Zentalis Pharmaceuticals, Inc. · NASDAQ:ZNTL
Zentalis Pharmaceuticals — Investor Presentation (November 2023)
55 slides from Zentalis Pharmaceuticals's investor presentation, Nov 6, 2023
Slide 1: Corporate Presentation
Corporate Presentation Nasdaq: ZNTL November 2023 Exhibit 99.2
Slide 2: Forward Looking Statements and Disclaimer
2 Forward Looking Statements and Disclaimer 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 Securi
Slide 3: First-in-class WEE1 Inhibitor with Broad Franchise Potential
3 First-in-class WEE1 Inhibitor with Broad Franchise Potential Abbreviations: PROC, platinum resistant ovarian cancer; USC, uterine serous carcinoma; ORR, objective response rate; NDA, New Drug Application; mPFS, median progression free survival Statements comparing azenosertib to other agents, not
Slide 4: Building Azenosertib Franchise in Gynecologic Cancers and Beyond
4 Building Azenosertib Franchise in Gynecologic Cancers and Beyond INDICATION TRIAL NAME + DEVELOPMENT APPROACH Phase 1 Phase 1b Phase 2 Phase 3 EXPECTED MILESTONES Azenosertib WEE1 Inhibitor GY N EC O LO G IC M AL IG N AN CI ES Platinum Sensitive Ovarian Cancer 1L maintenance setting Provide additi
Slide 5: Ovarian Cancer is the Leading Cause of Death Across Gynecologic Cancers
5 New therapeutic strategies are needed Ovarian Cancer is the Leading Cause of Death Across Gynecologic Cancers and Remains a Significant Unmet Need 47,451 Newly Diagnosed Annually1 32,018 Deaths Annually1 1 American Cancer Society Ovarian Cancer Key Statistics 2023, ECIS and SEER 2023; 2 Figures re
Slide 6: Uterine Serous Carcinoma Represents High Unmet Medical Need
6 Uterine Serous Carcinoma Comprises 10% of Endometrial Cancer But is the Subgroup with the Highest Mortality 1 Monk B, et al. Gynecologic Oncology 2022;164:325-332; 2 Ferriss JS, et al. International Journal of Gynecologic Cancer 2021;31:1165-1174; 3 American Cancer Society Ovarian Cancer Key Stati
Slide 7: Clinical Programs Position Zentalis for Multiple Datasets with Value-creating Potential
7 2023 2024 2025 2026 Multiple Tumor Types (Includes Ovarian and Uterine Serous Carcinoma) Platinum Resistant Ovarian Cancer Platinum Sensitive Ovarian Cancer Uterine Serous Carcinoma Abbreviations: 1H, first half; 2H, second half Clinical Programs Position Zentalis for Multiple Datasets with Value-
Slide 8: Azenosertib's Mechanism of Action Causes Accumulation of DNA Damage
8 azenosertib WEE1 CDK2/Cyclin E Cell death S G2 M G1 1 Ghelli Luserna di Rorà A, et al. J Hematol Oncol 2020;13:126; 2 Elbæk CR, et al. Cell Rep 2022 Azenosertib’s Mechanism of Action Causes Accumulation of DNA Damage Leading to Cancer Cell Death CDK1/ Cyclin A • Azenosertib dephosphorylates CDK1 a
Slide 9: Azenosertib Treatable Patient Population More Than Doubles as Franchise Expands
9 ‘Drug treatable’ estimates from DRG Clarivate. For ‘Other Cyclin E1+ tumors’ used incidence reported by SEER and ECIS. HRD Post PARPi tumor types: Prostate, Pancreas and Breast; Other Cyclin E1+ Tumor Types include bladder, stomach, esophageal, lung, and breast cancer Abbreviations: PROC, platinum
Slide 10: Azenosertib Monotherapy Updated Results
Azenosertib Monotherapy Updated Results Monotherapy Anti-tumor Activity in Gynecologic Malignancies with Favorable Safety and Tolerability Profile
Slide 11: Strong Safety and Tolerability of Azenosertib Monotherapy
11 Established monotherapy RP2D of 400 mg 5:2 Median follow up has increased by nearly 5 months and mPFS has increased to 6.5 months 37% Objective Response Rate using intermittent dosing in ovarian and USC patients Maintained excellent safety and tolerability with intermittent dosing CORPORATE CALL
Slide 12: Intermittent Monotherapy Patient Population Was Heavily Pretreated and Treatment Refractory
