8-K

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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

March 16, 2026

Date of Report (Date of earliest event reported)

Aprea Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

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Delaware	001-39069	84-2246769
(State or other jurisdiction <br>of incorporation)	(Commission <br>File Number)	(IRS Employer <br>Identification No.)
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3805 Old Easton Road<br>Doylestown , PA<br>(Address of principal executive offices)	18902 <br>(Zip Code)

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Registrant’s telephone number, including area code: (215) 948-4119

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

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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:

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☐	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))

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

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

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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. ☐

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Item 2.02Results of Operations and Financial Condition.

On March 16, 2026, Aprea Therapeutics, Inc. (the “Company”) issued a press release announcing its financial results for the three and twelve months ended December 31, 2025, 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.

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Item 8.01Other Events.

On March 16, 2026, 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.

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Item 9.01Financial Statements and Exhibits.

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(d) Exhibits.

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Exhibit <br>Number	​ ​ ​	Description
99.1	​	Press release issued by Aprea Therapeutics, Inc. dated March 16, 2026.
99.2	​	Corporate Presentation (March 2026).
104	​	Cover Page Interactive Data File (embedded within the inline XBRL document).

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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.

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​	Aprea Therapeutics, Inc.
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Dated: March 16, 2026	By:	/s/ Oren Gilad
​	Name:	Oren Gilad, Ph.D.
​	Title:	President and Chief Executive Officer

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Exhibit 99.1

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Aprea Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides a Corporate Update

●	Early clinical proof-of-concept for WEE1 inhibitor APR-1051 in the ongoing ACESOT-1051 trial with two partial responders at first scan in endometrial cancer patients with PPP2R1A mutation
●	Clinical team strengthened with the appointment of Eugene (Gene) Kennedy, MD, as Chief Medical Advisor to support next phase of clinical development
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●	Capital is in place to support key milestones, including additional enrollment of patients at key dose levels in ongoing ACESOT-1051 trial
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DOYLESTOWN, PA, March 16, 2026 (GLOBE NEWSWIRE) – Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage precision medicine oncology company focused on the discovery and development of targeted therapies for patients with biomarker-defined cancers, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided a business update.

“We enter 2026 with strong momentum following a year of meaningful execution across our portfolio,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “We are particularly encouraged by the most recent data from the ongoing ACESOT trial evaluating APR-1051, including two patients achieving unconfirmed partial responses at first scan. These results provide early proof of clinical concept for APR-1051 and strengthen our conviction in the product’s ability to deliver a favorable therapeutic window, supporting its potential to be a differentiated WEE1 kinase inhibitor for patients with genomically defined solid tumors who have limited treatment options. We strengthened our balance sheet with successful private placements in late 2025 and early 2026, enhancing our financial flexibility and positioning the Company to execute on key development milestones. Taken together, we believe the recent progress underscores the opportunity within our DDR portfolio and reinforces our goal of developing targeted cancer therapies that have the potential to improve outcome and quality of life for patients, while also creating value for our shareholders.”

Key Business Updates and Potential Upcoming Key Milestones

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

●	APR-1051 is a potent and selective, oral small molecule WEE1 inhibitor designed to potentially address therapeutic window limitations observed with earlier WEE1 programs. APR-1051 is being evaluated as a monotherapy in biomarker-defined cancers likely to respond to WEE1 inhibition. Among these, mutated PPP2R1A, FBXW7, HPV+ related and Cyclin E over expressing tumors represent a patient population with significant unmet medical need. These patient populations have a poor prognosis and limited effective treatment options.
●	On January 29, 2026, we announced the first unconfirmed partial response (uPR) observed in a patient enrolled in the ongoing Phase 1 ACESOT-1051 dose-escalation study: a patient with PPP2R1A-mutated uterine serous carcinoma, a form of endometrial cancer, treated at the 150 mg dose level of APR-1051. At the protocol-defined 8-week first imaging assessment, the patient achieved a 50% reduction in target lesion size per RECIST v1.1 criteria, along with a marked reduction in cancer antigen 125 (CA-125) levels, from 732 to 70 U/mL. CA-125 is a well-recognized
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tumor marker in endometrial cancer. On February 18, 2026, we announced the second uPR observed in a patient with PPP2R1A-mutated endometrial cancer, treated at the 220 mg dose level: at the first imaging assessment the patient achieved a 50% reduction in target lesion size, along with a marked decline in CA-125 from 362 at baseline to 47 U/mL, further supporting the anti-tumor activity of APR-1051.
●	Five other patients in ACESOT-1051 have achieved stable disease, including patients with HPV+ head and neck squamous cell carcinoma (HNSCC), colorectal and endometrial cancers with relevant genomic alternations.
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●	APR-1051 has been safe and well tolerated with top two adverse events reported as Grade 1 or 2 were primary consistent of nausea and fatigue.
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●	Dose escalation is ongoing, with patients currently being treated at Dose Level 8 (220 mg once daily) as the study continues to evaluate doses intendent to optimize therapeutic benefit while maintaining an acceptable safety profile. The company also plans to enroll additional patients to enrich for endometrial, colorectal and HPV+ tumors. A further update from ACESOT-1051 is expected in the second quarter of 2026.
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●	For more information on ACESOT-1051, refer to ClinicalTrials.gov NCT06260514.
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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 and developed to be used in patients with tumors harboring mutations in DDR-related genes. Cancers with mutations in DDR-related genes represent a high unmet medical need. These patients often have a poor prognosis and currently lack effective therapeutics options.
●	During 4Q 2025 Aprea determined the recommended Phase 2 dose (RP2D) to be 1,100 mg for the once daily dosing for ATRN-119.
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●	Following RP2D determination, Aprea has strategically paused further enrollment and has started an orderly wind-down of certain clinical trial site activities associated with the monotherapy arms as the Company explores ATRN-119 in potential combination approaches that may unlock greater clinical benefit. The Company is currently in discussions with leading academic institutions to evaluate ATRN-119 in combination with radiation in HPV+ head and neck cancer. Additional investigator-led studies evaluating ATRN-119 with immuno-oncology therapies and antibody-drug conjugates are also being explored.
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●	For more information on ABOYA-119, please refer to clinicaltrials.gov NCT04905914.
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Corporate

