EDGAR 10-K Filing

Company CIK: 1633932
Filing Year: 2024
Filename: 1633932_10-K_2024_0001558370-24-016318.json

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ITEM 1. BUSINESS
Item 1.
Business
Overview
ESSA is a clinical stage pharmaceutical company that, prior to the discontinuation of its clinical trials and preclinical and other development programs, has been focused on developing novel therapies for the treatment of prostate cancer with a primary focus on patients whose disease is still predominantly driven by the androgen axis. ESSA’s development of proprietary small molecule inhibitors of the N-terminal domain (“NTD”) of the androgen receptor (“AR”) was focused on the treatment of these patients in combination with second-generation antiandrogen drugs such as abiraterone, enzalutamide, apalutamide, and darolutamide.
In October 2024, ESSA announced that it decided to terminate its clinical trials evaluating masofaniten (EPI-7386). This decision was mutually agreed upon by both senior management and the board of directors (the “Board”). The decision was based on the results of a protocol-specified interim review of available safety, PK and efficacy data from ESSA’s Phase 2 clinical trial evaluating in a 2:1 randomization masofaniten (EPI 7386) combined with enzalutamide versus enzalutamide single agent in patients with mCRPC naïve to second-generation antiandrogens. This data 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 (EPI-7386) plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study.
As part of its efforts to focus its resources, ESSA also announced that the other remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) either as a monotherapy or in combination with other agents will be terminated. ESSA also decided to withdraw its Investigational New Drug (“IND”) application and CTAs that have been submitted to date.
In connection with these events, ESSA has initiated a comprehensive review process to review its strategic options to maximize shareholder value. ESSA expects to devote significant time and resources to its review of strategic options. There can be no assurances that the strategic review process will deliver the anticipated benefits thereof or enhance shareholder value. Strategic options may include, but are not limited to, a merger, amalgamation, arrangement, reverse take-over, business combination, asset sale or acquisition, shareholder distribution, wind-down, liquidation and dissolution or other strategic transaction or the operation of its business and election to seek new product candidates for development.
There can also be no assurance that ESSA will be able to successfully consummate any particular strategic transaction, or any transaction at all. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we may incur significant costs related to this continued evaluation. ESSA may also incur additional unanticipated expenses in connection with this process. A considerable portion of these costs will be incurred regardless of whether any such course of action is implemented or transaction is completed. Any such expenses will decrease the remaining cash available for use in ESSA’s business and may diminish or delay any future distributions to our shareholders.
Background and History
The Company believed its latest series of investigational compounds, including its previously planned product candidate masofaniten (formerly known as EPI-7386), had the potential to significantly expand the interval of time in which patients with earlier stage prostate cancer can benefit from anti-hormone-based therapies. Specifically, the compounds were designed to disrupt the androgen receptor AR signaling pathway, the primary pathway that drives prostate cancer growth and prevent AR activation through binding to the NTD of the AR. In this respect, the Company believed its compounds
differed mechanistically from classical non-steroid antiandrogens. These classic antiandrogens interfere either with androgen synthesis (i.e., abiraterone), or with the binding of androgens to the ligand-binding domain (“LBD”), located at the opposite end of the receptor from the NTD (i.e., “lutamides”). A functional NTD is essential for the functionality of the AR; blocking the NTD inhibits AR-driven transcription and therefore androgen-driven biology.
The Company believed that the transcription inhibition mechanism of its preclinical compounds was unique and had the potential advantage of bypassing several of the identified mechanisms of resistance to the antiandrogens currently used in the treatment of castration-resistant prostate cancer (“CRPC”). The Company was granted by the United States Adopted Names (“USAN”) Council a unique USAN stem “-Aniten” to recognize this new first-in-class mechanistic class. The Company refers to this series of proprietary investigational compounds as the “Aniten” series. In preclinical studies, blocking the NTD demonstrated the capability to prevent AR-driven gene expression. A previously completed Phase 1 clinical trial of ESSA’s first-generation agent, ralaniten acetate (“EPI-506”) administered to patients with metastatic CRPC (“mCRPC”) refractory to current standard of care therapies demonstrated prostate-specific antigen (“PSA”) declines, a sign of inhibition of AR-driven biology. This inhibition, however, was neither deep nor sustained enough to confer clinical benefit and the Company made the decision to develop a more potent next generation drug which would also have a longer half-life. The Company attempted to develop such a drug and conducted clinical trials with this next generation Aniten, masofaniten (EPI-7386), which focused on the treatment of earlier stage, more homogeneously androgen-driven tumors, in combination with one or another of the current latest generation classic antiandrogens.
