Core Insights - Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, with a significant emphasis on developing new therapeutics targeting the DDR pathway for cancer treatment [1][3] Company Overview - Aprea's lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor aimed at solid tumor indications [3] - The company has completed all IND enabling studies for its oral, small molecule WEE1 inhibitor, APR-1051, and is targeting FDA clearance of its IND during Q1 2024 [3] Event Participation - Dr. Oren Gilad, President and CEO of Aprea, will present at the 7th DDR Inhibitors Summit from January 30 to February 1, 2024, in Boston, MA [1] - The presentation titled "Prioritizing Patient Selection for Combination Studies to Optimize Treatments" is scheduled for February 1, 2024, at 9 am ET [2] - Following the presentation, there will be a roundtable panel discussion on defining clinical success for current and next-generation DDR inhibitors [2]

Company Overview - Aprea Therapeutics is focused on precision oncology through synthetic lethality, with a pipeline enriched by integrated discovery technologies[73]. - The acquisition of Atrin Pharmaceuticals was completed on May 16, 2022, and is now fully integrated into Aprea's operations[74]. - Aprea has shifted focus from reactivating mutant p53 tumor suppressor proteins to developing molecules targeting DDR pathways through synthetic lethality[79]. Product Development - The company’s lead product candidate, ATRN-119, is currently in a Phase 1/2a clinical trial, with tolerability and pharmacokinetic data expected in Q1 2024[76]. - Aprea anticipates filing an IND for its WEE1 inhibitor, ATRN-1051, by the end of 2023[77]. - The company has no ongoing preclinical studies or clinical trials involving reactivators of mutant p53, focusing instead on synthetic lethality[79]. Financial Performance - The company has not generated any revenue from product sales and relies primarily on grant revenue from government organizations[86][87]. - Grant revenue for the three months ended September 30, 2023 was approximately $0.3 million, compared to $0 for the same period in 2022, representing a change of $319,468[113]. - Grant revenue for the nine months ended September 30, 2023 was approximately $0.6 million, compared to no grant revenue for the same period in 2022[122]. - Total operating expenses for the three months ended September 30, 2023 were approximately $3.8 million, compared to $4.2 million for the same period in 2022, a decrease of $357,876[113]. - Total operating expenses decreased to $12.4 million for the nine months ended September 30, 2023, down from $110.7 million in 2022, a reduction of $98.4 million[121]. - The net loss for the three months ended September 30, 2023 was $3.2 million, compared to a net loss of $4.0 million for the same period in 2022, an improvement of $820,203[113]. - Net loss for the nine months ended September 30, 2023 was $10.8 million, significantly improved from a net loss of $110.2 million in 2022, an improvement of $99.4 million[129]. Expenses - Research and development expenses are expected to increase as clinical trials for ATRN-119 and other candidates are initiated[91]. - Research and development expenses increased to approximately $2.1 million for the three months ended September 30, 2023, up from approximately $1.1 million in the same period of 2022, an increase of $1.0 million[115]. - The increase in research and development expenses was primarily due to a $1.2 million increase related to IND enabling studies for ATRN-1051, a small molecule WEE1 inhibitor[117]. - General and administrative expenses decreased to approximately $1.7 million for the three months ended September 30, 2023, down from approximately $3.1 million in the same period of 2022, a decrease of $1.4 million[116]. - General and administrative expenses decreased to approximately $6.8 million for the nine months ended September 30, 2023, down from $18.8 million in 2022, a reduction of $12.1 million[126]. - The company expects general and administrative expenses to increase in the future due to headcount growth and commercialization activities[95]. Cash Flow and Financing - Cash and cash equivalents as of September 30, 2023 were $25.4 million, expected to fund operations through the end of Q4 2024[135]. - Net cash used in operating activities was $8.4 million for the nine months ended September 30, 2023, compared to $21.0 million in 2022, a decrease of $12.6 million[130]. - Net cash provided by financing activities was $5.1 million for the nine months ended September 30, 2023, attributed to the sale of common stock[131]. - The company raised approximately $4.9 million from the sale of 1,050,000 shares of common stock at a public offering price of $5.25 per share in February 2023[146]. - During the nine months ended September 30, 2023, the company issued 26,302 shares under the ATM offering program, resulting in net proceeds of approximately $0.3 million[145]. - The company is subject to a limitation on raising funds through primary public offerings, restricted to one-third of the aggregate market value of common equity held by non-affiliates until the public float exceeds $75 million[145]. - The company expects to incur significant expenses related to ongoing development activities and may require additional financing to support operations[138]. Other Financial Information - The company has provided a valuation allowance for the full amount of net deferred tax assets, indicating uncertainty in realizing benefits from these items[99]. - The company does not currently have any off-balance sheet arrangements[148]. - The company does not believe that inflation has had a material effect on its business during the three months ended September 30, 2023[151]. - The company has not used derivative financial instruments to hedge foreign exchange risk, as it does not currently have significant direct foreign exchange exposure[150]. - The company does not believe that any recently issued accounting pronouncements will have a material impact on its financial statements[147]. - A reverse stock split at a ratio of one-for-20 was approved and became effective on February 10, 2023[85]. - As of September 30, 2023, the company’s cash equivalents consisted of bank deposits and money market accounts, with no significant historical fluctuations in interest income[149]. - Foreign currency loss for the three months ended September 30, 2023 was $2,880, compared to a foreign currency gain of $24,353 for the same period in 2022, a change of $27,233[120].

