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ZNTL • CIK 0001725160
Overview We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), an investigational, potentially first-in-class and best-in-class WEE1 inhibitor, for patients with ovarian cancer and other tumor types. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types. We are currently focused on advancing the clinical development of azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer, or PROC. We believe that our DENALI (ZN-c3-005) Part 2 clinical trial of azenosertib in patients with Cyclin E1-positive PROC, if successful, has the potential to support an accelerated approval, subject to U.S. Food and Drug Administration, or FDA, review. Azenosertib also has broad franchise potential beyond Cyclin E1-positive PROC. We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib. Strategy Our strategy includes the following key components: • Rapidly advance the clinical development of azenosertib as a monotherapy toward first regulatory approval in Cyclin E1-positive PROC . We believe azenosertib has the potential to set a new standard of care in patients with Cyclin E1-positive PROC. Many patients with PROC receive single-agent chemotherapy, which has modest clinical benefits. In January 2025, we disclosed a significant amount of clinical data showing an objective response rate, or ORR, of over 30% and a manageable safety profile in patients with Cyclin E1-positive PROC who received azenosertib at our primary dose-of-interest, 400 mg QD 5:2 (single daily dose on an intermittent schedule of five days on and two days off). We completed enrollment in Part 2a of our Phase 2 DENALI clinical trial of azenosertib in patients with Cyclin E1-positive PROC in 2025 and anticipate a topline readout from the trial by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. • Advance the development of azenosertib outside of Cyclin E1-positive PROC, as resources allow. We believe that the opportunity for azenosertib is broad, and we plan to advance the clinical development of azenosertib outside of Cyclin E1-positive PROC, as our resources allow. We are evaluating azenosertib in combination with bevacizumab as maintenance therapy in patients with ovarian cancer in our MUIR (ZN-c3-002) Phase 1 clinical trial. In addition, we are leveraging our extensive experience and capabilities to translate our science to advance research on additional areas of opportunity for azenosertib in other tumor types beyond ovarian cancer. • Evaluate additional strategic opportunities to maximize the value of our pipeline . We previously had development collaborations for azenosertib with Pfizer Inc., GSK plc, and Dana-Farber Cancer Institute. While these collaborations have completed, we will continue to selectively evaluate new collaborations for azenosertib with partners whose assets and capabilities complement our own. Azenosertib (WEE1 Inhibitor) Mechanism of Action Azenosertib is an investigational, potentially first-in-class and best-in-class oral, small molecule WEE1 inhibitor. The inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death and thereby preventing tumor growth and potentially causing tumor regression. We have designed azenosertib to have advantages over other investigational therapies targeting WEE1, including superior selectivity and pharmacokinetic, or PK, properties. Cyclin E1 Expression as a Sensitive and Specific Predictive Biomarker Cells with Cyclin E1 activation are exquisitely sensitive to WEE1 inhibition via azenosertib because Cyclin E1 activation further accelerates cancer cells into the DNA replication phase without adequate DNA repair. As a result, we have used retrospective analyses to establish Cyclin E1 as a sensitive and specific predictive biomarker that can be used to identify patients who might benefit from azenosertib.…
From recent Form 4 filings