12 Intermittent Monotherapy Patient Population Was Heavily Pretreated and Treatment Refractory USC and HGSOC subjects who received at least one dose of azenosertib with intermittent dosing schedule, have baseline measurable disease by RECIST 1.1, and at least one post-baseline scan. *Platinum Resist
Slide 13: Monotherapy Azenosertib Results in a 37% Confirmed Response Rate
13Subjects who received at least one dose of azenosertib with intermittent dosing schedule, have baseline measurable disease by RECIST 1.1, and at least one post-baseline scan. Abbreviations: +, patients remain on therapy at the time of data cut-off; CR, complete response; PR, partial response; SD,
Slide 14: Monotherapy Azenosertib Has Meaningful and Durable Benefit
14 Monotherapy Azenosertib Has Meaningful and Durable Benefit to Platinum Resistant Ovarian Cancer/USC Patients * Subjects who received at least one dose of azenosertib with intermittent dosing schedule, have baseline measurable disease by RECIST 1.1, and at least one post-baseline scan. Abbreviatio
Slide 15: Azenosertib Monotherapy Continues to Demonstrate Excellent Safety Profile
15 ALL GRADES GRADE 3/4 Fatigue 18 (39.1) 5 (10.9) Hematologic Anemia 11 (23.9) 5 (10.9) Thrombocytopenia 9 (19.6) 4 (8.7) Neutropenia 9 (19.6) 7 (15.2) ALL GRADES GRADE 3/4 Gastrointestinal Nausea 20 (43.5) 2 (4.3) Diarrhea 22 (47.8) 4 (8.7) Vomiting 8 (17.4) 1 (2.2) Decreased appetite 4 (8.7) 1 (2
Slide 16: Azenosertib is Well Tolerated Compared to Other Gynecologic Malignancy Therapies
16 24% 35% 0% 28% 52% 12% 20% 39% 11% 54% 72% 5% 51% 50% 15% 0% 10% 20% 30% 40% 50% 60% 70% 80% Reductions Interruptions Discontinuations Azenosertib is Well Tolerated with Similar or Better Tolerability Compared to Other Gynecologic Malignancy Therapies Safety Evaluable Population (All tumor types;
Slide 17: Data Supports Ongoing Potentially Registrational Studies
17 Data Supports Ongoing Azenosertib Monotherapy Potentially Registrational Studies in Ovarian Cancer and Uterine Serous Carcinoma Monotherapy Conclusions EXCELLENT TOLERABILITY & SAFETY MONOTHERAPY EFFICACY 37% confirmed ORR IMPROVED mPFS of 6.5 MONTHS Supports differentiation from other clinical W
Slide 18: Multiple Ongoing Phase Trials of Azenosertib
Multiple Ongoing Phase 2 Trials of Azenosertib Potential Paths to Registration in Ovarian Cancer and Uterine Serous Carcinoma
Slide 19: Platinum Resistant Ovarian Cancer: Opportunity for Monotherapy Approval
19 Platinum Resistant Ovarian Cancer: High Unmet Need Provides Opportunity for Monotherapy Approval 1 Figures represent Company estimates of U.S. and EU5 patients with conditions covered by the Company’s targeted indications; Source: IQVIA, DRG Clarivate; 2 Matulonis U. JCO 2023 41:13:2436-2445; Abb
Slide 20: DENALI (ZN-c3-005) Trial in Platinum Resistant Ovarian Cancer
20 Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate; DOR, Duration of Response; 1H, first half DENALI (ZN-c3-005): Prospective Evaluation of CCNE1 Amplification and Cyclin E1+ in Platinum Resistant High-Grade Serous Ovarian Cance
Slide 21: MAMMOTH (ZN-c3-006) Trial in PARP-Resistant Ovarian Cancer
21 Abbreviations: PARP, poly-ADP ribose polymerase; QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate DOR, duration of response; PFS, progression free survival; 2H, second half MAMMOTH (ZN-c3-006): Phase 1/2 Study of Azenosertib in Combination wi
Slide 22: New Treatment Options Needed in 2L+ Uterine Serous Carcinoma
221 Figures represent Company estimates of U.S. patients with conditions covered by the Company’s targeted indications and are dependent upon regulatory approvals; Source: IQVIA, DRG Clarivate, Kantar Health; Abbreviations: 2L+, second line maintenance plus; USC, uterine serous carcinoma; 1L, first
Slide 23: TETON (ZN-c3-004) Trial in Uterine Serous Carcinoma
