EPIX: Phase 2 Trial of EPI-7386 in Combination with Enzalutamide to Initiate in Calendar 3Q23…
NASDAQ:EPIX
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Business Update
Moving Towards Phase 2 Trial of EPI-7386 in Combination with Enzalutamide
ESSA Pharma Inc (NASDAQ:EPIX) is developing EPI-7386 as a treatment for prostate cancer. It is a member of a novel class of compounds known as ‘anitens’, which specifically target the androgen receptor (AR). The AR is the main signaling mechanism driving the growth of prostate tumors. Anitens bind the AR at the N-terminal domain (NTD), which is unique compared to other available anti-androgen therapies that target the ligand binding domain (LBD). The following graphic shows the structure of the AR along with the various resistance mechanisms that develop to counteract therapies that target the LBD. Anitens are fully differentiated from current AR-targeted therapies through binding of the NTD.
ESSA is testing EPI-7386 as both a monotherapy and in combination with existing second-generation antiandrogens. The company has completed the Phase 1a monotherapy trial of EPI-7386 in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on two or more systemic therapies, including at least one second generation anti-androgen therapy (NCT04421222). Key findings from the monotherapy Phase 1a trial include:
The Phase 1b portion of the trial has two cohorts enrolling in parallel:
• Cohort A (Dose Expansion) – The primary objective of Cohort A is to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity (changes in tumor burden and PSA levels over time) of EPI-7386 at 600 mg BID and 600 mg QD. The patients enrolled into this cohort will be similar to the ones enrolled in the Phase 1a portion of the study except patients will not be allowed to have had prior chemotherapy.
• Cohort B (Window of Opportunity) – The primary objective of Cohort B is to assess the anti-tumor activity (measured by changes in PSA over time) of EPI-7386 administered 600 mg BID for a limited period of time (up to 12 weeks before patients start standard of care therapy) in non-metastatic CRPC (nmCRPC) patients whose disease is unperturbed by previous second generation anti-androgen therapies or chemotherapy.
Upon completion of the Phase 1 trial, ESSA will review the totality of the data to determine the design and timing of the Phase 2 clinical trial along with which patient population would be best suited for the study.
EPI-7386 is also being tested in combination with second-generation antiandrogens:
• In February 2021, ESSA announced a collaboration with Astellas Pharma to evaluate EPI-7386 in combination with enzalutamide in patients with mCRPC. ESSA is funding and operating the trial, which consists of an initial Phase 1 dose equilibration followed by a randomized Phase 2 trial with a planned enrollment of 120 patients (optimal combination doses from Phase 1, N=80; 160 mg enzalutamide, N=40). The company reported initial data on the safety, tolerability, pharmacokinetics, and initial PSA responses in June 2022, provided a clinical update in October 2022, and presented analyses of initial clinical data at ASCO-GU in February 2023. Of the six evaluable patients treated as of the last update, five of them achieved PSA90 (a 90% decrease in PSA level from baseline) with four of those achieving it by three months (shown in the figure below), which compares very favorably to historical controls (PSA90 levels at three months of 13% to 37%). We anticipate completion of the Phase 1 portion of the study and establishment of the recommended Phase 2 dose in the third calendar quarter of 2023, with initiation of the Phase 2 portion of the study shortly thereafter.
• In April 2023, ESSA announced a clinical trial support agreement with Janssen to enable evaluation of EPI-7386 in combination with apalutamide as well as in combination with abiraterone acetate plus prednisone. ESSA will sponsor and conduct a Phase 1 clinical trial with Janssen supplying clinical supplies of apalutamide and abiraterone acetate. In June 2023, ESSA modified the protocol design by adding combination treatment through two parts: a Part A monotherapy study and a Part B combination study. Part A has two phases, a Phase 1a dose escalation and Phase 1b dose expansion as described above. Part B will be conducted in two cohorts, Cohort 1 will evaluate EPI-7386 in combination with abiraterone acetate/prednisone for patients with mHSPC or mCRPC who receive abiraterone acetate/prednisone as part of their standard of care treatment and Cohort 2 (previously the “windown of opportunity cohort”) will evaluate single agent EPI-7386 for 12 weeks in patients with nmCRPC before apalutamide is added.
• In April 2021, ESSA announced a collaboration with Bayer for a clinical trial testing EPI-7386 and darolutamide in patients with mCRPC. In addition, ESSA previously announced its intention to initiate a Phase 2 investigator-sponsored neoadjuvant study to evaluate EPI-7386 in combination with darolutamide compared to darolutamide alone.
Financial Update
On August 8, 2023, ESSA announced financial results for the third quarter of fiscal year 2023 that ended June 30, 2023. For the third quarter of fiscal year 2023, the company reported a net loss of $7.3 million, or $0.17 per share, compared to a net loss of $8.8 million, or $0.20 per share, for the third quarter of fiscal year 2022. R&D expenses for the third quarter of fiscal year 2023 were $6.3 million compared to $6.4 million for the third quarter of fiscal year 2022. The decrease was primarily due to decreased non-cash share-based payments, legal patents, and license fees along with lower manufacturing costs related to the Phase 1 clinical trial of EPI-7386. G&A expenses for the third quarter of fiscal year 2023 were $2.6 million compared to $2.9 million for the third quarter of fiscal year 2022. The decrease was primarily due to lower non-cash share-based payments, salaries, and professional fees.
As of June 30, 2023, ESSA had approximately $152.5 million in cash, cash equivalents, and short-term investments. As of August 8, 2023, the company had approximately 44.1 million shares outstanding and, when factoring in stock options and warrants, a fully diluted share count of approximately 55.2 million.
Conclusion
We look forward to updates on the combination trial of EPI-7386 and enzalutamide in the third quarter of 2023, at which time we anticipate the Phase 1 portion of the trial completing and the company establishing the recommended Phase 2 dose such that the Phase 2 trial can initiate shortly thereafter. We anticipate results from the Phase 1 combination study being presented at the ESMO 2023 Meeting in October 2023. With no changes to our model our valuation remains at $27 per share.
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