Zentalis Pharmaceuticals : Corporate Presentation – November 2023

Corporate Presentation

November 2023

Nasdaq: ZNTL

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 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 potential for azenosertib (ZN-c3) to be first-in-class and best-in-class; the franchise potential of azenosertib; the potential applicability of azenosertib to a broad array of tumor types, including in combination with molecularly targeted agents; the potential timing of filing our first New Drug Application for azenosertib; potential for azenosertib to have real impact for patients; our positioning to execute; our projected cash runway; our development approach for our product candidates; planned clinical trials for our product candidates, including our strategy with respect to azenosertib in platinum sensitive ovarian cancer; the potential that we are generating registrational data; the potential of azenosertib to address large unmet need across a broad array of tumor types; the potential for studies to be registrational; potential paths to registration; the potential and suitability of azenosertib to address tumors with high genomic instability; the opportunity for azenosertib in first-line maintenance in homologous repair proficient platinum sensitive ovarian cancer; the opportunity for a monotherapy approval of azenosertib in platinum resistant ovarian cancer; our strategy for azenosertib development, including in platinum sensitive ovarian cancer; the potential for azenosertib to provide prolonged benefit for the greatest number of ovarian cancer patients in the first-line maintenance setting; the potential for CCNE1 amplification and Cyclin E1 IHC as potential patient enrichment strategies; the opportunity to address unmet need in relapsed or refractory acute myeloid leukemia by combining azenosertib and ZN-d5; building the azenosertib franchise, including that the franchise opportunity for azenosertib more than doubles as it expands beyond gynecologic malignancies; the potential unmet need in a particular indication and/or patient population; potential for generating datasets with value-creating potential; potential for combinations including our product candidates and the potential benefits thereof; our potential positioning for success with the azenosertib franchise; the potential benefits of the designs of our product candidates; the target profiles and potential benefits of our product candidates and their mechanisms of action, including as a monotherapy and/or in combination; the market opportunities for and market potential of our product candidates, including the number of potential patients per year; 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 "anticipate," "building," "estimate," "expect," "may," "milestone," "opportunity," "plan," "positioned," "potential," "strategy," "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 any diagnostic tools; 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.

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.

2

Advancing Azenosertib

First-in-class WEE1 Inhibitor with Broad Franchise Potential

Highly Specific Agent Targeting WEE1

• Clinical-stageasset generating potentially registrational data
• Intermittent dosing allows for maximized efficacious exposures
• Differentiated from and years ahead of other agents against this target in development

Real Impact for Patients

• Monotherapy efficacy; 37% ORR and 6.5 month mPFS in heavily pretreated ovarian and USC
• Excellent safety and tolerability profile compared to other commercially successful anti-cancer agents
• Established dosing and efficacy in combination with multiple chemotherapeutic agents

Blockbuster Opportunity

• At least 2 gynecologic malignancies (PROC/USC)
• Expanding to a broad array of tumor types in combination with molecularly targeted agents
• More than 10 ongoing and planned trials
• Potential first NDA in 2026

Positioned to Execute

• Deep oncology expertise
• Industry-leadingscientific and clinical advisors
• Partnerships with Pfizer and GSK
• Cash runway into 2026

Abbreviations: PROC, platinum resistant ovarian cancer; USC, uterine serous carcinoma; ORR, objective response rate; NDA, New Drug Application; mPFS, median progression free survival	3
Statements comparing azenosertib to other agents, not head-to-head comparisons

Building Azenosertib Franchise in Gynecologic Cancers and Beyond

Azenosertib

WEE1 Inhibitor

ZN-d5

BCL-2 Inhibitor

GYNECOLOGIC MALIGNANCIES

OTHER TUMOR TYPES

INDICATION	TRIAL NAME + DEVELOPMENT APPROACH	Phase 1	Phase 1b	Phase 2	Phase 3	EXPECTED
MILESTONES
Platinum Sensitive	1L maintenance setting					Provide additional details
Ovarian Cancer					2H 2024
Platinum Resistant	DENALI (ZN-c3-005)					Topline data anticipated
Ovarian Cancer	Monotherapy					1H 2025
PARPi Resistant	MAMMOTH (ZN-c3-006)					Topline data anticipated
Ovarian Cancer	Azenosertib monotherapy, or with niraparib					2H 2024
Uterine Serous	TETON (ZN-c3-004)					Topline data anticipated
Carcinoma	Monotherapy, FDA Fast Track Designation					2H 2025
Platinum Resistant	ZN-c3-002					Data presented ASCO
Ovarian Cancer	Azenosertib + multiple chemo backbones					2023
Solid Tumors	ZN-c3-001					Final results anticipated
Monotherapy					2H 2024
Osteosarcoma	ZN-c3-003					Final results anticipated
Azenosertib + gemcitabine					1H 2024
BRAF Mutant	ZN-c3-016					Initial data anticipated
Colorectal Cancer	Azenosertib + encorafenib and cetuximab					2H 2024
Pancreatic Cancer	Azenosertib + gemcitabine					Investigator initiated
				study
Breast Cancer	ZAP-IT					Investigator initiated
Azenosertib + carboplatin + pembrolizumab					study
Acute Myeloid	ZN-d5-004C					Initial data anticipated
Leukemia	ZN-d5 + azenosertib					2H 2024