23 CURRENTLY ACCRUING - FDA Fast Track Designation Abbreviations: 2L, two lines; QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate; DOR, duration of response; 2H, second half; The FDA granted Fast Track designation in November 2021 to azenosertib
Slide 24: Azenosertib in Platinum Sensitive Ovarian Cancer: Revised Strategy
Azenosertib in Platinum Sensitive Ovarian Cancer Revised Strategy 1L Maintenance Opportunity to Provide Prolonged Benefit for a Larger Number of Patients
Slide 25: Opportunity for Azenosertib in First Line Maintenance HRP Ovarian Cancer
25 PFI<6m Second Line Therapy Combination Chemotherapy Platinum Doublet PFI>6m PFI<6m Platinum Resistant Single Agent Chemotherapy or Mirvetuximab (~35% pts)3 Opportunity for Azenosertib in First Line Maintenance in Homologous Repair Proficient (HRP) Platinum Sensitive Ovarian Cancer 1 Ray-Coquard I
Slide 26: Potential to Impact the Greatest Number of Ovarian Cancer Patients in 1L Maintenance
26 Potential for Azenosertib to Impact the Greatest Number of Ovarian Cancer Patients in the 1L Maintenance Setting 1 Figures represent Company estimates of U.S. and EU5 patients with conditions covered by the Company’s targeted indications; Source: IQVIA, DRG Clarivate Kantar and DRG; 2 Ray-Coquar
Slide 27: Azenosertib as 1L Maintenance Therapy in Platinum Sensitive Ovarian Cancer
27 Additional trial details in 2H 2024 Azenosertib as 1L Maintenance Therapy in Platinum Sensitive Ovarian Cancer Patients Professor Alexandra Leary, MD, PhD Deputy Chair of Medical Oncology, Institut de Cancérologie Gustave Roussy, France GINECO and ENGOT Investigator “Zentalis’ frontline maintenan
Slide 28: Azenosertib Combination with Chemotherapy Clinical Data
Azenosertib Combination with Chemotherapy Clinical Data Shows Strong Efficacy and Favorable Safety Profile in Platinum Resistant Ovarian Cancer
Slide 29: ZN-c3-002: Phase 1b Combination Study in Platinum Resistant Ovarian Cancer
29 Azenosertib + Paclitaxel Azenosertib + Gemcitabine Azenosertib + PLD Azenosertib + Carboplatin Liu JF, et al. Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 5513-5513; Abbreviations: CRM, continuous reassessment model; QD, once daily; D, day; AUC, area under the curve; PLD, pegylat
Slide 30: Encouraging Efficacy and Durability in Combination with Chemotherapy
30 *Response-evaluable subjects are treated subjects with baseline measurable disease per RECIST version 1.1 and at least one post-baseline assessment. All objective responses were confirmed per RECIST v 1.1. Data include patients on all schedules of azenosertib plus chemotherapy. Liu JF, et al. J
Slide 31: Combination with Chemotherapy Demonstrates Favorable Safety Profile
31*All doses were at or below MTD and were intermittent; **A MTD for gemcitabine + azenosertib has not been determined, further dose cohorts are ongoing. Liu JF, et al. Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 5513-5513; Abbreviations: MTD, maximum tolerated dose; PLD, pegylate
Slide 32: Addition of Azenosertib Increases Response Rates and Durability
32Liu JF, et al. Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 5513-5513; Abbreviations: SOC, standard of care; PLD, pegylated liposomal doxorubicin Addition of Azenosertib to Single Agent Chemotherapy Increases Response Rates and Durability of Response in Ovarian Cancer Compared to
Slide 33: Targeting Tumors with High Genomic Instability Using Azenosertib
Targeting Tumors with High Genomic Instability Using Azenosertib
Slide 34: Multiple Mechanisms Leading to Genomic Instability Enhance Sensitivity
34 CDK2/Cyclin E S G1 1 Fagundes R, et al. Front Cell Dev Biol. 2021; 2 Stewart MD, Oncologist. 2022; 3 Zhang, J, et al. Genes 2016; Abbreviations: BRAF, V-Raf Murine Sarcoma Viral Oncogene Homolog B; KRAS, Kirsten rat sarcoma viral oncogene homolog Multiple Mechanisms Leading to Genomic Instability
