On August 9, 2023 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported financial results for the quarter ended June 30, 2023, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, AUG 9, 2023, View Source [SID1234634092]).

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"We have strong azenosertib data that creates the potential to build a meaningful franchise around this exciting product candidate with the possibility of near-, mid- and long-term opportunities across multiple tumor types," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "As a monotherapy, azenosertib achieved an objective response rate of 36.8% in ovarian cancer and uterine serous carcinoma patients who received intermittent dosing. Azenosertib plus chemotherapy combinations also demonstrated positive results in women facing heavily pretreated ovarian cancer. Taking these results together, we believe there is the potential for azenosertib to transform the standard of care for patients with ovarian and uterine cancers, and ultimately other solid tumors. We are well positioned to advance this program with a strong cash position resulting from our recent offering that extended our cash runway and will sustain our corporate and clinical strategy for the next several years."

WEE1 Inhibitor (Azenosertib) Program Highlights

•Identified monotherapy recommended Phase 2 dose (RP2D) and reported positive safety and efficacy data. Based on encouraging Phase 1 dose optimization clinical data, the Company identified 400 mg daily (QD) on a 5 days on 2 days off (5:2) administration schedule as the monotherapy RP2D. Intermittent dosing more than doubled steady state drug exposure to achieve an objective response rate (ORR) of 36.8% in ovarian cancer and uterine serous carcinoma (USC) patients, while maintaining safety and improving tolerability in comparison to continuous dosing. For a more detailed summary of the Phase 1 monotherapy dose optimization data, click here. To listen to a replay of the call, click here.

•Presented positive azenosertib + chemotherapy combination data at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The Company presented positive data from its Phase 1b chemotherapy combination trial in platinum-resistant ovarian cancer at the ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago on June 5, 2023. Azenosertib was well tolerated in combination with multiple types of chemotherapy and demonstrated strong anti-tumor activity, with noteworthy improvements in ORRs and median progression free survival (mPFS) in all patients, especially those with Cyclin E1+ tumors, a subgroup recognized to have a poor prognosis and relatively poor outcomes following chemotherapy. Azenosertib combined with paclitaxel resulted in an ORR of 50.0% and mPFS of 7.4 months. An ORR of 35.7% and mPFS of 10.4 months was observed in azenosertib combined with carboplatin. Zentalis is preparing for a Phase 3 trial of azenosertib using intermittent dosing in combination with chemotherapy in Cyclin E1+ platinum-sensitive ovarian cancer. To review the Phase 1b results in more detail, click here.
•Biomarker enrichment strategies. Zentalis is exploring biomarker enrichment strategies for azenosertib targeting tumors of high genomic instability, such as Cyclin E1+ tumors and homologous recombination deficient tumors. In April 2023, the Company presented preclinical data supporting the rationale for the Cyclin E1 enrichment strategy at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023.

Corporate Highlights

•In August 2023, the Company announced the appointment of Kimberly Freeman as Chief Strategy Officer. In this role, she will support and implement Zentalis’ long-term portfolio strategy. Ms. Freeman joins Zentalis with over 25 years of clinical development and strategic leadership experience, including deep expertise in oncology, particularly in gynecologic malignancies and the DNA damage response (DDR) pathway. Ms. Freeman brings an outstanding track record of building and executing drug development and franchise strategies that will be invaluable to the Company as it seeks to capitalize on the significant opportunity with azenosertib across a broad array of tumor types.
•In June 2023, the Company closed an underwritten public offering of 11,032,656 shares of its common stock at a public offering price of $22.66 per share. The total gross proceeds were approximately $250.0 million.
•In May 2023, the Company appointed Diana Hausman, M.D., to its Board of Directors. Dr. Hausman is an oncologist with extensive experience in all aspects of drug development, including development and implementation of clinical strategy. Dr. Hausman is currently serving as Chief Medical Officer of Link Immunotherapeutics. Dr. Hausman previously served as Chief Medical Officer of Lengo Therapeutics, Zymeworks and Oncothyreon. Prior to Oncothyreon, Dr.

Hausman held positions of increasing responsibility at ZymoGenetics, Berlex Laboratories and Immunex. Dr. Hausman currently serves on the Board of Directors of Immuneering.
•In May 2023, the Company announced that it had appointed Funda Meric-Bernstam, M.D., a widely recognized Phase 1 trial expert and experimental therapeutics researcher in oncology, to its Scientific Advisory Board. Dr. Meric-Bernstam is the Chair of the Department of Investigational Cancer Therapeutics — the Phase 1 Program at The University of Texas MD Anderson Cancer Center. Her clinical research is focused on novel therapeutics, novel combination therapies and biomarkers to predict and monitor drug response.
Second Quarter 2023 Financial Results

•Cash and Marketable Securities Position: As of June 30, 2023, Zentalis had cash, cash equivalents and marketable securities of $553.0 million. The Company believes that its existing cash, cash equivalents and marketable securities as of June 30, 2023 will be sufficient to fund its operating expenses and capital expenditure requirements into 2026.
•Research and Development Expenses: Research and development (R&D) expenses for the three months ended June 30, 2023 were $42.7 million, compared to $43.8 million for the three months ended June 30, 2022. The decrease of $1.1 million was primarily due to $1.7 million in decreased collaboration costs, a $1.1 million decrease related to clinical trials and R&D supplies, and a $0.6 million reduction in personnel and related expense. These decreases were partially offset by a $1.5 million increase in Zentera Therapeutics cost sharing and a $0.8 million increase in consulting and other expense.
•General and Administrative Expenses: General and administrative expenses for the three months ended June 30, 2023 were $15.7 million, compared to $19.6 million during the three months ended June 30, 2022. This decrease of $3.9 million was primarily attributable to a $4.2 million decrease in non-cash, stock-based compensation expense and a $0.8 million decrease related to other personnel expenses. These decreases were partially offset by an increase of $0.8 million in allocated overhead expenditures and a $0.3 million increase in outside services and other costs.
•Zentera-Related Expenses: On June 15, 2023, the Company announced that it had regained worldwide development and commercialization rights to azenosertib, ZN-d5 and ZN-c5 as a result of the termination of its collaboration with Zentera Therapeutics in certain Asian countries, including China. In connection with the Zentera termination, the Company incurred one-time expenses totaling $45.6 million.

About Azenosertib

Azenosertib is a potentially first-in-class and best-in-class small molecule WEE1 inhibitor in development for the treatment of cancer. Inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved WEE1 inhibitors, and azenosertib has been designed for superior selectivity and pharmacokinetic properties. Azenosertib is being developed in therapeutic areas of high unmet need and is being evaluated as a monotherapy, in combination with chemotherapy, and in combination with molecularly targeted agents.