Azenosertib is a potentially first-in-class and best-in-class small molecule Wee1 inhibitor in development for the treatment of cancer. Inhibition of Wee1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved Wee1 inhibitors, and we have designed ZN-c3 to have advantages over other investigational therapies, including superior selectivity and pharmacokinetic properties.
Azenosertib is being developed in three therapeutic settings of high unmet need:
1. As a monotherapy
- Phase 2 Monotherapy Study in Uterine Serous Carcinoma
- Phase 1 Monotherapy Dose Optimization Study in Solid Tumors
- Phase 1/2 Monotherapy Study in Cyclin E1 Driven High Grade Serous Ovarian Cancer
2. In combination with traditional chemotherapy and DNA damaging agents
- Phase 1b Combination Study of Azenosertib and PARPi in PARP Resistant Ovarian Cancer
- Phase 1/2 Combination Study of Azenosertib and Chemotherapy in Ovarian Cancer
- Phase 1/2 Combination Study of Azenosertib and Gemcitabine in Osteosarcoma
3. In combination with molecularly targeted agents
The Company has announced it will collaborate with Pfizer on a Phase 1/2 dose escalation study of azenosertib in combination with encorafenib and cetuximab in patients with BRAF V600E-mutated colorectal cancer. The Company initiated enrollment in this clinical trial in the first quarter of 2023.
ZN-d5 is a selective, oral small molecule inhibitor of B-cell lymphoma 2 (BCL-2), which is currently being evaluated in patients with hematologic malignancies. BCL-2 is a protein that plays a critical role in the regulation of cell death, known as apoptosis. The overexpression of BCL-2 is frequently detected in numerous cancer types, which prevents apoptosis of cancer cells. Utilizing our medicinal chemistry expertise, we have designed ZN-d5 to have best in class potency, selectivity and pharmacokinetic properties.
ZN-d5 is being studied in both monotherapy and combination settings:
- Phase 1/2 Study of Monotherapy in Relapsed or Refractory Light Chain (AL) Amyloidosis
- Phase 1 Study of Monotherapy in Relapsed or Refractory Acute Myeloid Leukemia (AML) and Non-Hodgkin’s Lymphoma (NHL)
- Phase 1/2 Study in Combination with Azenosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
BCL-xL is a member of the anti-apoptotic BCL-2 proteins. Its overexpression in tumor cells contributes to tumor survival and therapeutic resistance mechanisms. Our protein degrader candidate is designed to have better efficacy and tolerability over other clinical-stage BCL-xL targeted inhibitors and has demonstrated potent anti-cancer activity in several preclinical models.