●	Aprea completed two private placements in December 2025 and January 2026, raising gross proceeds of approximately $3.1 million and $5.6 million, respectively, before deducting the placement agent’s fees and other estimated offering expenses.
●	In February 2026, the company appointed Eugene (Gene) Kennedy, MD, as Chief Medical Advisor. Dr. Kennedy is a highly accomplished physician scientist and biopharmaceutical executive with more than 20 years of experience spanning oncology clinical development, regulatory strategy, and senior corporate leadership across both public and private biotechnology companies.
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Select Financial Results for the Fourth Quarter Ended December 31, 2025

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●	As of December 31, 2025, Aprea reported cash and cash equivalents of $14.6 million compared to $22.8 million as of December 31, 2024. The Company believes its cash and cash equivalents as of December 31, 2025, together with the proceeds from the private placement completed in January 2026 will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the first quarter of 2027.
●	For the fourth quarter ended December 31, 2025, the Company reported an operating loss of $2.6 million, compared to an operating loss of $3.2 million in the fourth quarter of 2024.
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●	Research and Development (R&D) expenses were $1.0 million for the quarter ended December 31, 2025, compared to $2.4 million for the fourth quarter of 2024. The decrease in R&D expenses was primarily related to lower expenses related to the ACESOT-1051 clinical trial to evaluate APR-1051 and the ABOYA-119 clinical trial to evaluate ATRN-119, which was voluntarily paused in October 2025, as well as a decrease in personnel costs primarily related to new hires and severance incurred during the fourth quarter of 2024.
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●	General and Administrative (G&A) expenses were $1.6 million for the quarter ended December 31, 2025, compared to $1.1 million for the fourth quarter of 2024. The increase in G&A expenses was primarily related to personnel costs related to incentive compensation for our executive employees.
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●	The Company reported a net loss of $2.5 million ($0.32 per basic share) on approximately 7.7 million weighted average common shares outstanding for the quarter ended December 31, 2025, compared to a net loss of $2.9 million ($0.49 per basic share) on approximately 6.0 million weighted average common shares outstanding for the comparable period in 2024.
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Select Financial Results for the Year ended December 31, 2025

●	For the year ended December 31, 2025, the Company reported an operating loss of $13.2 million, compared to an operating loss of $14.3 million for the year ended December 31, 2024.
●	Grant revenues were $0.3 million for the year ended December 31, 2025, compared to $1.5 million for the year ended December 31, 2024.
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●	R&D expenses were $7.0 million for the year ended December 31, 2025, compared to $9.4 million for the year ended December 31, 2024. The decrease in R&D expense was primarily related to lower expenses related to the ACESOT-1051 clinical trial to evaluate APR-1051 and the ABOYA-119 clinical trial to evaluate ATRN-119, which was voluntarily paused in October 2025, as well as a decrease in consulting expenses and personnel costs primarily related to new hires and severance incurred during the fourth quarter of 2024.
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●	G&A expenses were $6.5 million for the year ended December 31, 2025, compared to $6.5 million for the year ended December 31, 2024.
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●	The Company reported a net loss of $12.6 million ($1.93 per basic share) on approximately 6.5 million weighted-average common shares outstanding for the year ended December 31, 2025, compared to a net loss of $13.0 million ($2.35 per basic share) on approximately 5.5 million weighted average common shares outstanding for the comparable period in 2024.
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About Aprea

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Aprea is a clinical-stage precision medicine oncology company focused on the discovery and development of targeted therapies for patients with biomarker-defined cancers. The Company is pioneering a new approach to treat cancer by exploiting vulnerabilities associated with cancer cell mutations. This approach was developed to kill tumors while minimizing the effect on normal, healthy cells. Aprea’s technology has potential applications across multiple cancer types, enabling it to target a range of tumors, including ovarian, endometrial, colorectal and head and neck squamous cell carcinoma. The company’s lead programs are APR-1051, an oral, small-molecule inhibitor of WEE1 kinase, and ATRN-119, a small molecule ATR inhibitor, both in clinical development for solid tumor indications. For more information, please visit the company website at www.aprea.com.

