8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

November 7, 2024

Date of Report (Date of earliest event reported)

Aprea Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-39069	84-2246769
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

3805 Old Easton Road
Doylestown, PA
(Address of principal executive offices) 18902
(Zip Code)

Registrant’s telephone number, including area code: (617) 463-9385

(Former name or former address, if changed since last report): Not applicable

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common stock, par value $0.001 per share	APRE	The Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

Item 2.02Results of Operations and Financial Condition.

On November 7, 2024, Aprea Therapeutics, Inc. (the “Company”) issued a press release announcing its financial results for the three months ended September 30, 2024, and provided an update on the Company’s operations for the same period. The Company is furnishing a copy of the press release, which is attached hereto as Exhibit 99.1.

In accordance with General Instruction B.2 of Form 8-K, the information included in this Item 2.02, including Exhibit 99.1 hereto, shall not be deemed "filed" for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing made by the Company under the Exchange Act or Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such a filing.

Item 8.01Other Events.

On November 7, 2024, the Company updated its corporate presentation slide deck. A copy of the corporate presentation slide deck is filed as Exhibit 99.2 hereto and incorporated herein by reference.

Item 9.01Financial Statements and Exhibits.

(d) Exhibits.

Exhibit Number	Description
99.1	Press release issued by Aprea Therapeutics, Inc. dated November 7, 2024.
99.2	Corporate Presentation (November 2024).
104	Cover Page Interactive Data File (embedded within the inline XBRL document).

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	Aprea Therapeutics, Inc.
Dated: November 7, 2024	By:	/s/ Oren Gilad
	Name:	Oren Gilad, Ph.D.
	Title:	President and Chief Executive Officer

EX-99.1

Exhibit 99.1

Aprea Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update

Preliminary results from Phase 1 ACESOT-1051 trial of WEE1 inhibitor, APR-1051, demonstrate the product to be well-tolerated with no unexpected toxicities

Philippe Pultar, MD engaged as senior medical advisor to support the development and advancement of APR-1051

$26.2 million in cash and cash equivalents as of September 30, 2024 with cash runway for at least twelve months

DOYLESTOWN, PA, November 7, 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 reported financial results for the third quarter ended September 30, 2024, and provided a business update.

“We continue to make meaningful progress advancing our pipeline of two clinical stage therapeutic candidates as well as strengthening our clinical team,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “We are ahead of schedule with the enrollment of the Phase 1 ACESOT-1051 trial evaluating our next generation WEE1 inhibitor, APR-1051. Preliminary results at subtherapeutic doses demonstrate the product to be well-tolerated with no unexpected toxicities. APR-1051 has been designed to limit off target toxicity and, based on its unique characteristics, we believe it will be best-in-class. Active enrollment is also ongoing in the Phase 1/2a ABOYA-119 study evaluating ATRN-119, our first-in-class macrocyclic ATR inhibitor. To optimize dosing and scheduling we added a twice-daily dosing regimen.”

Key Business Updates and Potential Upcoming Key Milestones

ACESOT-1051: A Biomarkers Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051

● APR-1051 is a potent and selective small molecule that has been designed to potentially solve tolerability challenges of the class and may achieve greater clinical activity than other WEE1 programs currently in development. Aprea is advancing APR-1051 as monotherapy in cancers with Cyclin E over-expression, as well as other biomarkers that may predict sensitivity to WEE1 inhibition. Cancers over-expressing Cyclin E represent a high unmet medical need. Patients with Cyclin E over-expression have poor prognosis and, currently, have no effective therapies available.

● Enrollment is ongoing in the ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) Phase 1 clinical trial evaluating single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. The primary objectives of the Phase 1 study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and recommended Phase 2 dose (RP2D); secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamic parameters are exploratory objectives.

● In October 2024, preliminary findings from the ACESOT-1051 trial were reported in a poster at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, in Barcelona,

Spain. As of October 7, 2024, three patients were enrolled (sub-therapeutic doses of 10 mg, 20 mg and 30 mg) in the first three Cohorts with data available on two of these patients. Preliminary results to date have demonstrated that APR-1051 is well-tolerated with no unexpected toxicities. The poster can be viewed on Aprea’s corporate website here.

● Cohort 3 has been cleared ahead of schedule, with no safety concerns noted. Accelerated titration is complete and, in November 2024, the trial begun enrolling at Cohort 4 (50 mg) within the BOIN (Bayesian Optimal Interval) design.

● Preliminary efficacy data from ACESOT-1051 are expected in the first half of 2025. For more information, refer to ClinicalTrials.gov NCT06260514.

ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119

● ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed to be used in patients with mutations in DDR-related genes. Cancers with mutations in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have a poor prognosis and, currently, there are no effective therapies available for them.

● ATRN-119 is currently being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. The primary endpoint of this Phase 1 trial is the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous schedule.

