# EDGAR Filing Document

**Accession Number:** 0001725160
**File Stem:** 0001725160-23-000047
**Filing Date:** 2023-3
**Character Count:** 74034
**Document Hash:** bb946d0167b1e41ea2d4a18081ee20e0
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001725160-23-000047.hdr.sgml**: 20230301

**ACCESSION NUMBER**: 0001725160-23-000047

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 68

**CONFORMED PERIOD OF REPORT**: 20230301

**ITEM INFORMATION**: Results of Operations and Financial Condition

**ITEM INFORMATION**: Regulation FD Disclosure

**FILED AS OF DATE**: 20230301

**DATE AS OF CHANGE**: 20230301

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Zentalis Pharmaceuticals, Inc.
- **CENTRAL INDEX KEY:** 0001725160
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **IRS NUMBER:** 823607803
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-39263
- **FILM NUMBER:** 23689680

**BUSINESS ADDRESS:**
- **STREET 1:** 1359 BROADWAY, SUITE 1710
- **CITY:** NEW YORK
- **STATE:** NY
- **ZIP:** 10018
- **BUSINESS PHONE:** (212) 433-3791

**MAIL ADDRESS:**
- **STREET 1:** 1359 BROADWAY, SUITE 1710
- **CITY:** NEW YORK
- **STATE:** NY
- **ZIP:** 10018

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Zentalis Pharmaceuticals, LLC
- **DATE OF NAME CHANGE:** 20200107

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Zeno Pharma, LLC
- **DATE OF NAME CHANGE:** 20171212

?xml version="1.0" ? zntl-20230301

    

**UNITED STATES** 

**SECURITIES AND EXCHANGE COMMISSION** 

**Washington, D.C. 20549**

**——————————————**

**FORM 8-K**

**——————————————**

**CURRENT REPORT** 

**Pursuant to Section 13 or 15(d)** 

**of the Securities Exchange Act of 1934** 

**Date of report (Date of earliest event reported): March 1, 2023**

**——————————————** 

**ZENTALIS PHARMACEUTICALS, INC.** 

**(Exact name of registrant as specified in its charter)** 

**——————————————**

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| | | |
|:---|:---|:---|
| **Delaware** | **001-39263** | **82-3607803** |
| **(State or other jurisdiction**<br>**of incorporation or organization)** | **(Commission**<br>**File Number)** | **(I.R.S. Employer**<br>**Identification No.)** |

---

**1359 Broadway, Suite 1710** 

**New York, New York 10018**

**(Address of principal executive offices) (Zip Code)** 

**(212) 433-3791**

**(Registrant's telephone number, include area code)** 

**N/A** 

**(Former name or former address, if changed since last report)** 

**——————————————**

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

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**Securities registered pursuant to Section 12(b) of the Act:**

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| | | |
|:---|:---|:---|
| **Title of each class** | **Trading Symbol(s)** | **Name of each exchange on which registered** |
| Common Stock, $0.001 par value per share | ZNTL | The Nasdaq Global Market |

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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**Item 2.02 Results of Operations and Financial Condition.**

On March 1, 2023, Zentalis Pharmaceuticals, Inc. (the "Company") announced its financial results for the year ended December 31, 2022. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

**Item 7.01 Regulation FD Disclosure.**

Beginning on March 1, 2023, spokespersons of the Company plan to present the information in the Corporate Presentation attached hereto as Exhibit 99.2 at conferences and in meetings with investors and analysts.

The information contained in Items 2.02 and 7.01 of this Current Report on Form 8-K (including Exhibits 99.1 and 99.2 attached hereto) shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, except as expressly provided by specific reference in such a filing.

By providing the information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.2 hereto, the Company is not making an admission as to the materiality of any information herein. The information contained in this Current Report on Form 8-K is intended to be considered in the context of more complete information included in the Company's filings with the U.S. Securities and Exchange Commission (the "SEC") and other public announcements that the Company has made and may make from time to time by press release or otherwise. The Company undertakes no duty or obligation to update or revise the information contained in this Current Report on Form 8-K, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or through other public disclosures.

**Item 9.01. Financial Statements and Exhibits.** 

(d) Exhibits

The following exhibits relating to Items 2.02 and 7.01 shall be deemed to be furnished, and not filed:

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| | |
|:---|:---|
| **Exhibit<br>No.** | **Description** |
| <u>[99.1](zntl_q42022earningspr.htm)</u> | <u>[Press Release issued on March 1, 2023](zntl_q42022earningspr.htm)</u> |
| <u>[99.2](zentaliscorporatedeck-ma.htm)</u> | <u>[Corporate Presentation, dated March 1, 2023](zentaliscorporatedeck-ma.htm)</u> |
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) |

---

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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| | | |
|:---|:---|:---|
| | ZENTALIS PHARMACEUTICALS, INC. | ZENTALIS PHARMACEUTICALS, INC. |
| Date: March 1, 2023 | By: | /s/ Kimberly Blackwell, M.D. |
|  |  | Kimberly Blackwell, M.D. |
|  |  | Chief Executive Officer |

---

## Exhibit 99.1

![image_0.jpg](image_0.jpg)

**Zentalis Pharmaceuticals Reports Full Year 2022 Financial Results and Operational Updates**

*On track to declare monotherapy RP2D for potentially first-in-class/best-in-class Wee1 inhibitor, azenosertib (ZN-c3), and provide program updates and potential paths to registration in 1H 2023*

*Pursuing Cyclin E1 as a patient enrichment strategy for azenosertib monotherapy in ovarian cancer; Cyclin E1 preclinical data with azenosertib to be presented at scientific conference in 1H 2023* 

*Phase 1 ovarian chemotherapy + azenosertib combination trial readout, including Cyclin E1 translational clinical data, planned for 2H 2023*

*Initiated enrollment in Phase 1/2 azenosertib + BEACON regimen combination study in collaboration with Pfizer in BRAF V600E mutated metastatic colorectal cancer (mCRC)*

*Enrollment ongoing in clinical trials investigating ZN-d5, our BCL-2 inhibitor, including in (AL) amyloidosis* 

*$437 million cash balance as of December 31, 2022, with projected cash runway into Q2 2025*

NEW YORK and SAN DIEGO — March 1, 2023 — Zentalis<sup>TM</sup> Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today announced financial results for the year ended December 31, 2022 and highlighted recent corporate accomplishments.

"2022 was a year of considerable progress for Zentalis. We prioritized our portfolio, accelerated our clinical development strategy for our potentially first-in-class Wee1 inhibitor, azenosertib, and further strengthened our management team to drive execution," said Kimberly Blackwell, MD, Chief Executive Officer. "We are building on the momentum generated in 2022 with many clinical milestones and new programs planned for 2023. Our dose optimization activities for azenosertib remain a top priority, and we are on track to declare a monotherapy recommended Phase 2 dose in the first half of the year. We are also advancing our Cyclin E1 enrichment strategy in ovarian cancer, and we look forward to sharing Cyclin E1 preclinical data in the first half of the year and Cyclin E1 clinical data as part of the chemotherapy combination readout in the second half of the year. In addition, we plan to share progress on ZN-d5, our BCL-2 inhibitor, later this year. I am incredibly proud of the entire organization and our patient-driven mission, which guides our strategy and motivates us to continually accelerate our efforts."

**<u>Azenosertib (ZN-c3) Wee1 Inhibitor Program Highlights</u>**

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **Dose optimization**. The Company continues to optimize monotherapy dosing across the azenosertib program with the aim of maximizing exposure and tolerability, as well as enabling the potential clinical benefits of the agent to reach the broadest range of patients in need. The Company remains on track to provide an update on azenosertib monotherapy dose optimization activities in the first half of 2023, including declaring a monotherapy recommended Phase 2 dose (RP2D), as well as providing updates on program timelines and potential paths to registration.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **Cyclin E1 enrichment strategy**. Zentalis identified high Cyclin E1 protein expression and/or CCNE1 gene amplification in high-grade serous ovarian cancer as a patient enrichment strategy

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![image_0.jpg](image_0.jpg)

for azenosertib, which has become the focus of its ongoing Phase 1/2 clinical study examining enrichment strategies for azenosertib. The Company plans to present preclinical data supporting the rationale for the Cyclin E1 enrichment strategy at a scientific conference in the first half of 2023. In addition, Zentalis plans to report results from the Phase 1b chemotherapy combination clinical trial in ovarian cancer, which will include Cyclin E1 translational data, in the second half of 2023.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **BRAF V600E study**. In October 2022, Zentalis and Pfizer announced a clinical development collaboration on a Phase 1/2 dose escalation study of azenosertib in combination with encorafenib and cetuximab (BEACON regimen) in BRAF V600E-mutated metastatic colorectal cancer (mCRC) patients. We initiated enrollment in this clinical trial in the first quarter of 2023.