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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.

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Forward-Looking Statement

Certain 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 our ability to predict clinical outcomes based on such preclinical and early clinical results, our ability to continue as a going concern, 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.

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Investor Contact:

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Mike Moyer

LifeSci Advisors

mmoyer@lifesciadvisors.com

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Aprea Therapeutics, Inc.
Consolidated Balance Sheets
	December 31,			December 31,
	2025		​ ​ ​	2024
Assets	****
Current assets:
Cash and cash equivalents	$	14,599,347		$	22,849,885
Prepaid expenses and other current assets		961,899			726,254
Total current assets		15,561,246			23,576,139
Property and equipment, net		59,807			81,522
Restricted cash		41,186			40,170
Other noncurrent assets		271,162			281,662
Total assets	$	15,933,401		$	23,979,493
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable	$	713,668		$	1,352,240
Accrued expenses		2,050,690			2,008,735
Total current liabilities		2,764,358			3,360,975
Commitments and contingencies
Series A convertible preferred stock, 0.001 par value, 40,000,000 shares authorized; 31,194 and 56,227 shares issued and outstanding at December 31, 2025 and December 31, 2024, respectively		727,361			1,311,063
Stockholders’ equity:
Common stock, 0.001 par value, 400,000,000 shares authorized, 8,192,538 and 5,481,055 shares issued and outstanding at December 31, 2025 and December 31, 2024, respectively		8,192			5,481
Additional paid-in capital		356,709,645			350,971,225
Accumulated other comprehensive loss		(10,634,714)			(10,627,379)
Accumulated deficit		(333,641,441)			(321,041,872)
Total stockholders’ equity		12,441,682			19,307,455
Total liabilities and stockholders' equity	$	15,933,401		$	23,979,493

All values are in US Dollars.

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Aprea Therapeutics, Inc.
Consolidated Statements of Operations and Comprehensive Loss
		Three Months Ended December 31,						Year Ended December 31,
	​ ​ ​	2025		​ ​ ​	2024		​ ​ ​	2025		​ ​ ​	2024
		(unaudited)
Grant revenue		$	3,337		$	205,817		$	285,759		$	1,502,581
Operating expenses:
Research and development			1,008,839			2,359,086			7,043,035			9,363,537
General and administrative			1,637,591			1,072,776			6,476,560			6,458,699
Total operating expenses			2,646,430			3,431,862			13,519,595			15,822,236
Loss from operations			(2,643,093)			(3,226,045)			(13,233,836)			(14,319,655)
Other income (expense):
Interest income, net			118,664			274,626			652,086			1,289,144
Other income			77,500			—			77,500			—
Foreign currency (loss) gain			(8,701)			56,620			(95,319)			71,800
Total other income			187,463			331,246			634,267			1,360,944
Net loss		$	(2,455,630)		$	(2,894,799)		$	(12,599,569)		$	(12,958,711)
Other comprehensive (loss) income:
Foreign currency translation			(5,180)			(22,632)			(7,335)			(16,106)
Total comprehensive loss		$	(2,460,810)		$	(2,917,431)		$	(12,606,904)		$	(12,974,817)
Net loss per share attributable to common stockholders, basic and diluted		$	(0.32)		$	(0.49)		$	(1.93)		$	(2.35)
Weighted-average common shares outstanding, basic and diluted			7,687,961			5,954,700			6,538,722			5,509,921

