Zentalis Pharmaceuticals (ZNTL) Corporate presentation summary

Strategic and clinical progress in azenosertib development

• Completed enrollment in DENALI Part 2a to confirm dose for registration-intent trial; FDA alignment achieved for ASPENOVA Phase 3 design.

• Strong efficacy data in platinum-resistant ovarian cancer (PROC), especially Cyclin E1-positive patients, with >30% ORR and ~6 months mDOR at 400mg QD 5:2.

• Maintained robust cash position ($280.7M as of September 30, 2025), supporting operations into late 2027.

• Anticipated 2026 milestones include DENALI Part 2a dose confirmation and ASPENOVA Phase 3 trial initiation in 1H 2026, with DENALI Part 2 topline readout expected by year-end 2026.

Clinical rationale and biomarker strategy

• Cyclin E1 overexpression sensitizes cancer cells to azenosertib by increasing CDK2 activity and DNA damage susceptibility.

• Companion diagnostic for Cyclin E1 is ready for registration studies, identifying ~50% of PROC patients as eligible.

• Cyclin E1 positivity more than doubles the eligible patient population beyond CCNE1 gene amplification alone.

• Cyclin E1 by IHC is a predictive biomarker for response, with ORR of ~35% and mDOR of 6.3 months in positive patients.

Market opportunity and unmet need

• No approved therapies specifically for Cyclin E1-positive PROC; estimated 21,500 patients in US/EU4+UK.

• Elahere’s $338M 1H 2025 sales in FRα+ PROC highlight demand for biomarker-driven therapies.

• Standard chemotherapy in PROC yields low ORR (4–13%), underscoring need for more effective options.

• Additional opportunities exist in earlier ovarian cancer lines and other Cyclin E1-overexpressing tumors (breast, endometrial, bladder).