On May 7, 2024 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 March 31, 2024, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, MAY 7, 2024, View Source [SID1234642804]).

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"Zentalis continues to advance towards a catalyst-rich period during the second half of 2024 and into 2025, with a clear path to demonstrating the clinical profile of azenosertib, our potentially first-in-class and best-in-class WEE1 inhibitor, across various tumor types," said Kimberly Blackwell, M.D., Chief Executive Officer. "We believe that the data emerging this year and next have the potential to establish azenosertib’s monotherapy activity, differentiated safety and efficacy profile, and its ability to address significant unmet need for patients with serious gynecological cancers. Our clinical development plan remains on track as we work to bring azenosertib to patients living with gynecological cancers and other solid tumors."

Program Updates and Highlights
•Phase 1 azenosertib clinical data in osteosarcoma to be presented at ASCO (Free ASCO Whitepaper). In accordance with the Company’s guidance, Phase 1 results of azenosertib in combination with gemcitabine in adult and pediatric patients with relapsed or refractory (R/R) osteosarcoma will be presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
•Azenosertib preclinical data at AACR (Free AACR Whitepaper). On April 9, 2024, Zentalis presented preclinical data demonstrating that azenosertib exerts synergistic anti-tumor activity with KRASG12C inhibitors at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. This research supports azenosertib’s potential to be highly synergistic in combination with KRAS targeted cancer therapeutics, creating an additional large opportunity to combine with other standard of care targeted agents.
•Azenosertib development continues to progress on track across gynecological and other tumor types. Azenosertib is being evaluated in more than 10 ongoing and planned clinical trials as a monotherapy and in combinations supported by compelling scientific rationales across a broad array of tumor types, including platinum resistant ovarian cancer (PROC), platinum sensitive ovarian cancer (PSOC), uterine serous carcinoma (USC), BRAF mutant metastatic colorectal cancer, and other solid tumors. In addition, the Company is evaluating azenosertib and its BCL-2 inhibitor (ZN-d5) in patients with R/R acute myeloid leukemia (AML).

Corporate Updates

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•On April 5, 2024, Cam Gallagher was appointed interim Chief Financial Officer while the Company conducts a search for a new Chief Financial Officer.

Anticipated Upcoming Milestones
•1H 2024
◦Presentation of final results of Phase 1 (ZN-c3-003) azenosertib + chemotherapy (gemcitabine) trial in R/R osteosarcoma at 2024 ASCO (Free ASCO Whitepaper) Annual Meeting
•2H 2024
◦Presentation of final results of Phase 1b (ZN-c3-001) azenosertib monotherapy trial in solid tumors
◦Topline data from Phase 1/2 MAMMOTH (ZN-c3-006) azenosertib + PARP inhibitor (niraparib) and azenosertib monotherapy trial in platinum resistant ovarian cancer in partnership with GSK
◦Presentation of initial data from Phase 1 (ZN-c3-016) azenosertib + BEACON regimen (encorafenib + cetuximab) trial in BRAF mutant metastatic colorectal cancer in partnership with Pfizer
◦Initial data from Phase 1 (ZN-d5-004C) azenosertib + ZN-d5 trial in R/R AML
◦Additional details on design of planned registration-enabling trial of azenosertib in PSOC in the 1L maintenance setting
•1H 2025
◦Topline data from registration-enabling Phase 2 DENALI study (ZN-c3-005) of azenosertib monotherapy in platinum resistant high-grade serous ovarian cancer
•2H 2025
◦Topline data from registration-enabling Phase 2 TETON study (ZN-c3-004) of azenosertib monotherapy in recurrent or persistent USC
•2025
◦Initiate registration-enabling trial of azenosertib in PSOC in the 1L maintenance setting
•2026
◦First NDA for azenosertib in a gynecologic malignancy

First Quarter 2024 Financial Results
•Cash, Cash Equivalents and Marketable Securities Position: As of March 31, 2024, Zentalis had cash, cash equivalents and marketable securities of $489.0 million, which includes $56.7 million representing the March 31, 2024 fair value of Immunome common stock received by the Company as part of its upfront payment for the out-licensing of its ROR1 antibody-drug conjugate (ADC) product candidate and ADC platform in January 2024. The Company believes that its existing cash, cash equivalents and marketable securities (excluding the Immunome

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stock) as of March 31, 2024 will be sufficient to fund its operating expenses and capital expenditure requirements into mid-2026.
•Research and Development Expenses: Research and development (R&D) expenses for the three months ended March 31, 2024, were $49.6 million, compared to $48.6 million for the three months ended March 31, 2023. The increase of $1.0 million was primarily due to increases of $2.4 million and $2.2 million from drug product and clinical expense, respectively. We also saw increases of $0.7 million and $0.7 million from consulting and R&D cost sharing, respectively. These increases were partially offset by a decrease of $4.7 million in overhead allocations and a $0.3 million decrease of personnel expense.
•General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2024, were $15.7 million, compared to $16.4 million during the three months ended March 31, 2023. This decrease of $0.7 million was primarily attributable to $0.8 million and $0.7 million decreases in depreciation and other expenses, respectively. This was partially offset by $0.8 million increase related to personnel expense, of which $0.2 million is from non-cash stock-based compensation expense.

About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.