Zentalis Pharmaceuticals (ZNTL) H.C. Wainwright 4th Annual BioConnect Investor Conference summary

Pipeline and clinical strategy

• Focused on completing registration clinical studies for azenosertib, a WEE1 inhibitor, targeting platinum-resistant ovarian cancer, with DENALI as the accelerated approval trial and ASPENOVA as the confirmatory phase III trial.

• DENALI trial expects top-line data by year-end, enrolling patients with one to four prior therapies; ASPENOVA has begun enrollment globally for full approval.

• Expansion studies underway for azenosertib in combination with bevacizumab and other cytotoxic agents, aiming to broaden its application across tumor types.

Scientific rationale and dose selection

• Cyclin E1 is highly expressed in about half of platinum-resistant ovarian cancer patients, making WEE1 inhibition particularly effective in this subgroup.

• 400 mg QD (five days on, two days off) was selected as the optimal dose after demonstrating superior efficacy and similar safety compared to 300 mg in phase II.

• All future DENALI and ASPENOVA trial patients will receive the 400 mg dose, solidifying it as the monotherapy standard.

Efficacy, safety, and regulatory positioning

• Azenosertib has shown response rates above 30%, with duration of response around five to six months, outperforming standard salvage chemotherapy.

• Safety profile at 400 mg is comparable to other cytotoxic agents, with manageable hematological and GI toxicities through proactive measures.

• Regulatory discussions with the FDA have focused on ensuring trial designs and endpoints meet accelerated and full approval requirements.