Zentalis Pharmaceuticals (ZNTL) FY 2025 Conference May 20, 2025 11:30 AM ET Speaker0 Great. I'd like to welcome everybody back to our morning session. I'd like to welcome everybody again to the H. C. Wainwright BioConnect Investor Conference at Nasdaq. Presenting, with us next is Zentalis Pharmaceuticals, and we have chief executive officer and president Julie Eastland, and we have Zentalis' CMO, Igmar Ber Burns Bruns. Welcome, and it's my pleasure to host you today. Speaker1 Thanks for having us as always ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________________ to ___________________ Commission File Number: 001-39263 Zentalis Pharmaceuticals, Inc. (Exact name of registrant as specified in its charte ...

Exhibit 99.1 Zentalis Pharmaceuticals Reports First Quarter 2025 Financial Results and Operational Progress First patient dosed in DENALI Part 2a clinical trial of azenosertib in patients with Cyclin E1+ PROC Topline data from DENALI Part 2 anticipated by year end 2026 with the potential to support an accelerated approval, subject to FDA feedback $332.5 million cash, cash equivalents and marketable securities supports operational runway into late 2027 SAN DIEGO, Calif. — May 14, 2025 — Zentalis® Pharmaceuti ...

Core Insights - Zentalis Pharmaceuticals has initiated the DENALI Part 2a clinical trial for azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC), with topline data expected by the end of 2026, potentially supporting accelerated approval from the FDA [1][6][9] - The company reported a cash position of $332.5 million as of March 31, 2025, which is projected to fund operations into late 2027 [5][7][19] Company Developments - The first patient has been dosed in Part 2a of the DENALI clinical trial, which aims to confirm the primary dose of azenosertib with a target enrollment of approximately 30 patients at two dose levels [6][9] - Azenosertib has shown clinically meaningful response rates in previous studies, with an objective response rate (ORR) of 34.9% and a median duration of response (mDOR) of 6.3 months in patients with Cyclin E1+ PROC [6][12] Financial Performance - Research and development expenses for Q1 2025 were $27.2 million, a decrease from $49.6 million in Q1 2024, primarily due to reductions in clinical expenses and other operational costs [12][16] - General and administrative expenses also decreased to $10.6 million in Q1 2025 from $15.7 million in Q1 2024, mainly due to lower non-cash stock-based compensation [12][16] Upcoming Events - Zentalis plans to participate in several upcoming scientific and investor conferences, including the ASCO Annual Meeting and the Jefferies Healthcare Conference [4][6]

Core Insights - Zentalis Pharmaceuticals has initiated dosing for the first patient in Part 2 of the Phase 2 DENALI clinical trial for azenosertib, targeting Cyclin E1+ platinum-resistant ovarian cancer [1][3] - The company anticipates topline data from DENALI Part 2 by the end of 2026, which could support accelerated approval from the FDA [2][3] - Azenosertib is a novel WEE1 inhibitor being evaluated as a monotherapy and in combination therapies across multiple tumor types [5][6] Clinical Trial Details - The DENALI trial is designed in two parts, with seamless enrollment; Part 2a aims to confirm the primary dose of azenosertib with approximately 30 patients at two dose levels: 400mg QD 5:2 and 300mg QD 5:2 [7] - Part 2b will enroll around 70 additional patients based on the results from Part 2a, pending FDA feedback [7] Clinical Data and Biomarkers - Previous data from Part 1b of the DENALI study indicated an objective response rate (ORR) of 34.9% among 43 response-evaluable patients, with a median duration of response (mDOR) of 6.3 months [3][4] - Cyclin E1 protein overexpression has been identified as a predictive biomarker for patient selection, with an estimated 50% of PROC patients overexpressing this protein [4] Company Overview - Zentalis Pharmaceuticals is focused on developing azenosertib as a potentially first-in-class and best-in-class treatment for Cyclin E1+ PROC, with ongoing research into additional applications [6] - The company has demonstrated that azenosertib is well tolerated and shows anti-tumor activity across various tumor types [6]

