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Corporate Presentation March 2025 Nasdaq: ZNTL
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2 Zentalis Pharmaceuticals, Inc. (“we,” “us,” “our,” “Zentalis” or the “Company”) cautions that this presentation (including oral commentary that accompanies this presentation) contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential for azenosertib (ZN-c3) to be best-in-class; the potential regulatory pathway for azenosertib, including the potential for azenosertib to utilize an accelerated approval pathway and obtain accelerated approval, and the potential for studies to be registrational or intended for registration; our development and regulatory strategy and approach for azenosertib, including our strategy to focus on bringing azenosertib to patients with PROC who are Cyclin E1+; our planned strategy, vision and path forward; the market opportunity for azenosertib, including the potential size of the patient population; existing data being supportive of the go-forward azenosertib development strategy; our plans to bring azenosertib to patients quickly and efficiently; the importance a Cyclin E1+ companion diagnostic for our go-forward strategy; the potential for the opportunity for azenosertib to be broad; our belief that a Cyclin E1+ companion diagnostic test substantially enhances the risk benefit profile of azenosertib; the encouraging nature of the azenosertib clinical data; the potential opportunities for azenosertib in combination or across different tumor types; our ability to recognize the benefits of our strategic restructuring; our belief that our resources are aligned and our strategy is highly focused; azenosertib’s therapeutic value as a single agent; the potential for Cyclin E1 to serve as a highly sensitive and specific predictive biomarker for response to azenosertibthe opportunity to improve outcomes in the next stage of development, including the potential for trial management and mitigation strategies to help in reducing the rate of discontinuations and improve duration on therapy and the potential for enhanced monitoring, guidance and supportive care to help increase the time on treatment; our positioning to execute; our projected cash runway; planned clinical trials for our product candidates; the potential of azenosertib to address a significant unmet need in patients with PROC who are Cyclin E1+; the potential benefits of azenosertib, including compared to available therapies and therapies in development (not head-to-head comparisons); the potential unmet need in a particular indication and/or patient population; the timing and content of our anticipated milestones, including the timing of initiation of clinical trials and disclosure of clinical data; as well as statements that include the words such as “ahead,” “anticipate,” “believe,” “beyond,” “confident,” "continue," "could," “estimate,” “expect,” “forward,” “future,” “goal,” “go-forward,” “hope,” “intended,” “may,” “milestone,” “ongoing,” “opportunity,” “path forward,” “plan,” “positioning,” “potential,” “predictive,” “prepare,” “strategy,” "support," “vision,” “will” and similar statements of a future or forward-looking nature. 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 a companion diagnostic; 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; and significant costs as a result of operating as a public company. Other risks and uncertainties include those identified under the caption “Risk Factors” in our most recently filed periodic reports on Forms 10-K and 10-Q and subsequent filings with the U.S. Securities and Exchange Commission in the future could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management’s estimates as of the date of this presentation. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While we may elect to update these forward-looking statements at some point in the future, we assume no obligation to update or revise any forward-looking statements except to the extent required by applicable law. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Neither we nor our affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or undertake to update such data after the date of this presentation. Statements such as “not head-to-head” and similar references indicate that no head-to-head clinical trial has been conducted evaluating azenosertib against the indicated therapies. Notable differences exist between the Company’s trial designs, conditions under study and subject characteristics as compared to the evaluated third party results and caution should be exercised when comparing data across these studies. ZENTALIS® and its associated logos are trademarks of Zentalis and/or its affiliates. All other trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. All website addresses given in this presentation are for information only and are not intended to be an active link or to incorporate any website information into this document. Zentalis’ product candidates are investigational drugs and have not yet been approved by the U.S. Food and Drug Administration or any other regulatory authority. Forward Looking Statements and Disclaimer