**<u>BCL-2 Inhibitor (ZN-d5) Update</u>**

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **Amyloidosis study**. Zentalis plans to announce interim clinical data and declare the RP2D for the Phase 1/2 monotherapy clinical trial of ZN-d5 in relapsed or refractory light chain (AL) amyloidosis in the second half of 2023.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **AML study**. The Company has initiated a Phase 1/2 combination study of ZN-d5 and azenosertib in relapsed or refractory acute myeloid leukemia (AML) and expects to provide preliminary data from the trial in the second half of 2023.

**<u>BCL-xL Degrader Update</u>**

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• In November 2022, the Company announced that it declared its BCL-xL degrader candidate and had initiated IND-enabling studies. The BCL-xL degrader candidate demonstrates potent anti-cancer activity in several preclinical models.

**<u>Corporate Highlights</u>**

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• In February 2023, the Company appointed Iris Roth, PhD, as Chief Operating Officer. Dr. Roth joins Zentalis with over two decades of biopharmaceutical experience building and executing clinical and operational strategies, successfully advancing the development of multiple investigational therapies in oncology.

**<u>Full Year 2022 Financial Results</u>**

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **Cash and Marketable Securities Position:** As of December 31, 2022, Zentalis had cash, cash equivalents and marketable securities of $437.4 million. The Company believes that its existing cash, cash equivalents and marketable securities as of December 31, 2022 will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2025.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **Research and Development Expenses**: Research and development (R&D) expenses for the year ended December 31, 2022 were $172.7 million, compared to $175.6 million for the year ended December 31, 2021. Total R&D expenses for the year ended December 31, 2022 were in line with the comparable period; however, the year-over-year composition shifted from spend across multiple programs to spend primarily focused on azenosertib and ZN-d5. The decrease of $2.9 million was primarily due to non-recurring charges incurred in 2021 of $10.0 million for

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![image_0.jpg](image_0.jpg)

milestone payments and an impairment charge of $8.8 million for in-process research and development. Other reductions in R&D expenses in 2022 as compared to 2021 included $14.0 million of decreased manufacturing costs, $2.7 million of decreased collaborative and consulting costs and a $5.7 million increase in R&D expense reimbursements from Zentera. These reductions were partially offset by increases in clinical trial related expenditures of $19.8 million, increases in personnel costs of $14.4 million and increases in facility, overhead allocations, and other costs of $4.1 million.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• **General and Administrative Expenses**: General and administrative (G&A) expenses for the year ended December 31, 2022 were $54.5 million, compared to $40.9 million during the year ended December 31, 2021. The increase of $13.6 million was primarily attributable to an increase of $8.5 million in employee-related costs, $5.5 million of which represents non-cash stock-based compensation. Other increases in 2022 as compared to 2021 include $7.2 million of higher facilities, software and supplies costs, $6.0 million of which related to rent and common area maintenance expenses, $1.5 million of higher consulting services and $1.3 million of increased legal expenses. These amounts were partially offset by a reduction of $1.4 million for permits, fees and other expenses and increased allocations to R&D from G&A of $3.5 million.

Melissa Epperly, Chief Financial Officer, stated, "We are pleased to have extended our cash runway into the second quarter of 2025 through portfolio prioritization and disciplined spending, coupled with sales of common stock via our at-the-market facility."

**About Zentalis Pharmaceuticals**

Zentalis™ Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers. Utilizing its Integrated Discovery Engine, the Company is developing a focused pipeline of potentially best-in-class oncology candidates, which include azenosertib (ZN-c3), a Wee1 inhibitor for advanced solid tumors, ZN-d5, a BCL-2 inhibitor for hematologic malignancies and related disorders, and a heterobifunctional degrader of BCL-xL for solid and hematological malignancies. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders and other undisclosed targets. Zentalis has operations in New York and San Diego.

For more information, please visit www.zentalis.com. Follow Zentalis on Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals.

**Forward-Looking Statements**

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements relating to the potential for a product candidate to be first-in-class or best-in-class; the potential benefits of our dose optimization work, including plans to declare a monotherapy RP2D for azenosertib and the timing thereof; accelerating our efforts; plans to provide program updates and potential paths to registration for azenosertib and the timing thereof; clinical milestones and new programs planned for 2023; advancing our Cyclin E1 patient enrichment strategy; projected cash runway; potential benefits of our product candidates; plans to present preclinical data relating to Cyclin E1 and the timing thereof; plans to report results from the Phase 1b chemotherapy combination trial in ovarian cancer, including Cyclin E1 data, and the timing thereof; plans to present interim clinical data and declare the RP2D for the ZN-d5 Phase 1/2 monotherapy trial in AL amyloidosis and the timing thereof; and plans to provide

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![image_0.jpg](image_0.jpg)

preliminary data from the Phase 1/2 combination study of ZN-d5 and azenosertib in AML and the timing thereof. The terms "aim," "believe," "continue," "look forward," "on track," "optimize," "plans," "potential," "projected," "to be," "will," and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. 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 substantial dependence on the success of our lead product candidates; 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; significant costs as a result of operating as a public company; the COVID-19 pandemic has adversely impacted and may continue to adversely impact our business, including our preclinical studies and clinical trials; and the other important factors discussed under the caption "Risk Factors" in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

ZENTALIS™ and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.

**Investor Contacts:** 

Adam D. Levy, PhD, MBA

alevy@zentalis.com

Alexandra Roy

Solebury Strategic Communications

aroy@soleburystrat.com

**Media Contact:** 

Julia Deutsch

Solebury Strategic Communications

jdeutsch@soleburystrat.com

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![image_0.jpg](image_0.jpg)

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| | | | |
|:---|:---|:---|:---|
| **Zentalis Pharmaceuticals, Inc.** | **Zentalis Pharmaceuticals, Inc.** | **Zentalis Pharmaceuticals, Inc.** | **Zentalis Pharmaceuticals, Inc.** |
| **Consolidated Statements of Operations** | **Consolidated Statements of Operations** | **Consolidated Statements of Operations** | **Consolidated Statements of Operations** |
| **(In thousands, except per share amounts)** | **(In thousands, except per share amounts)** | **(In thousands, except per share amounts)** | **(In thousands, except per share amounts)** |
| | **Year ended December 31,** | **Year ended December 31,** | **Year ended December 31,** |
|  | **2022** | **2021** | **2020** |
| **Operating Expenses** |  |  |  |
| Research and development | $172734 | $175601 | $84901 |
| General and administrative | 54553 | 40941 | 33886 |
| Total operating expenses | 227287 | 216542 | 118787 |
| Loss from operations | (227287) | (216542) | (118787) |
| **Other Income (Expense)** |  |  |  |
| Investment and other income, net | 5987 | 401 | 683 |
| Gain on deconsolidation of Zentera |  | 51582 |  |
| Net loss before income taxes | (221300) | (164559) | (118104) |
| Income tax expense (benefit) | (469) | (297) | 444 |
| Loss on equity method investment | 16282 | 1831 |  |
| Net loss | (237113) | (166093) | (118548) |
| Net loss attributable to noncontrolling interests | (307) | (7368) | (707) |
| Net loss attributable to Zentalis | $(236806) | $(158725) | $(117841) |
| Net loss per common share outstanding, basic and diluted | $(4.48) | $(3.72) | $(4.19) |
| Common shares used in computing net loss per share, basic and diluted | 52857 | 42688 | 28113 |

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![image_0.jpg](image_0.jpg)

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| | | |
|:---|:---|:---|
| **Zentalis Pharmaceuticals, Inc.** | **Zentalis Pharmaceuticals, Inc.** | **Zentalis Pharmaceuticals, Inc.** |
| **Selected Condensed Consolidated Balance Sheet Data** | **Selected Condensed Consolidated Balance Sheet Data** | **Selected Condensed Consolidated Balance Sheet Data** |
| **(Unaudited)** | **(Unaudited)** | **(Unaudited)** |
| **(In thousands)** | **(In thousands)** | **(In thousands)** |
| | **December 31,** | **December 31,** |
|  | **2022** | **2021** |
| Cash, cash equivalents and marketable securities | $437371 | $339887 |
| Working capital <sup>(1)</sup> | 395286 | 306826 |
| Total assets | 539310 | 454507 |
| Total liabilities | 105286 | 90025 |
| Total Zentalis equity | $434024 | $364482 |
| <sup>(1)</sup> The Company defines working capital as current assets less current liabilities. | <sup>(1)</sup> The Company defines working capital as current assets less current liabilities. |  |