According to the American Cancer Society, in the United States, prostate cancer is the second most frequently diagnosed cancer among men, behind skin cancer. Approximately one-third of all prostate cancer patients who have been treated for local disease with curative intent will subsequently have rising serum levels of PSA, which is an indication of recurrent disease with or without development of distant metastasis. Patients with recurrent disease as indicated by rising PSA or nodal or bone metastasis usually undergo initial androgen ablation therapy using analogues of luteinizing hormone releasing hormone or surgical castration; this approach is termed “androgen deprivation therapy” (“ADT”). Most of these patients initially respond to ADT; however, many experience a recurrence in tumor growth despite the reduction of testosterone to castrate levels, and at that point are considered to have CRPC. Following diagnosis of CRPC, patients have been generally treated with antiandrogens that block the binding of androgens (enzalutamide) to the AR, or inhibit synthesis of androgens (abiraterone). More recently, significant improvements in progression free survival and overall survival have been achieved by utilizing this latest generation of antiandrogens in combination with ADT earlier in the disease natural history (i.e., metastatic hormone-sensitive prostate cancer (“mHSPC”) and non-metastatic castration-resistant prostate cancer (“nmCRPC”)).
Since the mid-20th century, it has been recognized that the growth of prostate tumors is in large part mediated by an activated AR. Generally, there are three means of activating the AR. First, androgens, such as dihydrotestosterone can activate AR by binding to its LBD. Second, CRPC can be driven by variants of AR that lack an LBD, are constitutively activated, and consequently do not require androgen for activation. A third mechanism, of less certain clinical significance, may involve certain signaling pathways that activate AR independent of androgen activity. Generally, current drugs for the treatment of prostate cancer are directed against the first mechanism by either (i) interfering with the production of androgen, or (ii) preventing androgen from binding to the LBD. Over time, these approaches eventually fail due to mechanisms of resistance which involve the LBD end of the receptor, whether at the DNA (AR amplification or LBD mutations) or RNA level (emergence of AR splice variants). With respect to the development of alternative pathway mechanisms of AR activation, tumors may also become insensitive to antiandrogen activity. Finally, in patients who have been treated for years with various antiandrogen therapies, genomic changes may lead to additional, non-AR-related oncogenic drivers, also insensitive to inhibition of AR biology.
The Company believed that through their potential to block androgen-driven gene transcription by using a unique mechanism involving the NTD and thereby bypassing these known mechanisms of resistance to current antiandrogens, the Aniten series of compounds might have held the potential to be effective in cases where LBD-based mechanisms of resistance to second generation antiandrogens in otherwise AR-driven disease are operating. The results from both extensive preclinical studies and the initial clinical experience, prior to October 2024, supported the Company’s belief. In preclinical studies, the Aniten series of compounds was observed to shrink AR-dependent prostate cancer xenografts, including tumors both sensitive and resistant to the second-generation antiandrogens, such as enzalutamide. Plasma PSA level declines and increases in PSA doubling time as well as declines in circulating tumor DNA and decreases in
radiographic tumor measurements were observed in a subset of patients enrolled in the Phase 1 study of masofaniten (EPI-7386) as described below. Importantly with respect to the potential clinical application of NTD inhibition during the natural history of the disease, earlier studies by the Company and its collaborators had also suggested the potential advantage for combinations of the Company’s Aniten compounds with currently approved antiandrogens to inhibit AR-driven biology more completely than AR inhibition from either end of the receptor alone. This hypothesis was then-supported by the clinical trial results obtained in recent years of the superior overall survival obtained in the hormone-sensitive prostate cancer (“HSPC”) setting by combining ADT and the latest generation antiandrogens earlier in the course of the disease versus the administration of these two therapies sequentially.
While the potential importance of the NTD as a drug target has been appreciated for more than two decades, for technical reasons this has been a difficult target for therapeutic agent development. The NTD of the AR is flexible with a high degree of intrinsic disorder making it difficult for use in classic crystal structure-based drug design. The Company is not currently aware of any clinical-stage NTD AR inhibitors that are in development by other drug development companies. The nature of the binding of the Aniten compounds to the NTD, and the biological consequences of that binding, have been defined in scientific studies. The selectivity of the binding, based on in vivo imaging as well as in vitro studies, has been consistent with the favorable toxicological results observed in preclinical studies of the first-generation EPI-506 and the subsequent safety results observed in the Phase 1 trial of EPI-506. Subsequent to this trial and following the decision to pursue masofaniten (EPI-7386) as the Company’s lead product candidate, the Company completed a series of biophysical and biological studies revealing the interaction and binding of masofaniten (EPI-7386) to the NTD of the AR and presented these findings at several medical conferences in 2021. See “Completed Phase 1 Clinical Study of EPI-506” and “Next generation Aniten molecules” below.
