Zentalis Pharmaceuticals (ZNTL) Wells Fargo 21st Annual Healthcare Conference summary

Recent progress and strategic focus

• Over the past year, enrollment began for two parts of the DENALI registration-intended study targeting platinum-resistant ovarian cancer, especially in high cyclin E1 expressers.

• The ASPENOVA phase III trial design was aligned with the FDA to support both accelerated and full approval, with global commercialization in mind.

• The MUIR trial was initiated to study azenosertib in combination with bevacizumab for patients progressing on PARP inhibitors.

• The monotherapy dose was confirmed at 400 mg daily, five days on, two days off.

Safety, monitoring, and differentiation

• The FDA lifted the clinical hold on azenosertib without requiring changes to dose or schedule, reflecting confidence in the safety approach.

• Real-time study oversight and enhanced investigator education were implemented to proactively manage safety signals.

• Supportive care protocols, such as antiemetic and antidiarrheal regimens, were clarified to improve patient experience.

• Hematological toxicity rates, including grade 3 neutropenia, were modest and compared favorably to other oncology drugs.

Clinical development and efficacy expectations

• The 5-on, 2-off dosing schedule was established to balance efficacy and tolerability, with no evidence of compromised efficacy.

• DENALI Part 2 aims for a top-line readout in H1 2027, with a win defined as an overall response rate of 30%+ and duration of response of at least five months.

• Azenosertib offers a non-chemo oral option, providing a break from chemotherapy for patients with high cyclin E1 expression.