WEE1

Financing led by Sphera Healthcare with participation from new and existing healthcare-focused institutional investors $16.0 million in upfront gross proceeds with the potential to receive up to an additional $18.0 million in potential warrant exercise proceeds for an aggregate of up to $34.0 million in total gross proceeds DOYLESTOWN, Pa., March 11, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced that it has entered into a securities purchase agreement with new and existing healthcare focused institutional investors and certain Company insiders to raise up to $34.0 million in gross proceeds, including initial upfront funding of $16.0 million and up to an additional $18.0 million upon cash exercise of accompanying warrants at the election of the investors. The financing is being led by Sphera Healthcare and includes participation from new and existing healthcare-focused investors, including Nantahala Capital, DAFNA Capital Management, Exome Asset Management and Stonepine Capital Management, among others, as well as certain Company insiders. “This meaningful financing led by high quality healthcare institutions will support Aprea in our goal to be a leader in the field of Synthetic Lethality (SL) and DNA Damage and Response (DDR),” said Dr. Oren Gilad, President and CEO of Aprea. “It will provide the capital to fund our Phase 1 ACESOT-1051 clinical trial evaluating a highly potent, oral WEE1 inhibitor for Cyclin E over-expressing cancers including breast and ovarian cancers as well as continuation of patient enrollment in the dose expansion portion of the Phase 1/2a clinical trial (AR-276-01) evaluating ATR inhibitor, ATRN-119, in patients with advanced solid tumors having mutations in defined DDR-related genes.” Maxim Group LLC is acting as the sole placement agent for the private placement. Pursuant to terms of the securities purchase agreement, Aprea will issue an aggregate of 2,194,788 shares of its common stock (or pre-funded warrants in lieu thereof) and accompanying warrants to purchase up to an aggregate of 2,194,788 shares of its common stock at a combined purchase price of $7.29 per share and accompanying warrants, in accordance with the "Minimum Price" requirement as defined in the Nasdaq rules. The accompanying warrants will consist of two tranches: Tranche A warrants to purchase up to 1,097,394 shares of common stock at an exercise price of $7.29 per share for an aggregate of up to $8.0 million and will expire at the earlier of (i) 30 days following the announcement of the recommended Phase 2 dose for the Company’s ATR inhibitor program for ATRN-119 and the daily VWAP of the Company’s common stock equaling or exceeding $14.58 per share for 30 consecutive trading days following the announcement and (ii) three years from the date of issuance. Tranche B warrants to purchase up to 1,097,394 shares of common stock at an exercise price of $9.1125 per share for an aggregate of up to $10.0 million and will expire at the earlier of (i) 30 days following the announcement of the recommended Phase 2 dose for the Company’s WEE1 inhibitor program for APR-1051 and the daily VWAP of the Company’s common stock equaling or exceeding $18.225 per share for 30 consecutive trading days following the announcement and (ii) five years from the date of issuance. In lieu of shares of common stock, certain investors are purchasing pre-funded warrants at a combined purchase price of $7.289 per pre-funded warrant and accompanying warrants, which equals the purchase price per share of common stock and accompanying warrant, less the $0.001 per share exercise price of each pre-funded warrant. The private placement is expected to close on or about March 13, 2024 subject to satisfaction of customary closing conditions. Aprea intends to use the upfront net proceeds from the private placement for general corporate purposes and to fund clinical development of APR-1051, the Company’s WEE1 inhibitor product candidate which recently received IND clearance. The aggregate net proceeds (assuming the cash exercise of all accompanying warrants) are expected to be sufficient to fund the Company into 2026. The offer and sale of the foregoing securities are being made in a transaction not involving a public offering, and the securities have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or applicable state securities laws. Accordingly, the securities may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. The Company has agreed to registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock purchased in the private placement and shares of common stock underlying the warrants. This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be made by means of a prospectus. 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. Aprea has completed all IND enabling studies for its oral, small molecule WEE1 inhibitor, APR-1051, and recently received FDA clearance of its IND. Forward-Looking Statements 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 the Company’s ability to close this offering and the timing thereof, 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 ability to continue as a going concern, 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 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

Company plans to initiate Phase 1 ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051)clinical trial evaluating, highly selective, oral WEE1 inhibitor, for monotherapy treatment of Cyclin E overexpressing cancers including breast and ovarian cancers Update from the ACESOT-1051 clinical trial expected in Q4 2024 DOYLESTOWN, Pa., March 11, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application (IND 169359) for APR-1051. “APR-1051 is a next-generation inhibitor of WEE1 kinase and, based on its unique characteristics, we believe it will be best in class,” said Dr. Oren Gilad, President and CEO of Aprea. “The FDA's clearance of our IND is a critical step in the APR-1051 development program. We look forward to evaluating therapeutic activity in patients, focusing on Cyclin E overexpressing cancers, including ovarian and breast cancers.” Based on preclinical studies, APR-1051 is differentiated from other WEE1 inhibitors in its: Molecular structure; Selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; Potentially superior pharmacokinetic (PK) properties; Potential absence of QT prolongation at doses that significantly inhibit WEE1* APR-1051 was discovered and preclinically evaluated by Aprea’s team of chemists and scientists. Aprea has conducted extensive pre-clinical studies with APR-1051, which have demonstrated that the molecule has potent anti-tumor activity, along with a favorable pharmacokinetic (PK) profile. Additionally, pre-clinical data show that APR-1051 may demonstrate less toxicity than other WEE1 inhibitors.* Clearance of the IND application will allow Aprea to initiate the Phase 1 ACESOT-1051 dose escalation trial to evaluate the safety, tolerability, and preliminary efficacy of APR-1051. Enrollment of the first patient in this study is expected in the first half of 2024 with an update expected in the fourth quarter of the year. * No head-to-head studies have been conducted with APR-1051 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. Aprea has received FDA clearance on an IND to begin clinical studies of APR-1051, its oral, small molecule WEE1 inhibitor. For more information, please visit the company website at . The Company may use, and intends to use, its investor relations website at as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. 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 ability to continue as a going concern, 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 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