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3 Azenosertib Potential Best-in-Class Therapy for Cyclin E1+ PROC Recent launch of approved therapy in biomarker selected PROC demonstrates the large commercial opportunity Cyclin E1+ PROC, ~21,500 patients*, linked to poorer outcomes; no approved, targeted therapies SOC: mono chemo 4-13% ORR1 Other tumor types with Cyclin E1+ expression include breast, endometrial, bladder 2 Market Opportunity >30% ORR and 5.5 mos mDOR in Cyclin E1+ patients at monotherapy dose of 400mg QD 5:2 350+ PROC patients treated at active doses in monotherapy Manageable safety profile, potentially best-in-class WEE1 inhibitors Supportive Data Cash runway extended into late 2027 beyond anticipated topline data from DENALI Part 2 Resources now aligned with addition of key leadership on highly focused strategy Potential for accelerated approval pathway in PROC, Cyclin E1+ patients** Path Forward * US and EU4 (France, Germany, Italy, Spain) + UK; **Subject to supportive data and FDA feedback 1. Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228 2. NAKAYAMA, K. et al. Int. J. Oncol. 48, 506–516 (2015); Aziz, D. et al. J. Pathol.: Clin. Res. 8, 355–370 (2022); Lotan, Y. et al. Eur Urol 64, 465– 471 (2013). Abbreviations: PROC, platinum-resistant ovarian cancer; mDOR, median duration of response; SOC, standard of care 3. Based on internal clinical data * PROC FRα+ ~35% Overlap <20% Cyclin E1+ ~50% 3
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4 * Cyclin E1 IHC+ based on Zentalis proprietary IHC cutoff and Cyclin E1 IHC assay developed from the existing clinical data † Cyclin E1 IHC+% based on literature (~20% CCNE1 amplification) and the unbiased CCNE1 amp & Cyclin E1 overlapping data generated from Zentalis clinical trial samples ‡ Source: DRG Clarivate for US, UK and EU4 (France, Germany, Italy, Spain) IHC - immunohistochemistry • Cyclin E1+ is a biomarker of poor prognosis • Companion diagnostic ready for use in registration-intent studies Cyclin E1+ Tumors Comprise a Significant Portion of the PROC Population Including Vast Majority That Are CCNE1 Amplified ~20% of PROC The majority are also Cyclin E1+ All PROC ~50%† of PROC ~21,500‡ patients Cyclin E1 IHC+ * CCNE1 amplified Cyclin E1+ represents a significant opportunity in PROC
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5 PARP Inhibitor or Bevacizumab + Olaparib Bevacizumab Combination Chemotherapy Platinum Doublet HRP PFI>6m PFI<6m PFI<6m Carboplatin + Paclitaxel High Unmet Need in Cyclin E1+ PROC Patients (2L+) Approved 2L+ Therapy Chemo Mono ORR 4 – 13%1 Mirvetuximab (FRα+ ~35% of PROC) ORR 32% - 42%2 No approved therapies specifically for Cyclin E1+ PROC Platinum Resistant Ovarian Cancer: High Unmet Need Provides Opportunity for Azenosertib Monotherapy First Line Maintenance Second Line Therapy First Line Therapy BRCAm/HRD Untreated Stage III/IV Ovarian Cancer PROC, platinum-resistant ovarian cancer; FRα, Folate Receptor alpha 1 Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228;*2Clinical Trial SORAYA ORR 32%, MIRASOL ORR 42%
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6 Azenosertib Monotherapy Studies Provide Large Amount of Safety Data and Meaningful Antitumor Activity to Support the PROC Registration-intent Study Well characterized safety profile in 356 patients Including PROC patients at 400mg 5:2 (N=165) and 300mg 5:2 (N=38) First-in-human in solid tumors dose escalation/expansion N=193 total daily dose ≥ 300mg PARPi resistant PROC 300mg & 400mg 5:2 N=61 PROC 400mg 5:2 N=102 001 MAMMOTH DENALI Part 1b Integrated efficacy analysis on Patients in PROC, Cyclin E1+ 400mg 5:2 (N=73) and 300mg 5:2 (N=20)
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7 Safety and Tolerability at 300 and 400 mg 5:2 Broadly Comparable Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. 300mg (N=38) 400mg (N=165) Treatment-related AEs*, N (%) All Grade Grade 3+ All Grade Grade 3+ Gastrointestinal Decreased appetite 8 (21.1%) 1 (2.6%) 40 (24.2%) 2 (1.2%) Diarrhea 18 (47.4%) 1 (2.6%) 86 (52.1%) 12 (7.3%) Nausea 23 (60.5%) 0 101 (61.2%) 6 (3.6%) Vomiting 3 (7.9%) 0 17 (10.3%) 3 (1.8%) Dehydration 1 (2.6%) 0 14 (8.5%) 1 (0.6%) Fatigue 14 (36.8%) 2 (5.3%) 90 (54.5%) 20 (12.1%) Sepsis 0 0 4 (2.4%) 4 (2.4%) Hematologic Anemia 13 (34.2%) 3 (7.9%) 53 (32.1%) 20 (12.1%) Thrombocytopenia 13 (34.2%) 2 (5.3%) 36 (21.8%) 8 (4.8%) Neutropenia 4 (10.5%) 3 (7.9%) 30 (18.2%) 21 (12.7%) Febrile Neutropenia 0 0 4 (2.4%) 4 (2.4%) Monotherapy Safety Profiles in PROC Patients 300 mg & 400mg QD 5:2 Treatment-related AEs, N (%) 300mg (N=38) 400mg (N=165) Treatment-Related SAE 6 (15.8%) 31 (18.8%) TRAE leading to dose reduction 13 (34.2%) 69 (41.8%) TRAE leading to dose interruption 16 (42.1%) 89 (53.9%) TRAE leading to discontinuation 5 (13.2%) 26 (15.8%) TRAE leading to death 0 3 (1.8%) * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules • While numerically different, broadly comparable safety profiles at 300mg and 400mg 5:2 • Low frequency of previously reported G5 TRAEs, G3+ febrile neutropenia and sepsis observed at 400mg 5:2 Integrated Analysis Data Cutoff Dec 2 2024 Active database; subject to further change
