On May 10, 2023 Zentalis 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, reported financial results for the quarter ended March 31, 2023, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, MAY 10, 2023, View Source [SID1234631407]).

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"We believe that azenosertib has the potential to benefit large numbers of patients who are facing difficult-to-treat cancers. As a result, our highest priority remains the successful execution of our development strategy for this promising therapeutic," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "We began the year by initiating enrollment in our Pfizer-partnered clinical trial combining azenosertib with the BEACON regimen in BRAF V600E mutant metastatic colorectal cancer. At AACR (Free AACR Whitepaper) in April, we presented preclinical data supporting the use of CCNE1 amplification and/or Cyclin E1 expression as a potential marker for the enrichment of patient populations for treatment with azenosertib. We are driving toward two additional milestones for azenosertib in the first half of the year – disclosing our monotherapy dose, and sharing positive clinical data from our chemotherapy combination trial in ovarian cancer at ASCO (Free ASCO Whitepaper) in June."

The Company also announced the appointment of Diana Hausman, M.D., to the Board of Directors. "I share Zentalis’ passion and commitment to developing therapeutics for difficult-to-treat cancers," said Dr. Hausman. "I believe azenosertib has the potential to be a game-changing therapeutic for cancer patients, and I look forward to working with the other members of the Board and the Zentalis management team to help the Company achieve its goals."

WEE1 Inhibitor (Azenosertib) Program Highlights

•On track to announce monotherapy dose in first half 2023. The Company is optimizing monotherapy dosing across the azenosertib program with the goal of maximizing exposure and tolerability, as well as enabling the potential clinical benefits of the agent to reach the broadest range of patients. The Company remains on track to provide an update on azenosertib monotherapy dosing in the first half of 2023.

•Company to present positive chemotherapy combination data at 2023 ASCO (Free ASCO Whitepaper) Annual Meeting. The Company will present results from its Phase 1b chemotherapy combination trial in ovarian cancer, which will include Cyclin E1 translational data, at the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, on June 5, 2023.

•Preclinical support for Cyclin E1 as a predictive marker presented at AACR (Free AACR Whitepaper). Zentalis identified high Cyclin E1 protein expression and/or CCNE1 gene amplification in high-grade serous ovarian cancer as a patient enrichment strategy for azenosertib, which is currently enrolling its Phase 2 clinical study in high-grade serous ovarian cancer. In April, 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.

•Initiated mCRC study in collaboration with Pfizer. As previously disclosed, in the first quarter of 2023, Zentalis initiated enrollment for its Phase 1/2 dose escalation study of azenosertib in combination with encorafenib and cetuximab (BEACON regimen) in BRAF V600E mutant metastatic colorectal cancer (mCRC) patients. Zentalis is collaborating with Pfizer Inc. on this study.

•Collaborations with Foundation Medicine and Roche Diagnostics. In April, the Company announced separate agreements with Foundation Medicine, Inc., an independent affiliate of the Roche Group, and with Roche Diagnostics. The current Foundation Medicine partnership involves global prospective genomic profiling for potential patient enrollment in Zentalis’ Phase 2 clinical trial of azenosertib in Cyclin E1 driven high-grade serous ovarian cancer. The Roche Diagnostics agreement is focused on the development of an immunohistochemistry-based clinical trial assay that evaluates Cyclin E1 protein levels and that can potentially identify a broader patient population with high protein expression in the absence of amplification.

BCL-2 Inhibitor (ZN-d5) 2023 Milestones

•Amyloidosis study. As previously communicated, Zentalis plans to announce interim clinical data and disclose the dose 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.

•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, as previously disclosed, expects to provide preliminary data from the trial in the second half of 2023.

Corporate Highlights

•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 February 2023, the Company 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.

First Quarter 2023 Financial Results

•Cash and Marketable Securities Position: As of March 31, 2023, Zentalis had cash, cash equivalents and marketable securities of $392 million. The Company believes that its existing cash, cash equivalents and marketable securities as of March 31, 2023 will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2025.

•Research and Development Expenses: Research and Development Expenses: Research and development (R&D) expenses for the quarter ended March 31, 2023 were $48.6 million, compared to $46.1 million for the three months ended March 31, 2022. The increase of $2.5 million was primarily due to a $3.2 million increase in overhead allocations driven by an operating lease impairment charge, and an increase of $1.9 million in personnel costs. These increases were partially offset by a $1.8 million decrease in clinical trial-related costs and $0.8 million in decreased collaborative costs.

•General and Administrative Expenses: General and administrative (G&A) expenses for the quarter ended March 31, 2023 were $16.4 million, compared to $11.8 million during the three months ended March 31, 2022. This increase of $4.6 million was primarily attributable to a $5.0 million operating lease impairment charge and a $3.0 million increase in personnel costs, of which $2.7 million was non-cash stock-based compensation. These increases were partially offset by $3.1 million related to the allocation of overhead expenditures, and net reductions in outside services and supplies of $0.3 million.

About Azenosertib

Zentalis’ azenosertib (ZN-c3) has been designed to be a highly potent and selective WEE1 inhibitor.
Azenosertib is currently being evaluated in the clinic for advanced solid tumors and hematological malignancies in the following three therapeutic settings of high unmet medical need: (1) as a monotherapy, (2) in combination with traditional chemotherapy and DNA damaging agents, and (3) in combination with molecularly targeted agents. As a monotherapy, azenosertib is currently being evaluated in a Phase 2 clinical trial in adult women with uterine serous carcinoma (USC), an aggressive form of endometrial cancer that accounts for approximately 10-15% of all endometrial cancers. We are also evaluating azenosertib as a monotherapy in a Phase 2 clinical trial in patients with Cyclin E1 driven high-grade serous ovarian cancer (HGSOC). The Company is evaluating azenosertib as a monotherapy in a Phase 1 dose optimization clinical trial in patients with advanced solid tumors, and plans to disclose the monotherapy dose and provide an update on dose optimization activities in the first half of 2023. In chemotherapy combinations, azenosertib is currently being evaluated in combination with each of paclitaxel, carboplatin, pegylated liposomal doxorubicin (PLD) and gemcitabine in four cohorts in a Phase 1b clinical trial in patients with advanced platinum-resistant ovarian, peritoneal or fallopian tube cancer. The Company plans to disclose results from this study in the first half of 2023, in advance of original guidance. Azenosertib is also currently being evaluated in combination with gemcitabine in a Phase 1/2 clinical trial in adult and pediatric patients with relapsed or refractory osteosarcoma. In combination with molecularly targeted agents, the Company is studying azenosertib in combination with GlaxoSmithKline plc’s (GSK’s) PARP inhibitor, niraparib (ZEJULA), in a Phase 1/2 clinical trial in platinum-resistant ovarian cancer patients who have failed PARP inhibitor maintenance treatment as part of a clinical collaboration with GSK. The Company is also collaborating with Pfizer Inc. to evaluate azenosertib in combination with encorafenib and cetuximab, an FDA-approved standard of care known as the BEACON regimen, in patients with BRAF V600E mutant metastatic colorectal cancer in a Phase 1/2 clinical trial.