Core Viewpoint - Zentalis Pharmaceuticals is advancing its clinical-stage biopharmaceutical development of azenosertib, a WEE1 inhibitor, with a poster presentation scheduled at the 2025 ASCO Annual Meeting, showcasing its potential in treating metastatic colorectal cancer and other tumor types [1][2][4]. Company Overview - Zentalis Pharmaceuticals, Inc. is focused on developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor targeting Cyclin E1+ platinum-resistant ovarian cancer and other tumor types [4]. - The company is conducting clinical trials to evaluate azenosertib both as a monotherapy and in combination therapies, demonstrating anti-tumor activity and good tolerability across various cancer types [4]. Clinical Trial Details - An abstract has been accepted for a poster presentation at the 2025 ASCO Annual Meeting, detailing the Phase 1/2 clinical trial results of azenosertib in combination with encorafenib and cetuximab for patients with metastatic BRAF V600E mutant colorectal cancer [2]. - The poster presentation is scheduled for May 31, 2025, and will include clinical data up to an April 4, 2025 cutoff [2]. Mechanism of Action - Azenosertib functions as a selective and orally bioavailable WEE1 inhibitor, which regulates the G1-S and G2-M cell cycle checkpoints, allowing for cell cycle progression despite DNA damage, ultimately leading to cancer cell death [3].

Exhibit 99.1 Zentalis Pharmaceuticals Reports Full Year 2024 Financial Results and Operational Updates Positive azenosertib clinical data demonstrated clinically meaningful results in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC) Topline data from registration-intent DENALI Part 2 anticipated by year end 2026 Strengthened management team to support execution of highly focused strategy $371.1 million cash, cash equivalents and marketable securities balance as of December 31, 2024, with pr ...