Slide 35: Tumors with CCNE1 Amplification or Cyclin E1 Positivity are Highly Sensitive
35 1 Etemadmoghadam D, et al. Proc Natl Acad Sci U S A. 2013; 2 Zhao H, et al. J Cancer. 2018; 3 Ma, et al. Cancer Res 2023 83 (7_Supplement): 2153; 4 Kok, YP et al. Oncogenesis 9, 88 2020 Tumors with CCNE1 Amplification or Cyclin E1 Positivity are Highly Sensitive to Azenosertib • CCNE1 gene amplif
Slide 36: Higher DNA Damage and Tumor Growth Inhibition in Cyclin E1 Positive Tumors
36 1800 1500 12009 00 600 300 0 0 4 8 12 16 20 24 28 • Azenosertib treatment results in 88% Tumor Growth Inhibition (TGI) in xenografted Cyclin E1 positive OVCAR3 tumors Ma, et al. Cancer Res (2023) 83 (7_Supplement): 2153; Abbreviations: PO, orally; QD, daily Azenosertib Results in Higher Levels of
Slide 37: Cyclin E1 Amplification Prevalent in Gynecologic Malignancies
37 1 Etemadmoghadam D., et al. Proc Natl Acad Sci USA 2013; 2 Yao, S., et al. Sci Rep 12, 8701 2022 Cyclin E1 Amplification Particularly Prevalent in Gynecologic Malignancies But Occurs in Many Other Tumor Types TCGA Pan Cancer Analysis (6547 samples)1 Frequency of CCNE1 Amplification Across Tumor T
Slide 38: CCNE1 Alteration and Outcomes Across Tumor Types
38 1 Shariat SF, et al. Human Path. 2006; 2 Matsushita R, et al. British J Cancer 2015; 3 Lotan Y, et al. Euro Assoc Urology 2013; 4 Stronach E, et al. Mol Cancer Res 2018; 5 Pils D, et al. Euro J Cancer 2014; 6 Petersen S, et al. Gynecol Oncol 2020; 7 Nakayama N, et al. Cancer 2010; 8 Kang E, et al
Slide 39: CCNE1 Amplified/Cyclin E1+ Ovarian Cancers Have Worse Outcome After Platinum Chemotherapy
391 Stronach, et al. Mol Cancer Res 2018;16:1103-11; 2 Pils, et al. Eur J Cancer 2014;50:99-110; 3 Peterson, et al. Gynecol Oncol 2020;157:405-10; 3 Nakayama, et al. Cancer 2010;116:2621-34; 5 Kang, et al. Cancer 2023;129:697-713; 6 Chan, et al. J Pathol Clin Res 2020;6:252-62; *Timing of tissue col
Slide 40: Cyclin E1 Protein Expression is High in Majority of Ovarian Cancers
40 *H-scores calculated by multiplying the percentage of cells (0 to 100%) with intensity of Cyclin E1 expression (0 to 3). Harismendy, et al. Presented at the AACR Special Conference in Cancer Research: Ovarian Cancer. October 5 - 7, 2023 - Boston, MA; Abbreviations: HGSOC, high-grade serous ovaria
Slide 41: Progression Free Survival Triples in Patients with Cyclin E1+ Tumors
41H-scores calculated by multiplying the percentage of cells (0 to 100%) with intensity of Cyclin E1 expression (0 to 3); Liu JF., et al. Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 5513-5513; Abbreviations: CI, confidence interval; PFS, progression free survival Progression Free S
Slide 42: Azenosertib +/- PARP Inhibitor Combinations Active in HRD Tumors
42 1600 1200 800 400 0 0 10 20 30 Zentalis data on file; Abbreviations: PARP, poly-ADP ribose polymperase; HRD, homologous recombination repair deficient; PARPi, PARP inhibitor; CDX, cell line derived xenograft; PDX, patient derived xenograft; TNBC, triple-negative breast cancer Monotherapy Azenoser
Slide 43: Preclinical Data Supports Combination with Encorafenib and Cetuximab
43 • Oncogene-induced replication stress in mutationally driven cancers leads to DNA damage and genomic instability1 • Azenosertib further increases replication stress and DNA damage, providing mechanistic basis for synergy with EGFR/BRAF inhibition • Addition of azenosertib to the BEACON regimen is
Slide 44: ZN-c3-016: Phase 1/2 Trial in BRAF mCRC in Collaboration with Pfizer
44Abbreviations: BRAF, V-Raf Murine Sarcoma Viral Oncogene Homolog B; mCRC, metastatic colorectal cancer; EGFR, epidermal growth factor receptor; MTD, maximum tolerated dose; RP2D, recommended phase 2 dose; ORR, objective response rate; DOR, duration of response; DCR, disease control rate; PFS, prog