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## Exhibit 99.2

![](zentaliscorporatedeck-ma001.jpg)

1 CORPORATE PRESENTATION March 2023

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![](zentaliscorporatedeck-ma002.jpg)

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 potential for our product candidates to be first-in-class and/or best-in-class; potential for accelerated approval paths; potential for our product candidates to be developed as monotherapies and in combination; potential for azenosertib (ZN-c3) to address large populations with significant unmet need; our development approach for our product candidates, including azenosertib and ZN-d5; plans for and potential benefits of dose optimization, and the anticipated timing of updates on dosing optimization, including timing of declaring a monotherapy RP2D for azenosertib; timing of providing updates on azenosertib program timelines and potential paths to registration; timing of preclinical and clinical program updates; the potential unmet need in a particular indication and/or patient population; potential for combinations including our product candidates and the potential benefits thereof; the target profiles and potential benefits of our product candidates and their mechanisms of action, including as a monotherapy and/or in combination; our belief that we have strengthened our clinical development plans, including for azenosertib; clinical and regulatory progress of our product candidates, including the estimated timing of IND-enabling studies, enrollment, initiation of clinical trials and data announcements; the market opportunities for and market potential of our product candidates; timing of providing preclinical rationale for our Cyclin E1 enrichment strategy for azenosertib; timing of advancement of our preclinical programs, including BCL-xL and protein degrader programs; our anticipated milestones, as well as statements that include the words "design," "estimate," "expect," "may," "milestone," "opportunity," "plan," "potential," "strategy," "to come," "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: the outbreak of the novel coronavirus disease, COVID-19, has adversely impacted and may continue to adversely impact our business, including our preclinical studies and clinical trials; 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 substantial dependence on the success of our lead product candidate; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; 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; interim, initial, "topline", and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data; 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 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. ZENTALISTM 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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![](zentaliscorporatedeck-ma003.jpg)

3 Company Overview Lead Program: Wee1i azenosertib (ZN-c3), potentially first- and best-in-class • Potential accelerated approval paths for monotherapy in multiple biomarker enriched populations • Enriched patient populations including Uterine Serous Carcinoma (USC), Cyclin E1 driven and post-PARP progression • Investigating highly synergistic concurrent combinations, including BRAF/MEK inhibitors in BRAF mutant mCRC and PARP inhibitors in high grade serous ovarian cancer • Fast Track designation granted in USC BCL-xL heterobifunctional degrader for liquid and solid tumors (preclinical) BCL-2 inhibitor ZN-d5: broad applicability as anti-apoptotic target; potential as monotherapy and in combination, including with azenosertib Additional discovery programs against validated cancer targets Integrated Discovery Engine: 4 FDA-cleared INDs within 5 years

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![](zentaliscorporatedeck-ma004.jpg)

4 COMPOUND INDICATION DEVELOPMENT APPROACH PRECLINICAL EARLY CLINICAL DEVELOPMENT LATE CLINICAL DEVELOPMENT STATUS / EXPECTED MILESTONES Azenosertib (ZN-c3) Wee1 Inhibitor Uterine Serous Carcinoma Monotherapy FDA Fast Track Designation Solid Tumors Monotherapy Update on azenosertib dosing 1H 2023 including RP2D Cyclin E1 Driven Ovarian Cancer Monotherapy Enrolling; preclinical update to come in 1H 2023 PARP Resistant Ovarian Cancer Monotherapy alternating with niraparib or concurrent with niraparib Enrolling; opened alternating cohort in 4Q 2022 Ovarian Cancer + Multiple Chemotherapy Backbones Enrolling; Phase 1 dose escalation results in 2H 2023 Osteosarcoma + gemcitabine Presented data CTOS Conf Nov 2022 BRAF Mutant Colorectal Cancer + encorafenib and cetuximab Initiated enrollment in Q1 2023 Pancreatic Cancer + gemcitabine Dana Farber Cancer Institute, funded by SU2C/Lustgarten ZN-d5 BCL-2 Inhibitor AL Amyloidosis Monotherapy Provide interim clinical data and declare RP2D for monotherapy NHL Monotherapy Continues to enroll AML + azenosertib Provide preliminary data from clinical trial BCL-xL Degrader Solid Tumors and Heme Malignancies Declared development candidate; IND enabling activities initiated Advancing Focused Pipeline with Multiple Clinical Opportunities

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![](zentaliscorporatedeck-ma005.jpg)

Wee1 Inhibitor Azenosertib (ZN-c3)

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6 Wee1: A Critical Cell Cycle Regulation Target • Wee1 is a protein kinase that inhibits the activity of both CDK1 and CDK2 kinases and is involved in the regulation of G1/S, G2/M, and M phase cell cycle checkpoints • Wee1 plays an important role during normal cell cycle progression but also in response to DNA damage and interacts with DNA damage response (DDR) pathways Azenosertib (ZN-c3): Wee1 Inhibitor G1G2 P Wee1 CDK1 Cyclin B1 P G2/M Checkpoint P Wee1 CDK2 Cyclin A/E1 P G1/S Checkpoint S M P Wee1 CDK1 Cyclin B1 P Mitosis Exit

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7 Wee1 Inhibition by Azenosertib Forces Cancer Cells to Proceed into Mitosis • Wee1 inhibition causes cancer cells to proceed into mitosis without being able to repair damaged DNA, resulting in premature mitotic entry and apoptosis 1 • Wee1 inhibition also increases replication stress by inducing aberrant firing of replication origins and depletion of nucleotide pools 1 G1G2 S M 1. Kok, et al. Overexpression of Cyclin E1 or Cdc25A leads to replication stress, mitotic aberrancies, and increased sensitivity to replication checkpoint inhibitors. Oncogenesis 9, 88 (2020) P Wee1 CDK1 Cyclin B1 G2/M Checkpoint Wee1 CDK1 Cyclin B1 Mitosis Exit P Wee1 CDK2 Cyclin A/E1 G1/S Checkpoint P Azenosertib (ZN-c3): Wee1 Inhibitor

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8 Structure-Based Drug Design (SBDD) Led to the Discovery of a Highly Potent and Selective Wee1 Inhibitor Azenosertib with Improved ADME Properties Asn376 Tyr378 Cys379 Phe310 Ile305 azenosertib potency and ADME Wee1 IC50 3.8 nM H23 IC50 103 nM A427 IC50 75 nM Log D 2.4 hPPB 66% hHep <18 mL/min/kg solubility > 2000 µM CYP3A4 7 µM hERG > 30 µM Huang, PQ; et al. J. Med. Chem. 2021, 64, 13004-13024 Hydrogen bonding with the Wee1 gatekeeper Asn376 Ethyl CH-π interactions with Phe310 of the G- loop Effective bidentate hydrogen-bond interactions with the hinge element Electron-deficient pyrimidine interacts with Phe433 via π-π stacking Sandwiched between Gly382 and Ile305 (CH- π). Additional π-π interactions with Tyr378 Hydrogen bonding to the Ile305 backbone carbonyl. Important for ADME properties Chiral OH engaged in polar interactions with Asn431 and Ser430 Allyl occupying a lipophilic pocket formed by Ala326, Ile327, Lys328, and Asn376 Azenosertib (ZN-c3): Wee1 Inhibitor

