Zentalis Pharmaceuticals (ZNTL) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Strategic focus and clinical development

• Leadership joined in fall 2024, attracted by robust clinical data for azenosertib as a first oral non-chemo option for biomarker-selected PROC patients.

• Over 500 patients have been treated with azenosertib, showing response rates above 30% and around six months duration of response, outperforming standard chemo.

• Two pivotal studies are underway: DENALI (for accelerated approval) and ASPENOVA (phase III confirmatory trial for full approval).

• DENALI is enrolling, aiming for 100 patients at the selected dose with a readout by year-end; ASPENOVA will support full approval.

• Regulatory alignment with the FDA has been established for both accelerated and full approval pathways.

Differentiation and competitive landscape

• Azenosertib offers a non-chemo, oral alternative, addressing quality-of-life and convenience for patients who otherwise face frequent IV infusions.

• ADCs are seen as complementary rather than competitive, with potential for combination regimens.

• The oral regimen is particularly valuable for older patients and those distant from cancer centers.

• Quality of life and convenience are emphasized as key differentiators.

Trial design, biomarker strategy, and regulatory process

• DENALI includes a two-dose randomized portion; dose selection will be confirmed with the FDA before public disclosure.

• Both 300mg and 400mg doses show similar safety, with higher efficacy expected at 400mg based on prior data.

• Cyclin E1 protein overexpression, not just gene amplification, is used as the biomarker to maximize patient benefit.

• Biomarker cutoffs are validated across multiple retrospective and prospective studies, with ongoing prospective validation in DENALI.

• ASPENOVA mirrors the MIRASOL trial design but selects for Cyclin E1 positive patients, who have a poorer prognosis.