On April 10, 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 new preclinical data on ESSA’s lead product candidate, EPI-7386, at the 2021 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place virtually April 10-15, 2021 (Press release, ESSA, APR 10, 2021, View Source [SID1234577875]). EPI-7386 is an investigational, highly selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor, which exhibits high potency, low metabolism and on-target specificity.

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An e-poster presentation titled, "Comprehensive in vitro characterization of the mechanism of action of EPI-7386, an androgen receptor N-terminal inhibitor" (Abstract number: 1209) was published and available for viewing starting April 10th at 8:30 a.m. ET.

"Previously, we presented in vitro data demonstrating that EPI-7386 binds to the full-length androgen receptor, inhibits the transcription of AR-regulated genes, and physically interacts with the splice variant form AR-V7. Today, we added to these data by demonstrating that EPI-7386 can prevent the androgen receptor from binding to genomic DNA and is active against additional androgen receptor splice variants, including AR-v567es," said Dr. David R. Parkinson, President and Chief Executive Officer, ESSA Pharma, Inc. "These preclinical data suggest EPI-7386 can potentially inhibit AR related transcription, a key driver of prostate cancer, and further supports our ongoing Phase 1 dose escalation study for metastatic-castration resistant prostate cancer patients, which is now dosing patients in the 800 mg cohort."

Dr. David R. Parkinson added, "Our data also showed that EPI-7386, in combination with enzalutamide, may result in broader and deeper inhibition of the AR pathway, underscoring the potential clinical benefit of combining EPI-7386 with current standard-of-care anti-androgen therapies for prostate cancer patients at earlier stages of the disease. We have recently entered into Phase 1/2 trial clinical partnerships with Janssen to evaluate EPI-7386 in combination with apalutamide or with abiraterone acetate + prednisone, as well as with Astellas to evaluate EPI-7386 in combination with enzalutamide."

The studies highlight new information about EPI-7386 including:

In an in vitro cellular thermal shift assay (CETSA), EPI-7386 was shown to physically interact with both the full-length and the splice variant (AR-V7) form of AR.

In the cellular model CWR-R1-AD1, driven by full-length AR, EPI-7386 inhibited the transcriptional activity of the AR similar to enzalutamide. EPI-7386 was also active in inhibiting AR transcriptional activity and reducing the cell viability in the AR splice variant AR-v567es-driven cellular model CWR-R1-D567 while enzalutamide showed no activity in this model. The AR-v567es splice variant is a clinically-detected AR splice variant that is constitutively active and is unresponsive to anti-androgens.

EPI-7386 demonstrated the ability to strongly reduce binding of AR to genomic DNA in a chromatin immunoprecipitation with sequencing (ChIP-seq) assay conducted in the full-length AR driven model LNCaP.

EPI-7386 exhibits superior activity to enzalutamide in the AR-V7-driven cellular model LNCaP95 by modulating AR-driven gene expression with or without the addition of an external androgen.

In the full-length AR-driven cellular model LNCaP, EPI-7386 inhibits the androgen regulated transcriptome similar to enzalutamide but with a few notable qualitative and quantitative differences.

In the same cellular model, combination treatment of EPI-7386 with enzalutamide displayed broader and deeper inhibition of AR-associated transcriptional activity than higher doses of each single agent alone.

EPI-7386 in combination with ‘lutamide molecules, including apalutamide, enzalutamide, and darolutamide, inhibited AR-associated transcriptional activity, demonstrating broader and deeper inhibition of the AR pathway in the AR amplified VCaP cellular model.
The poster is available on AACR (Free AACR Whitepaper)’s e-poster website and on the "Events & Presentations" section of the Company’s website at www.essapharma.com.

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 calendar 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 ten years. Despite these advances, many patients with mCRPC fail or develop resistance to existing treatments, leading to continued disease progression and limited survival rates.