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9 Indication Incidence Estimates (US+EU) Development Approach Ovarian Cancer 46,700 1 Strategic commitment to patients with multiple ongoing studies in monotherapy and combination settings High Grade Serous Ovarian Cancer (HGSOC) (75% of Ovarian Cancer) 35,000 2 Ongoing study combining azenosertib with common chemotherapy backbones in platinum resistant populations. Additional ongoing study examining PARP inhibition in PARP resistant populations with GSK Cyclin E1 Driven Ovarian Cancer (~25% of HGSOC) 8,800 3 Ongoing biomarker study with monotherapy regimen exploring high cyclin E1 protein expression and CCNE1 gene amplification Other Cyclin E1 Driven Solid Tumors 80,000+ 3 Potential follow-on opportunities including prostate, lung, breast, etc. Uterine Serous Carcinoma 10,100 4 Fast track designation monotherapy program Colorectal (BRAF mutant) 36,300 5 Initiated enrollment of azenosertib + BEACON regimen in Q1 2023 as part of Pfizer development partnership Osteosarcoma 4,300 6 Azenosertib + gemcitabine combination. Initial data readout at 2022 CTOS Conference Pancreatic Cancer 108,000 7 Azenosertib + gemcitabine combination. Potential to demonstrate POC via investigator sponsored trial at Dana Farber. AML 25,600 8 Combine azenosertib with ZN-d5, BCL-2 inhibitor Azenosertib: Significant Market Opportunity Across a Broad Range of Solid and Liquid Tumors Azenosertib (ZN-c3): Wee1 Inhibitor 1. Cancer of the Ovary - Cancer Stat Facts. (n.d.). SEER. Retrieved November 2, 2022, from https://seer.cancer.gov/statfacts/html/ovary.html for US and ECIS - European Cancer Information System for EU (applying EU27 female population to incidence cited) 2. Ovarian Cancer Research Alliance. Retrieved November 4, 2022. https://ocrahope.org/2021. 3. Chen at al Mol Cell Proteomics. 2019 Aug 9;18(8 suppl 1):S15-S25 and TCGA dataset 4. Trastuzumab for Rare Form of Endometrial Cancer. (2020, August 13). National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2020/endometrial-cancer-usc-her2-trastuzumab (US only). 5. Cancer of the Colon and Rectum - Cancer Stat Facts. (n.d.). SEER. Retrieved November 2, 2022, from https://seer.cancer.gov/statfacts/html/colorect.html and ECIS - European Cancer Information System and applying estimated BRAF V600E proportion. 6. Cancer of the Bones and Joints - Cancer Stat Facts. (n.d.). SEER. Retrieved November 2, 2022, from https://seer.cancer.gov/statfacts/html/bones.html and Annals of Oncology, VOLUME 32, ISSUE 12, P1520-1536, DECEMBER 01, 2021 7. Cancer of the Pancreas - Cancer Stat Facts. (n.d.). SEER. Retrieved November 2, 2022, from https://seer.cancer.gov/statfacts/html/pancreas.html and ECIS - European Cancer Information System 8. Acute Myeloid Leukemia - Cancer Stat Facts. (n.d.). SEER. Retrieved November 2, 2022, from https://seer.cancer.gov/statfacts/html/amyl.html and Acute Myeloid Leukaemia: Mapping the Policy Response to an Acute Cancer in France, Germany, Italy, Spain, and the UK. (2019). The Economist Intelligence Unit.

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Uterine Serous Carcinoma Azenosertib (ZN-c3)

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11 • USC is molecularly distinct from endometrial cancer with frequent alterations in p53 (90%), CCNE1 (25%) and HER2 (25%) 4 • High amounts of oncogene-driven replicative stress • Wee-1 is a validated target in USC with reported ORR of 29.4% and a PFS6 rate of 47.1% with adavosertib 5 • USC is an aggressive form of endometrial cancer that accounts for 10-15% of all endometrial cancers 1 • The 5-year survival for late-stage is approx. 41% compared to 75% in women with the most common form of endometrial cancer 2 • USC is responsible for ~40% of endometrial cancer deaths 3 Unmet Need in Uterine Serous Carcinoma is Significant Azenosertib's emerging efficacy and tolerability profile show promise in addressing unmet need in USC 0% 50% 100% New Cases Deaths USC Endometrial • Current standards of care for USC: - First line: Platinum based chemotherapy - Second line: Pembro + Lenvatinib - Third Line: No specific recommendations, single-agent chemotherapy (4-9%) and some limited use of bevacizumab 6 • There is a high need for a therapeutic option in later line patients after prior platinum containing chemotherapy and pembrolizumab + lenvatinib treatment • Azenosertib is potentially a first-in-class treatment option for USC 1. https://www.cancer.gov/news-events/cancer-currents-blog/2020/endometrial-cancer-usc-her2-trastuzumab 2. Boruta DM II, Cancer 101:2214-2221, 2004. 3. McGunigal M. Int J Gynecol Cancer 27:85-92, 2017. 4. Cancer Genome Atlas Research Network, Kandoth C. Nature 497:67-73, 2013. 5. Liu J. J Clin Oncol 39, 14:1531-1539, 2021. 6. CancerMPact, Future Trends and Insights Endometrial cancer June 2021; data on file. UNMET NEED UNIQUE BIOLOGY COMPETITIVE LANDSCAPE Azenosertib (ZN-c3): USC

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12 ZN-c3-001: Summary of Clinical Activity – Meaningful and Durable Responses Seen in USC Best Overall Response N = 11†; n (%) Complete Response (unconfirmed)\* 1 (9.1) Partial Response (confirmed) 2 (18.2) Stable Disease 7 (63.6) ≥ 12 weeks 4 (36.3) < 12 weeks 3 (27.3) Progressive Disease 1 (9.1) Overall Response Rate (95% CI = 6.0%, 61.0%) 3 (27.3) DCR (CR + PR + SD) (95% CI = 58.7%, 99.8%) 10 (90.9) Median Duration of Response 5.6 months mPFS 4.2 months Best Overall Response and Reduction of Target Lesions \*\* Prior pembrolizumab + lenvatinib use 4.3% 2.9% -2.9% -3.1% -3.3% -4.7% -6.7% -14.4% -43.3% -48.9% -100.0%-100% -80% -60% -40% -20% 0% 20% 40% 60% 80% 100% PD PR SD PD SD SD SD SD SD SD PR PR uCR \*\* \*\* \*\* \*\* \*\* \*\* \*\* \* Best overall response for this subject is PR. † N=11 subjects with measurable disease and at least 1 post-baseline tumor assessment. At time of data cutoff 2 SDs were ongoing on study DCR=disease control rate; uCR=unconfirmed complete response. Meric-Bernstam et al. Presentation at American Association for Cancer Research 2022 Meeting. Safety and clinical activity of single-agent azenosertib, an oral Wee1 inhibitor, in a Phase 1 trial in subjects with recurrent or advanced uterine serous carcinoma (USC). Data cutoff January 21, 2022. Azenosertib (ZN-c3): USC

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13 85.7 64.3 42.9 42.9 28.6 28.6 21.4 14.3 14.3 14.3 14.3 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 14.3 020406080100 Nausea Vomiting Fatigue Diarrhea Decreased Appetite Dehydration Anaemia Thrombocytopenia Weight Decreased Dizziness Headache Neutropenia Leukopenia Dysgeusia Abdominal pain Rash Hypoalbuminaemia Oedema Peripheral Blood Alkaline Phosphatase Increased Constipation Chills Hepatic Enzyme Increased Tachycardia Onychomadesis Dyspepsia All Grades (All AEs) Grade ≥ 3 (All AEs) 60.5 32.6 46.5 37.2 14.0 7.0 9.3 7.0 7.0 4.7 2.3 7.0 4.7 4.7 4.7 2.3 2.3 2.3 7.0 9.3 7.0 9.3 7.0 4.7 2.3 2.3 2.3 2.3 20 40 60 80 100 All Grades (Related AEs) Grade ≥ 3 (Related AEs) Azenosertib Continues to Show Favorable Tolerability Profile in Monotherapy USC Setting 1. Presented at AACR 2022 by F. Meric-Bernstam September 14, 2022 Dataset Treatment Related Adverse Events n=43 January 21, 2022 Dataset Treatment Related Adverse Events 1 n=14 Patients with Adverse Events (%) Azenosertib (ZN-c3): USC

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Dose Optimization Azenosertib (ZN-c3)

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15 Azenosertib: Multiple PRs Across Tumor Types as Monotherapy AmVate 300 Ovar 300 Panc 350 Pros 350 Panc 450 CRC 350 SCLC 450 RCC 300 Ovar 300 Brea 350 CRC 350 CRC 300 USC 300 CRC 350 USC 300 CRC 300 NSCLC 300 Gast 350 Panc 400 450 CRC 300 Ovar 350 CRC 300 USC 300 USC 300 LeiS 350 CRC 350 LeiS 300 CRC 300 USC 300 USC 350 USC 350 NSCLC 450 CRC 350 Ovar 70% 60% 50% 40% 30% 20% 10% 0% -10% -20% -30% -40% -50% -60% -70% PD PR PD, 63 PD, 46 PD, 32 PD, 31 PD, 27 PD, 25 PD, 23 PD,17 PD, 13 PD, 10 PD, 8 SD, 5 SD4, 0 CPD, 4 PD, 3 SD+, 2 PD, 0 PD, -1 SD, -1 SD, -2 SD+, -5 SD+, -5 SD, -10 SD, -18 SD+, -22 PD, -24 uPR+, -33 cPR+, -43 cPR+, -49 cPR, -49 cPR, -51 cPR+, -69 Inv Dec, 0 SD, 0 Waterfall as of 05/15/2021; 3 subjects with no treatment scans (CRC, USC, Pancreas), and experienced clinical progressive disease (CPD) + denotes treatment ongoing. Newly reported uPR in USC is included. ORR based on radiographic responses. Both uPRs reported at AACR 2021 as of 03/15/2021 in USC were confirmed. ZN-c3-001 Dose Escalation and Expansion – 300mg QD and Above Dose Cohorts Best % Change in Target Lesion Size and Best Overall Response Azenosertib (ZN-c3): Wee1 Inhibitor