● An update from ABOYA-119 was provided in a poster at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics on October 25, 2024. Patients are currently being enrolled at dose level 6 (800mg once daily) in the dose escalation part of the trial. As of October 2, 2024, 14 of 20 patients experienced adverse events (AEs) considered to be possibly/probably related to ATRN-119. No related SAE or grade 4-5 AEs have been observed. No signs of hematological toxicity have been registered and no DLTs have been observed to date. Preliminary signs of clinical benefit were observed in two patients treated at the 50 mg and 200 mg dose level. A copy of the poster can be viewed here.

● In order to optimize dosing and scheduling early in the development process, a protocol amendment has been submitted to add dose level 9 (1500 mg once daily) and twice-daily (400mg to 750mg) dosing. The addition of twice-daily dosing is supported by the pharmacodynamic properties of the drug and the favorite safety profile observed to date. The dose escalation for the once-daily and the twice-daily schedules will be studied independently. Under the current updated protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the second half of 2025.

● For more information, please refer to clinicaltrials.govNCT04905914. 

Corporate

● In October 2024, the Company engaged Philippe Pultar, MD as senior medical advisor to support the development and advancement of APR-1051. Dr. Pultar is a seasoned pharmaceutical executive with extensive experience in oncology. He was most recently employed at Zentalis Pharmaceuticals where he played a key role in the strategy and execution of the global clinical development of azenosertib, a WEE1 inhibitor.

Select Financial Results for the third quarter ended September 30, 2024

● As of September 30, 2024, the Company reported cash and cash equivalents of $26.2 million, compared to $21.6 million at December 31, 2023. The Company believes its cash and cash equivalents as of September 30, 2024, will be sufficient to fund the Company’s operating expenses and capital expenditure requirements through at least twelve months from the date of issuance of the condensed consolidated financial statements on Form 10-Q for the quarter ended September 30, 2024.

● For the quarter ended September 30, 2024, the Company reported an operating loss of $4.1 million, compared to an operating loss of $3.5 million in the comparable period in 2023.

● Grant revenue primarily from the National Cancer Institute of the National Institutes of Health (“NIH”) for the three months ended September 30, 2024 and 2023 was approximately $0.4 million and $0.3 million, respectively.

● Research and development expenses for the three months ended September 30, 2024 were approximately $2.8 million, compared to approximately $2.1 million for the three months ended September 30, 2023. The overall increase was primarily due to an increase in costs related to the ABOYA-119 clinical trial to evaluate ATRN-119 and personnel costs. These were offset in part by a decrease in costs related to IND enabling studies for ATRN-1051.

● General and administrative expenses for the three months ended September 30, 2024 were approximately $1.6 million, compared to approximately $1.7 million for the three months ended September 30, 2023. The decrease was primarily related to a decrease in insurance costs.

● The Company reported a net loss of $3.8 million ($0.64 per basic share) on approximately 5.9 million weighted-average common shares outstanding for the quarter ended September 30, 2024, compared to a net loss of $3.2 million ($0.86 per basic share) on approximately 3.7 million weighted average common shares outstanding for the comparable period in 2023.

About Aprea

Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small-molecule WEE1 inhibitor, is our second clinical program. For more information, please visit the company website at www.aprea.com.

The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

Forward-Looking StatementCertain information contained in this press release 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 study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current

and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law.

Investor Contact:

Mike Moyer

LifeSci Advisors

mmoyer@lifesciadvisors.com

Media Contact:

Ignacio Guerrero-Ros, Ph.D., or David SchullRusso Partners, LLCIgnacio.guerrero-ros@russopartnersllc.comDavid.schull@russopartnersllc.com(858) 717-2310

Aprea Therapeutics, Inc.
Consolidated Balance Sheets
	September 30,		December 31,
	2024		2023
Assets
Current assets:
Cash and cash equivalents	$	26,249,625	$	21,606,820
Prepaid expenses and other current assets		234,195		914,275
Total current assets		26,483,820		22,521,095
Property and equipment, net		86,950		88,362
Restricted cash		41,537		40,717
Other noncurrent assets		281,662		—
Total assets	$	26,893,969	$	22,650,174
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable	$	1,153,880	$	1,670,369
Accrued expenses		2,482,008		2,186,262
Deferred revenue		—		528,974
Total current liabilities		3,635,888		4,385,605
Total liabilities		3,635,888		4,385,605
Commitments and contingencies
Series A convertible preferred stock, $0.001 par value, 40,000,000 shares authorized; 56,227 shares issued and outstanding at September 30, 2024 and December 31, 2023, respectively.		1,311,063		1,311,063
Stockholders’ equity:
Common stock, $0.001 par value, 400,000,000 shares authorized, 5,434,903 and 3,736,673 shares issued and outstanding at September 30, 2024 and December 31, 2023, respectively.		5,435		3,736
Additional paid-in capital		350,693,403		335,644,204
Accumulated other comprehensive loss		(10,604,747)		(10,611,273)
Accumulated deficit		(318,147,073)		(308,083,161)
Total stockholders’ equity		21,947,018		16,953,506
Total liabilities and stockholders' equity	$	26,893,969	$	22,650,174