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Exhibit 99.2

1<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>A clinical-stage precision<br>medicine oncology company<br>focused on the discovery and<br>development of targeted<br>therapies for patients with<br>biomarker-defined cancers<br>March 2026
2<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Forward-Looking Statements<br>Certain information contained in this presentation includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as<br>amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected<br>cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,”<br>“intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify<br>these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information<br>currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this<br>presentation other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and<br>achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other<br>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<br>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<br>uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of<br>our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment<br>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),<br>futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any<br>preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates<br>mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs and our ability to predict clinical outcomes<br>based on such preclinical and early clinical result, and our ability to continue as a going concern, and the other risks, uncertainties, and other factors described<br>under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with<br>the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or<br>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<br>of this presentation. We undertake no obligation to update such forward-looking statements for any reason, except as required by law. This presentation shall not<br>constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of any securities in any state or jurisdiction in which such<br>offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. This presentation may not<br>be reproduced, forwarded to any person or published, in whole or in part.
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3<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Aprea Therapeutics (NASDAQ: APRE)<br>One Critical Pathway - Multiple Targets<br>DNA Damage Response (DDR)<br>1. Ngoi N, et al. Targeting the replication stress response through synthetic lethal strategies in cancer medicine.<br>Trends in Cancer. (2021); 7(10):930-957<br>Precision<br>Medicine<br>Synthetic<br>Lethality Aprea<br>DYRK1<br>Target<br>Trends in Cancer 1<br>Positioned at the Forefront of Synthetic Lethality and Precision Medicine<br>Transition from broad, toxic chemotherapy<br>to potentially safer, precision-guided<br>targeted therapies<br>Targeted Oncology<br>Develop highly selective cancer therapies<br>that exploit tumor-specific mutations to<br>maximize cancer cell killing while sparing<br>healthy tissue<br>Precision-Driven<br>Development<br>All programs are designed to address<br>significant unmet medical needs across<br>genetically defined cancer populations<br>Pipeline with<br>Clinical Momentum<br>Single agent activity demonstrated in<br>ongoing Phase 1 trial<br>Early Clinical<br>Proof-of-Concept
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4<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Robust DDR Development Pipeline Milestones<br>2024-2026 Accomplished and anticipated clinical milestones<br>2024 2025 2026<br>H1 H2 H1 H2 H1 H2<br>ATR<br>ATRN-119<br>WEE1<br>APR-1051<br>RP2D for<br>QD dosing<br>ACESOT-1051: Phase 1 – Monotherapy Dose Escalation<br>Enrolled<br>First Patient<br>Complete Dose<br>Escalation<br>IND<br>Cleared<br>ABOYA-119: Phase 1/2a – Monotherapy Dose Escalation: QD*<br>BOIN Design<br>Initiate<br>BID Regimen<br>Optimization<br>ABOYA-119: Phase 1/2a –<br>Monotherapy Dose Escalation: BID*<br>* Further monotherapy enrollment paused, with consideration of further ATRN-119<br>development in combination approaches that could expand its therapeutic potential<br>Safety &<br>Efficacy Data<br>Safety &<br>Efficacy Data<br>Combinations<br>Safety &<br>Efficacy Data
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5<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Strong Drug Development and Commercial Expertise<br>Experienced team in synthetic lethality and targeted therapy<br>Management<br>Board of Directors<br>Richard Peters, M.D., Ph.D.<br>Chairman of the Board<br>Oren Gilad, Ph.D.<br>President and CEO<br>Jean-Pierre Bizzari, M.D.<br>Director<br>Marc Duey<br>Director<br>Michael Grissinger<br>Director<br>Gabriela Gruia, M.D.<br>Director<br>John Henneman<br>Director<br>Rifat Pamukcu, M.D.<br>Director<br>Bernd R. Seizinger, M.D., Ph.D.<br>Director<br>Oren Gilad, Ph.D.<br>President and CEO<br>John P. Hamill<br>Sr. Vice President and<br>CFO<br>Eugene Kennedy, MD<br>Chief Medical Advisor<br>Ze’ev Weiss, CPA,<br>B.Sc.<br>Chief Business Advisor<br>Mike Carleton, Ph.D.<br>Translational Medicine<br>Advisor<br>Brian Wiley<br>SVP, Corporate<br>Strategy
