ZN-c3 is an oral inhibitor of WEE1 in development for the treatment of advanced solid tumors. The inhibition of WEE1, a DNA damage response kinase protein, aims to generate sufficient DNA damage in cancer cells, causing cell death, thereby preventing tumor growth and potentially causing tumor regression. Currently, there are no FDA-approved WEE1 inhibitors, and we have designed ZN-c3 to have advantages over other investigational therapies with superior solubility, selectivity, and PK properties. We believe ZN-c3 has broad potential to treat patients with cancer, both as a monotherapy and in combination, including with chemotherapy agents, PARP inhibitors and other targeted therapies.
The CTA for ZN-c3 was approved by the China National Medical Products Administration (NMPA) in April 2021. We have recently initiated an open label, multi-center, Phase 1b study, evaluating the safety, tolerability, PK characteristic and preliminary efficacy of ZN-c3 as a monotherapy in Chinese subjects with advanced solid tumors. Additionally, the CTA for ZN-c3 in combination was approved by the China NMPA in [insert] 2021. Global Phase I/II studies are ongoing simultaneously.
ZN-c5, is an oral selective estrogen receptor degrader (SERD) being developed for the treatment of ER+/HER2- advanced or metastatic breast cancer. ER+/HER2- breast cancer, which is reliant on the estrogen receptor (ER) for tumor growth and survival, affects approximately 70% of all breast cancer patients. Despite treatment advances, we believe the currently approved hormonal therapies—including the only FDA-approved SERD— have safety and efficacy limitations that create an opportunity for the development of a differentiated candidate. We have designed ZN-c5 to overcome these limitations and have a potentially superior product profile with convenient oral administration. We have also entered into clinical collaborations with Pfizer to evaluate ZN-c5 in combination with palbociclib and also with and Eli Lilly to evaluate ZN-c5 in combination with abemaciclib.
The CTA for ZN-c5 was approved by the NMPA in March 2021. We have initiated the Phase Ib open label, multi-center study, which is evaluating the safety, tolerability, PK characteristic and preliminary efficacy in Chinese subjects with advanced ER+/HER2- breast cancer. Simultaneously, Phase I/II studies are ongoing globally.
ZN-d5 is an oral selective inhibitor of B-cell lymphoma 2 (BCL-2), in development initially for the treatment of hematologic malignancies. BCL-2 and BCL-xL are proteins that play a critical role in the regulation of cell death. The overexpression of BCL-2 and/or BCL-xL are frequently detected in numerous cancer types, which prevent apoptosis of cancer cells. We believe a BCL-2 inhibitor will restore the normal apoptosis process, making it an important target for cancer treatments. Utilizing our medicinal chemistry expertise, we have designed ZN-d5 to have optimized potency, selectivity and PK. We believe ZN-d5 is an attractive candidate for evaluation as a monotherapy and in combination with other therapies, including our oral SERD (ZN-c5), for the treatment of breast cancer.
We submitted the CTA for ZN-d5 to the NMPA in May 2021. In parallel, a global Phase 1 study is ongoing.