Aprea Therapeutics, Inc.
Consolidated Statements of Operations and Comprehensive Loss
	Three Months Ended September 30,				Nine Months Ended September 30,
	2024		2023		2024		2023
	(Unaudited)
Grant revenue	$	354,621	$	319,468	$	1,296,764	$	569,156
Operating expenses:
Research and development		2,846,399		2,122,603		7,004,451		5,581,802
General and administrative		1,605,238		1,719,715		5,385,923		6,784,388
Total operating expenses		4,451,637		3,842,318		12,390,374		12,366,190
Loss from operations		(4,097,016)		(3,522,850)		(11,093,610)		(11,797,034)
Other income (expense):
Interest income, net		348,741		321,215		1,014,518		913,846
Foreign currency (loss) gain		(35,494)		(2,880)		15,180		39,686
Total other income		313,247		318,335		1,029,698		953,532
Net loss	$	(3,783,769)	$	(3,204,515)	$	(10,063,912)	$	(10,843,502)
Other comprehensive loss:
Foreign currency translation		23,557		(1,002)		6,526		(12,466)
Total comprehensive loss		(3,760,212)		(3,205,517)		(10,057,386)		(10,855,968)
Net loss per share attributable to common stockholders, basic and diluted	$	(0.64)	$	(0.86)	$	(1.88)	$	(3.03)
Weighted-average common shares outstanding, basic and diluted		5,939,755		3,735,176		5,360,579		3,577,482

EX-99.2

Exhibit 99.2

Precision Oncology Through Synthetic Lethality November 2024

2 © 2024 Aprea Therapeutics, Inc. All Rights Reserved 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,” “plans,” “intends,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. The forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions our management team might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success and timing of our clinical trials or other studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Forward-looking statements regarding our product candidates are also subject to additional risks and uncertainties, including without limitation, with respect to: our dependence on additional financing to fund our operations and complete the development and commercialization of our product candidates, and the risks that raising such additional capital may restrict our operations or require us to relinquish rights to our technologies or product candidates; our limited history and preclinical status of the assets we acquired from Atrin Pharmaceuticals Inc.; our business plan or the likelihood of the successful implementation of such business plan; the timing of initiation of planned clinical trials for our product candidates; the future success of such trials; the successful implementation of our research and development programs and collaborations and the interpretation of the results and findings of such programs and collaborations and whether such results are sufficient to support the future success of our product candidates; the success, timing and cost of our anticipated clinical trials for our current product candidates; the timing of initiation, futility analyses, data presentation, reporting and publication and receipt of interim results (including, without limitation, any preclinical results or data); any statements about our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs and any collaboration studies; and other factors, including legislative, regulatory, political and economic developments not within our control. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this presentation. We undertake no obligation to update such forward-looking statements to reflect subsequent events or circumstances, except to the extent required by law or regulation.

3 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) All programs address significant unmet medical need, are synergistic with other anticancer therapies, and potentially differentiated in safety and tolerability ATR – Ataxia telangiectasia and Rad3‐related DDR – DNA Damage Response BID – twice daily Precision Oncology via Novel Synthetic Lethality Therapeutics • Lead optimization • Target identified from our RepliBiom discovery platform • Identify lead candidate by year-end 2024 WEE1 Inhibitor: APR-1051 ATR Inhibitor: ATRN-119 DDR Inhibitor: Undisclosed • First macrocyclic ATR inhibitor • Highly selective with continuous daily dosing • Pre-clinical proof-of-principle • Anti-tumor activity at nanomolar concentration • Preserved hematologic safety profile • Phase 1/2a – ongoing • Approaching therapeutic dose • No hematologic toxicity observed • BID regimen added • Readout H2 2025 • Best in class, next generation • Well clinically validated target • Pre-clinical proof-of-principle • Highly potent and selective anti-tumor activity • Minimal off-target effect • Ovarian cancer with Cyclin E over expression (OVCAR-3) • Favorable pharmacokinetics • Phase 1 study – enrolling 4th cohort • No hematologic toxicity observed • Safety/efficacy data expected H1 2025

4 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Robust DDR Development Pipeline Milestones 2024-2026 Anticipated Clinical Milestones 2024 2025 2026 H1 H2 H1 H2 H1 H2 ATR ATRN-119 WEE1 APR-1051 Complete Dose Escalation RP2D Enroll First Patient Additional Open-Label Efficacy Data ACESOT-1051 : Phase 1 – Monotherapy Dose Escalation Enrolled First Patient Complete Dose Escalation Open Label Data IND Cleared ABOYA-119: Phase 1/2a – Monotherapy Dose Expansion ABOYA-119: Phase 1/2a – Monotherapy Dose Escalation Open Label Data BOIN Design Cohort 4 Enrolling Initiate BID Regimen ACESOT-1051: Phase 1 – Dose Selection Optimization

