On August 9, 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 June 30, 2024, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, AUG 9, 2024, View Source [SID1234645694]).
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"While we faced challenges this quarter with regards to the ongoing partial clinical hold on azenosertib, we remain steadfast in our confidence in the program’s therapeutic potential and in our commitment to bringing this investigational medicine to patients with gynecological malignancies," said Kimberly Blackwell, M.D., Chief Executive Officer. "We continue to engage with regulators to resolve the hold and advance our clinical development efforts, which have already made important progress this year. Notably, we announced this quarter that we look forward to sharing the results of Cohort 1b of our DENALI study, a study that enrolled heavily pretreated platinum resistant ovarian cancer patients. We are grateful to our study investigators who continue to believe in the potential of azenosertib, to our employees who are laser-focused on our goal of making azenosertib available to patients, and most importantly, our clinical study participants and their families for their support."
Program Updates
•Azenosertib development update. On June 18, 2024, Zentalis disclosed that the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on certain clinical studies of azenosertib. The action followed two recent deaths in the DENALI study. Zentalis will provide additional updates to the azenosertib clinical development and certain data timelines following resolution of the partial clinical hold.
•Phase 1 azenosertib clinical data in osteosarcoma 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 were presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
•Acute myeloid leukemia (AML) program update. Today, Zentalis is disclosing that it is no longer developing the combination of its BCL-2 inhibitor, ZN-d5, with azenosertib, and is discontinuing development of ZN-d5. The combination of ZN-d5 and azenosertib was studied in 27 patients with R/R AML in a Phase 1 study. Thirteen patients were evaluable for efficacy, and the other 14 patients experienced progressive disease prior to efficacy evaluation or withdrew. The combination demonstrated clinical activity in patients who had been previously treated with venetoclax. Of the 6 patients who completed at least two cycles of therapy and underwent a cycle 3, day 1 bone marrow (BM) aspirate: 1 achieved a complete remission with incomplete hematologic recovery (CRi) and became transplant eligible, 2 patients had decreased BM blast counts, 2 had stable BM blasts, and 1 patient had increased BM blasts. The safety profile was manageable and in-line with other combinations in the R/R AML disease setting.
Corporate Updates
•Today, Zentalis is disclosing that effective August 8, 2024, Diana Hausman, M.D., has stepped down and is no longer serving as the Company’s Chief Medical Officer. The Company is conducting a search for a new Chief Medical Officer. Dr. Blackwell will serve as the Company’s Interim Chief Medical Officer.
•On May 29, 2024, Zentalis announced the appointment of Luke Walker, M.D., to its Board of Directors. Dr. Walker is the Chief Medical Officer of Harpoon Therapeutics, a subsidiary of Merck & Co., Inc., Rahway, NJ, and brings nearly three decades of experience as a practicing oncologist and drug developer advancing new cancer therapies.
Anticipated Upcoming Milestones
•2H 2024
◦Topline results from Cohort 1b of the Phase 2 DENALI study (ZN-c3-005) of azenosertib monotherapy in platinum resistant high-grade serous ovarian cancer
◦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
◦Additional updates to the azenosertib clinical development and other data timelines to be provided following resolution of the partial clinical hold.
Second Quarter 2024 Financial Results
•Cash, Cash Equivalents and Marketable Securities Position: As of June 30, 2024, Zentalis had cash, cash equivalents and marketable securities of $426.4 million, which includes $27.8 million representing the June 30, 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 stock) as of June 30, 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 June 30, 2024, were $48.4 million, compared to $42.7 million for the three months ended June 30, 2023. The increase of $5.7 million was primarily due to increases of $7.4 million for clinical and certain translational expenses and $1.0 million for drug manufacturing and supplies costs. The Company also saw increases of $1.4 million resulting from no R&D cost sharing arrangement with Zentera. These increases were partially offset by a decrease of $2.7 million of personnel expense of which $1.5 million is related to non-cash stock-based compensation and $1.4 million of facilities and allocated expenses.
•General and Administrative Expenses: General and administrative expenses for the three months ended June 30, 2024, were $16.8 million, compared to $15.7 million during the three months ended June 30, 2023. This increase of $1.1 million was primarily attributable to an increase in personnel expenses of $1.3 million and lease termination costs of $0.5 million. This was partially offset by a decrease of other expenses of $0.7 million, net.
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.