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8 Abbreviations: CI, confidence interval; cPR, confirmed partial response; mDOR, median duration of response; PD, progressive disease; SD, stable disease; NE, not estimable due to small number of subjects and events. 400mg 5:2 Shows Meaningful Response Rates >30% and mDOR >5 mos 300 mg 5:2 400 mg 5:2 ORR in response evaluable (95% CI) 22.2% (4/18) (6.4 - 47.6) 33.8% (23/68) (22.8 - 46.3) ORR in intent-to-treat (95% CI) 20.0% (4/20) (5.7 – 43.7) 31.5% (23/73) (21.1 – 43.4) mDOR (mos) (95% CI) 3.9 (2.8, NE) 5.5 (3.5, 6.3) mPFS (mos) (95% CI) 4.1 (1.3, 6.6) 4.4 (2.8, 6.8) + + + + + + + + +-100 — -80 — -60 — -40 — -20 — 0 — 20 — 40 — 60 — 80 — 100 — Best Percent Change from Baseline in Sum of Diameter (%) PR PD 300mg 5:2 (N=18) 400mg 5:2 (N=68) PDSDcPRBest Overall Response # # # # # # # # # ‡ ‡ ‡ + = treatment ongoing # = best % change ~0% ‡ = received a post-baseline scan as SD but did not qualify as SD due to the post-baseline scan occurring outside of a protocol defined window Integrated Analysis Data Cutoff Dec 2 2024 Active database; subject to further change
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9 Randomized Study vs. Standard of Care Same Patient Population Initiation Planned Post-Dose Confirmation Detailed Design to be Discussed with FDA Abbreviations: 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; IHC= immunohistochemistry; MIRV, mirvetuximab soravtansine; PROC=platinum resistant ovarian cancer. DENALI PART 2 FOR POTENTIAL ACCELERATED APPROVAL (N= ~100 at selected dose) PHASE 3 CONFIRMATORY STUDY (Pending FDA feedback) Platinum-resistant ovarian cancer 1-3 prior lines of therapy Prior MIRV if high FRα Cyclin E1+ by proprietary IHC cutoff criteria Key Eligibility Registration-Intent Studies for Azenosertib Monotherapy in PROC, Cyclin E1+ Population Part 2a (Alignment with FDA) Part 2b (Pending FDA feedback) Continuous Enrollment Across Part 2a and 2b with Dose Confirmation at Interim Analysis PROC Pts Cyclin E1+ Tumors 400mg 5:2 (N=30) 300mg 5:2 (N=30) 1:1 Randomization Dose TBD 5:2 (N=~70) Endpoints PFS Safety and Tolerability ORR, DOR Prescreening / Tissue Consent Seamless Enrollment Dose Confirmation
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10 Subgroup Analysis by Prior Line of Therapy Cyclin E1+ PROC patients treated at 400mg 5:2 in 001, MAMMOTH and DENALI Integrated Analysis Data Cutoff Dec 2 2024 Active database; subject to further change Overall 1-3 PLoT 4+ PLoT ORR in response evaluable (95% CI) 33.8% (23/68) (22.8 – 46.3) 40.0% (16/40) (24.9 – 56.7) 25.0% (7/28) (10.7 – 44.9) ORR in intent-to-treat (95% CI) 31.5% (23/73) (21.1 – 43.4) 36.4% (16/44) (22.4 – 52.2) 24.1% (7/29) (10.3 – 43.5) mDOR (mos) (95% CI) 5.5 (3.5 – 6.3) 5.5 (3.5 – 6.3) NE (2.7 – NE) mPFS (mos) (95% CI) 4.4 (2.8 – 6.8) 5.4 (2.8 – 6.8) 4.1 (2.6 – 8.5) Abbreviations: CI, confidence interval; mDOR, median duration of response; mPFS, median progression free survival; NE, not estimable due to small number of subjects and events; PLoT, prior line of therapy
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11 INDICATION TRIAL NAME + DEVELOPMENT APPROACH PHASE 1 PHASE 2 PHASE 3 MILESTONE* Studies for Lead Indication PROC Monotherapy DENALI Part 1b Updated Data at 1H 2025 Medical Meeting DENALI Part 2a + Part 2b Registration-intent Cyclin E1+ FDA Fast Track Designation Part 2a initiation 1H25 Topline Data 2026 Randomized Confirmatory Study Azenosertib vs. SOC chemo Cyclin E1+ Initiation 2026 Other Studies Ongoing Uterine Serous Carcinoma Monotherapy TETON (ZN-c3-004) FDA Fast Track Designation Data 1H26 Ovarian Cancer Combination ZN-c3-002 Azenosertib + multiple chemo backbones and bevacizumab Currently Enrolling BRAF Mutant Colorectal cancer Combination ZN-c3-016 Azenosertib + encorafenib and cetuximab Planned Data at 2025 Medical Meeting Ongoing Study Planned Study *Anticipated Cash Runway into Late 2027, Beyond Potential Registration Data Readout from DENALI Part 2 in Cyclin E1+ PROC Azenosertib Opportunity Remains Broad
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zentalis.com Science Center 10275 Science Center Drive Suite 200 San Diego, CA 92121 Julie Eastland Chief Executive Officer jeastland@zentalis.com Haibo Wang Chief Business Officer hwang@zentalis.com