Slide 45: Strong Rationale Supports Ongoing Clinical Development of Azenosertib
45 3 2 1 Abbreviations: IHC, immunohistochemistry; PARP, poly-ADP ribose polymerase; BRAF, V-Raf Murine Sarcoma Viral Oncogene Homolog B; EGFR, epidermal growth factor receptor; HRD, homologous recombination repair deficient Strong Rationale Supports Ongoing Clinical Development of Azenosertib in Ca
Slide 46: BCL-2 Inhibitor (ZN-d5) in Combination with Azenosertib in AML
BCL-2 Inhibitor (ZN-d5) in Combination with Azenosertib Represents Opportunity to Address Acute Myeloid Leukemia Patients with Known Poor Prognosis and High Unmet Need
Slide 47: Relapsed/Refractory AML Remains a Major Unmet Medical Need
47 1. American Cancer Society. Cancer Facts & Figures 2023, SEER and ECIS. 2 Figures represent company best estimates based on US patients with conditions covered by the companies target indication. Sources DRG Clarivate, Kantar Health 3 Shimony, S, et al. Am J Hematol. 2023; 98(3): 502-526; 4 Maiti
Slide 48: ZN-d5 and Azenosertib Combination Results in Synergistic Anti-Tumor Activity in AML Model
48 HL-60 (in vitro)HL-60 (in vitro) 1. Izadi H, et al. AACR 2022 Cancer Res (2022) 82 (12_supplement):2591; Data / Report On File, Zentalis Pharmaceuticals Combination of ZN-d5 and Azenosertib Results in Enhanced Apoptosis, DNA Damage and Synergistic Anti-Tumor Activity in an AML Model - - + - + - +
Slide 49: Many AML Patients Still Lack Treatment Options After Relapse
49 Adapted from Heuser, Y. et. Al. Annals of Oncology 31 (6) 697-712 2020; Abbreviations: AML, acute myeloid leukemia; SCT, stem cell transplant Despite Recent Progress and Evolving Treatment Paradigm in AML, Many Patients Still Lack Treatment Options After Relapse 1st Relapse Chemo/SCT Ineligible:
Slide 50: ZN-d5-004C: Phase 1/2 Study of ZN-d5 and Azenosertib in R/R AML
50 ZN-d5-004C: Enrolling Phase 1/2 Study of ZN-d5 and Azenosertib in R/R AML Abbreviations: R/R, relapsed/refractory; AML, acute myeloid leukemia; RP2D, recommended Phase 2 dose; PK, pharmacokinetics; ORR, objective response rate; CR, complete response; CRi: complete response with incomplete count r
Slide 51: Executing on the Franchise Potential of Azenosertib
Executing on the Franchise Potential of Azenosertib
Slide 52: 2023 Milestones Achieved
52 2023 Milestones Achieved ZN-d5 BCL-2 Inhibitor Discovery 1Q 2023 Initiate enrollment in the BRAF mutant colorectal cancer BEACON regimen combination clinical trial in collaboration with Pfizer 1H 2023 Provide preclinical rationale for Cyclin E1 enrichment strategy at a scientific conference 1H 20
Slide 53: Upcoming Clinical Milestones
53Abbreviations: 1H, first half; 2H second half; BRAF, V-Raf murine sarcoma viral oncogene homolog B; mCRC, metastatic colorectal cancer; PARPi, poly-ADP ribose polymerase inhibitor; R/R AML, relapsed or refractory acute myeloid leukemia; PROC, platinum resistant ovarian cancer; USC, uterine serous
Slide 54: Zentalis is Positioned for Success with Azenosertib Franchise
54Abbreviations: mPFS: median progression free survival; ORR, objective response rate; mPFS, median progression free survival; USC, uterine serous carcinoma; 1L, first line NDA, New Drug Application; Statements comparing azenosertib to other agents, not head-to-head comparisons Zentalis is Positione
Slide 55: zentalis.com
zentalis.com Kimberly Blackwell, M.D. Chief Executive Officer kblackwell@zentalis.com (212) 433-3787 Melissa Epperly Chief Financial Officer mepperly@zentalis.com (215) 290-7271 Corporate Office 1359 Broadway Suite 801 New York, NY 10018 Science Center 10275 Science Center Drive Suite 200 San Diego,
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