Zentalis Pharmaceuticals (ZNTL) Corporate presentation summary

Clinical development progress

• Established a strong clinical foundation for azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer (PROC), with pivotal dose selection and completion of key enrollment milestones for registration-intent studies in 2025 and 2026.

• DENALI Part 2 topline readout is expected by year-end 2026, potentially supporting accelerated approval, while the ASPENOVA Phase 3 confirmatory trial is set to initiate in Q2 2026.

• Strategic restructuring has extended the cash runway into late 2027, with $245.9M in cash and equivalents as of December 31, 2025.

• FDA alignment achieved on the design of the randomized, confirmatory ASPENOVA Phase 3 trial.

• Launch preparedness activities are underway to support commercialization.

Efficacy and safety data

• Azenosertib demonstrated >30% objective response rate (ORR) and ~6 months median duration of response (mDOR) in Cyclin E1-positive PROC at the 400mg QD 5:2 dose.

• Safety profile is manageable, with most common adverse events being nausea, diarrhea, and fatigue; discontinuation rates due to adverse events are lower at the pivotal dose.

• Integrated analyses show broadly comparable safety at 300mg and 400mg doses, with low rates of severe hematologic toxicities and treatment discontinuations.

• Higher response rates and longer progression-free survival (PFS) observed in patients with fewer prior lines of therapy.

• Consistent antitumor activity and tolerability in heavily pre-treated and PARPi-resistant populations.

Biomarker and patient selection

• Cyclin E1 overexpression, present in ~50% of PROC patients, is a predictive biomarker for response to azenosertib, regardless of CCNE1 amplification status.

• Companion diagnostic is ready for use in registration-intent studies to identify eligible patients.

• Cyclin E1-positive patients have worse outcomes with standard therapies, highlighting the unmet need.

• All PROC patients should be screened for Cyclin E1 overexpression to maximize eligible population.