Clinical Development and Trials - Azenosertib (ZN-c3) is a clinical-stage WEE1 inhibitor showing an objective response rate (ORR) of over 30% in Cyclin E1+ platinum-resistant ovarian cancer (PROC) patients[26]. - The DENALI Part 1b trial included 102 PROC patients, revealing an ORR of 34.9% in response-evaluable patients and 31.3% in the intent-to-treat population[32]. - The median duration of response (mDOR) for the intent-to-treat population was approximately 5.5 months, with ongoing maturation of data[32]. - The company plans to initiate enrollment for the DENALI Part 2 trial in the first half of 2025, aiming to disclose topline data by the end of 2026[26]. - Azenosertib is also being evaluated in other solid tumor types, including uterine serous carcinoma (USC), with data expected in the first half of 2026[29]. - In the monotherapy arm of the MAMMOTH study, patients treated with azenosertib at 400 mg QD 5:2 showed an overall response rate (ORR) of 31.3% and a median duration of response (mDOR) of 4.2 months[37]. - Among Cyclin E1+ patients treated at the 300 mg QD 5:2 dose level, the ORR was 21.4% with an mDOR of 4.9 months[37]. - In the ZN-c3-001 study, 23 patients with Cyclin E1+ PROC on intermittent schedules had an ORR of 34.8% and an mDOR of 5.2 months[40]. - For 11 patients with Cyclin E1+ USC on intermittent schedules, the ORR was 36.4% with an mDOR of 5.5 months[41]. - Across all tumor types in the ZN-c3-001 study, azenosertib was well-tolerated with a low treatment-related adverse event discontinuation rate of 5.2%[42]. - The company is developing a companion diagnostic test to identify PROC patients with Cyclin E1 overexpression, with a prototype ready for use in DENALI Part 2[27]. - Patient enrollment in clinical trials is critical, and difficulties in recruitment could lead to significant delays or abandonment of trials, impacting development timelines and costs[191]. - Initial, topline, or preliminary data from clinical trials may change as more data becomes available, necessitating caution in interpreting early results[184]. Market and Financial Overview - Approximately 50% of PROC patients are estimated to overexpress Cyclin E1, translating to about 21,500 patients annually in the U.S. and EU4[28]. - The global ovarian cancer market was valued at approximately $3 billion in 2022, with significant growth expected in the coming years[28]. - Zentalis incurred net losses of $165.9 million and $292.3 million for the years ended December 31, 2024 and December 31, 2023, respectively, with an accumulated deficit of $1.1 billion as of December 31, 2024[137]. - The company has not generated any revenue from product sales to date and does not anticipate generating revenue for the next several years[139]. - The company anticipates incurring significant commercialization expenses related to drug sales, marketing, manufacturing, and distribution if azenosertib is approved for commercial sale[142]. - The company estimates the addressable patient population for azenosertib, but inaccuracies in these estimates could adversely affect revenue projections and business operations[201]. - Coverage and reimbursement for pharmaceutical products are uncertain and vary by third-party payors, impacting sales and physician utilization[111][113]. - The company may face challenges in obtaining adequate reimbursement for its products, impacting their market adoption and revenue generation[216]. Regulatory Environment - Azenosertib has received Fast Track Designation from the FDA for the treatment of PROC patients who are Cyclin E1 positive[30]. - The FDA requires a New Drug Application (NDA) or Biologics License Application (BLA) for a new drug to be legally marketed in the U.S., which involves substantial time and financial resources[60][61]. - The FDA aims to review and act on a standard NDA/BLA for a new molecular entity within ten months from the date of filing[70]. - The FDA conducts a preliminary review of an NDA/BLA within the first 60 days after submission to determine if it is complete enough for substantive review[70]. - The FDA may issue a Complete Response Letter if the NDA/BLA has deficiencies, requiring the sponsor to address these before resubmission[75]. - Regulatory approval may come with limitations on the indicated uses for the product, including the requirement for a Risk Evaluation and Mitigation Strategy (REMS)[76]. - The FDA requires that companion diagnostics be approved simultaneously with the therapeutic product they support, ensuring safety and effectiveness[118][119]. - The approval of product candidates may be contingent on the successful completion of costly post-marketing clinical trials[164]. - Regulatory authorities may impose limitations on product approvals, affecting the commercialization of product candidates[164]. - The company must navigate various ex-U.S. regulatory requirements, which may differ significantly from U.S. regulations and impact approval timelines[222]. Competition and Market Risks - The company faces significant competition from larger pharmaceutical and biotechnology companies with greater resources and expertise[47]. - There are currently no FDA-approved WEE1 inhibitors, but several companies are in various stages of clinical evaluation for their WEE1 inhibitors[49]. - The company faces significant competition in oncology, with numerous products under development that may impact the market opportunity for azenosertib and other product candidates[202]. - Competitors may develop safer, more effective products, potentially leading to reduced market opportunities for the company's candidates[205]. - The company may face significant competition in seeking collaborators for product development, which could impact its ability to capitalize on market potential[153]. Operational and Strategic Considerations - The company currently relies on third-party contract manufacturing organizations (CMOs) for the production of azenosertib and has no plans to establish its own manufacturing facilities[43]. - The company has incurred significant expenses primarily from research and development and management costs, expecting to continue incurring substantial losses in the foreseeable future[138]. - The company is collaborating with Pfizer, GSK, and Dana Farber on the development of azenosertib, which may limit control over the resources dedicated to its development[149]. - The company has no committed external source of funds and may need to seek additional funding through equity offerings or collaborations, which could dilute stockholder value[145]. - The company acknowledges that the success of azenosertib and future product candidates depends on various factors, including clinical trial outcomes and regulatory approvals[148]. - The company is developing azenosertib in combination with other therapies, which introduces additional risks related to supply and regulatory approval of those therapies[198]. - The company may need to conduct additional studies or collect more data independently if third-party collaborators do not perform as expected[168]. - The company is exposed to significant product liability risks, which could adversely affect its business and financial condition if sufficient insurance coverage is not obtained[208]. Corporate Governance and Workforce - Zentalis is committed to enhancing diversity and inclusivity within its workforce and has implemented various employee training programs[133]. - The company prioritizes governance systems that promote fair and transparent business practices, including a Code of Business Conduct and Ethics[131]. - As of December 31, 2024, Zentalis had a total of 166 full-time employees and announced a strategic restructuring to reduce its workforce by approximately 40%[128]. - The company has a defined information security incident response plan to manage cybersecurity incidents and conducts regular employee training on data privacy[133].

