being a public company, including costs related to compliance and investor relations[102] - The company is exposed to market risks related to interest rate changes, with cash equivalents primarily in bank deposits and money market accounts[148] - The company faces foreign currency exchange rate risks, particularly with its subsidiary Aprea AB, but does not currently have significant direct foreign exchange risk[149] - The company has not experienced any significant historical fluctuations in interest income[148] Corporate Governance - The company has not recorded any income tax expense or benefits due to uncertainty in realizing a benefit from net losses incurred[105] - There have been no changes in internal control over financial reporting that materially affected the company's controls[153] - The company is not currently subject to any material legal proceedings[154] - The company may remain classified as an emerging growth company (EGC) until the end of the fiscal year in which the fifth anniversary of its IPO occurs, unless certain revenue or market value thresholds are met[117]

Financial Performance - As of June 30, 2021, the company reported net losses of $10.3 million and $19.9 million for the three and six months ended June 30, 2021, respectively, with an accumulated deficit of $163.9 million[79]. - The net loss for Q2 2021 was $10.3 million, compared to a net loss of $16.4 million in Q2 2020, representing an improvement of 37.3%[116]. - Total operating expenses for the six months ended June 30, 2021 were $20.2 million, down from $26.4 million in the same period of 2020, a decrease of 23.4%[121]. - Research and development expenses for Q2 2021 were $6.7 million, down from $10.7 million in Q2 2020, a decrease of 37.8%[117]. - Research and development expenses for the six months ended June 30, 2021 totaled $13.4 million, down 32.2% from $19.8 million in the same period of 2020[122]. - General and administrative expenses for Q2 2021 were $3.4 million, a decrease of 10.8% from $3.8 million in Q2 2020[119]. - The company experienced a net cash used in operating activities of $19.3 million for the six months ended June 30, 2021, compared to $17.2 million in the same period of 2020, an increase of 12.3%[129]. - The company has not generated any revenue from product sales and does not expect to do so in the near future[87]. - Interest income has decreased as cash balances decline and interest rates fall[100]. - The company reported a foreign currency loss of $0.3 million in Q2 2021, significantly improved from a loss of $1.9 million in Q2 2020, a decrease of 84.2%[120]. Clinical Trials and Research - The company is focused on developing eprenetapopt, a small molecule p53 reactivator, for hematologic malignancies, with FDA designations including orphan drug and breakthrough therapy for MDS and AML[65]. - The pivotal Phase 3 trial of eprenetapopt with azacitidine for frontline treatment of TP53 mutant MDS completed enrollment of 154 patients but failed to meet its primary endpoint of complete remission rate[67][70]. - In a Phase 2 trial for post-transplant maintenance therapy, the 1-year relapse-free survival rate was 58% and overall survival rate was 79% in 33 patients[71]. - The Phase 1/2 AML trial showed a complete remission rate of 37% and a composite response rate of 53% in 30 evaluable patients[72]. - The company is currently conducting multiple clinical trials for eprenetapopt, including a Phase 3 trial in the U.S. for TP53 mutant MDS[95]. - A partial clinical hold has been placed by the FDA on the company's clinical trials of eprenetapopt in combination with azacitidine, which the company intends to resolve[95]. - The company plans to expand its clinical trials and continue research on additional product candidates, which will increase expenses significantly[80]. - Research and development expenses are expected to continue increasing as the company initiates additional clinical trials and develops new product candidates[90]. Financial Position and Funding - The company had cash and cash equivalents of $69.8 million as of June 30, 2021, expected to fund operations into 2023[83]. - Cash and cash equivalents as of June 30, 2021 were $69.8 million, following net proceeds of $223.9 million from stock sales since inception[127]. - The company has received approximately $223.9 million in net proceeds from sales of preferred and common stock through June 30, 2021[78]. - The company anticipates substantial increases in expenses related to ongoing development activities for eprenetapopt and other product candidates[136]. - Future capital requirements will depend on the scope and costs of clinical trials, drug discovery, and regulatory reviews[138]. - The company has filed a universal shelf registration statement for the issuance of securities up to an aggregate of $350.0 million, including an at-the-market offering program for $50.0 million of common stock[143]. - The company does not currently have any committed external sources of funds and may face dilution if additional capital is raised through equity sales[140]. - The company may need to relinquish valuable rights or grant licenses on unfavorable terms if additional funds are raised through collaborations or licensing arrangements[141]. Operational Risks and Challenges - The company is currently facing partial clinical holds on multiple trials and is working with the FDA to resolve these issues[66][67]. - The COVID-19 pandemic has not materially affected the company's financial results for the three and six months ended June 30, 2021, but uncertainties remain regarding its future impact[86]. - The company is classified as an emerging growth company and a smaller reporting company, allowing it to delay adopting certain accounting standards[112][114]. - The company tracks outsourced development costs by product candidate but does not allocate internal personnel costs to specific programs[89]. - The company recognizes research and development costs as incurred, with expenses related to clinical trials based on evaluations of progress[89]. - The company has incurred additional costs associated with operating as a public company, which are expected to increase as development activities expand[136]. - The company is exposed to interest rate risk, with cash equivalents primarily in bank deposits and money market accounts[146]. - The company faces foreign currency exchange rate risk related to its non-U.S. dollar functional currency foreign subsidiaries[147]. - The company has no off-balance sheet arrangements during the periods presented[145].

