Zentalis Pharmaceuticals (ZNTL) Stifel 2026 Targeted Oncology Virtual Forum summary

Strategic focus and clinical development

• Focused on registration-directed development of azenosertib, a first-in-class Wee1 inhibitor, for platinum-resistant ovarian cancer in cyclin E1 positive patients.

• Two registration trials are ongoing: DENALI (multi-part, including dose selection and expansion) and ASPEN-OVA (phase III confirmatory trial).

• DENALI is designed for accelerated approval, with a top-line data readout expected by year-end 2024; ASPEN-OVA supports full approval.

• Additional studies are exploring azenosertib’s potential as a single agent and in combination across other tumor types.

• Cash runway extends through the end of 2027, supporting ongoing and planned trials.

Clinical trial updates and data insights

• 400 mg QD dose selected for further development based on superior efficacy and comparable safety to 300 mg in DENALI part two-A.

• Interim analysis showed about 50% lower discontinuation rates versus prior phase, attributed to improved site support and management of adverse events.

• No grade five or treatment-related deaths observed; improved tolerability profile noted.

• DENALI part two’s primary endpoint is overall response rate (ORR), with data expected by year-end 2024.

• Part two C of DENALI expands representation of taxane-exposed patients, aligning with recent treatment landscape changes.

Companion diagnostic and regulatory strategy

• Prospective validation of cyclin E1 positivity via IHC assay is integral to both DENALI and ASPEN-OVA entry criteria.

• Companion diagnostic commercialization is on track, aiming for simultaneous regulatory submission with azenosertib.

• Confident in meeting FDA requirements for confirmatory trial enrollment at time of accelerated approval.