5 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Synthetic Lethality • Cancer cell death only upon the loss of function of two codependent pathways • DNA Damage Response (DDR) allows cells to pause and self repair during replication (mitosis) overcoming affected pathway • Inhibition of DDR leads to mitotic catastrophe and cell death • ATR and WEE1 inhibitors are integral to stopping DDR and are emerging targets for cancer cell death • Builds on scientific innovation led by Aprea founder and key personnel1 1 Gilad et al, (2010) Cancer Res. Healthy cell Pathway A Pathway B Active cancer cell Pathway A Pathway B Dead cancer cell Pathway A Pathway B Active cancer cell Pathway A Pathway B

6 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Strong Drug Development and Commercial Expertise Leaders in Synthetic Lethality and Targeted Therapy Management Board of Directors Richard Peters, M.D., Ph.D. Chairman of the Board Oren Gilad, Ph.D. President and CEO Jean-Pierre Bizzari, M.D. Director Marc Duey Director Michael Grissinger Director Gabriela Gruia, M.D. Director John Henneman Director Rifat Pamukcu, M.D. Director Bernd R. Seizinger, M.D., Ph.D. Director Oren Gilad, Ph.D. President and CEO John P. Hamill Sr. Vice President and CFO Philippe Pultar, MD Head of WEE1 Clinical Development Ze’ev Weiss, CPA, B.Sc. Chief Business Advisor Mike Carleton, Ph.D. Translational Medicine Advisor Brian Wiley SVP, Corporate Strategy

7 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 Potentially Differentiated Clinical Stage WEE1i

8 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 – Clinically Validated Target: An Unmet Medical Need Examples for Phase 2 Studies with Adavosertib as monotherapy 1 AZD-1775. AstraZeneca announced in July 2022 the discontinuation of development of AZD-1775 due to its tolerability profile 2 Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma, Liu et al, J Clin Oncol. 2021;39:1531–9. 3 IGNITE: A phase II signal-seeking trial of Adavosertib targeting recurrent high-grade, serous ovarian cancer with cyclin E1 overexpression with and without gene amplification. Au-Yeung et al, Int J Gynecol Cancer 2023;33(Suppl 4):A1–A278 4 Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring CCNE1 Amplification, Fu et al, J Clin Oncol. 2023 Mar 20; 41(9): 1725–1734. Phase 2 Study Indication Evaluable Patients N ORR PFS NCT03668340 2 Recurrent uterine serous carcinoma 34 29.4% 1 CR 9 PR mPFS – 6.1 months PFS6 – 16 Pt (47.1%) IGNITE 3 Recurrent high-grade, serous ovarian cancer with CCNE1 overexpression with (Cohort 1) and without (Cohort 2) gene amplification 79 Cohort 1 - 21 Cohort 2 - 58 Cohort 1: 38% 7 PR 1 CA125 Cohort 2: 45% 3 CR 18 PR 5 CA125 No PD for ≥ 18 weeks: Cohort 1: 53% Cohort 2: 48% NCT03253679 4 Refractory solid tumors harboring CCNE1 amplification 30 Ovarian - 14, Breast - 3, Uterine - 3, Other - 10 All Pt: 27% (8 PR) Ovarian Pt: 36% (5 PR) mPFS: All Pt: 4.1 Ovarian Pt: 6.3 Multiple Phase 2 Studies Show Substantial Single-Agent Activity Of A WEE1 Inhibitor (Adavosertib1 ) WEE1 Inhibitors have been associated with significant Grade ≥3 hematological, GI and CV toxicities The Need – a highly efficient WEE1 inhibitor with an improved safety and tolerability profile

9 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Potentially Best in Class WEE1 Inhibitor Potent and Structurally Differentiated, with High Selectivity to Limit Off-target Toxicity AstraZeneca Adavosertib (AZD-1775) Zentalis Azenosertib (ZN-c3) Aprea APR-1051 Undisclosed

