Zentalis to Cut 40% of Workforce Under Strategic Restructuring Plan

Approximately 40% of the current workforce of Zentalis Pharmaceuticals, a clinical-stage biopharmaceutical company headquartered in San Diego, Calif., will be separated from the company as part of a “strategic restructuring” announced on Jan. 28, 2025 (1).

A press release from Zentalis said the restructuring of its business operations and research and development organization will support late-stage development of azenosertib, its inhibitor product candidate that targets the protein kinase WEE1 and extend the company’s cash runway beyond a data readout from a potentially registration-enabling study that is anticipated by the end of 2026 (1).

Azenosertib, which Zentalis describes as “novel, selective, and orally bioavailable,” is currently being evaluated as a monotherapy as well as in combination clinical studies in ovarian cancer and other tumor types (1). Information provided in the press release identified WEE1 as a master regulator of the G1-S and G2-M cell cycle checkpoints through negative regulations of proteins CDK1 and CDK2, preventing replication of cells with damaged DNA.

By inhibiting WEE1, azenosertib—despite allowing for high levels of DNA damage—enables cell cycle progression, resulting in further accumulation of DNA damage that Zentalis says leads to mitotic catastrophe and, eventually, cancer cell death (1).

Zentalis said azenosertib has been well tolerated in clinical trials thus far, demonstrating anti-tumor activity across multiple tumor types as a single agent, and working well when combined with various chemotherapy backbones (1). The clinical development program supporting the product candidate has led Zentalis to explore enrichment strategies that target tumors of high genomic instability, homologous recombination-deficient tumors, and tumors with oncogenic driver mutations.

Julie Eastland, Zentalis CEO, recognized the soon-to-depart employees in a statement within the company press release.

"Zentalis is sharply focused on our goal of bringing azenosertib to patients with gynecological malignancies,” Eastland said in the release. “To support this goal, we have made the necessary decisions to efficiently organize our company and allocate our capital resources to extend cash runway beyond an anticipated azenosertib data readout that we believe has the potential to be registration-enabling. I want to thank all the individuals departing the company for their valuable contributions to all Zentalis programs and the development of azenosertib.”

Zentalis held a virtual corporate event on the morning of January 29 to further detail data findings from its studies of azenosertib and provide both development and regulatory updates (1).

As Zentalis continues development of this candidate in the United States, a treatment for ovarian as well as fallopian tube and primary peritoneal cancers, Abbvie’s Elahere (mirvetuximab soravtansine), was recommended for approval across the European Union by the European Medicines Agency’s Committee for Human Medicinal Products in September 2024, among eight new medicines and new indications for 12 existing drugs at that time (2).

References

1. Zentalis. Zentalis Pharmaceuticals Announces Strategic Restructuring to Support Late-Stage Azenosertib Development. Press Release. Jan. 28, 2025.
2. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 16-19 September 2024. Press Release. Sept. 20, 2024.