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6<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved 6<br>WEE1 Inhibitor: APR-1051<br>ACESOT-1051:<br>Clinical Proof-Of-Concept
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7<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>APR-1051: Next–Generation WEE1 Inhibitor Expanding the<br>Therapeutic Index<br>1. Zentalis Corporate Presentation, January 2026<br>2. Debio 0123-101, A Phase 1 Trial of Debio 0123 In Combination With Carboplatin In Advanced Solid Tumors:<br>Safety, Pharmacokinetic, And Preliminary Antitumor Activity Data, Poster ASCO 2023<br>3. Results of A Phase 1, Dose-Finding Study of Debio 0123 As Monotherapy In Adult Patients With Advanced Solid<br>Tumors —Safety, Pharmacokinetic, And Preliminary Antitumor Activity Data, Poster ASCO 2024<br>Targeting the clinically validated WEE1 pathway with an engineered profile aimed at widening the<br>therapeutic window and improving tolerability versus earlier inhibitors<br>Program Clinical Limitation Strategic Outcome What It Signals<br>Adavosertib<br>(AstraZeneca)<br>Hematologic & GI toxicity limited<br>dose intensity<br>Terminated further clinical development<br>Returned by AstraZeneca to<br>Merck & Co.<br>Biology works, narrow<br>therapeutic window<br>Azenosertib<br>(Zentalis) Continuous dosing not tolerated1 Ongoing dosing and schedule<br>optimization<br>Biology works, therapeutic<br>window still being defined<br>Debio 0123<br>(Debiopharm)<br>QT prolongation liability at high<br>doses2<br>Limited single-agent activity – no<br>clinical responses at doses up to and<br>including at MTD3<br>Cardiac safety restricts<br>exposure<br>APR-1051<br>(Aprea Therapeutics)<br>Early signals of tumor reduction<br>without class-limiting tox to date Dose escalation progressing Potentially widened<br>therapeutic window<br>No head-to-head studies have been conducted. Trial information is based on publicly available data and should be interpreted cautiously.
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8<br>	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>ACESOT-1051: Phase 1 Study Design<br>* Higher doses permitted if indicated<br>Multi-center, open-label Phase 1 single-agent dose escalation and dose selection optimization<br>Part 1 Dose escalation<br>up to 50 patients<br>RP2D<br>Oral single-agent APR-1051 will be administered once-daily for 28-day cycles<br>Objectives<br>Primary: Safety, DLT, MTD/MAD, RP2D<br>Secondary: Pharmacokinetics, Antitumor activity (RECIST/PCWG3)<br>Exploratory: Pharmacodynamics<br>= cleared<br>Accelerated titration; 1-6 patients per dose level<br>BOIN design; 3-12 patients per dose level<br>Part 2 Dose selection optimization<br>Up to 80 patients<br>Selected<br>dose 2<br>Selected<br>dose 1<br>1:1<br>randomization<br>R<br>Currently<br>enrolling<br>Dose level 1<br>10 mg<br>Dose level 2<br>20 mg<br>Dose level 3<br>30 mg<br>Dose level 4<br>50 mg<br>Dose level 5<br>70 mg<br>Dose level 6<br>100 mg<br>Dose level 7<br>150 mg<br>Dose level 8<br>220 mg<br>Dose level 9<br>300mg*<br>Backfill<br>to enrich<br>endometrial, CRC<br>and HPV+ Second uPR<br>Observed<br>First uPR<br>Observed<br>Select 2<br>dose levels<br>Eligible patients<br>≥ 18 yo with advanced solid<br>tumor harboring cancer-associated gene alterations<br>o CCNE1,CCNE2, FBXW7<br>or PPP2R1A<br>o USC regardless biomarker<br>status<br>o HPV+ oropharyngeal<br>squamous cell carcinoma,<br>cervical, vaginal, or vulvar<br>carcinoma<br>o KRAS-GLY12/GLY13 &<br>TP53 colorectal cancer
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9<br>© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>50<br>36<br>44<br>21<br>22<br>42<br>44<br>55<br>56<br>43<br>49<br>223<br>36<br>56<br>112<br>181<br>28<br>111<br>85<br>12<br>58<br>63<br>7<br>0 50 100 150 200 250<br>02-001<br>01-001<br>01-002<br>01-003<br>01-004<br>02-002<br>03-002<br>03-003<br>03-004<br>02-003<br>03-005<br>01-005<br>03-007<br>01-006<br>03-008<br>03-006<br>03-010<br>01-010<br>01-008<br>03-011<br>03-012<br>01-011<br>01-012<br>220 mg 150 mg<br>100 mg 70 mg<br>50 mg 30 mg<br>20 mg 10 mg<br>Days on treatment<br>Study patient<br>APR-1051 once-daily dose<br>Not all data source verified<br>✼<br>Data cutoff: February 18, 2026<br>✼<br>Progressive disease (PD)<br>Stable disease (SD)<br>Consent withdrawn<br>Treatment continues<br>Physician decision<br>Unrelated death<br>Partial response* (PR)<br>APR-1051 Summary of Duration of Treatment (n=23)<br>* Unconfirmed<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>✼<br>Enrollment status
