Zentalis Pharmaceuticals (ZNTL) Leerink Global Healthcare Conference 2026 summary

Program highlights and strategic focus

• Focused on developing azenosertib, a Wee1 inhibitor, for platinum-resistant ovarian cancer with high cyclin E1 expression, targeting a high unmet need population.

• DENALI Part 2 trial is ongoing for accelerated approval, with the first portion (dose comparison) completed and a readout expected by year-end 2026.

• ASPENOVA, a phase 3 confirmatory randomized controlled trial, is being initiated in the same patient population to support full approval.

• Historical data show consistent response rates above 30% and manageable tolerability, especially at the 400 mg dose.

• Dose selection between 300 mg and 400 mg is based on efficacy and safety, with the primary outcome measured in patients on the selected dose.

Clinical landscape and trial design

• Standard of care for platinum-resistant ovarian cancer yields low response rates (4%-13%) and minimal PFS benefit, highlighting significant unmet need.

• Mirvetuximab has shown ~30% response rates and 5-6 months duration, setting a benchmark for new therapies.

• Prior studies included all-comers, but retrospective analysis identified cyclin E1 as a key biomarker for response, guiding current trial enrollment.

• Response rates in cyclin E1-positive patients at 400 mg were consistently above 30%, with the largest dataset showing mid-30s%.

• Fewer prior lines of therapy correlate with higher response rates, but durable responses are seen even in heavily pretreated patients.

Regulatory and operational updates

• ASPENOVA uses an adaptive design to allow early initiation before DENALI readout, expediting the path to full approval.

• The confirmatory trial is operationalized, with sites opening and first patient enrollment expected in the first half of the year.

• FDA expects the majority of the confirmatory trial to be enrolled by the time of accelerated approval, influencing the decision to start ASPENOVA early.

• ASPENOVA will enroll 420-450 patients, with more sites and countries than DENALI.