10 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Potentially Best-in-Class WEE1 Inhibitor Potent WEE1i that Does Not Substantially Inhibit PLK1, PLK2 or PLK3 -10 -9 -8 -7 -6 -5 -4 0 25 50 75 100 125 PLK1 IC50 Determination Log10 [conc] (M) % Activity ZN-c3 APR-1051 -10 -9 -8 -7 -6 -5 -4 0 25 50 75 100 125 PLK2 IC50 Determination Log10 [conc] (M) % Activity ZN-c3 APR-1051 -10 -9 -8 -7 -6 -5 -4 0 25 50 75 100 125 PLK3 IC50 Determination Log10 [conc] (M) % Activity ZN-c3 APR-1051 ZN-c3 = 92.1 nM APR-1051 = 15,900 nM PLK1 Inhibition IC50 >150-fold difference ZN-c3 = 32.0 nM APR-1051 = 1,800 nM PLK2 Inhibition IC50 >50-fold difference ZN-c3 = 52.2 nM APR-1051 = 31,600 nM PLK3 Inhibition IC50 >600-fold difference On-target WEE1 activity Off-target inhibition of PLK1, PLK2 and PLK3 ZN-c3 = 2.9 nM APR-1051 = 1.6 nM WEE1 Inhibition IC50 similar to ZN-c3 1 1 1 8 P 1 1 c3 WEE1 IC50 Determination % Activity Log10 [conc] (M) AACR-NCI-EORTC Meeting, Poster B323, 2024

11 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function 1 PLK1 protects against sepsis-induced intestinal barrier dysfunction, Cao et al, Scientific Reports (2018). 2 PLK1 protects intestinal barrier function in sepsis: A translational research, Cao et al, Cytokine (2023). 3 PLK1 protects intestinal barrier function in sepsis: A translational research, Cao et al, Molecular Medicine (2022). 4 LncRNA DANCR improves the dysfunction of the intestinal barrier and alleviates epithelial injury by targeting the miR‐1306‐5p/PLK1 axis in sepsis, Wang et al., Cell Biology International (2021).

12 © 2024 Aprea Therapeutics, Inc. All Rights Reserved PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors Minimal PLK1 Co-inhibition Enables Full Therapeutic Potential Of APR-1051 37 nM 111 nM 333 nM 1 µM 37 nM 111 nM 333 nM 1 µM Phos-H2AX Control (MCM3) NT Phos-CDK1 APR-1051 75 nM GSK-461364 0 nM NT 675 nM 25 nM 225 nM 75 nM Phos– H2AX Control (MCM3) Phos-CDK1 300 nM APR-1051 + increasing GSK-461364 Control (MCM3) 37 nM 111 nM 333 nM 1 µM 37 nM 111 nM 333 nM NT 1 µM Phos-H2AX 400 nM BI-2536 APR-1051 Phos-CDK1 Dose range of PLK inhibitor GSK-461364 in combination with a single dose of APR-1051 in OVCAR-3 cells PLK inhibitor, GSK-461364 interferes with the effects of APR-1051 in OVCAR-3 cells PLK inhibitor, BI-2536, interferes with the effects of APR-1051 in OVCAR-3 cells AACR-NCI-EORTC Meeting, Poster B323, 2024

13 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties Note: Head-to-head studies have not been conducted 1 Data from an exploratory formulation of APR-1051 administered to fasted Balb/c mice 2 Data from study in A-427 NSCLC xenograft model as reported in Zentalis Corporate Overview, March 2022 Based on Pre-clinical Studies, APR-1051 Shows Potentially Favorable Drug Exposure APR-10511 Zentalis Azenosertib (ZN-c3)2 AstraZeneca Adavosertib (AZD-1775)2 Dose (mg/kg/d) 10 20 40 80 20 40 80 Cmax ng/ml 1,460 1,167 1,997 5,100 635 2,460 4,703 Tmax hr 3 1 1 1 1 1 1 AUC0-24, ng*hr/ml 16,739 4,863 17,088 39,722 1,494 6,313 13,408 AACR-NCI-EORTC Meeting, Poster C147, 2023

14 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Shows Negligible Inhibition of hERG Channels In vitro kinase assays IC50 Average WEE1 kinase IC50 hERG inhibition IC50 Average hERG IC50 Fold difference between kinase IC50 and hERG IC50 LanthaScreen (Thermo) Hotspot (Reaction Biology) HEK293 cells (Medicilon) CHO cells (WuXi) hERG inhibition over WEE1 kinase inhibition 2.2 nM 41.4 nM 21.8 nM 8,840 nM 660 nM 4,750 nM 218-fold (range 16- to 3,946-fold) QT prolongation AEs were reported with some competitor WEE1 inhibitors No ECG changes related to APR-1051 were observed in IND enabling studies Potential absence of QT prolongation at doses that significantly inhibit WEE1 AACR-NCI-EORTC Meeting, Poster B323, 2024

15 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity Pre-clinical studies with APR-1051 Data on file N=7 mice per group, APR-1051, 30 mg/kg/day Preclinical Tumor Growth Inhibition OVCAR-3