The incidence of prostate cancer continues to rise. In 2024, 35,250 men are estimated to die of prostate cancer with 299,010 new estimated cases of the disease1. According to a prostate cancer market mapping assessment conducted by IQVIA, there were approximately 260,000 men with prostate cancer treated in the U.S. in 2023 with systemic treatments who had not yet received a second-generation antiandrogen2. The Company believed that the Aniten series of compounds could ultimately hold potential benefit for many of those patients. In its early clinical development, the Company focused on patients who have failed second-generation antiandrogen therapies (i.e., abiraterone and/or lutamides) for the following reasons:
● CRPC treatment remains a prostate cancer market segment with an apparent and significant unmet therapeutic need and is a potentially large market;
● the Company believed that the unique mechanism of action of its Aniten compounds is well suited to treat those patients who have failed AR LBD focused therapies and whose biological characterization reveals that their tumors are still largely driven by AR biology; and
● the Company expected that the relatively large number of patients with an apparent unmet therapeutic need in this area will facilitate timely enrollment in its clinical trials.
The Company believed that the demonstration of favorable safety and tolerability in the initial Aniten Phase 1 clinical trial, together with the compelling preclinical rationale, enabled and emphasized the importance of the study of the combination of masofaniten (EPI-7386) with second-generation antiandrogens. Furthermore, the Company believed that this application of two independent, complementary mechanisms of AR transcription inhibition may result in greater suppression of androgen activity and the delay or prevention of drug resistance. Recent progress in the clinical treatment of prostate cancer has resulted from the earlier utilization of antiandrogens in combination with classic ADT, consistent with the premise that more effective androgen suppression may yield clinical benefit. The Company believed that the introduction of NTD inhibitors, such as masofaniten (EPI-7386), therefore had the potential to improve androgen suppression, delay the emergence of resistance, and result in improved clinical benefit.
1 National Cancer Institute, Surveillance Epidemiology, and End Results Program (SEER), 2024. (https://seer.cancer.gov/statfacts/html/prost.html)
2 IQVIA: Oncology Analytics Platform and analytics for the period 2019-2024 reflecting estimates of real-world activity.
Completed Phase 1 Clinical Study of EPI-506
The Company conducted an initial proof-of-concept Phase 1 clinical study utilizing the first-generation Aniten compound, EPI-506 from 2015 to 2017. The objective of the EPI-506 Phase 1 clinical trial was to explore the safety, tolerability, maximum tolerated dose and pharmacokinetics of EPI-506, in addition to anti-tumor activity in asymptomatic or minimally symptomatic patients with mCRPC who were no longer responding to either abiraterone or enzalutamide treatments, or both. Efficacy endpoints, such as PSA reduction, and other disease progression criteria were evaluated. Details relating to the design of the Phase 1/2 clinical trial of EPI-506 are available on the U.S. National Institutes of Health clinical trials website (see https://clinicaltrials.gov under identifier NCT02606123).
The IND application to the FDA for EPI-506, to begin a Phase 1 clinical trial was allowed in September 2015, with the first clinical patient enrolled in November 2015. The Company’s Clinical Trial Application (“CTA”) submission to Health Canada was subsequently also cleared. Based on allometric scaling, an initial dose level of EPI-506 of 80 mg was determined. However, following the enrollment of the initial cohorts, it became apparent that EPI-506 exposure was much lower in humans than projected. EPI-506 dosing was escalated aggressively to allow patients in the clinical study greater exposure to the drug. The highest dose patients ultimately received was 3600 mg of EPI-506, administered in a single dose or split into two doses daily. The initial data from the Phase 1 clinical trial was presented at the European Society of Medical Oncology meeting in September 2017.
Conducted at five sites in the United States and Canada, the open-label, single-arm, dose-escalation study evaluated the safety, pharmacokinetics, maximum-tolerated dose and anti-tumor activity of EPI-506 in men with end-stage mCRPC who had progressed after prior enzalutamide and/or abiraterone treatment and who may have received one prior line of chemotherapy. Twenty-eight patients were available for analysis, with each patient having received four or more prior therapies for prostate cancer at the time of study entry. Patients self-administered oral doses of EPI-506 ranging from 80 mg to 3600 mg, with a mean drug exposure of 85 days (range of eight to 535 days). Four patients underwent prolonged treatment (with a median of 318 days, and a range of 219 to 535 days at data cut-off), following intra-patient dose escalation. PSA declines, a measure of potential efficacy, ranging from 4% to 37% were observed in five patients, which occurred predominantly in the higher dose cohorts (≥1280 mg).
