Zentalis Pharmaceuticals, Inc. · NASDAQ:ZNTL

Zentalis Pharmaceuticals — Investor Presentation (April 2026)

39 slides from Zentalis Pharmaceuticals's investor presentation, Apr 9, 2026

  1. Slide 1: Corporate Presentation April 2026

    Corporate Presentation April 2026 Nasdaq: ZNTL

  2. Slide 2: Forward-looking statements

    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 st

  3. Slide 3: Momentum Expected to Continue in 2026 for Azenosertib Development Program

    3 $245.9M cash, cash equivalents and marketable securities as of Dec 31, 2025 supports expected milestones with anticipated runway into late 2027 Momentum Expected to Continue in 2026 for Azenosertib Development Program with Registration-Intent Studies Established solid clinical foundation for the l

  4. Slide 4: Extensive Data Support Azenosertib as Potential Best-in-Class Non-Chemo Therapy

    4 Extensive Data Support Azenosertib as Potential Best-in-Class, Orally Available, Non-Chemo Therapy for Patients with Cyclin E1-Positive Platinum-Resistant Ovarian Cancer (PROC) >30% ORR, ~6 mos mDOR‡ ‡ As of Jan. 13, 2025 data cutoff in DENALI Part 1b, mDOR subject to change; † Not a head-to-head

  5. Slide 5: Cyclin E1 Overexpression Sensitizes Cancer Cells to Azenosertib

    5 • Cyclin E1 overexpression increases CDK2 activity and accelerates G1-S transition, rendering cells more dependent on the DNA repair at the G2-M checkpoint • Inhibition of WEE1 activates CDKs, accelerates G1-S and G2-M transitions, and increases DNA damage to intolerable levels, resulting in mitot

  6. Slide 6: Multiple Drivers of Cyclin E1 Protein Overexpression

    6 Multiple Drivers of Cyclin E1 Protein Overexpression Companion diagnostic ready for use in registration-intent studies to identify Cyclin E1-Positive patients, ~50% of PROC patient population† 1. Kim, D., et al. Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gyn

  7. Slide 7: Significant Market Opportunity in High Unmet Need Cyclin E1-Positive PROC

    7 Significant Market Opportunity in High Unmet Need Cyclin E1-Positive PROC * Based on 2024 annual estimates in US and EU4 (France, Germany, Italy, Spain) + UK 1. Abbvie Q4 2025 Earnings: https://news.abbvie.com/2026-02-04-AbbVie-Reports-Full-Year-and-Fourth-Quarter-2025-Financial-Results 2. ~20% of

  8. Slide 8: Platinum Resistant Ovarian Cancer: High Unmet Need

    8 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+) SOC 2L+ Therapy3 Chemo Mono ORR 4 – 13%1 Elahere (mirvetuximab) (FRα+ ~35% of PROC) ORR 32% - 42%2 No a

  9. Slide 9: DENALI Phase 2 Registration-Intent Study for Accelerated Approval

    9 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; DOR=duration of response; ORR=overall response rate; PFS=progression free surviv

  10. Slide 10: ASPENOVA Phase 3 Confirmatory Study for Full Approval

    10 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; PLD=pegylated liposomal doxorubicin; OS=overall survival; ORR=overall response

  11. Slide 11: Azenosertib Development Programs and Study Status

    11 TRIAL NAME DEVELOPMENT APPROACH PHASE 1 PHASE 2 PHASE 3 STUDY STATUS Cyclin E1-Positive PROC Monotherapy (lead indication) DENALI DENALI Part 1b Demonstrated Cyclin E1 protein overexpression as biomarker predicting response to azenosertib Ongoing In Long-term Follow-up Only DENALI Part 2a + Part

  12. Slide 12: Integrated Data of ZN-c3-001, MAMMOTH, and DENALI Part 1b

    Integrated Data of ZN-c3-001, MAMMOTH, and DENALI Part 1b

  13. Slide 13: Single-Agent Chemotherapy has Low Efficacy in PROC

    13 Standard of Care* Single-Agent Chemotherapy has Low Efficacy in PROC New Options with Greater Efficacy Needed bev, bevacizumab; FRα, folate receptor alpha; mo, months; ORR, objective response rate; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PROC, platinum-resistant ovar