16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Suppresses Tumor Growth with Little Effect on RBCs and Body Weight Tumor Volume (mm3 ) (Mean±SEM) Body Weight (g) (Mean±SEM) APR-1051 15mg/kg, PO, BID, 5 on/2 off x 28 days Vehicle 10mL/kg, PO, QD x 28 days OVCAR Xenograft Tumor Model in Female Nude Mice Heme Toxicity (Mean±SEM) 28 Days Post Treatment 0 5 10 15 20 25 30 0 200 400 600 800 1000 1200 1400 Days Post Treatment Tumor Volume (mm 3 ) 0 5 10 15 20 25 30 0 5 10 15 20 25 Days Post Treatment Body Weight (g) 0 5 10 15 RBC (1012/L) 0 200 400 600 800 Reticulocyte Count (10 9/L) AACR-NCI-EORTC Meeting, Poster B323, 2024

17 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-of-Concept

18 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ACESOT-1051: Clinical Study Overview Multi-center, Open-Label Phase1 Single-Agent Dose Escalation and Dose Selection Optimization 1 Colorectal cancer patients 2 Uterine serous carcinoma patients Patients aged 18 years or older with advanced solid tumor harboring cancer-associated gene alterations CCNE1 or CCNE2 FBXW7 or PPP2R1A, KRAS-GLY12 & TP531 USC2 regardless biomarker status Part 2 Dose selection optimization further evaluation of the selected 2 dose levels Up to 40 patients Part 1 Dose escalation accelerated titration followed by a BOIN design Up to 39 patients` Enrollment up to 79 patients Oral APR-1051 is administered once-daily for 28-day cycles Primary objectives: Safety, DLT, MTD/MAD, RP2D Secondary objectives: Pharmacokinetics, Antitumor activity (RECIST/PCWG3) Exploratory objectives: Pharmacodynamics RP2D Select two doses

19 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Part 2 Dose selection optimization Up to 40 patients Eligible patients ≥ 18 yo with advanced solid tumor harboring cancer-associated gene alterations ACESOT-1051: Study Design Part 1 Dose escalation up to 39 patients Select 2 dose levels RP2D Oral single-agent APR-1051 will be administered once-daily for 28-day cycles Selected dose 1 Selected dose 2 1:1 randomization Objectives Primary: Safety, DLT, MTD/MAD, RP2D Secondary: Pharmacokinetics, Antitumor activity (RECIST/PCWG3) Dose level 1 Exploratory: Pharmacodynamics 10 mg Dose level 2 20 mg Dose level 3 30 mg Dose level 4 50 mg Dose level 5 70 mg Dose level 6 90 mg Dose level 7 120 mg Dose level 8 150 mg = cleared Accelerated titration; 1-6 patients per dose level BOIN design; 3-12 patients per dose level R Currently enrolling

20 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ACESOT-1051: Summary of all-cause AEs Update - October 7, 2024 *One AE possibly related to APR-1051 AACR-NCI-EORTC Meeting, Poster B065, 2024

21 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Summary Potential best in class WEE1 inhibitor • High potency for WEE1 inhibition in vitro​ • Low off-target inhibition of the PLK family of kinases​ • Suppresses growth of CCNE1-amplified HGSOC xenografted tumors and relatively well-tolerated in mice​ ACESOT-1051: First-In-Human Study (NCT06260514) • Accelerated titration dose escalation completed, fourth cohort now enrolling • Safe and well tolerated to date with no hematologic toxicity observed • Biomarker-driven study in patients with advanced/metastatic solid tumors • Targeted gene alterations include CCNE1, CCNE2, FBXW7, PPP2R1A, or KRAS-G12 with TP53 • Open label data expected H1 2025 • MD Anderson Cancer Center lead study site, with up to 10 sites in U.S.

22 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 Potentially Differentiated Clinical Stage ATRi

23 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: First and Only Macrocyclic ATR Inhibitor1 Macrocycles: A Well-Evolved Approach for PIK-Related Kinase Inhibition (e.g., rapamycin and mTOR)2-4 1 Based on company knowledge 2 Brown, EJ et al, (1994) Nature 3 Brown, EJ et al, (1995) Nature 4 Brown, EJ and SL Schreiber, (1996) Cell Benefits of Unique Cyclic Skeleton Structure vs Competitors’ First-Generation Acyclic Structure • Increased selectivity • Improved tolerability Improved tolerability More efficacious dosing Macrocycles restrict number of conformations formed for increased selectivity Potential advantages for ATRN-119:

