Zentalis Pharmaceuticals, Inc. 8-K

What Happened
Zentalis Pharmaceuticals on April 9, 2026 announced that a prespecified interim analysis from DENALI Part 2a identified 400 mg once daily on a 5‑days‑on, 2‑days‑off schedule (400mg QD 5:2) as the optimal monotherapy dose of azenosertib in Cyclin E1‑positive platinum‑resistant ovarian cancer (PROC). The Company selected that dose over 300mg QD 5:2 based on a meaningfully higher response rate and comparable safety; recruitment at 300mg has been discontinued. Zentalis also expanded DENALI Part 2 (adding a Part 2c cohort) to better align with current treatment patterns and expects to initiate the confirmatory ASPENOVA Phase 3 trial in Q2 2026. The Company furnished a corporate presentation and press release under Regulation FD on the same date.

Key Details

• Dose selection: 400mg QD 5:2 chosen over 300mg QD 5:2 after prespecified interim analysis in DENALI Part 2a.
• Trial structure and enrollment targets: Part 2a had ~30 patients per dose group; Part 2b expansion will reach up to ~100 patients (including Part 2a patients at 400mg); new Part 2c will enroll ~40 taxane‑pretreated PROC patients (expected to start Q2 2026).
• Safety/readout: Comparable safety between doses, a discontinuation rate due to adverse events about half that reported in DENALI Part 1b, and no treatment‑related deaths reported in Part 2a interim data. Topline readout for DENALI Part 2 expected by year‑end 2026.
• Financial/corporate: Zentalis stated it expects existing cash, cash equivalents and marketable securities as of Dec 31, 2025 to fund operations into late 2027. Presentation and press release were furnished as Exhibits 99.1 and 99.2.

Why It Matters
Selecting a single optimal dose (400mg QD 5:2) streamlines ongoing DENALI enrollment and defines the regimen to be used in the planned ASPENOVA Phase 3 confirmatory trial, creating clearer near‑term clinical milestones (ASPENOVA start in Q2 2026; DENALI topline by year‑end 2026). The DENALI Part 2 design is intended to support an accelerated approval pathway, so these readouts may be material catalysts for the program. The Company’s disclosed cash runway into late 2027 indicates resources to fund these trials in the near term, though the filing reiterates standard forward‑looking risks (interim data may change, regulatory outcomes are uncertain, and additional funding could be needed).