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16 Optimizing the Therapeutic Index of Azenosertib • Only set dose of azenosertib has been in USC (004 trial) at 300mg QD continuous daily dosing • Monotherapy activity demonstrated • Well tolerated safety profile • From 300mg QD dosing, we will examine pushing the therapeutic index for monotherapy dosing across three trials as this represents the fastest path to regulatory approval considerations and meaningful clinical evidence • Our experience to date (>200 patients) is that exposure and maintenance of exposure drives efficacy (both response and duration of response) • Alternative dosing to date (>60 patients): • Less dose interruptions and modifications Dosing update planned 1H 2023 Minimal Effective Dose Maximum Well- Tolerated Dose Therapeutic Index A m o u n t o f D ru g in B lo o d Azenosertib (ZN-c3): Wee1 Inhibitor

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17 Azenosertib: Intermittent Dosing Increases Efficacy and Maintains Tolerability in Ovarian Cancer Models -1 2 5 8 11 14 17 20 23 26 0 400 800 1200 1600 2000 Days Post Treatment Initiation T u m o r V o lu m e (m m 3) Vehicle qd × 24 ZN-c3 60 mg/kg qd × 24 ZN-c3 80 mg/kg (qd × 5, 2 d off) ZN-c3 100 mg/kg (qd × 4, 3 d off) ZN-c3 90 mg/kg (qd × 4, 3 d off) Continuous dosing 5d on, 2d off 4d on, 3d off 4d on, 3d off OVCAR3 Model 2 5 8 11 14 17 20 23 26 -30 -20 -10 0 10 20 30 Days Post Treatment Initiation B o d y W e ig h t C h a n g e (%) Vehicle qd × 24 ZN-c3 60 mg/kg qd × 24 ZN-c3 80 mg/kg (qd × 5, 2 d off) ZN-c3 90 mg/kg (qd × 4, 3 d off) ZN-c3 100 mg/kg (qd × 4, 3 d off) Azenosertib (ZN-c3): Wee1 Inhibitor

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18 3. Skin Biopsy Decreases in p-CDK1 Show Target Engagement for Wee1 Inhibition Confirmation of Wee1 Target Engagement in Surrogate Tissue 1 1. CDK1 phosphorylation (p-CDK1) is mediated by Wee1 2. Inhibition of Wee1 will lead to inhibition of p-CDK1 3. Skin biopsies were performed at baseline and on treatment to verify p-CDK1 levels and level of target engagement of Wee1 1. Chalasani, P; et al. 526P Pharmacodynamic evidence for WEE1 target engagement in surrogate and tumor tissues from a phase I study of the WEE1 inhibitor ZN-c3. Annals of Onc. 2021, 526P 1. CDK1 phosphorylation by Wee1 2. p-CDK1 inhibition 1 1 CDK1 Wee1 Y15 Azenosertib p-CDK1 = Brown Staining (subject with cPR) Baseline On Treatment Decreases in p-CDK1 at Baseline vs on Treatment 40xHair bulb -99% -100% Basal epidermis Azenosertib (ZN-c3): Wee1 Inhibitor

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19 Azenosertib: PK/PD Correlation Shows Active Target Engagement • Inhibition of p-CDK1 demonstrated Wee1 target engagement • Increase in dose / drug exposure directly related to Wee1 target engagement • ≥300 mg QD showed highest AUC, with excellent target engagement and p-CDK1 levels decreased at least by 50% Wee1 Target Engagement AUC0-24 hr (ng\*h/mL) p -C D K 1 (% in h ib it io n) M o re W e e 1 Ta rg et E n g a g e m e n t 0 5000 10000 15000 20000 -100 -50 0 50 100 Average drug exposure at 300 mg QD Higher Drug ExposureSubjects with PR Target engagement (50%) 1. Chalasani, P; et al. 526P Pharmacodynamic evidence for WEE1 target engagement in surrogate and tumor tissues from a phase I study of the WEE1 inhibitor ZN-c3. Annals of Onc. 2021, 526P Azenosertib (ZN-c3): Wee1 Inhibitor

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Biomarker Approach: Cyclin E1 Driven Cancers Azenosertib (ZN-c3)

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21 Cyclin E1 High Cyclin E1 Expressing Cancer Cells are Highly Sensitive to Wee1 Inhibition • High cyclin E1 protein expression accelerates G1/S signaling, which cause high levels of replicative stress 1 • Wee1 inhibition further drives replicative stress, causing mitotic catastrophe and cell death G1G2 S M 1. Kok, et al. Overexpression of Cyclin E1 or Cdc25A leads to replication stress, mitotic aberrancies, and increased sensitivity to replication checkpoint inhibitors. Oncogenesis 9, 88 (2020) P Wee1 CDK1 Cyclin B1 G2/M Checkpoint Wee1 CDK1 Cyclin B1 Mitosis Exit P Wee1 CDK2 Cyclin E1 G1/S Checkpoint P High Cyclin E1 Protein Expression Cyclin E1 Cyclin E1 Cyclin E1 Cyclin E1 Cyclin E1 Cyclin E1 Azenosertib (ZN-c3): Cyclin E1

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22 CCNE1 Gene Amplification is Associated with Poor Prognosis and Chemotherapy Response Across Tumor Types 1. Liu, J. et al., Cell, 2018, 173, 400-416; (figure generated using cBioPortal.org, see Cerami et al. Cancer Discovery. 2012 2; 401 and Gao et al. Sci. Signal. , 2013, 6, pl1). 2. Huang, X. et al., Frontiers in Oncology, 2020, 10, Article 583314, 1-16 3. Stronach, E., et al., Molecular Cancer Research, 2018, 1103-1111. TCGA Pan Cancer Atlas 1 Triple Negative Breast Cancer (TNBC) 2 Carboplatin-treated Ovarian Cancer 3 CCNE1 amplified (N=410) CCNE1 not amplified (N=10,305) Log-rank test p-value=1.06 10-13 CCNE1 amplified (N=4) CCNE1 not amplified (N=50) CCNE1 amplified (N=47) CCNE1 not amplified (N=201) Azenosertib (ZN-c3): Cyclin E1

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23 High Cyclin E1 Protein Expression is Associated with Increased Sensitivity to Azenosertib in Ovarian Cell Lines 1. Azenosertib sensitivity is assessed by CellTiter Glo after 96 hours of culture. Data represent an average of at least 2 independent studies. Protein expression was assessed by Western Blot and is representative of 2 independent experiments. 2. Cyclin E1 was over-expressed in SKOV3 by lentivirus transduction followed by puromycin selection. Empty vector control was generated simultaneously. Azenosertib Sensitivity and Cyclin E1 Protein Expression 1 Azenosertib Sensitivity in SKOV3 High Expressing Cyclin E1 2 • Ovarian cell lines with high Cyclin E1 protein expression are more sensitive to azenosertib • High Cyclin E1 protein expression sensitizes the low-sensitive cell line SKOV- 3 to azenosertib P ro te in e xp re ss io n (a rb it ra ry u n it s) 0 1 2 3 4 5 6 7 OV90 KURAMOCHI TYK-nu OVCAR3 ZN-c3 sensitivity Protein expression az en o se rt ib se n si ti vi ty - IC 5 0 (m M) Azenosertib (ZN-c3): Cyclin E1

