Partnerships

Zenith has developed several important relationships that will help advance ZEN-3694 through development and global commercialization. The lead program counts Shanghai-based Newsoara as a partner which will advance ZEN-3694 through the regulatory process and maintain commercialization rights in China, Hong Kong, Macau and Taiwan. Newsoara agreed to pay $15 million in upfront and near-term development milestones plus another $63 million in sales milestones. It will also make 6% royalty payments that will decline to 4% after exceeding certain sales thresholds. 

The most important partnership is with Pfizer which is advancing the combination with PARPi for mTNBC. Pfizer will co-fund the TNBC study and provide talazoparib for use in the trial. Zenith has retained all rights to its drug. If this collaboration is successful and ZEN-3694 is able to sensitize wild-type BRCA patient tumors to PARPi, the therapies will be important companions and ZEN-3694 will likely benefit from Pfizer’s commercialization clout.

Pfizer first began commercializing talazoparib following its October 2018 approval. In the EMBRACA study that was used to support the new drug application (NDA), talazoparib provided a 50.2% objective response rate compared to an 18.4% rate for chemotherapy. The combination of talazoparib with ZEN-3694 can potentially expand the use of the therapy to wild type BRCA genotypes, which comprise the majority of TNBC patients. Research examining a broad selection of BET inhibitors found that the class may synergize with PARPi in HR-proficient cells and tumors to PARPi treatment (12). 

Safety and Adverse Events

Safety is a strong point for Zenith’s candidate. The toxicity profile of ZEN-3694 in combination with enzalutamide was favorable in the mCRPC study. The main adverse events were gastrointestinal (GI) toxicity which was managed with the use of anti-emetics. The safety profile for the mTNBC study found thrombocytopenia and GI effects for the BETi/PARPi combo, as expected. The doses of ZEN-3694 and talazoparib were optimized to mitigate these adverse events and the study is on track to define a recommended Phase II dose in the second quarter of 2020.

Summary

Employing epigenetics to cure cancer addresses multiple disease pathways by eliminating problematic proteins and addressing the root of the malignancy. The ability to allow normal expression of healthy genes and discourage the impact of oncogenes provides efficacy while limiting severe side effects. ZEN-3694 is capable of sensitizing cancer pathways for approved drugs that normally encounter resistance after a period of treatment. ZEN-3694 may be able to dramatically extend and expand the ability of these proven therapies to thwart specific types of prostate and breast cancer as well as other cancer areas such as ovarian. The company’s impressive partnerships boast strong collaborators that can efficiently and effectively help ZEN-3694 advance through the development, registration and commercialization process. With good data and friends at large global pharmaceutical companies, Zenith has a clear pathway forward with ZEN-3694.