Zentalis Pharmaceuticals (ZNTL) investor relations material

Strategic focus and clinical development

• Lead asset azenosertib is being advanced in platinum-resistant ovarian cancer, targeting patients with cyclin E1 protein overexpression.

• The Denali trial is a registration-intent study aiming for accelerated approval, with a phase 3 confirmatory trial planned.

• A clear strategic focus was established to prioritize azenosertib in ovarian cancer, with capital allocated to this path and ongoing trials in other indications.

• The company underwent restructuring to ensure sufficient capital, reporting $303 million in cash and equivalents, providing runway into late 2027.

Clinical data and trial design

• Integrated analysis across multiple studies showed consistent response rates and durability for azenosertib, with a 35% response rate and 6.3 months duration in Denali part 1.

• The selected dosing regimen is 400 mg, five days on, two days off, based on efficacy and tolerability.

• Cyclin E1 biomarker enrichment improved response rates by over 10%, and prospective enrichment is being used in Denali part 2.

• Denali part 2A is a randomized dose confirmation (300 mg vs 400 mg), with part 2B expanding to a registrational size; top-line data expected end of 2026.

• The FDA has aligned with the trial design, including the need for a confirmatory phase 3 trial in the same patient population.

Safety, regulatory, and market positioning

• Safety profile is considered manageable, with protocol updates and site management to address adverse events.

• A brief clinical hold was resolved without changes to dose or schedule, and the FDA expressed confidence in the program.

• The target market is about 21,500 patients annually in the US, representing 50% of the platinum-resistant ovarian cancer population.

• Expansion opportunities include earlier lines of ovarian cancer, combinations with other agents, and other tumor types such as HER2-positive and triple-negative breast cancer.

• The company remains focused on its lead indication but is open to further development if additional capital becomes available.