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24 CCNE1 Gene Amplification is Associated with Poor Prognosis and Chemotherapy Response Across Tumor Types Carboplatin-treated Ovarian Cancer 3 SKOV3 CCNE1 not amplified, TP53 mut HCC1806 CDX CCNE1 amp (CN=7), TP53 mut OVCAR3 CDX CCNE1 amp (CN=14) TGI(80 mpk, Day 28) = 88%TGI(80 mpk, Day 28) = 63.5%TGI(80 mpk, Day 28) = 51.5% 2 5 8 11 14 17 20 23 -30 -20 -10 0 10 20 30 Days Post Treatment Initiation B o d y W e ig h t C h a n g e (%) Vehicle qd × 21 ZN-c3 80 mg/kg qd × 21 Days Post Treatment Initiation -1 2 5 8 11 14 17 20 23 0 400 800 1200 1600 Days Post Treatment Initiation T u m o r V o lu m e (m m 3) Vehicle qd × 21 ZN-c3 80 mg/kg qd × 21 Days Post Tr ent Initiation Days Post Grouping (Day) Days Post Treatment Initiation Days Post Grouping (Day) Days Post Grouping (Day) Azenosertib (ZN-c3): Cyclin E1

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25 Moving Forward with Cyclin E1 patient enrichment in HGSOC: Revised ZN-c3- 005 Study Design CCNE1 Amp azenosertib monotherapy at doses and schedules deemed well tolerated in ZN-c3-001 azenosertib monotherapy Cohort A CCNE1 Amp PH 1b / SAFETY LEAD-IN PH 2 EXPANSION Cohort B CCNE1 Non-amp High Cyclin E1 Expression Platinum-resistant HGSOC 1-3 prior lines (prior bevacizumab required) Azenosertib (ZN-c3): Cyclin E1

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26 • In 2022, the total number of drug- treatable second line platinum-resistant ovarian cancer patients is estimated to be >14,000 in the United States, EU5 and Japan 2 • Platinum-resistant and -refractory ovarian cancer represents a high unmet need • It is associated with a poor prognosis and limited treatment options - ORR of 11.8% with standard of care 1 for platinum-resistant patients • Improvement in efficacy with acceptable safety profile would make a meaningful difference for patients Platinum-Resistant/Refractory Ovarian Cancer Remains an Unmet Need • Current standard of care for second line platinum-resistant ovarian patients is single-agent chemotherapy ± bevacizumab 3 • Ongoing pivotal trials focus on novel MOAs, including ADCs, and combinations with either PARPi or chemotherapy 3 • Azenosertib is potentially a first-in-class treatment option that works synergistically with other anticancer therapies UNMET NEED PATIENT POPULATION COMPETITIVE LANDSCAPE 1. Pujade-Lauraine et al. J Clin Oncol 2014; 32:1302-1308; AURELIA study 2. Decision Resources Group; data on file. 3. CancerMPact Treatment Architecture Ovarian cancer July 2021; data on file. 0 4,000 8,000 Drug-Treatable Patients by Region: 2022 U.S. EU5 Japan Azenosertib's efficacy and tolerability profile are well-positioned for the platinum-resistant/refractory ovarian population Azenosertib (ZN-c3): Ovarian

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27 ZN-c3-002: Summary of Clinical Activity Summary of Clinical Activity (All Cohorts) Group N Evaluable\* (n) PR/uPR (n) SD (n) PD (n) DCR (%) ORR (%) Azenosertib + Paclitaxel 9 8 5 3 – 100 62.5 Azenosertib + Carboplatin 17 11 5 4 2 81.8 45.5 Azenosertib + PLD 30 24 3 17 4 83.3 12.5 Total 56 43 13 24 6 86.0 30.2 Pasic, et al. Poster Presented at American Association for Cancer Research Annual Meeting (2022): Abstract CT148: A phase 1b dose-escalation study of ZN-c3, a WEE1 inhibitor, in combination with chemotherapy (CT) in subjects with platinum-resistant or refractory ovarian, peritoneal, or fallopian tube cancer. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 \* Patients with measurable disease and at least one post-baseline scan Of evaluable subjects, ORR is percentage with PR/uPR; DCR = disease control rate, percentage of ORR + SD; uPR = unconfirmed partial response Data cutoff January 28, 2022 Azenosertib (ZN-c3): Ovarian

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28 55.4 48.2 41.1 37.5 35.7 35.7 28.6 21.4 19.6 17.9 16.1 14.3 14.3 14.3 12.5 8.9 8.9 8.9 8.9 7.1 7.1 7.1 7.1 5.4 5.4 5.4 5.4 5.4 5.4 5.4 5.4 7.1 35.7 17.9 8.9 8.9 5.4 3.6 1.8 7.1 5.4 5.4 10.7 5.4 3.6 1.8 3.6 1.8 5.4 1.8 020406080100 Nausea Neutropenia Thrombocytopenia Anaemia Vomiting Fatigue Diarrhoea Hypoalbuminaemia Leukopenia Abdominal pain Hypokalaemia Alanine Aminotransferase Increased Lymphopenia Hypomagnesaemia Pain (any) Gamma-glutamyltransferase Increased Aspartate Aminotransferase Increased Pyrexia Headache Ascites Weight Decreased Blood Alkaline Phosphatase Increased Dyspnoea Small Intestinal Obstruction Decreased Appetite Muscle Spasms Face Oedema Dyspepsia Hyponatraemia Cough COVID-19 All Grades (All AEs) Grade ≥ 3 (All AEs) 48.2 41.1 37.5 26.8 30.4 23.2 16.1 5.4 16.1 3.6 1.8 14.3 3.6 3.6 3.6 7.1 5.4 3.6 1.8 1.8 1.8 3.6 3.6 3.6 3.6 1.8 1.8 5.4 32.1 17.9 7.1 7.1 3.6 1.8 7.1 1.8 10.7 1.8 1.8 1.8 1.8 20 40 60 80 100 All Grades (Related AEs) Grade ≥ 3 (Related AEs) ZN-c3-002: TEAEs ≥5% for All Patients (N=56) Adverse Events January 28, 2022 data cutoff. Pasic, et al. Poster Presented at American Association for Cancer Research Annual Meeting (2022): Abstract CT148: A phase 1b dose-escalation study of ZN-c3, a WEE1 inhibitor, in combination with chemotherapy (CT) in subjects with platinum-resistant or refractory ovarian, peritoneal, or fallopian tube cancer Related AEsTEAEs Azenosertib (ZN-c3): Ovarian

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PARP-Refractory Ovarian Cancer Azenosertib (ZN-c3)

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30 • Combination of PARP and Wee1 inhibitors in TNBC results in synergistic cell killing in preclinical models with either BRCA1 mutations or high levels of cyclin E1 1 • The combination of azenosertib and niraparib shows efficacy in both ovarian and TNBC in vivo models • Preclinically, sequential administration of PARP and azenosertib is efficacious but is better tolerated than concurrent based on body weight loss • Wee1 inhibition may broaden the application range of PARP inhibitors in ovarian cancer and TNBC, consistent with results from the EFFORT 2 and STAR trials 3 Azenosertib + PARP Inhibitor Combinations are Active in both Ovarian CDX and TNBC PDX Models OVCAR3 Model TGI Body Weight TNBC Model TGI Body Weight 1. Chen X Cancers (Basel). 2021 Apr 1;13(7):1656 2. Westin, S.; J Clinical Oncology, 39, N15 (Supplement). 2021, 5505. 3. Yap T. Eur J Cancer. Vol 174 (Supplement 1), S7: 2022. Days Post Treatment Initiation Days Post Treatment Initiation Days Post Treatment Days Post Treatment Azenosertib (ZN-c3): PARP Combinations

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31 Key Eligibility: • Recurrent high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer (serous, clear cell or endometrioid). • Prior therapy: 1 – 5 prior lines for advanced/metastatic disease • Disease progression while taking a PARPi as maintenance treatment (minimum of 3 months of treatment required). Primary Endpoint • Determine MTD/RP2D and optimal administration schedule 3+3 dose escalation design ZN-c3-006: Phase 1/2 Study of Azenosertib In Combination with Niraparib in Patients with PARP-Resistant Ovarian Cancer KEY ELIGIBILITY PHASE 1: SAFETY LEAD-IN azenosertib + niraparib administered concurrently azenosertib + niraparib administered in an alternating schedule Azenosertib (ZN-c3): PARP Combinations

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BRAF Metastatic Colorectal Cancer Azenosertib (ZN-c3)

