Zentalis Pharmaceuticals (ZNTL) investor relations material

Key clinical insights and data

• Azenosertib shows consistent response rates over 30% and duration of response exceeding six months in Cyclin E1-positive platinum-resistant ovarian cancer (PROC) patients at 400 mg, five days on, two days off dosing.

• Over 350 patients have been treated at active doses, with more than 200 in the PROC setting, demonstrating a manageable safety profile.

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

• Response rates are higher in patients with fewer prior lines of therapy, suggesting earlier intervention may improve outcomes.

• The companion diagnostic IHC assay is prospectively identifying eligible patients and is ready for clinical and future commercial use.

Strategic development plans and regulatory pathway

• Denali Part Two, a phase two, multi-part, registration-intended study, is underway with an accelerated approval pathway in mind.

• Dose selection in Part 2A will be determined in consultation with the FDA, with seamless transition to Part 2B to avoid enrollment pauses.

• A phase three confirmatory trial will run concurrently with Part 2B, aiming for initiation and significant enrollment by 2026.

• The company is funded through late 2027, supporting all planned clinical milestones and regulatory submissions.

• Regulatory discussions have been positive, with plans to reach at least 80% enrollment in the phase three trial by the time of accelerated approval submission.

Market opportunity and competitive landscape

• Cyclin E1-positive PROC represents about 50% of the market, or roughly 21,500 patients, with no approved therapies for this biomarker-defined group.

• The closest analog, Elahere, targets a smaller population (35%) and achieved over $330 million in sales in the first half of the year, highlighting strong demand.

• Azenosertib offers a non-chemotherapy, oral alternative, differentiating it from antibody-drug conjugates (ADCs) and standard chemo.

• The field is competitive, but the biomarker-driven approach and non-chemo profile provide a strategic advantage.

• Combination strategies with ADCs and expansion into other tumor types are under consideration for future development.