On October 7, 2021 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported the presentation of preclinical data characterizing the mechanism of action of EPI-7386, ESSA’s lead product candidate for the treatment of prostate cancer (Press release, ESSA, OCT 7, 2021, View Source [SID1234590962]). The data include the results of nuclear magnetic resonance (NMR) studies which confirm the binding of the compound to the N-terminal domain (NTD) of the androgen receptor (AR), a region not currently targeted by other antiandrogen therapies. Data were presented in a virtual video poster format at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper), National Cancer Institute (NCI), and European Organisation for Research and Treatment of Cancer (EORTC) Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place virtually from October 7-10, 2021.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The virtual poster presentation, titled, "Comprehensive preclinical characterization of the mechanism of action of EPI-7386, an androgen receptor N-terminal domain inhibitor," will be presented and available for viewing starting October 7, 2021 at 9:00 a.m. ET.
The preclinical data confirm EPI-7386’s target engagement with the NTD of the AR through multiple studies:
Three separate orthogonal NMR approaches confirm that EPI-7386 binds to the Tau5 region of the NTD
Cellular thermal shift assays (CETSA) confirm engagement of EPI-7386 with both full length AR (AR-FL) and AR-V567es, a splice variant lacking the ligand-binding domain (LBD)
Gene expression driven by the AR splice variant, AR-V567es, can be inhibited by EPI-7386 whereas enzalutamide and darolutamide, which bind to the LBD, cannot inhibit AR-V567es-driven gene expression
Chromatin immunoprecipitation sequencing (ChIP-Seq) data indicate that EPI-7386 inhibits androgen-induced changes at the AR cistrome and when combined with enzalutamide, can completely abrogate genome-wide androgen-induced AR binding
"We are excited by the data presented today, which support ESSA’s novel approach to prostate cancer by definitively demonstrating that EPI-7386 binds to the N-terminal domain of the androgen receptor—the primary driver of prostate cancer growth," said Dr. David R. Parkinson, M.D., President and Chief Executive Officer of ESSA Pharma Inc. "Through this unique mechanism of AR inhibition, EPI-7386 can inhibit AR-driven biology in both full length and splice variant-driven prostate cancer models. Additionally, the data demonstrate that the combination of EPI-7386 with enzalutamide results in complete inhibition of genome-wide androgen-induced AR binding, supporting the rationale for our upcoming Phase 1/2 combination trials of EPI-7386 with approved antiandrogens in patients with metastatic castration-resistant prostate cancer."
The poster is available on the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual International Conference website and on the "Events & Presentations" section of the Company’s website at www.essapharma.com.