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10 © 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>MedDRA Preferred Term APR-1051 All dose levels (N=23)<br>Treatment-related AEsa All Grades<br>n (%)<br>Grade ≥ 3b<br>n (%)<br>Nausea 7 (30.4) 0 (0)<br>Fatigue 4 (17.4) 0 (0)<br>Vomiting 2 (8.7) 0 (0)<br>Alanine aminotransferase increased 1 (4.3) 1 (4.3)c<br>Aspartate aminotransferase increase 1 (4.3) 1 (4.3)c<br>Anemia 1 (4.3) 0 (0)<br>Blood bilirubin increased 1 (4.3) 0 (0)<br>Constipation 1 (4.3) 0 (0)<br>Dehydration 1 (4.3) 0 (0)<br>Dysgeusia 1 (4.3) 0 (0)<br>Dyspepsia 1 (4.3) 0 (0)<br>Gastroesophageal reflux disease 1 (4.3) 0 (0)<br>Hypokalemia 1 (4.3) 0 (0)<br>Lymphocyte count decreased 1 (4.3) 1 (4.3)<br>Treatment-related AEs in Patients Treated with APR-1051 (N=23)<br>a A patient may have more than one AE and/or have the same AE more than once<br>b Grade 3 unless otherwise indicated<br>c Increased alanine aminotransferase and aspartate aminotransferase occurred in the same patient and was considered one DLT event<br>Not all data source verified<br>Data cutoff: February 18, 2026
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11	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Patient Example #1 (On Treatment):<br>Partial Response Observed in Target Indication and Alteration<br>APR-1051 shows single agent activity in cancer cells with mutated PPP2R1A<br>Clinical Data<br>220 mg Cohort<br>Patient: 63-year-old Female<br>Diagnosis: Uterine Serous Carcinoma (form of endometrial cancer (EC))<br>Key Mutations: PPP2R1A<br>Treatment History: 4 prior lines - heavily pretreated<br>• Line 1: Carboplatin + Paclitaxel → 126 days, PD<br>• Line 2: Pembrolizumab + Lenvatinib → ~17 months, PD<br>• Line 3: Doxorubicin → 56 days, PD<br>• Line 4: Topotecan → 70 days, PD<br>APR-1051 Activity:<br>• Current Status: On treatment<br>• Best Response: uPR at first scan (-50% tumor response)<br>Notes: uPR achieved with 50% tumor shrinkage and >85% reduction in CA-125 tumor<br>marker in heavily pretreated 63-year-old patient. Well tolerated with minimal toxicity.<br>PPP2R1A may be relevant to response.
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12	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Patient Example #2 (On Treatment):<br>Partial Response Observed in Target Indication and Alteration<br>Clinical Data<br>150 mg Cohort<br>Patient: 68-year-old Female<br>Diagnosis: Uterine Serous Carcinoma (form of EC)<br>Key Mutations: PPP2R1A<br>Treatment History: 4 prior lines - heavily pretreated<br>• Line 1: Paclitaxel/carboplatin → 105 days, CR (Completed Regimen)<br>• Line 2: Docetaxel/carboplatin → 134 days, PR (Completed Regimen)<br>• Line 3: Letrozole → 79 days, PD<br>• Line 4: Investigational agent (ATK-160) → 55 days, PD<br>APR-1051 Activity:<br>• Current Status: On treatment<br>• Best Response: uPR at first scan (-50% tumor response)<br>Notes: uPR achieved with 50% tumor shrinkage and >90% reduction in CA-125 tumor<br>marker in heavily pretreated 68-year-old patient. Well tolerated with minimal toxicity.<br>PPP2R1A may be relevant to response.<br>APR-1051 shows single agent activity in cancer cells with mutated PPP2R1A
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13	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Patient Example #3:<br>Disease Control Observed in Early Patient Outcomes<br>APR-1051 shows single agent activity in cancer cells with mutated FBXW7<br>Clinical Data<br>100 mg Cohort<br>Patient: 86-year-old Female<br>Diagnosis: Rectal Cancer<br>Key Mutations: FBXW7 (Drives Cyclin E accumulation and overexpression)<br>Treatment History: 5 prior lines - heavily pretreated<br>• Line 1: Capecitabine/XRT → 191 days, PD<br>• Line 2: Capecitabine/oxaliplatin/bevacizumab → 45 days, PD<br>• Line 3: FOLFIRI + bevacizumab → 43 days, PD<br>• Line 4: Local XRT (lung mets) → 12 days, not evaluable<br>• Line 5: Tretinoin/bevacizumab/Tecentriq (ATRT trial) → 50 days, PD<br>APR-1051 Activity:<br>• Current Status: Consent withdrawn after 181 days<br>• Best Response: SD at third scan (-15% tumor response)<br>Notes: Durable SD maintained 181 days in a heavily pretreated 86-year-old patient; well<br>tolerated with minimal toxicity. FBXW7 mutation may be relevant to response
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14	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Clinical Data<br>70 mg Cohort<br>Patient Example #4:<br>Disease Control Observed in Early Patient Outcomes<br>Patient: 52-year-old Male<br>Diagnosis: HPV+ Oropharyngeal Squamous Cell Carcinoma (base of tongue)<br>Key Mutations: P16+<br>Treatment History: 3 prior lines<br>• Line 1: Concomitant cisplatin/XRT → 49 days, PD<br>• Line 2: Taxol/carboplatin/bevacizumab → 84 days, PD<br>• Line 3: Paclitaxel/carboplatin → 184 days, PD<br>APR-1051 Activity<br>• Current Status: PD after 223 days of SD treatment<br>• Best Response: SD at first scan (-5% tumor response)<br>Notes: Stable disease maintained for 223 days.<br>APR-1051 shows single agent activity in HPV+ head and neck tumor cells