24 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Reported Challenges with Other ATR Inhibitors First Generation Compounds Share Similar Core, Backbone, Toxicity, and Intermittent Dosing Schedule Note: Head-to-head studies with ATRN-119 have not been conducted 1 Phase I study of ATR inhibitor, AZD6738, as monotherapy in advanced solid tumors (PATRIOT part A, B), Dillon et al, Ann. Oncol. 2019:30 (supplement 5), Pages v165-v166 2 Poster CT084: A Phase I dose-escalation study of ATR inhibitor monotherapy with AZD6738 in advanced solid tumors (PATRIOT Part A), AACR 2017 3 First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors, Yap et al, Cancer Discov. 2021;11:80-91 and 2019 ASCO Poster, De-Bono et al. 4 Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results, Yap et al. Nature Medicine 2023;29:1400-1411 Route of administration Oral Oral Oral MTD/RP2 dose schedule 160mg BID, 2-weeks-on, 2-weeks-off, or: Continuous dosing1 40mg BID, 3-days-on/4-days-off 160mg QD, 3-days-on/4-days-off Main Grade ≥3 hematological toxicities Patriot 1, Escalation Phase, 160mg, BID2 : Anemia (1/6, 17%) Patriot 2, Expansion Phase1 : Fatigue, anemia, nausea, and thrombocytopenia (not differentiated) (4/6, 67%) with continuous dosing (3/15, 20%) with 2-week-on, 2-week-off Anemia (2/2, 100%) Neutropenia (1/2, 50%) Anemia (25/95, 26%) Neutrophil count decreased (13/95, 14%) Platelet count decreased (7/95, 7%) AstraZeneca AZD67381,2 Bayer BAY18953443 Repare RP-35004 N N NH N N N N O N N N O S O HN CH3 N NH N N O N N HO O N NH

25 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Potential Best-in-Class Oral ATR Inhibitor Structurally Differentiated Core, Backbone and Toxicity Profile 1 ATRN-119, Phase 1/2a Clinical Study Protocol 2 Internal pre-clinical head-to-head tolerability study in male beagle dogs Route of administration Oral Dosing regimen Continuous daily dosing (RP2D TBD in Phase 1)1 Hematological toxicities in preclinical studies • Small magnitude and within normal range hematological changes in 28-day GLP tox dog study • Significantly less toxicity in head-to-head comparative tolerability study vs other clinical stage ATRI2 ATRN-1191 ATRN-119 potentially the preferred ATRi both as a single agent and in combination with standard-of-care therapies

26 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 Daily Dosing Supports Potential Continuous Tumor Suppression Intermittent Dosing May Lead to Tumor Resistance Tumor reduction and regrowth Continuous tumor reduction Drug “On” Drug “Off” Drug “On”

27 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-of-Concept

28 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Phase 1/2a - Study Overview A Phase 1/2a, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral ATRN-119 in Patients with Advanced Solid Tumors Objectives: Primary • Safety, MTD, RP2D • Pharmacokinetics Secondary • Antitumor activity (RECIST/PCWG3) Exploratory • Association between identified mutations and clinical outcomes Patient population: Male or female subjects 12 years of age or older with solid tumors harboring specific DDR mutations per NGS Sites: 5 US sites for dose escalation • University of Pennsylvania • Mary Crowley Cancer Research • University Hospitals Cleveland Medical Center • Yale Cancer Center • NEXT Oncology Patient enrollment: Up to 132 patients in total • Escalation phase: up to 72 patients • Expansion phase: up to 60 patients ATRN-119 is an oral ATR kinase inhibitor given daily Part 1 Up to 72 patients Dose escalation (9 dose levels) 3+3 design Part 2 Up to 60 patients Dose expansion, after MTD / RP2D established

29 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Clinical Study Design Dose level 1 50 mg Dose level 2 100 mg Dose level 3 200 mg Dose level 4 350 mg Dose level 5 550 mg Dose level 6 800 mg Dose level 7 1100 mg Dose level 8 1300 mg Dose level 9 1500 mg Once-daily dosing (up to 54 patients) Twice-daily dosing (up to 18 patients) Currently enrolling Part 1. Dose escalation (up to 72 patients) MTD/RP2D Single-agent ATRN-119 after MTD/RP2D is established Potential indications: colorectal, prostate, gastric, endometrial Dose level 6 400 mg Dose level 7 550 mg Dose level 8 650 mg Dose level 9 750 mg Cleared Part 2. Dose expansion (up to 60 patients)

30 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 Steady State Plasma Concentrations (Cycle 1 Day 7) ATRN-119 Exhibits Near-dose Proportional Exposure Following Oral Administration Dose Level mg, once daily N AUC 0-24hr (ng*h/mL) Cmax (ng/mL) Half-life (hours) Mean (SD) Mean (SD) Mean (SD) 50 3 180 (143) 57 (56) 2.1 (1.4) 100 3 1771 (920) 277 (151) 3.8 (1.6) 200 3 1024 (162) 149 (9.2) 3.2 (0.5) 350 3 5252 (4362) 525 (320) 5.9 (0.5) 550 3 6899 (6058) 797 (522) 5.5 (1.4) • Tmax is approximately 2 hours and the half-life is estimated between 4-6 hours • The duration of systemic exposure substantially increases with each dose level AACR-NCI-EORTC Meeting, Poster B336 , 2024

