Zentalis Pharmaceuticals (ZNTL) investor relations material

Focused strategy and unmet need

• Targeting approximately 21,500 Cyclin E1-positive platinum-resistant ovarian cancer (PROC) patients in the US and Europe who lack specifically targeted therapies.

• Azenosertib, a first-in-class oral WEE1 inhibitor, is positioned as a potential non-chemotherapy option for this population.

• Clear regulatory path: DENALI Part 2 topline readout expected by year-end 2026 for potential accelerated approval; ASPENOVA Phase 3 trial initiated to support full approval.

• Expansion plans include earlier lines of ovarian cancer and other tumor types.

• Cash reserves of $212M provide operational runway into late 2027.

Clinical development and trial progress

• Over 800 patients treated with azenosertib across multiple tumor types and regimens, informing registration strategy.

• DENALI Part 2 is enrolling Cyclin E1-positive PROC patients, with 400mg QD 5:2 selected as the pivotal monotherapy dose.

• ASPENOVA Phase 3 trial, aligned with FDA, is enrolling and designed to compare azenosertib to investigator's choice chemotherapy.

• MUIR Phase 1b study explores azenosertib in combination with chemotherapy and bevacizumab in ovarian cancer.

Efficacy and safety profile

• Integrated analysis shows >30% overall response rate (ORR) and ~6 month median duration of response (mDOR) at 400mg QD 5:2 in Cyclin E1-positive PROC.

• Durable responses observed regardless of CCNE1 amplification status, reinforcing Cyclin E1 IHC as the predictive biomarker.

• Safety profile at 400mg QD 5:2 is manageable, with most common adverse events being nausea, diarrhea, and fatigue.

• Enhanced trial management in later phases reduced discontinuation rates and treatment-related deaths.