Azenosertib

Julie Eastland appointed Chief Executive Officer, President and Director Ingmar Bruns, M.D., appointed Chief Medical Officer Scott Myers appointed to the Board of Directors as Chairperson SAN DIEGO, Nov. 13, 2024 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today announced changes to its executive leadership team to support the Company as it plans and executes registrational studies for its lead product candidate, azenosertib. Julie Eastland has been appointed Chief Executive Officer, President and Director, succeeding Kimberly Blackwell, M.D., who will remain as a strategic advisor to the Board of Directors. Ms. Eastland is an accomplished biopharmaceutical executive with substantial leadership experience operating late-stage oncology companies. She previously served as Chief Executive Officer at Harpoon Therapeutics until the company’s acquisition by Merck in early 2024. In addition to Ms. Eastland’s appointment, Ingmar Bruns, M.D., has been appointed Chief Medical Officer. The Company also announced that Scott Myers has been appointed as Chairperson of the Zentalis Board of Directors. "I am honored to join Zentalis during this exciting period as we execute azenosertib clinical development activities that, we believe, could support an accelerated approval,” said Julie Eastland, incoming Chief Executive Officer of Zentalis. “The azenosertib clinical results generated to date are compelling, and we believe this investigational medicine has the potential to become an important new treatment option for a significant segment of patients living with gynecological cancers. I look forward to working alongside the entire Zentalis team and Board, highly accomplished industry experts with a track record of successfully moving medicines through late-stage development and into commercialization.” Ms. Eastland continued: “We plan to proceed with a sharp focus on the advancement of azenosertib, taking necessary actions to ensure the Company has the resources to successfully proceed forward. Our priorities are clear – we will work to rapidly initiate and complete the studies needed to obtain regulatory authority approval to get azenosertib to patients, and we will operate in a capital efficient manner in order to maximize shareholder value. In January 2025, we plan to host an investor event, where we will share updated azenosertib clinical data and a regulatory update, including plans for registration-intent studies.” Kimberly Blackwell, M.D., added: “I am proud of our accomplishments advancing the development of azenosertib. We have administered azenosertib to approximately 800 patients with a variety of serious cancers in the clinic, as both a monotherapy and in combination with other modalities, and we’ve generated a substantial body of efficacy and safety data that inform further development. I believe that these data, in conjunction with the results of the pending studies, will ultimately support the approval of azenosertib as an entirely novel treatment option for gynecological cancers. I look forward to continuing to contribute and advise on the development of azenosertib.” “On behalf of the Board, we would like to thank Dr. Blackwell for her meaningful contributions to Zentalis and her efforts advancing the azenosertib clinical program,” said Scott Myers, incoming Chairperson of the Zentalis Board of Directors. “We would also like to express our deep appreciation to Dave Johnson for his many contributions as a highly productive chairperson and in supporting the organization during this period of growth. I look forward to working with him on the Board going forward.” Executive and Board Chairperson Biographies Julie Eastland served as the Chief Executive Officer and President of Harpoon Therapeutics, a publicly traded clinical stage oncology company, from November 2021, and a member of its Board of Directors from October 2018, until its acquisition by Merck Sharpe & Dohme in March of 2024. Ms. Eastland previously served as Chief Operating Officer and Chief Financial Officer of ReCode Therapeutics, a privately held genetics medicine company. Prior to ReCode, she served as Chief Financial Officer and Chief Business Officer of Rainier Therapeutics, a privately held biopharmaceutical company focused on bladder cancer. Before Rainier, she was Chief Financial Officer and Chief Business Officer of Cascadian Therapeutics, a publicly traded oncology company acquired by Seattle Genetics in 2018. Prior to Cascadian, Ms. Eastland served as Chief Financial Officer and Vice President of Finance and Operations of VLST Corporation, a privately held biotechnology company, and held various financial and strategic management positions at publicly traded biotechnology companies including Dendreon and Amgen. Ms. Eastland is an independent director of Dynavax Technologies Corporation, Lantheus, and Seismic Therapeutic. Ms. Eastland received an M.B.A. from Edinburgh University Management School and a B.S. in finance from Colorado State University. Scott Myers has worked in the global pharmaceutical and medical technology industries for nearly three decades. Mr. Myers was Chief Executive Officer, President and Director of Viridian Therapeutics, a publicly traded biotechnology company, until November 2023. He was previously Chief Executive Officer and served on the Board of Directors of AMAG Pharmaceuticals, where he led its turnaround and strategic sale to Covis Pharma, S.à.r.l., a pharmaceutical company. Mr. Myers served as Chief Executive Officer and Chairman of the Board of Directors of Rainier Therapeutics. Mr. Myers led Rainier’s asset sale of vofatamab to Fusion Pharmaceuticals. Prior to Rainier, Mr. Myers served as Chief Executive Officer, President and Director of Cascadian Therapeutics from April 2016 through its acquisition by Seattle Genetics. Mr. Myers serves as Chairperson of the Boards of Directors of Convergent Therapeutics and Dynavax Technologies Corporation. Mr. Myers previously served on the Boards of Directors of Harpoon Therapeutics, Selecta Biosciences, Trillium Therapeutics, and Ironshore Pharmaceuticals. Mr. Myers holds a B.A. in biology from Northwestern University and an M.B.A. from the Graduate School of Business (Booth) at the University of Chicago. Ingmar Bruns, M.D., brings two decades of hematology and oncology experience as a physician and scientist. Dr. Bruns served as Chief Medical Officer of Trillium Therapeutics, a publicly traded clinical stage oncology company, through its acquisition by Pfizer in November 2021, after which he served in clinical development roles at Pfizer, most recently as Development Head, Hematologic Malignancies, Pfizer Global Product Development. Dr. Bruns previously served as the Senior Vice President and Head of Clinical Development at Pieris Pharmaceuticals, a publicly traded clinical stage biotechnology company, where he built and led the clinical development organization. From 2013 through 2017, Dr. Bruns led clinical development of several high priority oncology assets at Bayer Pharmaceuticals. Previously, Dr. Bruns served as an attending hematologist and oncologist as well as a physician-scientist at the University Hospital of Dusseldorf in Germany and Albert Einstein College of Medicine in New York. Dr. Bruns has authored over 50 publications in the field of hematology and oncology, including several lead authorships in high impact journals such as Nature Medicine, Blood and Leukemia. He received his M.D. and Ph.D. from the University of Lubeck in Germany. About Zentalis Pharmaceuticals Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers. The Company’s lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors. Azenosertib is being evaluated as a monotherapy and in combination across multiple clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of its azenosertib clinical development program, the Company is exploring enrichment strategies targeting tumors of high genomic instability, such as Cyclin E1 positive tumors, homologous recombination deficient tumors and tumors with oncogenic driver mutations. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders. Zentalis has operations in San Diego. For more information, please visit www.zentalis.com. Follow Zentalis on X/Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the registrational studies of azenosertib; clinical development activities for azenosertib and data that could support accelerated approval; the potential of azenosertib; the Company’s plans to advance azenosertib, including initiating and completing studies to obtain approval; the Company’s plans to operate in a capital efficient manner in order to maximize shareholder value; the Company’s plans for an investor event and the timing thereof; and expected contributions from team members. The terms “believe,” “goal,” “intend,” “look forward,” “plan,” “potential,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of any diagnostic tools; our substantial dependence on the success of our lead product candidate, azenosertib; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. ZENTALIS® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release. Contact:Elizabeth Pingpank Hickinehickin@zentalis.com860-463-0469

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., Nov. 07, 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.gov NCT04905914. 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 MoyerLifeSci Advisorsmmoyer@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