On June 22, 2020 ESSA Pharma Inc. (Nasdaq: EPIX); (TSXV: EPI), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s clinical candidate, EPI-7386, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Virtual Annual Meeting II (Press release, ESSA, JUN 22, 2020, View Source [SID1234561367]).

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In an oral poster presentation titled, "Preclinical development of the second-generation N-terminal domain androgen receptor inhibitor, EPI-7386, for the treatment of prostate cancer", a robust preclinical characterization of EPI-7386 including androgen receptor (AR) binding, gene expression analyses and the toxicologic profile was presented. The studies highlight new information about EPI-7386 including:

Full-length AR target engagement by EPI-7386 was confirmed in a cellular thermal shift assay.
In vitro cellular gene expression analyses demonstrate that EPI-7386:
Inhibits AR transcriptional activity similar to enzalutamide but with a few notable qualitative and quantitative differences in an enzalutamide-sensitive cellular model.
In the same cellular model, combination treatment of EPI-7386 with enzalutamide displays broader and deeper inhibition of AR-associated transcriptional activity than higher doses of each single agent alone.
Shows superior activity to enzalutamide in an AR-V7-driven cellular model by modulating both AR-FL and AR-V7-driven gene expression.
Toxicology studies evaluating the safety profile of EPI-7386 demonstrate that:
Very high plasma exposures of EPI-7386 were achieved across all studies.
Tolerability in 28-days tox studies in rats and dogs at AUC ≤ 2,000,000 ng*hr/mL, with activity seen on androgen-sensitive target organs in dogs.
The highest doses tested were characterized as the HNSTD (highest non-severely toxic dose) and only exhibited body weight loss and reduced food consumption. The drug plasma exposures achieved at this high dose were 7-10 fold higher than the efficacious exposures achieved in mouse xenograft models.
The starting clinical dose of EPI-7386 will be 200 mg given once-daily
"Our latest transcriptomic analyses add to the breadth of preclinical data supporting the development of EPI-7386 broadly in prostate cancer. With the favorable toxicologic profile of EPI-7386 observed in our IND-enabling studies at very high exposures, we will initiate dosing at 200 mg per day, which potentially could allow us to efficiently reach biologically relevant blood levels of EPI-7386 in patients," said Dr. David R. Parkinson, President & Chief Executive Officer. "We will soon begin dosing patients in our Phase 1 monotherapy study of EPI-7386 in castration-resistant prostate cancer patients whose tumors are progressing on current anti-androgens.".