ZEN-3219 / Zenith Capital Corp - LARVOL DELTA

[VIRTUAL] Combination of ZEN-3694 with CDK4/6 inhibitors reverses resistance in ER-positive breast cancer (AACR-II 2020) - P1b/2a, P2 | "In spite of the great successes with the currents lines of therapies, the patients still acquire resistance over time and, the development of additional novel therapeutic strategies is needed.The bromodomain and extra-terminal domain (BET) proteins are key epigenetic regulators that interact with acetylated lysine (AcLys) residues of histones or transcription factors, leading to the regulation of gene transcription...To assess the effects of ZEN-3694 in the combination with CDK4/6 inhibitors as a potential therapy in a CDK4/6i resistant population, we have developed a panel of ER+ cell lines resistant to palbociclib or abemaciclib by continuous stepwise exposure to increasing concentrations of CDK4/6 inhibitors...The pathway analysis demonstrated that the combination of ZEN-3694 with CDK4/6 inhibitors led to the strong downregulation of multiple pathways including cell cycle regulation, signaling by Rho family GTPases, STAT3, IL6 and other pathways. We..."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • IL6 • STAT3

Preclinical development and clinical validation of a whole blood pharmacodynamic marker assay for the BET bromodomain inhibitor ZEN-3694 in metastatic castration-resistant prostate cancer (mCRPC) patients (AACR 2017) - P1,P1b; "Another candidate PD marker, HEXIM1, was evaluated in some of the clinical samples, and showed a modest modulation only at higher doses of ZEN-3694, similar to MYC, GPR183, and HISTH2BE. These results demonstrate that the activity of ZEN-3694 is consistent with a BET bromodomain inhibitor in mCRPC patient’s whole blood, and that whole blood can be used as a surrogate tissue for measuring the target modulation of ZEN-3694 in the clinic, and guide dose optimization for further development."

Late-breaking abstract • Acute Myelogenous Leukemia • Biosimilar • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer

[VIRTUAL] A Phase 1b/2 Study of the BET inhibitor ZEN003694 in combination with talazoparib for treatment of patients with TNBC without gBRCA1/2 mutations (SABCS 2020) - "Combination of ZEN003694 and talazoparib demonstrated anti-cancer activity in pretreated metastatic TNBC patients without gBRCA1/2 mutations. TCP is frequent but manageable with dose adjustments. PK is predictable, and PD data show meaningful target engagement."

Clinical • Combination therapy • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Triple Negative Breast Cancer • BRCA1 • BRCA2 • CXCL8 • HER-2 • HRD • IL1RN • RAD51

A Phase Ib/IIa study of the BET bromodomain inhibitor ZEN-3694 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) (AACR 2019) - P1b/2a; "Background: Abiraterone (ABI) and enzalutamide (ENZ) have significant activity in mCRPC yet demonstrate frequent cross-resistance limiting efficacy of sequential androgen receptor (AR) targeting. ZEN-3694 demonstrates an acceptable safety and PK profile, robust target modulation, and encouraging disease stabilization in combination with ENZ in ABI/ENZ-refractory mCRPC. Analysis of paired metastatic tumor biopsies, circulating tumor cells and ctDNA is ongoing. Further investigation of the combination is warranted."

Clinical • Combination therapy • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor