Our lead product candidate, 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 in the U.S. and is currently treated using a number of approved hormonal therapies. Despite treatment advances, we believe the currently approved hormonal therapies—including the only FDA-approved SERD— have 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 are currently conducting a Phase 1/2 clinical trial with ZN-c5 in patients with ER+/HER2- advanced or metastatic breast cancer as a monotherapy and in combination with palbociclib (marketed as Ibrance® by Pfizer) through a clinical research collaboration with Pfizer. Palbociclib is an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6) and is approved for the treatment of ER+/HER2- advanced or metastatic breast cancer in combination with hormonal therapies. In this collaboration, we maintain full ownership of ZN-c5. We plan to report data from the monotherapy dose escalation portion of this Phase 1/2 trial in the second half of 2020.
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 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.
We are evaluating ZN-c3 in a Phase 1/2 study in patients with advanced solid tumors. We expect to report data from the Phase 1 portion in 2021.
ZN-d5 is our 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 an IND to the FDA in March 2020 and plan to initiate a Phase 1 trial of ZN-d5 as a monotherapy in patients with AML or B-cell lymphoma in the first half of 2021.
ZN-e4 is our oral, small molecule inhibitor of mutant epidermal growth factor receptor (EGFR) initially being developed for the treatment of non-small-cell lung carcinoma (NSCLC). EGFR regulates many cellular functions, including cell proliferation and survival, and is responsible for tumor growth in a number of cancers, including lung cancer. The inhibition of EGFR has already been clinically validated as an effective approach to treating NSCLC. However, the FDA-approved third-generation inhibitor of EGFR still has toxicities, including skin rashes, associated with first- and second-generation inhibitors. ZN-e4 is designed to achieve a similar potency and inhibition of EGFR, but is also designed to be more selective, tolerable and soluble in comparison to the current approved therapies.
We are conducting a Phase 1/2 trial of ZN-e4 in patients with advanced NSCLC with activating EGFR mutations. In addition, we believe this candidate has the potential to be used as a monotherapy and in combination with a number of therapies. We are actively evaluating potential combination therapies for the future clinical development of ZN-e4.
We have out-licensed the development and commercialization rights of this candidate to SciClone in China, South Korea, Taiwan and Vietnam.