Zentalis Pharmaceuticals (ZNTL) investor relations material

Key program updates and clinical data

• Lead candidate azenosertib is in late-stage development for Cyclin E1-positive platinum-resistant ovarian cancer, showing over 30% response rates and duration of response exceeding six months at the 400 mg dose.

• Over 350 patients have been treated at active doses, with more than 200 in the target population, and the safety profile is considered manageable.

• Integrated analysis across multiple studies confirms consistent efficacy and tolerability at both 300 mg and 400 mg doses.

• The proprietary IHC assay is used to identify eligible patients, with the target population representing about 50% of the PROC market, or roughly 21,500 patients.

• The companion diagnostic is ready and being used in ongoing trials, with market opportunity compared to Elahere, which addresses a smaller patient subset.

Clinical development strategy and regulatory pathway

• Denali Part 2, a phase two, multi-part, registration-intended study, is underway with a seamless design to accelerate approval and minimize enrollment pauses.

• Dose selection in Part 2A will be followed by regulatory discussions, with top-line data expected by year-end 2026.

• A phase three confirmatory trial will run concurrently with Part 2B, aiming for at least 80% enrollment at the time of accelerated approval submission.

• The trial design and endpoints have been discussed with the FDA, and the company is funded through late 2027 to support these efforts.

• The phase three trial will use investigator's choice chemotherapy as the control arm and leverage up to 80 global sites.

Market landscape, competition, and patient impact

• Cyclin E1 overexpression is a poor prognostic marker, and no approved therapies exist for this biomarker-selected group.

• The market is large and underserved, with single-agent chemotherapy response rates as low as 4%-13%.

• Azenosertib offers a non-chemotherapy, oral alternative, differentiating it from ADCs, which are essentially targeted chemotherapies.

• The company anticipates that its biomarker-driven approach and companion diagnostic will facilitate patient identification and market adoption.

• Combination strategies with ADCs and expansion into other tumor types are under consideration, pending resources.