Revenue Generation - The company has not generated any revenue from product sales and does not expect to do so in the near future[87]. - The company does not expect to generate revenue from product sales for several years, if at all[120]. Clinical Trials and Product Development - The lead product candidate, eprenetapopt, is in clinical development for hematologic malignancies, with a pivotal Phase 3 trial involving 154 patients[67]. - In the Phase 3 trial, eprenetapopt with azacitidine showed a 53% higher complete remission (CR) rate compared to the control arm, although it did not reach statistical significance[67]. - The Phase 2 trial for post-transplant maintenance therapy showed a 62% rate of relapse-free survival (RFS) at 12 months, exceeding the benchmark of ~30%[68]. - The Phase 1/2 AML trial reported a 63% composite response rate and a 31% complete response rate among evaluable patients[72]. - The company is conducting multiple clinical trials for eprenetapopt, including a Phase 3 trial in the U.S. for TP53 mutant MDS[93]. - Eprenetapopt has received multiple designations from the FDA, including orphan drug and breakthrough therapy designations for MDS and AML[67]. - Future research and development expenses are expected to increase as the company initiates additional clinical trials and develops new product candidates[91]. Financial Performance - The company incurred net losses of $9.7 million for the three months ended March 31, 2021, and an accumulated deficit of $153.7 million[77]. - The net loss for Q1 2021 was $(9,668,755), compared to a net loss of $(9,400,257) in Q1 2020, an increase in loss of $268,498[114]. - Net cash used in operating activities was $11.5 million for Q1 2021, compared to $7.5 million in Q1 2020, an increase of $4.0 million[122]. Expenses - The company anticipates significant increases in expenses related to ongoing and future clinical trials, research, and commercialization efforts[79]. - Research and development expenses for Q1 2021 were $6,763,848, a decrease of $2,332,274 from $9,096,122 in Q1 2020[114]. - General and administrative expenses increased to $3,425,833 in Q1 2021 from $2,776,468 in Q1 2020, reflecting an increase of $649,365[114]. - Total operating expenses decreased to $10,189,681 in Q1 2021 from $11,872,590 in Q1 2020, a reduction of $1,682,909[114]. - The decrease in R&D expenses was primarily due to a $3.1 million reduction related to the Phase 3 clinical trial of eprenetapopt, which completed enrollment in Q2 2020[115]. - General and administrative expenses are anticipated to rise as the company increases headcount to support research and development activities[97]. Cash Position - As of March 31, 2021, the company had cash and cash equivalents of $77.6 million, expected to fund operations into 2023[81]. - As of March 31, 2021, the company's cash equivalents consisted of bank deposits and money market accounts, indicating a focus on liquidity management[135]. - The company has received net proceeds of $223.9 million from sales of preferred and common stock since inception[120]. Foreign Currency and Interest Rate Risks - The company is exposed to interest rate risk, with interest income sensitivity affected by changes in the general level of U.S. interest rates, although historical fluctuations have not been significant[135]. - The company faces foreign currency exchange rate risk related to its non-U.S. dollar functional currency foreign subsidiaries, impacting revenues, expenses, assets, and liabilities[136]. - The financial position of subsidiaries Aprea AB and Aprea Personal AB is measured using their local currency as the functional currency, with cash accounts holding U.S. dollars remeasured based on the exchange rate at the date of remeasurement[136]. - The company does not currently have any significant direct foreign exchange risk and has not used derivative financial instruments to hedge against such risk[136]. COVID-19 Impact - The company plans to continue monitoring the impact of the COVID-19 pandemic on its clinical trials and operations[86].