Core Insights - Zentalis Pharmaceuticals has reported positive clinical data for azenosertib, a WEE1 inhibitor, showing meaningful results in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC) [1][2] - The company anticipates topline data from the registration-intent DENALI Part 2 study by the end of 2026 [1][3] - Zentalis has strengthened its management team to support its focused strategy and has a cash position projected to last into late 2027 [1][2] Clinical Development - Updated clinical data from the DENALI Part 1b study showed an objective response rate (ORR) of 34.9% in patients with Cyclin E1+ PROC tumors, with a median duration of response (mDOR) of 6.3 months as of January 13, 2025 [3] - In the MAMMOTH study, Cyclin E1+ patients treated with azenosertib had an ORR of 31.3% and an mDOR of 4.2 months [3] - The ZN-c3-001 Phase 1 study reported an ORR of 34.8% and an mDOR of 5.2 months for patients treated with azenosertib [3] - The company has aligned with the FDA on the study design for DENALI Part 2, which will begin enrollment in the first half of 2025 [3] Financial Performance - As of December 31, 2024, Zentalis had cash, cash equivalents, and marketable securities totaling $371.1 million, sufficient to fund operations into late 2027 [1][5] - Research and development expenses for 2024 were $167.8 million, a decrease from $189.6 million in 2023, primarily due to reduced personnel expenses [5][12] - General and administrative expenses increased to $87.1 million in 2024 from $64.4 million in 2023, largely due to higher personnel costs [5][12] Corporate Updates - The company received Fast Track Designation from the FDA for azenosertib for treating PROC patients who are Cyclin E1 positive [4][6] - A strategic restructuring was announced in January 2025 to enhance efficiency in clinical development, which is expected to be completed by the second quarter of 2025 [4][6] - Zentalis has continued patient enrollment in various clinical trials, including studies for uterine serous carcinoma and in combination with bevacizumab [4][6]

Core Insights - Zentalis Pharmaceuticals is presenting four posters at the 2025 AACR Annual Meeting, focusing on the clinical efficacy and broad therapeutic applications of azenosertib, a WEE1 inhibitor for high-grade serous ovarian cancer [1][2][5] Group 1: Azenosertib Overview - Azenosertib is a novel, selective, and orally bioavailable WEE1 inhibitor currently being evaluated in clinical studies for ovarian cancer and other tumor types [3][5] - The mechanism of action involves inhibiting WEE1, which allows cell cycle progression despite DNA damage, leading to cancer cell death [3] Group 2: Clinical Research and Presentations - The poster titled "Loss of RB1 sensitizes TP53-mutated cancer cells to WEE1 inhibition by azenosertib" will be presented on April 27, 2024 [2] - Another poster, "Cell-free DNA molecular response predicts clinical efficacy in HGSOC patients treated with azenosertib," is scheduled for April 28, 2024 [2] - Azenosertib's potential as a potent and selective WEE1 kinase inhibitor with broad antitumor activity will be highlighted on April 29, 2024 [2] - The final poster presentation will discuss the synergistic anti-tumor activity of azenosertib in combination with encorafenib and cetuximab on April 29, 2024 [2] Group 3: Company Background - Zentalis Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing azenosertib for patients with Cyclin E1+ platinum-resistant ovarian cancer [5] - The company is leveraging its expertise to explore additional therapeutic opportunities for azenosertib beyond its current indications [5]