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. ZN-c5 was well tolerated and demonstrated initial signs of efficacy in the Phase 1 portion of the trial, and we plan to initiate the Phase 2 trial in the first half of 2021.
We are also investigating ZN-c5 in combination studies, including with palbociclib (Ibrance®) through a clinical research collaboration with Pfizer, abemaciclib (Verzenio®) through a clinical research collaboration with Eli Lilly, as well as Zentalis-discovered ZN-d5, our oral selective inhibitor of B-cell lymphoma 2 (BCL-2), which is expected to be initiated this year.
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 and reported data from the Phase 1 portion at AACR 2021. In addition, we initiated a Phase 1b combination dose escalation trial with ZN-c3 and chemotherapy in patients with advanced ovarian cancer in 4Q 2020. We plan to initiate a Phase 1/2 trial in combination with GSK’s niraparib in patients with advanced ovarian cancer, a Phase 1/2 trial in combination with chemotherapy in osteosarcoma and a Phase 2 trial investigating ZN-c3 as a monotherapy in patients with uterine serous carcinoma 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.
In 4Q 2020, we initiated a Phase 1 trial of ZN-d5 as a monotherapy in patients with AML and Non-Hodgkin’s Lymphoma.
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, with initial results from the Phase 1 portion expected in 2021. 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.