Financial Performance and Losses - The company has incurred significant losses since inception and expects to continue incurring losses for the foreseeable future, with no revenues generated to date[175]. - The company incurred significant net losses of $53.5 million, $28.1 million, and $15.5 million for the years ended December 31, 2020, 2019, and 2018, respectively, with an accumulated deficit of $144.0 million as of December 31, 2020[185]. - The company has not generated any revenue from drug sales to date and has financed operations primarily through private placements and IPO proceeds[185]. - The company expects to incur significant expenses and increasing operating losses for the foreseeable future, with future capital requirements dependent on various factors including clinical trial costs and regulatory reviews[189]. - The company expects substantial increases in expenses related to ongoing development activities for eprenetapopt and other product candidates[362]. Clinical Trials and Product Development - The pivotal Phase 3 MDS trial for the lead product candidate, eprenetapopt, failed to meet its predefined primary endpoint, which may materially harm the business[175]. - The pivotal Phase 3 trial for eprenetapopt failed to meet its predefined primary endpoint of complete remission (CR) rate[195]. - Clinical trials for eprenetapopt include patients with deteriorating health, with common adverse events reported such as nausea, vomiting, and fatigue[197]. - Serious adverse events in trials included febrile neutropenia, pneumonia, and sepsis, with some patient deaths reported possibly related to eprenetapopt[197]. - The company is conducting multiple clinical trials for its product candidates, including eprenetapopt and APR-548, with various phases currently enrolling patients[322]. Regulatory and Approval Challenges - The company has never obtained marketing approval for any product candidate, and the approval process is expensive, time-consuming, and uncertain[181]. - Regulatory authorities may require additional clinical trials or impose restrictions on approved products, affecting commercialization[199]. - The company faces challenges in obtaining marketing approval for p53 reactivators, as this has never been done before[195]. - The company may face significant delays in obtaining reimbursement for newly approved drugs, which could adversely affect its operating results[216]. - The company must comply with extensive regulatory requirements, including safety reporting, quality control, and advertising restrictions for approved drugs[267]. Competition and Market Risks - The company faces substantial competition, which may result in others commercializing products before it does[179]. - The company is dependent on the success of eprenetapopt, and difficulties in patient enrollment for clinical trials could delay necessary marketing approvals[175]. - The company operates in a highly competitive environment with major pharmaceutical and biotechnology companies, which may have greater resources and expertise[208]. - The success of product candidates will depend on market acceptance, efficacy, safety, and competitive pricing compared to existing treatments[206]. Intellectual Property and Patent Risks - The company may not be able to protect its intellectual property rights effectively, which could allow competitors to develop similar products[179]. - The company does not own or license any composition of matter patents for eprenetapopt, which is in the public domain[230]. - The current patent portfolio for eprenetapopt consists of method-of-use and formulation patent claims, which may not prevent competitors from using the same product candidate for other uses[232]. - The company may face challenges in maintaining valid and enforceable patents, which could adversely affect its business and financial condition[234]. - The company’s ability to stop unauthorized third parties from using its product candidates depends on valid and enforceable patents or trade secrets[230]. Funding and Financial Resources - The company may need substantial additional funding, which may not be available on acceptable terms, potentially delaying or eliminating research and development programs[175]. - Existing cash and cash equivalents as of December 31, 2020, are expected to fund operations into 2023, but changing circumstances may require seeking additional funds sooner[187]. - The company may need to transition from a research-focused entity to one capable of supporting commercial activities, which poses additional risks[187]. - If the company fails to raise additional capital when needed, it may have to delay or eliminate research and development programs or commercialization efforts[189]. Compliance and Legal Risks - The company must comply with Good Clinical Practice (GCP) regulations, and failure to do so could result in unreliable clinical data and delays in marketing approvals[222]. - The company is subject to ongoing changes in healthcare regulations that could impact the profitability of its products[273]. - The company faces substantial costs to ensure compliance with healthcare laws and regulations, and violations could lead to significant penalties, damages, and operational restructuring[283]. - The company is exposed to significant risks related to employee misconduct, which could lead to substantial fines or sanctions impacting business operations[285]. Market and Economic Conditions - The company expects that healthcare reform measures may lead to more rigorous coverage criteria and downward pressure on drug prices[275]. - Legislative changes may result in aggregate reductions in Medicare payments to providers of up to 2% per fiscal year through 2030[274]. - The company anticipates that pricing negotiations with governmental authorities outside the United States may delay revenue generation after marketing approval[275]. - The company may face significant costs and management diversion due to potential securities class action litigation following stock price declines, which is common in the pharmaceutical sector[309]. Employee and Operational Growth - The company anticipates significant growth in employee numbers and operational scope, particularly in drug development and clinical operations[294]. - The company may face challenges in managing growth due to limited financial resources and management experience[294]. - The company does not maintain "key person" insurance for its executives, which could impede its objectives if key personnel leave[294]. - General and administrative expenses are anticipated to rise as the company increases its headcount to support research and development activities[333].