EPI-506 was generally well-tolerated with favorable safety results observed across all doses up to 2400 mg. At a dose of 3600 mg, gastrointestinal adverse events (nausea, vomiting and abdominal pain) were observed in two patients: one patient in the once-daily (“QD”) dosing cohort and one patient in the 1800 mg twice-daily dosing cohort, leading to study discontinuation and a dose-limiting toxicity (“DLT”) due to more than 25% of doses being missed in the 28-day safety reporting period. A separate patient in the 3600 mg QD cohort experienced a transient Grade 3 increase in liver enzymes (AST/ALT), which also constituted a DLT, and enrollment was consequently concluded in this cohort.
Although the Company believed that the safety results and possible signs of anti-tumor activity observed at higher dose levels support the concept that inhibiting the AR-NTD may have provided a clinical benefit to mCRPC patients, the pharmacokinetic and metabolic studies revealed the limitations of the first-generation agent EPI-506. Through its discovery research, the Company had concluded that it should be feasible to develop a next generation of NTD inhibitor which would demonstrate greater potency, reduced metabolism and other improved pharmaceutical properties. As a result, the Company announced on September 11, 2017, its decision to discontinue the further clinical development of EPI-506 and to implement a corporate restructuring plan to focus research and development resources on its next-generation Anitens targeting the AR-NTD. This next generation Aniten compound included significantly more potent drugs designed to exhibit increased resistance to metabolism and therefore a longer predicted circulating half-life. The Company’s planned product candidate, masofaniten (EPI-7386), demonstrated these and other favorable characteristics in extensive preclinical characterization and clinical studies which the Company has presented in a series of poster presentations at scientific meetings.
Next generation Aniten molecules
The Company’s family of next-generation investigational Aniten compounds incorporated multiple chemical scaffold changes to the first-generation drugs which in preclinical studies retained NTD inhibition of the AR. In addition, they
showed improvement in a range of attributes when compared to the first-generation compound, EPI-506, in preclinical studies. In in vitro assays measuring inhibition of AR transcriptional activity, these product candidates demonstrated 20 times higher potency than EPI-506 or its active metabolite, EPI-002. In addition, the compounds demonstrated increased metabolic stability in preclinical studies, suggesting the potential for longer half-lives in humans. Lastly, the compounds demonstrated more favorable pharmaceutical properties relative to EPI-506. The Company believed that these product candidates, if successfully developed and approved, may have offered advancements in ease and cost of large-scale manufacture, drug product stability, and suitability for commercialization globally. Of these next-generation Anitens, masofaniten (EPI-7386) was selected for IND filing and a Phase 1 clinical trial. As discussed further herein, ESSA has decided to withdraw its IND and the CTAs relating to masofaniten (EPI-7386) that have been submitted to date.
Our Strategy
In October 2024, ESSA announced that it decided to terminate its clinical trials evaluating masofaniten (EPI-7386), and that the remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) will be terminated. ESSA has also decided to withdraw its IND and CTAs that have been submitted to date. In connection with these events, ESSA is undergoing a comprehensive review process to review its strategic options to maximize shareholder value.
In developing possible therapeutics that involve binding to the NTD of the AR, the Company’s strategic approach previously involved combining Aniten compounds with second generation antiandrogens in earlier lines of therapy. The Company, with industry partners, had been conducting clinical trials of combinations of masofaniten (EPI-7386) and second-generation antiandrogens in prostate cancer patients with nmCRPC, mCRPC, mHSPC and neo-adjuvant prostate cancer surgical treatment setting whose disease is thought to be still predominantly AR dependent. The Company was also completing the clinical development of masofaniten (EPI-7386) as a monotherapy treatment for patients with mCRPC, who are resistant to the current standard of care, to assess the drug’s performance as a single agent as completely as possible, with regards to safety, tolerability, and anti-tumor activity together with detailed pharmacological and biological studies. In parallel, the Company was continuing preclinical studies, including work on other Aniten molecules and other potential applications for AR NTD inhibitors.
The identification and characteristics of masofaniten (EPI-7386)
The purpose of the next-generation program had been to identify drug candidates with increased potency, reduced metabolic susceptibility and superior pharmaceutical properties compared to ESSA’s first-generation compounds. Structure-activity relation studies conducted on the chemical scaffold of ESSA’s first-generation compounds had resulted in the generation of a new series of compounds demonstrating higher potency and predicted longer half-lives. Multiple changes in the chemical scaffold were incorporated with the goal of improving ADME (absorption, distribution, metabolism, and excretion) and pharmaceutical properties of the chemical class.
