Zentalis Pharmaceuticals (ZNTL) TD Cowen 46th Annual Health Care Conference summary

Strategic focus and clinical development

• Emphasis on advancing azenosertib for platinum-resistant ovarian cancer (PROC) patients with high Cyclin E1 protein expression, supported by extensive data and a proprietary diagnostic assay.

• Enrollment in the DENALI trial began in 2025, with Part 2A (dose comparison) completed and a key readout expected by end of 2026.

• Confirmatory Phase III ASPENOVA trial to start enrollment in the first half of the year, using a randomized design against standard care.

• Capital allocation ensures runway through late 2027 to support both DENALI and ASPENOVA trials.

• Focus on expanding azenosertib into earlier ovarian cancer lines and other tumor types, with ongoing combination studies.

Patient population and market opportunity

• Approximately 50% of PROC patients have high Cyclin E1 protein expression, translating to about 21,500 patients in the US, EU4, and UK.

• High unmet need exists as these patients have no approved targeted therapies and poor prognosis with standard chemotherapy.

• Oral administration of azenosertib offers a non-chemo, more convenient alternative to IV therapies, addressing quality-of-life concerns.

• Biomarker-selected agents are in demand, as evidenced by strong revenue from similar products.

Clinical data and trial design

• Azenosertib demonstrated consistent 31%-35% ORR and 4.2-6.3 month duration of response in Cyclin E1+ PROC patients across trials.

• DENALI Part 2 uses a seamless design to compare 300mg and 400mg doses, with ongoing enrollment and dose selection based on maturing data.

• ASPENOVA Phase III trial will randomize patients to azenosertib or standard care, with PFS as the primary endpoint and OS/ORR as secondary endpoints.

• Regulatory alignment achieved for both accelerated and full approval pathways, with substantial ASPENOVA enrollment required by PDUFA.