Debiopharm aims to further characterize the safety, tolerability, and preliminary anti-tumor activity of its potent WEE1 inhibitor Debio 0123 as a monotherapy in three different expansion cohorts LAUSANNE, Switzerland--(BUSINESS WIRE)-- Debiopharm ( ), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard-of-care to cure cancer and infectious diseases, today announced the first patient dosed in the expansion of its open-label, non-randomized, multicenter Phase 1 study evaluating Debio 0123, an oral, potent, highly selective and brain-penetrant WEE1 inhibitor, as a monotherapy in patients with recurrent or progressive solid tumors. The expansion of this Phase 1 study, NCT05109975, is to characterize the safety, tolerability, and initial signs of antitumor activity of Debio 0123 when administered as monotherapy. Two out of the three expansion arms of the study will be using biomarkers to pre-select patients with different solid tumors while the third arm will be treating patients with recurrent serous endometrial carcinoma. Currently, sites are open for enrollment in the United States, Spain, and Switzerland. “Part of our strategy of utilizing OMICs* approaches to identify specific biomarkers and identify patient populations that will respond to Debio 0123 due to synthetic lethality will allow us to enroll patients who are most likely to benefit from treatment, thereby taking a truly precision medicine approach” expressed Dr. Victor Rodriguez-Freixinos, Medical Director, Debiopharm. Uterine serous carcinoma (USC) is an uncommon, but aggressive subtype of endometrial cancer. It represents approximately 10% of all endometrial cases, which translates to more than 6,000 newly diagnosed patients each year in the United States 1-2. Despite representing a small proportion of endometrial cancer cases, uterine serous carcinoma accounts for an alarming 39% of endometrial cancer-related deaths. Features highlighting the gravity of USC include the high rates of deep myometrial invasion, as well as metastatic spread to lymph nodes and peritoneal surfaces 1. These features largely affect the 5-year overall survival but compared with more common endometrial cancer, the prognosis for USC is generally poor and the risk of relapse is high 3. Similar to USC, epithelial ovarian cancer (EOC) is known for its poor prognosis due to the aggressive clinical course and the tendency to metastasize. However, EOC accounts for about 90% of all ovarian cancers and affects more than 17,000 American women each year, of which about 30% survive for 5 years after diagnosis 4-5. “This study’s population is mainly female, burdened by fatal malignancies like Uterine Serous Carcinoma, Epithelial Ovarian Cancer and fallopian tube cancer which are well-known hard-to-treat cancers. These patients need new treatment options, as the current standard of care is insufficient in assuring long-term progression free survival.” Dr. Manish R. Sharma, Principal Investigator at the START Midwest, Michigan. The Debio 0123 program originates from a growing awareness of DDR inhibition in fighting life-threatening cancers. Maximizing efficacy, while preserving safety are key elements that Debiopharm is eager to assess throughout the clinical development of Debio 0123. With the successful realization of these requirements, Debio 0123 could become the first choice WEE1 inhibitor. About Debio 0123 Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers. About DNA-Damage Response (DDR) When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells use their hyperactive DDR response to divide and grow uncontrollably, which promotes cancer expansion. Inhibition of DDR, particularly in combination with other anticancer agents, induces an overall arrest in the uncontrollable cancer cell cycle. This ultimately activates a self-destruction program in cancer cells. DDR inhibitors such as Debiopharm's WEE1 and USP1 inhibitors, are being tested in either clinical or preclinical studies. Debiopharm’s commitment to patients Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select large pharmaceutical commercialization partners to maximize patient access globally. For more information, please visit We are on Twitter. Follow us @DebiopharmNews at Sources 1 Hamilton CA, et al. Br J Cancer. 2006 Mar 13;94(5):642-6. doi: 10.1038/sj.bjc.6603012. PMID: 16495918; PMCID: PMC2361201. 2 Clement PB, Young RH. Adv Anat Pathol. 2004 May;11(3):117-42. doi: 10.1097/00125480-200405000-00001. PMID: 15096727. 3 Acharya S, et al. Lancet Oncol. 2005 Dec;6(12):961-71. doi: 10.1016/S1470-2045(05)70463-0. Erratum in: Lancet Oncol. 2006 Feb;7(2):105. PMID: 16321764. 4 American Cancer Society. Key Statistics for Ovarian Cancer. 5 Arter, Z.L., et al. Br J Cancer 130, 108–113 (2024). * OMICs = technologies that are primarily aimed at the universal detection of genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in a specific biological sample