Several next-generation Aniten molecules met prespecified preclinical target product profile goals regarding potency, stability, selectivity and pharmaceutical properties. On March 26, 2019, the Company announced the nomination of masofaniten (EPI-7386) as its lead clinical candidate for the treatment of mCRPC through inhibition of the NTD of the androgen receptor. In preclinical studies, masofaniten (EPI-7386) had displayed activity in vitro in numerous AR-dependent prostate cancer models including models where second-generation antiandrogens are inactive. In addition, masofaniten (EPI-7386) had shown to be significantly more potent, metabolically stable and more effective in preclinical studies compared to ESSA’s first-generation compound, EPI-506. Lastly, masofaniten (EPI-7386) had demonstrated a favorable tolerability profile in all animal studies of the compound conducted to that date.
From this series of next-generation compounds, masofaniten (EPI-7386) was selected as the lead candidate for the initial clinical development in mCRPC. An IND was submitted to the FDA on March 30, 2020, and was allowed by the FDA on April 30, 2020. A CTA was filed with Health Canada in April 2020 and clearance was subsequently received. Clinical testing of masofaniten (EPI-7386) commenced in July 2020, allowing for accommodations to the planned timeline as a result of the impact of COVID-19 at clinical trial sites (see “Risk Factors - Widespread health concerns, pandemics or epidemics, and other outbreaks of illness may negatively affect the Company’s ability to maintain operations and execute its business plan” in this Annual report on Form 10-K). In October 2024, ESSA announced that it decided to terminate its clinical trials evaluating masofaniten (EPI-7386), and that the remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) will be terminated. ESSA has also decided to withdraw its IND and CTAs that have been submitted to date. In connection with these events, ESSA is undergoing a comprehensive review process to review its strategic options to maximize shareholder value.
Advancing masofaniten (EPI-7386) through clinical development
In October 2024, the Company announced its decision to terminate its clinical trials evaluation masofaniten (EPI-7386), including each of the clinical trials described below.
The Company was previously advancing masofaniten (EPI-7386) through two clinical trials: EPI-7386-CS-001 and EPI-7386-CS-010. The clinical trial of EPI-7386-CS-001 had two arms that represent a monotherapy and combination component of the study schema, as outlined below:
Notes: “mCRPC” means metastatic castration-resistant prostate cancer; “AAP” means abiraterone acetate/prednisone; “mHSPC” means metastatic hormone-sensitive prostate; and “nmCRPC” means non-metastatic castration-resistant prostate cancer
The clinical trial of EPI-7386-CS-010 was a combination trial with enzalutamide with a Phase 1 dose equilibration component and Phase 2 head-to-head comparison component, as outlined in the study schema below:
Notes: “ENZ” means enzalutamide
Phase 1 Clinical Trial - EPI-7386-CS-001
The Phase 1 clinical trial of masofaniten (EPI-7386) “Oral EPI-7386 in Patients With Castration-Resistant Prostate Cancer (EPI-7386)” completed enrollment in the Part A Monotherapy component of the study and, until October 31, 2024, was actively enrolling patients in the Part B Combination component of the study in two separate cohorts: Cohort 1 in
combination with abiraterone acetate and prednisone in patients with either mHSPC or mCRPC for whom abiraterone acetate with prednisone is standard of care, and Cohort 2, in nmCRPC patients naïve to second generation antiandrogens in combination with apalutamide. The primary objectives of these two combination cohorts was to assess the safety and possible drug-drug interactions between masofaniten (EPI-7386) and abiraterone or apalutamide to inform the recommended doses of masofaniten (EPI-7386) when used in combination with these standard of care drugs. This study was conducted in the U.S. and Canada (www.clinicaltrials.gov under identifier NCT04421222).
Part A Monotherapy - Phase 1a - Dose Escalation
The open-label, dose-escalation Phase 1a clinical trial was designed to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose and/or a recommended Phase 2 range of doses in line with the FDA’s Project Optimus, and to assess preliminary anti-tumor activity of the drug.
The design of the Phase 1 clinical trial included the standard 3+3 design per dose cohort for the Part 1a dose escalation phase, with subjects receiving a daily oral dose of masofaniten (EPI-7386) once a day QD until there is objective evidence of clinical disease progression, and or occurrence of an unacceptable toxicity.
The dose escalation Part 1a of the study completed enrollment. Patients enrolled in the Part 1a of the study were selected clinically, on the basis of having progressive mCRPC as exemplified by rising PSA values and/or radiological disease progression despite latest generation antiandrogen treatment. However, all patients were also retrospectively biologically characterized for underlying tumor genomic characteristics, for evidence of AR pathway activation as well as non-AR oncogenic pathways and during the conduct of the trial, for dose-related biological, pharmacological and pharmacodynamic effects.