  14. Slide 14: Integrated Safety Analysis in All Patients

    14 Integrated Safety Analysis in All Patients Total Daily Dose ≥300mg (N=356) Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: haematocrit decreased, haemoglobin decreased, RBC count decrea

  15. Slide 15: Safety and Tolerability at 300 and 400 mg 5:2 Broadly Comparable

    15 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 Abbrevia

  16. Slide 16: 400mg 5:2 Shows Meaningful Response Rates and mDOR

    16 *Includes patients who received at least one post-treatment scan 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 M

  17. Slide 17: Higher Response Rates and Longer PFS with Fewer Prior Lines of Therapy

    17 Higher Response Rates and Longer PFS with Fewer Prior Lines of Therapy 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

  18. Slide 18: DENALI Part 1b (ZN-c3-005)

    DENALI Part 1b (ZN-c3-005) NCT05198804 Updated data at SGO 2025, Data cutoff January 13, 2025

  19. Slide 19: Cyclin E1 Overexpression and CCNE1 Amplification Have Worse Outcomes

    19 Ovarian Cancer Patients With Cyclin E1 Overexpression and/or CCNE1 Amplified Ovarian Cancers Have Worse Outcomes DENALI Survival according to CCNE1 amplification status1 aTiming of tissue collection was not disclosed. OS, overall survival; PFS, progression-free survival. 1. Stronach EA, et al. Mo

  20. Slide 20: DENALI Part 1b Evaluated 400mg 5:2 QD and Confirmed Cyclin E1 Biomarker

    20 Study Design  Platinum-resistant ovarian cancer  1-5 prior lines of therapy  Tissue mandatory for biomarker assessment Key Eligibility DENALI Part 1b Evaluated 400mg 5:2 QD and Confirmed Cyclin E1 Biomarker DENALI Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off t

  21. Slide 21: DENALI Part 1b: Patient Baseline Characteristics

    21 DENALI Part 1b: Patient Baseline Characteristics DENALI Data cutoff date: January 13, 2025. aFull analysis set: all treated patients. Biomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. bHispanic. c85% (23/27) of patients with CCNE1-amplified tumors were also C

  22. Slide 22: Cyclin E1+ by IHC is a Biomarker Predicting Response to Azenosertib

    22 Cyclin E1+ by IHC is a Biomarker Predicting Response to Azenosertib DENALI Data cutoff date: Jan 13, 2025. aIntent to treat/Full analysis set: all treated patients. bBiomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. cIncludes patients who received at least on

  23. Slide 23: DENALI Part 1b: Duration of Response in Cyclin E1 IHC+ Ovarian Cancer

    23 DENALI Part 1b: Duration of Response in Cyclin E1 IHC+ Ovarian Cancer DENALI amDOR is subject to change, there are 4 ongoing responders as of the January 13, 2025 data cutoff. IHC, immunohistochemistry; cPR, confirmed partial response; SD, stable disease; PD, progressive disease; mDOR, median dur

  24. Slide 24: DENALI Part 1b: Safety and Tolerability Summary

    24 DENALI Part 1b: Safety and Tolerability Summary DENALI Data cutoff date: January 13, 2025 aIf a patient had multiple grades of the same adverse event, The worse grade was reported bOne patient had sepsis, and 1 patient had pancytopenia. ALT, alanine aminotransferase; AST, aspartate aminotransfera

  25. Slide 25: Zentalis contact information

    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 Aron Feingold VP, IR and Corporate Communications afeingold@zentalis.com

  26. Slide 26: Appendix

    APPENDIX

  27. Slide 27: ZN-c3-001 Dose-Escalating Monotherapy Study in Solid Tumors

    ZN-c3-001 Dose-Escalating Monotherapy Study in Solid Tumors NCT04158336

  28. Slide 28: First-in-Human Phase Dose and Schedule Optimization in Solid Tumors

    28 Total Enrollment First-in-Human Phase 1 Dose and Schedule Optimization in Solid Tumors: Therapeutic Window Established N=274 across all tumor types and dose* N=193 at total daily dose ≥ 300mg; evaluated for safety and anti-tumor activity ZN-c3-001 * Total enrollment (N=274) included cohorts for f

