Our lead product candidate, ZN-c3, is a potentially first-in-class and best-in-class oral WEE1 inhibitor 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.
ZN-c3 has broad potential as a monotherapy and in combination and we are currently evaluating this candidate in several ongoing and planned studies, including two potentially registrational monotherapy trials in USC and a biomarker-driven setting, as well as combination studies with chemotherapy and GSK’s niraparib (Zejula®) in patients with advanced ovarian cancer. We also recently received orphan drug and rare pediatric disease designations by the FDA for osteosarcoma and initiated a Phase 1/2 trial in combination with chemotherapy. Additionally, we will support two planned investigator-initiated trials with the Ivy Brain Center in glioblastoma multiforme (GBM) and with Dana Farber in combination with immunotherapy in triple negative breast cancer.
ZN-c5 is a potentially best-in-class 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 conducting multiple ongoing trials of ZN-c5 in patients with ER+/HER2- advanced or metastatic breast cancer in monotherapy and in combination settings, including a Phase 2 monotherapy trial, as well as combination studies with palbociclib (Ibrance®) through a clinical collaboration with Pfizer and abemaciclib (Verzenio®) through a clinical collaboration with Eli Lilly.
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 and we are currently conducting a Phase 1 trial of ZN-d5 in patients with AML and Non-Hodgkin’s lymphoma (NHL). Future clinical development will also include combination studies.
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.
Our Phase 1/2 trial of ZN-e4 in patients with advanced NSCLC with activating EGFR mutations is ongoing and continues to enroll. We are also actively evaluating potential combination therapies for the future clinical development of ZN-e4.