Zentalis Pharmaceuticals (ZNTL) TD Cowen 45th Annual Healthcare Conference summary

Strategic vision and market opportunity

• Focus on advancing azenosertib for PROC patients, especially Cyclin E1 positive, addressing a significant unmet need.

• Cyclin E1 positive patients represent at least 50% of PROC and have poor prognosis with current therapies.

• Ovarian cancer market expected to nearly triple in coming years, with targeted therapies in high demand.

• Proprietary IHC assay and companion diagnostic enable precise patient identification for trials and commercialization.

• Recent staff reduction and resource reallocation extend cash runway into late 2027, supporting clinical milestones.

Clinical data and trial design

• Azenosertib demonstrated >30% objective response rate and median response duration of 5.5 months in Cyclin E1+ PROC patients at 400mg monotherapy dose.

• Safety profile in over 350 patients is manageable and compares favorably to other WEE1 inhibitors, with low rates of severe adverse events at 300mg and 400mg.

• Subgroup analysis showed higher response rates in patients with fewer prior lines of therapy, with ORR up to 40% in 1-3 prior lines.

• Denali trial uses a seamless design, with dose confirmation (300 vs 400 mg) leading directly into registrational cohort, and FDA has agreed to this design for accelerated approval.

• Over 350 PROC patients have been treated at active doses, providing a robust safety and efficacy dataset.

Operational execution and regulatory alignment

• Enhanced trial management includes closer site engagement, continuous data review, and protocol improvements.

• Resource allocation prioritized for clinical, manufacturing, and medical affairs functions after a 40% workforce reduction.

• Denali Part 2A will enroll 60 patients (30 per arm), with interim analyses to expedite dose selection.

• Upon dose confirmation, up to 100 patients will be enrolled in the registrational cohort without enrollment pause.

• Confirmatory phase III trial to start in parallel with Part 2B, targeting several hundred patients.