The protocol amendments filed with the FDA in September 2021 and July 2022 allow for monotherapy development in less heavily pretreated patients (as described above) in whom the androgen receptor pathway is more likely to be the primary driver of tumor growth. The Company’s goal was to establish, one or more doses/schedules to be tested in the expansion Phase 1b study in alignment with the FDA Project Optimus guidance, based on multiple inputs, including pharmacokinetic and biological observations, in addition to clinical experience. Two dose levels were advanced to Phase 1b dose expansion testing: 600 mg QD and 600 mg BID.
Part A Monotherapy - Phase 1b - Dose Expansion
The primary objective of Phase 1b was to further evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity (as measured by changes in tumor burden measured by imaging and changes in PSA levels over time) of masofaniten (EPI-7386) at 600 mg BID and 600 mg QD in a patient population enrolled under eligibility criteria similar to the one adopted for the Phase 1a with a focus on chemo-naïve mCRPC patients whose diseases have progressed after two lines of treatment including at least one line of second-generation antiandrogens. The 600 mg BID cohort and the 600 mg QD cohorts were fully enrolled at the time of the study termination.
Combination studies
Demonstration of the favorable safety and tolerability profile of masofaniten (EPI-7386) in the Phase 1a, together with clinical evidence for its mechanism of action and efficacy, were necessary to enable the study of patient populations with less advanced and less heavily pre-treated prostate cancer. The experience in the initial Phase 1a trial provided evidence for both an antiandrogen biological effect as well as some clinically relevant anti-tumor activity. The biological characterization of these patients also demonstrated favorable safety profiles.
The Company’s preclinical data and other evidence suggest earlier patient populations are more homogeneously AR-driven, and the favorable safety profile demonstrated in the Phase 1a dose escalation trial justified the study of the combination of masofaniten (EPI-7386) with classic antiandrogens. As a result, the Company, together with its collaborators, conducted, and prior to October 2024, planned to continue to conduct, a series of clinical trials in this regard. As mentioned above the Phase 1 clinical trial of masofaniten “Oral EPI-7386 in Patients With Castration-Resistant Prostate Cancer (EPI-7386)” was amended to include a Part B evaluating the combination of masofaniten (EPI-7386) with
abiraterone acetate or apalutamide in earlier patient populations to assess safety and potential drug interactions of these combinations. In addition, a separate Phase 1/2 study was being conducted to evaluate the safety and efficacy of masofaniten (EPI-7386) in combination with enzalutamide in patients with mCRPC naïve to second generation antiandrogens.
An activated AR is required for the growth and survival of most prostate cancer. Unlike current antiandrogen therapies which can only inhibit full-length AR, NTD inhibition of AR-directed biology occurs both in full length AR and splice variant ARs. The Company believed that the AR-NTD was an ideal target for next-generation antiandrogen hormone therapy.
Clinical Trial - EPI-7386-CS-010 - Combination Treatment with Enzalutamide
The Company was also running a Phase 1/2 study of masofaniten (EPI-7386) in combination with enzalutamide compared with enzalutamide alone in patients with mCRPC. Phase 1 of the study was a single-arm dose escalation study of masofaniten (EPI-7386) in combination with a fixed dose of enzalutamide.
A collaboration and supply agreement with Astellas Pharma Inc. (“Astellas”) to evaluate masofaniten (EPI-7386) in combination with Astellas and Pfizer Inc.’s (“Pfizer”) AR inhibitor, enzalutamide, in patients with mCRPC was announced on February 24, 2021. ESSA was paying for and was operationally conducting this trial, with an initial Phase 1 dose equilibration followed by a randomized Phase 2 trial planned to involve 120 patients. The enzalutamide for this trial was supplied by Astellas. The first patient in this Phase 1/2 study was dosed in January 2022 and the safety, tolerability, pharmacokinetics, and initial PSA responses were originally reported in the June 2022 clinical update in poster presentations at the Prostate Cancer Foundation Retreat in October 2022 and the American Society of Clinical Oncology Genitourinary Cancers Symposium in February 2023. In the Phase 1 dose equilibration, masofaniten (EPI-7386) was evaluated at escalating dose levels including 600 mg QD, 800 mg QD and 600 mg BID in combination with 120 mg and 160 mg enzalutamide in patients with mCRPC naïve to second generation antiandrogens. The Phase 1 part of the study had completed enrollment at the time of the study termination. The recommended Phase 2 combination doses for the Phase 2 randomized phase was 600 mg BID masofaniten (EPI-7386) with 160 mg enzalutamide (the highest dose levels tested). The Phase 2 study, planned to involve 120 patients and had two arms consisting of the following: a planned 80 patients with doses of 600 mg BID masofaniten and 160 mg QD ENZ, and 40 patients with a dose of 160 mg ENZ. The Phase 2 study was enrolling patients in the U.S., Canada certain countries in Europe, and Australia at the time of the study termination.
