Zentalis Pharmaceuticals, Inc. · NASDAQ:ZNTL
Zentalis Pharmaceuticals — Investor Presentation (August 2025)
37 slides from Zentalis Pharmaceuticals's investor presentation, Aug 6, 2025
Slide 1: Corporate Presentation August 2025
Corporate Presentation August 2025 Nasdaq: ZNTL
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
Slide 3: Extensive Data Support Azenosertib as Potential Best-in-Class Therapy for Cyclin E1-Positive PROC
3 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
Slide 4: Projected Cash Runway into Late 2027 and Upcoming Milestones
4 Projected Cash Runway into Late 2027, Beyond Anticipated Registration- Intent Phase 2 Topline Data o 2026: Initiate Phase 3 confirmatory trial following FDA feedback o YE 2026: Topline data from registration-intent† DENALI Part 2 o Potential for FDA accelerated approval in Cyclin E1- Positive PROC
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
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
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 Q2 2025 Earnings: https://news.abbvie.com/2025-07-31-AbbVie-Reports-Second-Quarter-2025-Financial-Results 2. NAKAYAMA, K. et al. I
Slide 8: High Unmet Need in Cyclin E1+ PROC Patients
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+) Approved 2L+ Therapy Chemo Mono ORR 4 – 13%1 Elahere (mirvetuximab) (FRα+ ~35% of PROC) ORR 32% - 42%2
Slide 9: Standard of Care Single-Agent Chemotherapy has Low Efficacy in PROC
9 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 ovaria
Slide 10: Integrated Data and Potential Path to Registration in PROC
Integrated Data and Potential Path to Registration in PROC
Slide 11: Integrated Safety Analysis in All Patients
11 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
Slide 12: Safety and Tolerability at 300 and 400 mg 5:2 Broadly Comparable
12 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
Slide 13: 400mg 5:2 Shows Meaningful Response Rates and mDOR
13 *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
Slide 14: Higher Response Rates and Longer PFS with Fewer Prior Lines of Therapy
14 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
Slide 15: Registration-Intent Studies for Azenosertib Monotherapy in PROC
15 Randomized Study vs. Standard of Care Same Key Eligibility as DENALI Part 2 Initiation Planned Post-Dose Confirmation Detail Design to be Discussed with FDA Abbreviations: 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; IHC= immunohistochemi
Slide 16: DENALI Part 1b (ZN-c3-005)
DENALI Part 1b (ZN-c3-005) NCT05198804 Updated data at SGO 2025, Data cutoff January 13, 2025
Slide 17: Cyclin E1 Overexpression and CCNE1 Amplified Ovarian Cancers Have Worse Outcomes
17 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
Slide 18: DENALI Part 1b Study Design
18 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
Slide 19: DENALI Part 1b: Patient Baseline Characteristics
19 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
Slide 20: Cyclin E1+ by IHC is a Biomarker Predicting Response to Azenosertib
20 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
Slide 21: DENALI Part 1b: Duration of Response in Cyclin E1 IHC+ Ovarian Cancer
21 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
Slide 22: DENALI Part 1b: Safety and Tolerability Summary
22 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
Slide 23: Registration-Intent DENALI Part 2 Topline Data Anticipated by YE2026
23 Registration-Intent DENALI Part 2 Topline Data Anticipated by YE2026 Cyclin E1+ / overexpression by IHC represents ~ 50%c of PROC • Cyclin E1+ IHC more than doubles the eligible patient population beyond CCNE1 amp Azenosertib demonstrates ORR of ~35% in evaluablea patients with Cyclin E1+ PROC •
Slide 24: ZN-c3-001 Dose-Escalating Monotherapy Study in Solid Tumors
ZN-c3-001 Dose-Escalating Monotherapy Study in Solid Tumors NCT04158336
Slide 25: Dose and Schedule Optimization in Solid Tumors: Therapeutic Window Established
25 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
Slide 26: Heavily Pre-Treated Patient Population with Multiple Tumor Types
26 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
Slide 27: Tolerable at Active Dose Levels Across Tumor Types
27 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
Slide 28: Clinical Activity Overview at Total Daily Doses ≥300 mg
28 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
Slide 29: Key Takeaways from Azenosertib Studied Across Multiple Tumor Types
29 Key Takeaways from 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 Meaningful
Slide 30: MAMMOTH (ZN-c3-006)
MAMMOTH (ZN-c3-006) NCT05198804
Slide 31: MAMMOTH: Two Clinically-active Monotherapy Doses in PARPi-resistant PROC
31 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
Slide 32: Heavily Pre-Treated PARPi-resistant PROC Population
32 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 (
Slide 33: Well-characterized Safety and Tolerability in PROC Monotherapy Cohorts
33 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
Slide 34: Azenosertib Demonstrated Clinically Meaningful Responses in PARPi-resistant PROC
34 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)
Slide 35: Key Takeaways from MAMMOTH Monotherapy Cohort
35 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
Slide 36: Azenosertib Development Studies and Milestones
36 INDICATION TRIAL NAME + DEVELOPMENT APPROACH PHASE 1 PHASE 2 PHASE 3 MILESTONE* Studies for Lead Indication PROC Monotherapy DENALI Part 1b DENALI Part 2a + Part 2b Registration-intent Cyclin E1-Positive FDA Fast Track Designation Topline Data YE2026 Randomized Confirmatory Study Azenosertib vs.
Slide 37: 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
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