Precision Oncology through Synthetic Lethality Forward-Looking Statements Certain information contained in this presentation includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials, regulatory submissions and strategic plans. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-39069 Aprea Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 84-2246769 (State or other ...

Financial Performance - Aprea Therapeutics has not generated any revenue from product sales and does not expect to do so in the near future[84]. - The net loss for Q1 2023 was $4.4 million, an improvement from a net loss of $7.9 million in Q1 2022, representing a reduction of $3.6 million[115]. - General and administrative expenses for Q1 2023 were approximately $3.4 million, a decrease of $0.6 million compared to $4.0 million in Q1 2022[113]. - Research and development expenses for Q1 2023 were approximately $1.3 million, down from approximately $4.1 million in Q1 2022, reflecting a decrease of $2.8 million[109]. - The total operating expenses for Q1 2023 were $4.6 million, down from $8.1 million in Q1 2022, a decrease of $3.5 million[108]. - Net cash used in operating activities was $3.0 million for the three months ended March 31, 2023, a decrease of $2.5 million compared to $5.5 million for the same period in 2022[118]. - Net cash provided by financing activities was $5.1 million for the three months ended March 31, 2023, primarily from the sale of 1,050,000 shares of common stock[119]. - The accumulated deficit as of March 31, 2023, was $298.2 million, primarily due to research and development costs and general administrative expenses[115]. - As of March 31, 2023, the company had cash and cash equivalents of $31.0 million, expected to fund operations into Q3 2024[114]. - The company expects to require additional financing to support ongoing operations and product development[123]. - The company has no committed external source of funds and may face dilution if additional capital is raised through equity sales[126]. Clinical Development - The company is currently enrolling patients in a Phase 1/2a clinical trial for ATRN-119, with tolerability and pharmacokinetic data expected in Q1 2024[73]. - Aprea anticipates filing an IND for its lead WEE1 inhibitor product candidate, ATRN-1051, by the end of 2023[74]. - The company has shifted its focus to developing synthetic lethality-based cancer therapeutics following the acquisition of Atrin[77]. - Aprea's most advanced product candidate, ATRN-119, targets the ATR kinase involved in DNA damage response pathways[73]. - The company is exploring combination therapies with poly (ADP-ribose) polymerase inhibitors to enhance synthetic lethality[76]. - Aprea has no ongoing preclinical studies or clinical trials involving reactivators of mutant p53, focusing instead on DDR pathways[77]. - Research and development expenses are expected to increase as Aprea initiates clinical trials for ATRN-119 and other candidates[89]. - The company anticipates increased expenses related to clinical trials, product development, and commercialization efforts[120]. Acquisition and Stock Information - The acquisition of Atrin Pharmaceuticals was completed on May 16, 2022, with Aprea issuing 55,869 shares of common stock and 2,949,630 shares of Series A Non-Voting Convertible Preferred Stock[80]. - As of March 31, 2023, a total of 2,893,403 shares of Series A Non-Voting Convertible Preferred Stock were converted into 1,446,701 shares of common stock[81]. - Acquired in-process research and development expense from the Atrin Acquisition in May 2022 was recorded as an expense at the acquisition date, with no additional IPR&D expense expected in future periods[94]. - The company issued 26,302 shares under the ATM offering program, resulting in net proceeds of approximately $0.3 million during the three months ended March 31, 2023[130]. Other Financial Information - Interest income for Q1 2023 was $256,410, a significant increase from $1,971 in Q1 2022, reflecting a change of $254,439[108]. - The company incurred a foreign currency loss of $13,797 in Q1 2023, compared to a gain of $136,211 in Q1 2022, indicating a change of $150,008[113]. - The company expects to continue incurring increased expenses associated with being a public company, including compliance and regulatory costs[94]. - The company is exposed to interest rate risk, but historical fluctuations in interest income have not been significant[133]. - The company does not currently have any off-balance sheet arrangements[132]. - The company is not currently subject to any material legal proceedings[139].

Precision Oncology through Synthetic Lethality Forward-Looking Statements Certain information contained in this presentation includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials, regulatory submissions and strategic plans. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” ...

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].