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33 Preclinical Data Supports the Combination of Azenosertib with Encorafenib and Cetuximab: BEACON REGIMEN • Oncogene-induced replication stress in mutationally driven cancers such as BRAF mutant colorectal cancer leads to DNA damage and genomic instability • Oncogene activation disrupts replication regulation leading to slow and stalled replication forks and other defects and leads to DNA damage • Dependency of cancers with replication stress on Wee1 signaling provides a mechanistic basis for synergy with EGFR/BRAF inhibition • Addition of azenosertib to the BEACON regimen is well tolerated and provides superior efficacy in an in vivo model of BRAF mutant CRC LS411N -1 2 5 8 11 14 17 20 0 250 500 750 1000 1250 1500 Days Post Treatment Initiation T u m o r V o lu m e (m m 3) SOC Vehicle A qd × 21 Encorafenib 20 mg/kg qd × 21 Cetuximab 15 mg/kg BIW × 3 ZN-c3 60 mg/kg qd × 21 Cetuximab 15 mg/kg BIW × 3 + Encorafenib 20 mg/kg qd × 21 ZN-c3 60 mg/kg qd × 21 + Encorafenib 20 mg/kg qd × 21 + Cetuximab 15 mg/kg BIW × 3 Days Post Treatment Initiation 2 5 8 11 14 17 20 -30 -20 -10 0 10 20 30 B o d y W e ig h t C h a n g e (%) Days Post Treatment InitiationDays Post Treatment Initiation LS411N (BRAF mutant CRC) Azenosertib (ZN-c3): BRAF mCRC

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34 PHASE 2: DOSE EXPANSION N: Up to 80 patients • Phase 1 Endpoints: Safety, tolerability, MTD, RP2D • Phase 2 Endpoint(s): ORR; DOR, DCR, PFS, TTP Encorafenib + Cetuximab + Escalating Dose Levels of azenosertib PHASE 1: DOSE FINDING BRAF mCRC Study in Collaboration with Pfizer • Patients with mCRC and documented BRAFV600E mutation • Disease progression after 1 or 2 previous regimens for metastatic disease • Prior therapy may include BRAF and/or EGFR directed therapy (e.g. may have progressed after BEACON regimen) Phase 1/2, Open-Label, Multi-center Study Of Azenosertib In Adults With Metastatic Colorectal Cancer Large Patient Population… • Up to 21% of mCRC patients have BRAF mutations (~15,000 patients per year, U.S.) with over 90% V600E1 • Testing for BRAF mutations is routine, providing opportunity to identify patients With Significant Unmet Need • Median OS in BRAF mutant CRC patients <1 year, vs. BRAF WT >2 years2 • While targeted BRAF inhibition (e.g., vemurafenib) has been successful in melanoma with response rates >80%, this strategy has failed in CRC (OR ~5%) due to innate resistance3 • Encorafenib in combination with cetuximab (BEACON) was approved for BRAF V600E mCRC in April 2020 and is now the standard of care 1 Sorbye H, Dragomir A, Sundström M, et al. High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. PLoS One. 2015;10(6):e0131046. 2 Corcoran et al. Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600–Mutant Colorectal Cancer. J Clin Oncol (2015) Dec 1; 33(34): 4023-4031 3 Kopetz et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. NEJM (2019) 381: 1632-1643 Zentalis maintains full economic ownership and control of azenosertib, apart from Greater China rights (Zentara). Azenosertib (ZN-c3): BRAF mCRC

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BCL-2 Inhibitor ZN-d5

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36 BCL-2: A Clinically Validated Oncology Target • BCL-2 is an anti-apoptotic protein involved in tumor survival and chemo resistance 1 • The intrinsic apoptotic pathway is controlled by the BCL-2 protein family on the mitochondrial outer membrane 2, 3 • BCL-2 inhibitors may restore the normal apoptosis process, making it an important target for cancer treatments Mechanism of Action of BCL-2 Inhibitors 1 BAXBIM BCL2 BCL2 BCL-2i BAX BCL-XL MCL1 BIM BCL2 BCL2 BIM BAX BAX BAX Cytochrome c Apoptosis 1. Konopleva M et al. Cancer Discov. 2016 Oct;6(10):1106-1117 2. Konopleva M and Letai A. Blood. 2018 Sep 6;132(10):1007-1012 3. Bhola PD and Letai A. Mol Cell. 2016;61(5):695-704 ZN-d5: BCL-2 Inhibitor

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37 ZN-d5: A Potent BCL-2 Inhibitor Designed with Improved Selectivity for BCL-2 ZN-d5 has 10x Improved Selectivity for BCL-2 vs BCL-xL and Binds With Higher Affinity to BCL-2 Mutants than Venetoclax Compound ID Affinity (Kd, nM) IC50 (nM) BCL-2 Type BCL-2 BCL-xL MCL-1 WT G101V F104L D103Y Venetoclax 0.41 28 >30000 1.3 7.3 8.4 18.3 ZN-d5 0.29 190 >30000 1.4 3.7 1.4 5.0 Compound ID CTG (24 h) IC50 (mM) Venetoclax 0.6 ZN-d5 2.4ZN-d5 Exhibits Potent In Vitro Activity Across Multiple Tumor Cell Lines Compound ID CTG IC50 (nM) ALL MCL DLBCL AML RS4;11 Mino-1 Granta- 519 DOHH-2 Toledo HL-60 Molm-13 MV4-11 Venetoclax 2.9 1.1 161 43 191 26 18 3.8 ZN-d5 5.1 0.1 89 50 92 21 39 5.1 0.0010.010.1110 0 20 40 60 80 Compound [mM] In h ib it io n (%) Venetoclax ZN-d5 ZN-d5: Less Human Platelet Toxicity Compared to Venetoclax in an In Vitro Assay • ZN-d5 shows activity in preclinical models of ALL, NHL and AMLZN-d5 shows activity in preclinical models of ALL, NHL and AML Venetoclax data based on evaluation of comparable proxy chemical compound purchased from commercial sources rather than obtained from the pharmaceutical company developing the compound ZN-d5: BCL-2 Inhibitor

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38 ZN-d5: May Bind with Higher Affinity to BCL-2 Mutants than Venetoclax Compound ID IC50 (nM) BCL-2 Type WT G101V F104L D103Y Venetoclax 1.3 7.3 8.4 18.3 ZN-d5 1.4 3.7 1.4 5.0 Mutations in BCL-2 May be Driving Sub-Clonal Pockets of Resistance to Venetoclax in CLL 55% (16/29) patients acquired mutations in BCL-2 family members • 41% (14/29) with mutations in BCL-2 • 21% (6/29) with mutations in PMAIP1 (NOXA), BAX or BAD Majority (9/14) were detected with BCL-2 mutations after 24 months on venetoclax • 55% (16/29) of patients with CLL progression CLL Progression on Venetoclax Acquired post-therapy No mutation detected Note: Competition assay for displacing BAK peptide bound to BCL-2 Source: Chyla, B. ASH Presentation (2019) Venetoclax data based on evaluation of comparable proxy chemical compound purchased from commercial sources rather than obtained from the pharmaceutical company developing the compound. ZN-d5: BCL-2 Inhibitor

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39 ZN-d5 Clinical Development Plan • Improved in vitro potency and has 10x improved selectivity for BCL-2 vs BCL-xL compared to venetoclax • Observed to bind with higher affinity to BCL-2 mutants than venetoclax in in vitro assay - Mutations in BCL-2 may be driving sub-clonal pockets of resistance to venetoclax • Preclinical combination data of ZN-d5 + azenosertib (ZN-c3) utilizing novel biology showed synergistic and additive activity across multiple indications in both solid and liquid tumors, often at subtherapeutic doses Ongoing and Planned Clinical Programs Indication Treatment Trial Updates Non-Hodgkin's Lymphoma ZN-d5 Continues to enroll AL Amyloidosis ZN-d5 Continues to enroll AML ZN-d5 & azenosertib Trial initiated in 4Q 2022 ZN-d5: BCL-2 Inhibitor

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40 ZN-d5: Favorable Early Comparison to Venetoclax in NHL ZN-d5: NHL Upper respiratory tract infections • ZN-d5 100-1200mg, empty stomach • Venetoclax 200-1200mg with food • Early toxicity profile in NHL favorable vs. published venetoclax data 1 - Fewer AEs of any Grade, Grade ≥3 - No TLS observed - Venetoclax AEs not dose-dependent 1. Davids et al, J Clin Oncol 2017;35:826-833; emergent AEs reported in ≥15% of subjects. ZN-d5 results as of 03 Nov 2021 data cutoff. Not a head-to-head study

