On October 31, 2024 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 that it has made the decision to terminate the Phase 2 clinical trial evaluating in a 2:1 randomization masofaniten combined with enzalutamide versus enzalutamide single agent in patients with metastatic castration-resistant prostate cancer ("mCRPC") naïve to second-generation antiandrogens (Press release, ESSA, OCT 31, 2024, View Source [SID1234647614]). This decision, mutually agreed upon by both senior management and the board of directors, was based on a protocol-specified interim review of the safety, PK and efficacy data, which showed a much higher rate of PSA90 response in patients treated with enzalutamide monotherapy (which is standard of care for this patient population) than were expected based upon historical data. In addition, there was no clear efficacy benefit seen with the combination of masofaniten plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study. The combination of masofaniten plus enzalutamide was well-tolerated with no new safety signals and a safety profile similar to that seen in Phase 1 studies.

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"Providing a meaningful clinical benefit to patients in our clinical trials, along with a robust safety profile, is of utmost importance to us at ESSA," said David Parkinson, MD, President and CEO. "We designed this randomized study to rigorously evaluate the clinical benefit of adding masofaniten to enzalutamide. We made the difficult decision to terminate this Phase 2 study following the interim analysis because we concluded that the emerging efficacy profile of masofaniten combined with enzalutamide would not likely meet the primary endpoint of the study, nor our internal requirements for a prostate cancer therapy candidate. We would like to thank our partners, investigators, employees, and most importantly, the patients and their families involved in our clinical trials."

Richard Glickman, LLD, Chairman of the Board of Directors of ESSA, commented, "Senior management, together with the board of directors, are actively focused on preserving capital and will initiate a strategic process to explore and review a range of strategic options focused on maximizing shareholder value."

The Phase 2 study (NCT05075577) was designed as an open label, two-arm randomized (2:1) trial and was planned to enroll a total of 120 patients (80 in the combination arm and 40 in the enzalutamide single agent arm). The efficacy interim analysis included 52 enrolled patients (48% of the total planned patients) who had at least one PSA measurement after baseline and 41 patients (34% of total planned patients) who completed at least three months follow up. Enrolled patients were from clinical sites located in the United States, Canada, Australia and France. The primary study endpoint is the proportion of patients reaching PSA90. Additional PSA-based secondary endpoints included PSA50 response as well as PSA50 and PSA90 response rates at 12 weeks as well as time to event parameters (which were not mature at the time of the interim analysis).

Primary and PSA-related Secondary Endpoints of the Study

Primary

Secondary

Secondary

Secondary

Phase 2 Study Arm

PSA90

response

rate*

PSA50

response

rate*

PSA50 @ 90

days response

rate

PSA90 @ 90

days response

rate

Enzalutamide 160mg

QD

73 %

87 %

86 %

71 %

Masofaniten 600mg

BID + enzalutamide

160mg QD

64 %

88 %

93 %

67 %

*The PSA90 response rate was calculated in patients completing at least 1 month of treatment

As part of the effort to focus its resources, ESSA is also planning to terminate the other remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten either as a monotherapy or in combination with other agents.

Liquidity and Outstanding Share Capital

As of September 30, 2024, the Company had available cash reserves and short-term investments of $126.8 million and net working capital of $124.3 million (unaudited figures). The Company has no long-term debt facilities.
As of September 30, 2024, the Company had 44,388,551 common shares issued and outstanding, and there were 2,920,000 common shares issuable upon the exercise of prefunded warrants at an exercise price of $0.0001.
About the Phase 2 Study

The Phase 2 dose expansion portion of this Phase 1/2 study is a two-arm, randomized, open-label study (NCT05075577) that evaluated the safety, tolerability and preliminary efficacy of masofaniten, and was expected to enroll approximately 120 patients. Criteria for entry into the Phase 2 dose expansion were similar to those in the Phase 1 dose escalation. Patients continued to receive androgen deprivation therapy and were randomized 2:1 to receive either the combination of masofaniten (600mg twice-daily ("BID")) and enzalutamide (160mg once daily ("QD")) or enzalutamide (160mg QD) as a single agent. Patients were eligible to remain on study treatment as long as they tolerated treatment without disease progression based on RECIST v1.1 and/or Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.

About Masofaniten

Masofaniten (formerly known as EPI-7386) is a first-in-class investigational oral, small molecule inhibitor of the androgen receptor ("AR"). Masofaniten’s unique mechanism of action disrupts the AR signaling pathway, the primary pathway that drives prostate cancer growth. The U.S. Food and Drug Administration has granted Fast Track designation to masofaniten for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to masofaniten worldwide.