Clinical Trial - EPI-7386-CS-001 - Combination Treatments with Abiraterone and with Apalutamide
The first collaboration, with Janssen Research & Development, LLC (“Janssen”), to study in clinical trials the safety and potential benefit of the combination of masofaniten (EPI-7386) with abiraterone acetate with prednisone as well as the combination of masofaniten (EPI-7386) with apalutamide in patients with mCRPC, was announced on January 13, 2021. Under the collaboration agreement with Janssen, Janssen would pay for and conduct a clinical trial with masofaniten (EPI-7386) and in separate cohorts each of their antiandrogens, apalutamide and abiraterone acetate. This combination trial was initiated in March 2022. Enrollment was suspended by Janssen in October 2022 due to operational recruitment challenges. On April 12, 2023, ESSA announced that it had entered into a clinical trial support agreement with Janssen, with ESSA paying for and conducting a study of the combinations, in an earlier patient population, and with Janssen supplying apalutamide and abiraterone acetate.
The Company’s most recent protocol amendment in June 2023, modified the protocol design of this study by adding combination treatment with second-generation antiandrogens. Specifically, the amended protocol consisted of two parts: a Part A Monotherapy study and a Part B Combination study. Part A had two phases: a Phase 1a Dose Escalation and a Phase 1b Dose Expansion, as discussed above, with Part B conducted in two cohorts, Cohort 1 evaluating masofaniten (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 “window of opportunity cohort”, evaluating single agent masofaniten (EPI-7386) for 12 weeks in patients with nmCRPC before apalutamide was added.
Part B Combination - Cohort 1 - Combination with Abiraterone acetate/prednisone
The Company planned, before October 2024, to evaluate the combination of masofaniten (EPI-7386) with abiraterone acetate/prednisone (AAP) in patients with mHSPC or mCRPC. AAP was to be provided by Janssen under a clinical trial support agreement as described above.
Part B Combination - Cohort 2 - Window of opportunity with clinical endpoints followed by combination with Apalutamide
The primary objective of Cohort 2 was to assess the anti-tumor activity (as measured by changes of PSA over time) of masofaniten (EPI-7386) administered at 600 mg BID for a limited window of time (up to 12 weeks before patients start standard of care therapy) in nmCRPC patients whose disease is unperturbed by previous second-generation antiandrogen therapies or chemotherapy. Following the dosage of masofaniten (EPI-7386) as a single agent after the 12-week window, the Company planned to evaluate the combination of masofaniten (EPI-7386) with apalutamide. Apalutamide was to be provided by Janssen under the same clinical trial support agreement.
In addition to the agreements announced with Pfizer, and Janssen, a third collaboration was announced with Bayer. Bayer was to pay for and conduct a Phase 1/2 clinical trial with masofaniten (EPI-7386) to evaluate masofaniten (EPI-7386) in combination with darolutamide in earlier line mCRPC patients. ESSA planned to provide masofaniten (EPI-7386) for the combination trial. This clinical trial has not yet been initiated and the Company no longer plans to pursue initiation of the trial.
Preclinical Development of Anitens and other indications
The Company has decided to terminate its preclinical development programs and related work during the pendency of its strategic options review discussed further herein. Prior to October 2024, the Company was conducting research on other emerging potential clinical applications for NTD inhibitors. As part of that preclinical work on Aniten compounds, the Company also studied NTD degraders and presented data for its first generation of AR ANITAC NTD degraders at the AACR annual meeting on April 10, 2022 in a poster titled “Androgen receptor (AR) N-Terminal Domain degraders can degrade AR full length and AR splice variants in CRPC preclinical models.”
Recent Developments
Termination of Clinical Studies and Evaluation of Strategic Options
On October 31, 2024, ESSA announced that it decided to terminate its Phase 2 clinical trial evaluating in a 2:1 randomization masofaniten (EPI-7386) combined with enzalutamide versus enzalutamide single agent in patients with mCRPC naïve to second-generation antiandrogens. This decision, mutually agreed upon by both senior management and the Board, 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 (EPI-7386) plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study.
As part of its efforts to focus its resources, ESSA also announced the remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) either as a monotherapy or in combination with other agents, including each of the clinical studies described herein will be terminated. ESSA also decided to withdraw its IND and CTAs that have been submitted to date. In connection with these events, ESSA has initiated a comprehensive review process to review its strategic options to maximize shareholder value. ESSA expects to devote significant time and resources to its review of strategic options. There can be no assurances that the strategic review process will deliver the anticipated benefits thereof or enhance shareholder value. Strategic options may include, but are not limited to, a merger, amalgamation, arrangement, reverse take-over, business combination, asset sale or acquisition, shareholder distribution, wind-down, liquidation and dissolution or other strategic transaction or the operation of its business and election to seek new product candidates for development.
