ESSA Pharma Announces the Presentation of Preclinical Data Characterizing the Mechanism of Action of EPI-7386

-       Data presented at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics –

VANCOUVER, Canada and HOUSTON, Texas, Oct. 7, 2021 /PRNewswire/ - 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, today announced the presentation of preclinical data characterizing the mechanism of action of EPI-7386, ESSA's lead product candidate for the treatment of prostate cancer. 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), National Cancer Institute (NCI), and European Organisation for Research and Treatment of Cancer (EORTC) Virtual International Conference on Molecular Targets and Cancer Therapeutics, taking place virtually from October 7-10, 2021. 

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-NCI-EORTC Virtual International Conference website and on the "Events & Presentations" section of the Company's website at www.essapharma.com.

About ESSA Pharma Inc.
ESSA is a clinical-stage pharmaceutical company focused on developing novel and proprietary therapies for the treatment of patients with prostate cancer. For more information, please visit www.essapharma.com and follow us on Twitter under @EssaPharma.

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with metastatic castration-resistant prostate cancer ("mCRPC") whose tumors have progressed on current standard-of-care therapies. The Phase I clinical trial of EPI-7386 began in Q3 of 2020 following FDA allowance of the IND and Health Canada acceptance. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to EPI-7386 worldwide.

About Prostate Cancer
Prostate cancer is the second-most commonly diagnosed cancer among men and the fifth-most common cause of male cancer death worldwide (Globocan, 2018). Adenocarcinoma of the prostate is dependent on androgen for tumor progression and depleting or blocking androgen action has been a mainstay of hormonal treatment for over six decades. Although tumors are often initially sensitive to medical or surgical therapies that decrease levels of testosterone, disease progression despite castrate levels of testosterone can lead to metastatic castration-resistant prostate cancer ("mCRPC"). The treatment of mCRPC patients has evolved rapidly over the past 10 years. Despite these advances, many patients with mCRPC fail or develop resistance to existing treatments, leading to continued disease progression and limited survival rates.

Forward-Looking Statement Disclaimer
This release contains certain information which, as presented, constitutes "forward-looking information" within the meaning of the Private Securities Litigation Reform Act of 1995 and/or applicable Canadian securities laws. Forward-looking information involves statements that relate to future events and often addresses expected future business and financial performance, containing words such as "anticipate", "believe", "plan", "estimate", "expect", and "intend", statements that an action or event "may", "might", "could", "should", or "will" be taken or occur, or other similar expressions and includes, but is not limited to, statements regarding preclinical data characterizing the mechanism of action of EPI-7386 supporting ESSA's novel approach to prostate cancer, EPI-7386's ability to inhibit AR-driven biology in both full length and splice variant driven prostate cancer models, and the data supporting the rationale for the Company's upcoming Phase 1/2 combination trials of EPI-7386.

Forward-looking statements and information are subject to various known and unknown risks and uncertainties, many of which are beyond the ability of ESSA to control or predict, and which may cause ESSA's actual results, performance or achievements to be materially different from those expressed or implied thereby. Such statements reflect ESSA's current views with respect to future events, are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by ESSA as of the date of such statements, are inherently subject to significant medical, scientific, business, economic, competitive, political and social uncertainties and contingencies. In making forward looking statements, ESSA may make various material assumptions, including but not limited to (i) the accuracy of ESSA's financial projections; (ii) obtaining positive results of clinical trials; (iii) obtaining necessary regulatory approvals; and (iv) general business, market and economic conditions.

Forward-looking information is developed based on assumptions about such risks, uncertainties and other factors set out herein and in ESSA's Quarterly Report on Form 10-Q dated August 16, 2021 under the heading "Risk Factors", a copy of which is available on ESSA's profile on EDGAR at www.sec.gov.com and on the SEDAR website at www.sedar.com, and as otherwise disclosed from time to time on ESSA's EDGAR and SEDAR profiles. Forward-looking statements are made based on management's beliefs, estimates and opinions on the date that statements are made and ESSA undertakes no obligation to update forward-looking statements if these beliefs, estimates and opinions or other circumstances should change, except as may be required by applicable United States and Canadian securities laws. Readers are cautioned against attributing undue certainty to forward-looking statements.

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SOURCE ESSA Pharma Inc