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15	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>A Biomarker Defined Path to Registration<br>Data are preliminary from an ongoing dose-escalation study. Responses and stable disease require confirmation in<br>additional patients,and may change as follow-up matures. Safety and efficacy outcomes may vary by dose, schedule,<br>and patient characteristics.<br>Early responses across cohorts in PPP2R1A-mutated endometrial cancer, with additional disease<br>control signals across broader genomically defined tumors<br>Objective Responses<br>PPP2R1A-mutated endometrial cancer<br>• Response at 220 mg cohort<br>• Response at 150 mg cohort<br>Disease Control<br>FBXW7-mutated CRC<br>• Stable disease at 100 mg cohort<br>HPV+ Head and Neck<br>• Stable disease at 70 mg cohort<br>Safety<br>• Well tolerated to date<br>• Wide therapeutic window<br>• Responses across dose levels support a biomarker enriched expansion path<br>• Activity beyond endometrial cancer supports additional biomarker-defined cohorts<br>Clinical Activity by Biomarker and Dose Path to Registrational Cohort<br>1 Expand PPP2R1A-mutated cohort<br>Add additional cohorts<br>• FBXW7-mutated CRC<br>• HPV+ cancers<br>2<br>Confirm durability, consistency of<br>response and safety<br>3
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16	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>HPV+ Cancer – Collaboration with MD Anderson Ovarian Cancer*<br>UMSCC47 tumor cells OVCAR3 tumor xenograft<br>Tumor Volume (mm3<br>)<br>Vehicle<br>Aprea ATRi 30 mg/kg QD<br>Aprea WEE1i 30 mg/kg QD<br>Combination – half dose,<br>15mg/kg each<br>Days Post Treatment<br>Tumor Volume (mm3<br>)<br>Days since start of xenograft<br>mEER tumor cells<br>Tumor Volume (mm3<br>)<br>End of treatment<br>Days since start of xenograft<br>APR-1051 Demonstrated Preclinical Activity in Combination with<br>Chemo, IO and ATRi Across Multiple Cancer Models<br>* Data on file.<br>Start of<br>treatment<br> 3<br><br><br><br><br><br><br> rea ed<br>AP<br>Cis a i<br>C<br>Start of<br>treatment<br>** P<0.0001<br>* P=0.0067<br>**<br>** *
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17	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Summary<br>APR-1051 aims to be the first WEE1 inhibitor to translate validated biology into a scalable commercial<br>asset<br>1 Clinically validated target<br>• WEE1 inhibition has shown promising activity in genomically defined tumors<br>APR-1051 opportunity<br>• Early clinical proof-of-concept at 150 mg and 220 mg dose levels<br>• Potentially favorable safety profile at active dose levels<br>• Enrollment continues, additional clinical data expected over the next 3-6 months<br>• Clinical team strengthened to drive next phase of development<br>• Capital in place to achieve meaningful inflection points<br>• Valuation lags fundamentals, creating an asymmetric opportunity<br>Competitor programs constrained by low therapeutic index<br>• Dose intensity and duration limited by hematologic, GI or cardiac toxicity<br>2<br>3
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18	© 2026 Aprea Therapeutics, Inc. All Rights Reserved 18<br>APR-1051:<br>Potentially Differentiated WEE1 Inhibitor<br>Pre-Clinical
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19	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>APR-1051: Potentially Best-in-Class WEE1 Inhibitor<br>Potent and structurally differentiated, with high selectivity to limit off-target toxicity<br>AstraZeneca<br>Adavosertib (AZD-1775)<br>Zentalis<br>Azenosertib (ZN-c3)<br>Aprea<br>APR-1051<br>Undisclosed
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20	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>APR-1051: Potentially Best-in-Class WEE1 Inhibitor<br>Potent WEE1i that does not substantially inhibit PLK1, PLK2 or PLK3<br>-10 -9 -8 -7 -6 -5 -4<br>0<br>25<br>50<br>75<br>100<br>125<br>PLK1 IC50 Determination<br>Log10 [conc] (M)<br>% Activity<br>ZN-c3<br>APR-1051<br>-10 -9 -8 -7 -6 -5 -4<br>0<br>25<br>50<br>75<br>100<br>125<br>PLK2 IC50 Determination<br>Log10 [conc] (M)<br>% Activity<br>ZN-c3<br>APR-1051<br>-10 -9 -8 -7 -6 -5 -4<br>0<br>25<br>50<br>75<br>100<br>125<br>PLK3 IC50 Determination<br>Log10 [conc] (M)<br>% Activity<br>ZN-c3<br>APR-1051<br>ZN-c3 = 92.1 nM<br>APR-1051 = 15,900 nM<br>PLK1 Inhibition<br>IC50 >150-fold difference<br>ZN-c3 = 32.0 nM<br>APR-1051 = 1,800 nM<br>PLK2 Inhibition<br>IC50 >50-fold difference<br>ZN-c3 = 52.2 nM<br>APR-1051 = 31,600 nM<br>PLK3 Inhibition<br>IC50 >600-fold difference<br>Off-target inhibition of PLK1, PLK2 and PLK3 On 1<br>-target WEE1 activity1<br>ZN-c3 = 2.9 nM<br>APR-1051 = 1.6 nM<br>WEE1 Inhibition<br>IC50 similar to ZN-c3<br>125<br>100<br>75<br>50<br>25<br>0<br> 10 9 8 7 6 5<br>APR 1051<br> c3<br>WEE1 IC50 Determination<br>% Activity<br>Log10 [conc] (M)<br>1 AACR-NCI-EORTC Meeting, Poster B323, 2024 Data from exploratory in-vitro studies