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41 ZN-d5 in AL (Primary) Amyloidosis 1. Zhang et al. Clin Lymphoma Myeloma Leuk. 2019;19(suppl 10):e339 2. Kyle et al, Mayo Clin Proc. 2019;94:465-471 3. Premkumar et al, Blood Cancer J 2021;11:10; hematologic response rate in 38 evaluable patients. AL Amyloidosis study is currently enrolling patients • AL Amyloidosis: Deposition of immunoglobulin light chains - Clonal plasma cell population secretes misfolding light chain - Progressive systemic amyloid accumulation causes widespread organ damage - High morbidity and mortality • Orphan disease - Estimated worldwide prevalence is 75,000 1 - About 4k new cases/year in the US 2 • Not a cancer, but treated like one - Agents active in multiple myeloma used in first-line and relapsed/refractory settings - Daratumumab only approved therapy, for first-line use with CyBorD • Relapsed/refractory setting is a high unmet medical need 63% VGPR/CR 3 ZN-d5: AL Amyloidosis

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42 BCL-2 Inhibition has Shown Robust Clinical Activity in AL Amyloidosis • Patients with the t(11;14) translocation have a worse prognosis than the general AL amyloidosis population 1 • BCL-2 inhibition showed an improved response rate in the t(11;14) cohort with a trend towards better survival Best Response in Evaluable Patients 1. Premkumar et al, Blood Cancer J 2021;11:10; hematologic response rate in 38 evaluable patients. OS for All Patients ZN-d5: AL Amyloidosis

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Potential Combination of Azenosertib (ZN-c3) and ZN-d5

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44 The Combination of BCL-2 and Wee1 Inhibitors Results in Synergy in Several Tumor Models Including AML • ZN-d5 and azenosertib combination represents a novel therapeutic approach • Significant enhancement of activity than single agent in several indications, including AML • Combination regimen was well-tolerated in mice • Zentalis is the only company known to have both inhibitors in clinical development HL-60 AML Model ZN-d5 + Azenosertib (ZN-c3) 0 3 6 9 12 15 18 0 300 600 900 1200 1500 1800 2100 2400 2700 Vehicle ZN-d5 50 mg/kg, qd ZN-c3 60 mg/kg, qd Days Post Treatment T u m o r V o lu m e (m m 3) ZN-d5 50 mg/kg + ZN-c3 60 mg/kg, qd. Regression: 94% Presented at AACR 2022 by Izadi, H.; et. al. Cancer Res (2022) 82 (12_supplement): 2591.

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45 Antitumor Activity in Solid Tumor Models with the ZN-d5 + Azenosertib Combination Represents Market Expansion Opportunities 1. Izadi, H. et. al. Cancer Res (2022) 82 (12_Supplement): 2605. 0 3 6 9 12 15 18 21 0 200 400 600 800 1000 1200 1400 Vehicle ZN-d5 50 mg/kg ZN-c3 80 mg/kg ZN-d5 50 mg/kg + ZN-c3 80 mg/kg Days Post Treatment T u m o r V o lu m e (m m 3) SCLC Model (DMS53)1 Days t t ent TNBC Model (MDA-MB-436) Days Post Treatment NSCLC Model (H146) Days Post Treatment Neuroendocrine Prostate Model (H660) Days Post Treatment ZN-d5 + Azenosertib (ZN-c3)

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BCL-xL Protein Degrader

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47 Declared development candidate and initiated IND enabling activities BCL-xL Degrader Background and Rationale Background, Clinical Relevance, and Approach Therapeutic Hypothesis • BCL-xL is a member of the anti-apoptotic BCL-2 proteins and is clinically validated. 1, 2 • Expression of BCL-xL contributes to therapeutic resistance mechanisms. 3, 4, 5 • Degrading BCL-xL will induce cell death and overcome resistance mechanisms in multiple cancer types, while reducing the possibility of on- target thrombocytopenia. Patient Selection • Heme malignancies. • Solid tumors. Internal Combination Opportunities • Azenosertib (ZN-c3; Wee1 inhibitor) and ZN-d5 (BCL-2 inhibitor) Therapeutic Window • BCL-xL is required for platelet viability and BCL-xL inhibitors (e.g. navitoclax) are dose limited in the clinic due to on-target thrombocytopenia. 6 • A degradation approach with a E3 ligase low expressed in platelets could help mitigate thrombocytopenia. 7, 8 • Efficacy may be achieved at lower doses and frequencies due to the catalytic MOA of degraders, further reducing the chance of thrombocytopenia and increasing TI. Chemical Modality • Heterobifunctional degrader linking BH3-binding moiety. Competitive Landscape • Multiple inhibitors and one degrader in the clinic (Ph1/2). 1. Bhola PD and Letai A. Mol Cell. 2016;61(5):695-704 2. Konopleva M and Letai A. Blood. 2018 Sep 6;132(10):1007-1012 3. Rahman SFA et al., Future Oncology, 2020, 16(28) 4. Yue et al., Cnacer Cell Int., 2020, 20(254) 5. cbioportal.org 6. Wilson WY et al., Lancet Oncol., 2010; 11(12):1149-1159 7. Khan et al. Nature Med 12, 1938-1947 (2019) 8. He et al. Nature Comm 11, (2020) Figure from: Delbridge, A. R. D., et. al. Nat Rev Cancer 16, 99-109 (2016) BCL-xL Degrader

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48 BCL-xL IV Degrader is More Efficacious than BCL-xL Inhibitor (Navitoclax) in MOLT4 (T-ALL) Models Navitoclax data based on evaluation of comparable proxy chemical compound purchased from commercial sources rather than obtained from the pharmaceutical company developing the compound • BCL-xL degrader demonstrates excellent efficacy in the MOLT4 tumor model (T-ALL) and is well-tolerated at efficacious doses • BCL-xL degrader is more efficacious than Navitoclax -1 2 5 8 11 14 17 20 0 200 400 600 800 1000 1200 1400 Days Post Treatment Initiation T u m o r V o lu m e (m m 3) Navitoclax 100 mg/kg PO QD Navitoclax 100 mg/kg PO QW Navitoclax 20 mg/kg IV QW ZN Degrader 4, 20 mg/kg IV QW ZN Degrader 4, 40 mg/kg IV QW Vehicle i ti Days Post Treatment Initiation BCL-xL Degrader

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49 Azenosertib Combined with a Low Dose of Navitoclax (BCL-xL Inhibitor) Results in Synergistic Anti-tumor Activity in the T-ALL model MOLT-41 1. Izadi, H.; et. al. Cancer Res (2022) 82 (12_Supplement): 2605. TGI: Tumor Growth Inhibition ALL: Acute Lymphoblastic Leukemia MOLT-4 model is BCL-xL dependent, but is not on BCL-2 Navitoclax data based on evaluation of comparable proxy chemical compound purchased from commercial sources rather than obtained from the pharmaceutical company developing the compound • The MOA of the combination of the BCL-xL therapeutic and azenosertib represents a novel approach which results in synergistic anti-tumor activity. • Development of the BCL-xL degrader offers an opportunity to combine with other anti-cancer agents, such as azenosertib. Azenosertib (ZN-c3) + BCL-xL Days Post Treatment Days Post Treatment

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Conclusions

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51 4 ZENTALIS DRUGS Utilizing the Highly Efficient Integrated Discovery Engine to Generate Potentially Best-In-Class Drugs PATIENTS1 ZENTALIS DISCOVERY ENGINE2 3 Genomic FeaturesPathways Functional Screens Preclinical Models Chemistry Machine Learning • CRISPR screens • BH3 profiling • Genomics • 2D • 3D • Organoids • CDX • PDX • Enzymatic and allosteric inhibitors • Heterobifunctional Degraders and Molecular Glues • Crystallography and SBDD IDENTIFY1 ANALYZE2 CREATE3 GENERATE4

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52 2023 Key Milestones 1H 2023 Azenosertib (ZN-c3) Wee1 Inhibitor ZN-d5 BCL-2 Inhibitor Integrated Discovery Engine Initiate enrollment in the BRAF mutant colorectal cancer BEACON regimen combination clinical trial in collaboration with Pfizer Provide preclinical rationale for Cyclin E1 enrichment strategy at a scientific conference Declare monotherapy RP2D and provide update on dose optimization activities, program timelines and potential paths to registration Results from Phase 1b ovarian chemotherapy combination trial, including clinical translational data on Cyclin E1 amplification / overexpression 1H 2023 1Q 2023 2H 2023 2H 2023 Provide interim clinical data and declare RP2D for Phase 1/2 monotherapy trial in amyloidosis Provide preliminary data from clinical trial of azenosertib + ZN-d5 in relapsed / refractory acute myeloid leukemia 2023 Advance ongoing research on protein degrader programs of undisclosed targets 2H 2023 Continue to advance the BCL-xL protein degrader program through IND enabling studies 2023

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53 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 1710 New York, NY 10018 Science Center 10275 Science Center Drive Suite 200 San Diego, CA 92121

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