  29. Slide 29: Heavily Pre-Treated Patient Population with Multiple Tumor Types

    29 Heavily Pre-Treated Patient Population with Multiple Tumor Types; Patients with PROC had a Median of Five Prior Lines of Therapy PROC N = 69 USC N = 35 Other Solid Tumors* N = 89 Age (years) Median 66 66 64 Range (Min-Max) (48 – 83) (53 – 78) (26 – 81) ECOG PS (n, %) ECOG 0 19 (28%) 8 (23%) 32 (3

  30. Slide 30: Tolerable at Active Dose Levels Across Tumor Types

    30 Tolerable at Active Dose Levels Across Tumor Types Treatment Related AEs, n (%) Treatment-Related SAE 19 (9.8%) TRAE leading to dose reduction 76 (39.4%) TRAE leading to dose interruption 78 (40.4%) TRAE leading to discontinuation 10 (5.2%) TRAE leading to death 1 (0.5%) Treatment Related AEs*, n

  31. Slide 31: Clinical Activity Overview at Total Daily Doses ≥300 mg

    31 Clinical Activity Overview - Total Daily Doses ≥ 300 mg - Continuous and Intermittent (N=193) Azenosertib Demonstrated Encouraging ORR and DOR at ≥300mg Total Daily Dose, Intermittent in PROC Tumor Type PROC USC Other Solid Tumors Dose Schedule Intermittent Continuous Intermittent Continuous Inte

  32. Slide 32: Key Takeaways from ZN-c3-001

    32 Key Takeaways from ZN-c3-001 Azenosertib studied in a large patient population across multiple tumor types Platinum-resistant ovarian cancer (PROC) identified as an indication particularly susceptible to WEE1 inhibition Cyclin E1 identified as predictive biomarker for response to azenosertib Mean

  33. Slide 33: MAMMOTH (ZN-c3-006)

    MAMMOTH (ZN-c3-006) NCT05198804

  34. Slide 34: MAMMOTH: Two Clinically-active Monotherapy Doses in PARPi-resistant PROC

    34 MAMMOTH: Two Clinically-active Monotherapy Doses Studied in Heavily Pre-treated, PARPi-resistant PROC Patient Population Study Design  1-5 prior lines of therapy  Platinum-resistant, progressed while receiving an approved PARP inhibitor  Mandatory sufficient tissue for biomarker analysis Key E

  35. Slide 35: Heavily Pre-Treated PARPi-resistant PROC Population

    35 Heavily Pre-Treated PARPi-resistant PROC Population 300 mg 5:2 (N=25) 400 mg 5:2 (N=36) Age (years) Median 71.0 63.0 Range (Min-Max) 45 – 80 31 - 84 ECOG PS (n, %) ECOG 0 7 (28%) 16 (44%) ECOG 1 18 (72%) 20 (56%) Prior Lines of Treatment (n, %) 1-3 15 (60%) 20 (56%) ≥4 10 (40%) 16 (44%) PARP 25 (

  36. Slide 36: Well-characterized Safety and Tolerability in PROC Monotherapy Cohorts

    36 Well-characterized Safety and Tolerability in PROC Monotherapy Cohorts at 300mg QD and 400mg QD (5:2) Doses Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglo

  37. Slide 37: Clinically Meaningful Responses in PARPi-resistant Monotherapy Cohorts

    37 Azenosertib Monotherapy 300 mg & 400mg QD (5:2) Azenosertib Demonstrated Clinically Meaningful Responses in PARPi-resistant Monotherapy Cohorts Dose and Schedule 300mg 5:2 400mg 5:2 Cyclin E1 IHC Status All Cyclin E1+ All Cyclin E1+ Number of Patients 25 14 36 16 ORR, (%), n (95% CI) 20.0% (5/25)

  38. Slide 38: Key Takeaways from MAMMOTH Monotherapy Cohort

    38 Key Takeaways from MAMMOTH Monotherapy Cohort Consistent antitumor activity in PARPi-resistant patients Tolerability and toxicity consistent with 001 study and similar between the assessed doses 400mg QD 5:2 showed numerically higher response rates than 300mg QD 5:2 MAMMOTH Learnings continue to

  39. Slide 39: Zentalis

    ¢ zentalis

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