An emerging biotech called ESSA Pharma Inc. (EPIX) is developing treatments for prostate cancer that is no longer responding to current therapies. The venture is developing a series of compounds (antigens) that disrupt the androgen receptor (AR) signaling pathway via a novel mechanisms of action targeting the N-terminal domain (NTD) of the AR, as opposed to the ligand-binding domain (LBD) of the AR that is targeted by all other AR-directed prostate cancer treatments. A lead preclinical antigen called EPI-7386 has been selected to advance to clinical trials and the sponsor hopes to file an IND by the first quarter 2020.
The company had previously tested a first-generation antigen compound called EPI—002 in a Phase I clinical trial in patients with mCRPC that were progressing after abiraterone or enzalutamide with serially rising PSAs. While EPI-002 was shown to be safe and well tolerated, the compound exhibited a short half-life and minimal therapeutic exposure that led to suboptimal results. Consequently, ESSA decided to invest in a new discovery effort to develop next-generation antien’s.
Following the synthesis of >300 compounds, the venture identified EPI-7386 as the lead IND candidate due to it possessing a number of positive attributes compared to EPI-002, which included:
· Increased potency
· Reduced in vitro metabolism
· Activity against AR-V7 in vitro models
· Similar activity to enzalutamide in LNCaP xenograft models
· Enhanced activity in VCaP xenograft model
Forthcoming Phase I Clinical Trial of EPI-7386 in Q1 2020
The company will soon file an IND for EPI-7386 in Q 2020 and a Phase I clinical trial initiated soon thereafter in patients who are resistant to second-generation anti-androgen therapies (E.g. enzalutamide). The trial will include both a dose escalation phase and a dose expansion phase. The primary objective of the dose escalation portion is to establish the safety and efficacy of EPI-7386 with a secondary objective being to determine the maximum tolerated dose and recommended Phase II dose. In addition to a Phase II dose expansion, the company will plan to initiate a combination trial with EPI-7386 and a ‘lutamide’ (enzalutamide, apalutamide, or darolutamide) in mCRPC patients due to robust preclinical data evidencing increased activity with combination therapy.
Essa Pharmaceutical Profile
Vancouver, BC-based EPIX was founded in 2009 and is now publicly traded at $5.50 per share and a market capitalization of $110 million.
The company positions that it has the necessary financing to conduct the three clinical trials. Their most recent financial results for end of fiscal year are linked here.