Azenosertib Clinical Development & Strategy - Azenosertib, a WEE1 inhibitor, is being developed as a potential first-in-class and best-in-class therapy for Cyclin E1+ platinum-resistant ovarian cancer (PROC) patients[10] - Zentalis plans to seek FDA feedback on Phase 3 study design in the second half of 2025, initiate a Phase 3 confirmatory trial in 2026 following FDA feedback, and anticipates topline data from DENALI Part 2 by the end of 2026, with potential for FDA accelerated approval in Cyclin E1+ PROC patients[11] - The company has established Cyclin E1 as a predictive biomarker for azenosertib in Cyclin E1+ PROC[11] - Clinical data demonstrates clinically meaningful results and a manageable safety profile across multiple azenosertib monotherapy studies, with over 200 PROC patients treated at 300mg and 400mg QD 5:2[11] Market Opportunity & Data - Approximately 50% of PROC patients are Cyclin E1+ representing a significant opportunity in PROC, with ~21,500 patients in the US, UK, and EU4[13, 18] - In Cyclin E1+ patients at a monotherapy dose of 400mg QD 5:2, azenosertib demonstrated an ORR greater than 30% and a median duration of response (mDOR) of approximately 6 months, which is substantially superior to current standard of care (SOC)[12, 16] - The company has treated over 350 patients at active doses in monotherapy, including over 200 PROC patients treated at 300mg and 400mg 5:2, demonstrating a manageable safety profile[16] Financial Position - As of March 31, 2025, Zentalis had $332.5 million in cash, cash equivalents, and marketable securities, projecting a runway into late 2027 beyond anticipated DENALI Part 2 topline data[11] Safety and Efficacy - Safety profiles at 300mg and 400mg 5:2 are broadly comparable, with low frequency of previously reported Grade 5 treatment-related adverse events (TRAEs), Grade 3+ febrile neutropenia, and sepsis observed at 400mg 5:2[27] - In Cyclin E1+ PROC patients treated at 400mg QD 5:2, the ORR in response evaluable patients was 33.8% (23/68), with a median duration of response (mDOR) of 5.5 months[30]