31 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Site Key 001 - University of Pennsylvania 002 - Mary Crowley Cancer Research 003 - University Hospitals Cleveland Medical Center 004 - Yale Cancer Center 30 56 112 55 22 46 57 55 224 57 53 22 0 50 100 150 200 250 001-001 002-002 003-003 003-004 002-005 002-006 003-007 002-008 003-009 003-010 003-011 004-012 003-013 004-014 003-015 003-016 004-017 001-018 003-019 003-020 800 mg 550 mg 350 mg 200 mg 100 mg 50 mg * * * * Dose increased to 350 mg * Consent withdrawn * 30 * ABOYA-119 Summary of Duration of Treatment Update – Oct 7, 2024 Study patient Days on treatment ATRN-119 once-daily dose * * NE 57 18 5 13 NE = Not Evaluable Not all data source verified Unrelated death * * * * * * * * 53 55 70 Stable disease * Progressive Disease AACR-NCI-EORTC Meeting, Poster B336, 2024

32 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Summary of Related Adverse Events Update – October 2, 2024 Not all data source verified Gastrointestinal General Metabolism Vascular No ATRN-119 Related SAE or Grade 4 Adverse Events Reported AACR-NCI-EORTC Meeting, Poster, B336 2024

33 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Summary First and only macrocyclic ATR inhibitor • Potentially differentiated from other ATR inhibitors in selectivity and toxicity profile, permitting continuous dosing • Strong tumor control observed in vivo, including in challenging genetic backgrounds • Daily oral dosing provides potential continuous tumor suppression ABOYA-119: Ongoing Phase 1/2a Clinical Study (NCT04905914) • Patients with advanced solid tumors harboring specific DDR mutations • Well tolerated with no hematologic, target organ or DLTs to date • Near-dose proportional exposure following oral administration • Preliminary signs of clinical benefit already observed at low doses • Potential efficacy data readout in H2 2025

34 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

35 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Strong Intellectual Property Portfolio Four issued US patents protecting lead molecule and analogs Family 1: Ataxia Telengiectasia and Rad3-Related (ATR) Protein Kinase Inhibitors • Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13th, 2015 • Patents granted in AU, BR, CA, CN, EP, IL, IN, JP, KR, MX, HK. • 1.1: Issued on May 30, 2017 as U.S. Patent 9,663,535 • 1.2: Issued on May 29, 2018 as U.S. Patent 9,981,989 • 1.3: Issued on Feb. 5, 2019 as U.S. Patent 10,196,405 Family 2: ATR Inhibitors and Methods of Use • Carboxylic acid-containing macrocyclic ATR inhibitors, and prodrugs; methods of using these inhibitors to treat various cancers; filed on Apr. 12th, 2017 • Issued on May 28th, 2019 as U.S. Patent 10,301,324 Family 3: ATR Inhibitor Pharmaceutical Composition and Methods • International application filed on Apr. 14th, 2023 • Pharmaceutical formulation and composition of our lead molecule in the clinic • Nationalizations pending for US, AU, BR, CA, CN, EA, EP, IL, IN, JP, KR, MX, NZ, PH, SG, ZA Family 4: WEE1 Inhibitor Pharmaceutical Compositions and Methods • International Application filed on Jun. 3rd, 2022 • Composition of our lead WEE1 inhibitor compounds • Nationalizations in US, AU, BR, CA, CN, EP, IL, IN, JP, KR, MX, ZA Family 5: Methods of Treating Cancer • U.S. Provisional Application filed on Sep. 19th, 2024 • Clinical methods of treating advanced solid cancer tumors using lead molecule

36 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization Securities Common Equivalents as of November 7, 2024 Preferred Stock (as converted) 28,112 Common Stock 5,434,903 Warrants: Pre-Funded Tranche A Tranche B Total 507,076 1,097,394 1,097,394 2,701,864 Options 743,806 Restricted Stock Units 36,442 Fully Diluted Equivalents 8,945,127 Cash & Equivalents of ~$26.2M as of September 30, 2024 Closed approximately $16.0M (before deducing placement agent fees and offering costs of approximately $1.3M) from our private placement of our common stock in March 2024 with the potential to receive up to an additional $18.0M upon cash exercise of accompanying warrants at the election of the investors.

37 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Financed into Q4 2025 • Achieve short term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • H1 2025 open label data APR-1051; Complete dose escalation H2 2025 • H1 2025 open label data ATRN-119; Complete dose escalation H2 2025 Diversified portfolio with best in class, de-risked clinical and preclinical programs • Highly potent and selective WEE1 (APR-1051) and ATR (ATRN-119) inhibitors • Opportunities in ovarian, colorectal, prostate, and breast cancers • Single agent and combination therapies Technology developed by pioneers in synthetic lethality • Management with strong drug development and commercial expertise Investment Highlights

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Document and Entity Information	Nov. 07, 2024
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Document Information	Nov. 07, 2024
Document Information:
Document Type	8-K
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CIK	0001781983
Registrant Name	Aprea Therapeutics, Inc.
Period End Date	Nov. 07, 2024