Zentalis Pharmaceuticals (ZNTL) Leerink Global Healthcare Conference 2026 summary

Program highlights and clinical development

• Focused on developing azenosertib, a Wee1 inhibitor, for platinum-resistant ovarian cancer with high cyclin E1 expression, with DENALI Part 2 trial ongoing for accelerated approval.

• Enrollment for DENALI Part 2's dose comparison (300 mg vs 400 mg) completed, with a phase 3 confirmatory trial (ASPENOVA) set to begin in the same population.

• DENALI trial readout expected by year-end 2026, with ASPENOVA designed as a randomized controlled trial to support full approval.

• Historical studies showed consistent response rates above 30% and manageable tolerability, especially at 400 mg.

• Dose selection in DENALI is based on efficacy and safety, with the selected dose moving forward for primary outcome analysis.

Clinical landscape and regulatory considerations

• Standard of care for platinum-resistant ovarian cancer yields low response rates (4%-13%) and minimal PFS benefit, highlighting high unmet need, especially for cyclin E1 high patients.

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

• Regulatory bar for approval is considered around 30% ORR and 5-6 months duration, with examples like mirvetuximab and CDK4/6 inhibitors cited.

• ASPENOVA uses an adaptive design to allow early initiation before DENALI readout, aiming for rapid progression to full approval.

• ASPENOVA targets 420-450 patients, with site expansion planned beyond DENALI.

Expansion strategies and future directions

• MIRROR trial will explore azenosertib in combination with bevacizumab in second-line maintenance for patients progressing on PARP inhibitors, aiming for early proof of concept.

• MIRROR will enroll a mix of HRD positive and negative patients, reflecting real-world practice.

• CCNE1 and HRD status are not mutually exclusive; retrospective analysis will assess biomarker impact.

• Earlier line strategies are being considered, with pragmatic trial designs to efficiently generate data for broader indications.

• Ongoing engagement with regulatory agencies to align trial design and enrollment with evolving approval requirements.