4

Ovarian Cancer is the Leading Cause of Death Across Gynecologic Cancers and Remains a Significant Unmet Need

New therapeutic strategies are needed

Ovarian Cancer

• Approximately 80% of women with advanced stage disease who respond to first-line chemotherapy will relapse3
• Single agent chemotherapy response for heavily pretreated platinum resistant/refractory ovarian cancer is 10-15%3

US/EU5 OVARIAN

CANCER PATIENTS1

47,451

Newly

Diagnosed32,018 Annually1

Deaths

Annually1

US/EU5 DRUG

TREATABLE PATIENTS2

52,265

1L

Maintenance 42,891

PlatinumPlatinum

SensitiveResistant

1 American Cancer Society Ovarian Cancer Key Statistics 2023, ECIS and SEER 2023; 2 Figures represent Company estimates of U.S. patients in 2023 with conditions covered by the Company's targeted indications and are	5
dependent upon regulatory approvals; Source: IQVIA, DRG Clarivate, Kantar Health; 3 NCI Int J Gynaecol Obstet. 2021 Oct; 155(Suppl 1): 61-85. Abbreviation: 1L, first line

Uterine Serous Carcinoma

Uterine Serous Carcinoma Represents High Unmet Medical Need

Uterine Serous Carcinoma Comprises 10% of Endometrial Cancer But is the Subgroup with the Highest Mortality

• Uterine serous carcinoma (USC), a subtype of endometrial cancer, represents approximately
  10% of all endometrial cases1
• USC accounts for nearly
  40% of all endometrial cancer-related deaths1
• Chemotherapy resistant with single agent chemotherapy response rate of ~15% in heavily pretreated patients2

DIAGNOSED CASES OF			TOTAL DEATHS FROM
ENDOMETRIAL CANCER -
ALL STAGES	USC	ENDOMETRIAL CANCER
in the US/EU5 Annually	in the US/EU5 Annually	2023 US/EU5
	Patients
					DRUG TREATABLE4
10%	40%
113,070				24,584
PATIENTS3			DEATHS3

4,103

Treatable Patients

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 Statistics 2023 ECIS and SEER 2023;	6
4 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

Clinical Programs Position Zentalis for Multiple Datasets with Value-creating Potential

	2023	TODAY	2024	2025	2026
Multiple Tumor	ZN-c3-001: Dose Escalation/Expansion
Types		FINAL RESULTS 2H 2024
(Includes Ovarian and	Azenosertib monotherapy
Uterine Serous Carcinoma)
	DENALI (ZN-c3-005):		TOPLINE DATA 1H 2025
Platinum Resistant	Azenosertib monotherapy
Ovarian Cancer	MAMMOTH (ZN-c3-006):PARPi-resistant
	TOPLINE DATA 2H 2024
	Azenosertib monotherapy
Platinum Sensitive				First-Line Maintenance
Ovarian Cancer				Azenosertib
Uterine Serous	TETON (ZN-c3-004):		TOPLINE DATA 2H 2025
Carcinoma	Azenosertib monotherapy
Abbreviations: 1H, first half; 2H, second half				7

Azenosertib's Mechanism of Action Causes Accumulation of DNA Damage Leading to Cancer Cell Death

• Azenosertib dephosphorylates CDK1 and CDK2 which abrogates G1-Sand G2-Mcell cycle checkpoints, accelerating cell cycling1
• Acceleration of cell cycling does not allow for adequate DNA repair1,2
• DNA damage increases and accumulates1,2
• Cancer cell undergoes mitotic catastrophe1,2

Clinically active as a single agent in tumors with high genomic instability, such as ovarian and uterine serous carcinoma

CDK2/Cyclin E

azenosertib

WEE1

G1

S

M G2

Cell death

1 Ghelli Luserna di Rorà A, et al. J Hematol Oncol 2020;13:126; 2 Elbæk CR, et al. Cell Rep 2022	8

Azenosertib Treatable Patient Population More Than Doubles as Franchise Expands to Non-Gynecologic Malignancies

Potential US + EU5 Patients Per Year (2023 Estimates)

166,000

114,100

102,200

87,200

67,900

43,000 47,000

Gynecologic Malignancies	Non-gynecologic Malignancies

Monotherapy

PROC

2L USC

PSOC Maintenance

HRD Post PARPi

Combination

BRAFm CRC

R/R AML

Other Cyclin E1+ Tumors (w/ chemotherapy)

'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 resistant ovarian cancer; 2L, second line USC, uterine serous carcinoma; PSOC, platinum sensitive ovarian cancer; HRD, homologous recombination repair deficient;	9
PARPi, poly-ADP ribose polymerase inhibitor; BRAFm CRC, BRAF V600E mutant colorectal cancer; R/R AML, relapsed or refractory acute myeloid leukemia

Azenosertib Monotherapy

Updated Results

Monotherapy Anti-tumor Activity in Gynecologic Malignancies with Favorable Safety and Tolerability Profile