Zentalis Pharmaceuticals is strategically restructuring its operations to focus on the late-stage development of azenosertib, a WEE1 inhibitor, for the treatment of gynecological malignancies. The company aims to extend its cash runway beyond the anticipated data readout from the potentially registration-enabling DENALI Part 2 study, expected by the end of 2026. This restructuring includes a workforce reduction of approximately 40%.
Prioritizing Azenosertib Development
The strategic shift underscores Zentalis' commitment to bringing azenosertib to patients with ovarian, fallopian tube, and primary peritoneal cancers. "Zentalis is sharply focused on our goal of bringing azenosertib to patients with gynecological malignancies," said Julie Eastland, Chief Executive Officer. The company believes that the data readout from the DENALI Part 2 study has the potential to be registration-enabling, prompting the decision to allocate resources efficiently.
Clinical Data and Regulatory Update
Zentalis will host a corporate event on January 29, 2025, to present updated clinical data from studies of azenosertib and provide a development and regulatory update. This will include plans for registration-intent studies. Mid-trial data from the MAMMOTH and DENALI studies show a 5.5-month median duration of response and "no new safety signals."
About Azenosertib
Azenosertib is an orally bioavailable and selective WEE1 inhibitor. WEE1 regulates the G1-S and G2-M cell cycle checkpoints by negatively regulating CDK1 and CDK2, preventing the replication of cells with damaged DNA. By inhibiting WEE1, azenosertib allows cell cycle progression despite DNA damage, leading to mitotic catastrophe and cancer cell death. Azenosertib is being evaluated as a monotherapy and in combination clinical studies in ovarian cancer and other tumor types.
Azenosertib has received FDA Fast Track Designation for platinum-resistant forms of ovarian, fallopian tube, and peritoneal cancer. It is currently being assessed in multiple ongoing trials as both a monotherapy and in combination studies.