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21	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors1<br>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<br>Phos-H2AX<br>Control<br>(MCM3)<br>NT<br>Phos-CDK1<br>APR-1051<br>75 nM<br>GSK-461364<br>0 nM<br>NT<br>675 nM<br>25 nM<br>225 nM<br>75 nM<br>Phos–<br>H2AX<br>Control<br>(MCM3)<br>Phos-CDK1<br>300 nM APR-1051 +<br>increasing GSK-461364<br>Control<br>(MCM3)<br>37 nM<br>111 nM<br>333 nM<br>1 µM<br>37 nM<br>111 nM<br>333 nM<br>NT<br>1 µM<br>Phos-H2AX<br>400 nM<br>BI-2536<br>APR-1051<br>Phos-CDK1<br>Dose range of PLK inhibitor GSK-461364<br>in combination with a single dose of<br>APR-1051 in OVCAR-3 cells<br>PLK inhibitor, GSK-461364 interferes<br>with the effects of APR-1051 in<br>OVCAR-3 cells<br>PLK inhibitor, BI-2536, interferes with the<br>effects of APR-1051 in OVCAR-3 cells<br>1 AACR-NCI-EORTC Meeting, Poster B323, 2024 Data from exploratory in-vitro studies
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22	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Studies Show PLK1 Suppression is Associated with Sepsis-Induced<br>Loss of Intestinal Barrier Function<br>1 PLK1 protects against sepsis-induced intestinal barrier dysfunction, Cao et al, Scientific Reports (2018).<br>2 PLK1 protects intestinal barrier function in sepsis: A translational research, Cao et al, Cytokine (2023).<br>3 PLK1 protects intestinal barrier function in sepsis: A translational research, Cao et al, Molecular Medicine (2022).<br>4 LncRNA DANCR improves the dysfunction of the intestinal barrier and alleviates epithelial injury by targeting the<br>miR‐1306‐5p/PLK1 axis in sepsis, Wang et al., Cell Biology International (2021).
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23	© 2026 Aprea Therapeutics, Inc. All Rights Reserved 23<br>Intellectual Property Portfolio<br>Financial Summary & Capitalization<br>Investment Highlights
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24	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Robust Global Intellectual Property Protection<br>Family 1: Ataxia Telangiectasia and Rad3-Related (ATR) Protein Kinase Inhibitors<br>• Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13th, 2015<br>• Patents granted in AU, BR, CA, CN, EP, IL, IN, JP, KR, MX, HK.<br>• 1.1: Issued on May 30, 2017 as U.S. Patent 9,663,535<br>• 1.2: Issued on May 29, 2018 as U.S. Patent 9,981,989<br>• 1.3: Issued on Feb. 5, 2019 as U.S. Patent 10,196,405<br>Family 2: ATR Inhibitors and Methods of Use<br>• Carboxylic acid-containing macrocyclic ATR inhibitors, and prodrugs; methods of using these inhibitors to treat various cancers;<br>filed on Apr. 12th, 2017<br>• Issued on May 28th<br>, 2019 as U.S. Patent 10,301,324<br>Family 3: ATR Inhibitor Pharmaceutical Composition and Methods<br>• International application filed on Apr. 14th, 2023<br>• Pharmaceutical formulation and composition of our lead ATR inhibitor in the clinic<br>• Patent granted in JP; Applications pending US, AU, BR, CA, CN, EA, EP, HK, IL, IN, KR, MX, NZ, PH, SG, ZA<br>Family 4: WEE1 Inhibitor Pharmaceutical Compositions and Methods<br>• International Application filed on Jun. 3rd, 2022<br>• Composition of our lead WEE1 inhibitor compounds<br>• Patent granted in AU; Applications pending in US, AU, BR, CA, CN, EP, HK, IL, IN, JP, KR, MX, ZA<br>Family 5: Methods of Treating Cancer<br>• International application filed on Sept. 19, 2026<br>• Clinical methods of treating advanced solid cancer tumors using lead ATR inhibitor<br>Family 6: Macrocyclic Undisclosed DDR target Inhibitors and Methods of their Preparation and Use<br>• International application filed on Jan. 22, 2026<br>• U.S. Provisional Applications filed on Jun. 6, 2025, and Sep. 19, 2025
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25	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Securities Common Equivalents<br>as of March 9, 2026<br>Preferred Stock (as converted) 15,596<br>Common Stock (1) 11,452,452<br>Warrants (2) 16,212,687<br>Options 840,121<br>Restricted Stock Units 25,176<br>Fully Diluted Equivalents 28,546,032<br>Aprea Therapeutics (NASDAQ: APRE) Financial Summary and<br>Capitalization<br>1. 400,000,000 common shares authorized<br>2. Total warrants include pre-funded, Tranche A, Tranche B and Purchase<br>Cash and Equivalents of ~$14.6M as of December 31, 2025<br>$5.6M in gross proceeds raised in private placement Jan 30, 2026
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26	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Expected cash runway into Q1 2027<br>• Achieve near term inflection points and catalysts<br>• Evaluate optimal strategic partnerships<br>Near term catalysts<br>• APR-1051: Q1 2026 Safety/efficacy data ✓ Q3 2026 Complete dose escalation<br>• ATRN-119: October 2025 RP2D ✓ H2 2026 Potential collaborations on combinations<br>Diversified portfolio with best in class, de-risked clinical and preclinical programs<br>• Highly potent and selective WEE1 (APR-1051) and ATR (ATRN-119) inhibitors<br>• Early evidence of clinical activity including two uPRs with APR-1051<br>• Single agent and combination potential therapies<br>Technology developed by pioneers in synthetic lethality<br>• Management with strong drug development and commercial expertise<br>Investment Highlights
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27	© 2026 Aprea Therapeutics, Inc. All Rights Reserved<br>Aprea Therapeutics<br>(NASDAQ: APRE)
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