There can be no assurance that ESSA will be able to successfully consummate any particular strategic transaction, or any transaction at all. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we may incur significant costs related to this continued evaluation. ESSA may also incur additional unanticipated expenses in connection with this process. A considerable portion of these costs will be incurred regardless of whether any such course of action is implemented or transaction is completed. Any such expenses will decrease the remaining cash available for use in ESSA’s business and may diminish or delay any future distributions to our shareholders.
On September 13-17, 2024, the Company updated dose escalation data from its Phase 1/2 study evaluating masofaniten (formerly EPI-7386) in combination with enzalutamide at the 2024 European Society for Medical Oncology (ESMO).
The updated dose escalation data included that in patients evaluable for safety (n=18), masofaniten combined with enzalutamide, was well-tolerated at the dose levels tested through 32 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities (DLTs) were observed, therefore the maximum tolerated dose (MTD) was not reached. The recommended Phase 2 combination doses (RP2CDs) were identified as masofaniten 600 mg twice daily (BID) in combination with enzalutamide 160 mg once daily (QD).
At such time, in the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). Across all dose cohorts, 88% of patients (14 of 16) achieved PSA50, 88% of patients (14 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 63% of patients (10 of 16) achieved PSA <0.2ng/mL. With a median follow up of 15.2 months, the median time to PSA progression and radiographic progression free survival had not yet been reached.
The randomized, open-label, two arm, Phase 2 dose expansion portion of the study was underway and designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naïve to second generation anti-androgens. The study planned to enroll patients at approximately 33 sites in the USA, Canada and Australia, and an additional 22 sites in Europe.
On January 25-27, 2024, the Company presented updated dose escalation data from its Phase 1/2 study evaluating masofaniten (EPI-7386) in combination with enzalutamide at the 2024 ASCO Genitourinary Cancers Symposium.
The data included that in patients evaluable for safety (n=18), masofaniten combined with enzalutamide, was well-tolerated at the dose levels tested through 25 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities were observed, therefore the maximum tolerated dose was not reached. The recommended Phase 2 combination doses were identified as masofaniten 600 mg BID in combination with enzalutamide 160 QD.
In the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). Across all dose cohorts, 88% of patients (14 of 16) achieved PSA50, 81% of patients (13 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 63% of patients (10 of 16) achieved PSA <0.2ng/mL. While the data for disease PSA progression were still maturing with a median follow up of 11.1 months, the median time to PSA progression was at 16.6 months.
The randomized, open-label, two arm, Phase 2 dose expansion portion of the study was underway and designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naïve to second generation anti-androgens. The study planned to enroll patients in the U.S., Canada, certain countries in Europe, and Australia.
On October 26-28, 2023, the Company presented an update to the poster previously presented at the European Society of Medical Oncology (ESMO) 2023 Congress for its Phase 1/2 study evaluating masofaniten (EPI-7386) in combination with enzalutamide at the 30th Annual Prostate Cancer Foundation Scientific Retreat.
The data presented were from the four cohorts of patients in the Phase 1 dose escalation portion of the study. The data indicated that masofaniten (EPI-7386) had no effect on enzalutamide exposure, thus allowing the use of full dose per label (160mg) of enzalutamide in combination. It also indicated that enzalutamide reduces masofaniten (EPI-7386) exposure but twice daily dosing of masofaniten (EPI-7386) appears to mitigate the reduction and maintains clinically relevant drug exposures.
In patients evaluable for safety (n=18), masofaniten (EPI-7386) combined with enzalutamide, was well-tolerated at the doses tested through 21 cycles of dosing in some patients. The most frequent adverse events were Grade 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten (EPI-7386) combined with enzalutamide and deemed probably related.
In the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). In the first three cohorts, 90% of patients (9 of 10) achieved PSA50 and PSA90, 80% of patients (8 of 10) achieved PSA90 in less than 90 days, and 70% of patients (7 of 10) achieved PSA <0.2ng/mL. Across all dose cohorts including patients in the recently enrolled Cohort 4, 88% of patients (14 of 16) achieved PSA50, 81% of patients (13 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 56% of patients (9 of 16) achieved PSA <0.2ng/mL. The randomized Phase 2 dose expansion portion of the study has been discontinued.
On October 20-24, 2023, the Company presented updated dose escalation data from its Phase 1/2 study evaluating masofaniten (EPI-7386) in combination with enzalutamide at the European Society of Medical Oncology (ESMO) 2023 Congress.
The data presented included that in patients evaluable for safety (n=18), masofaniten combined with enzalutamide, was well-tolerated at the doses tested through 21 cycles of dosing in some patients. Most frequent adverse events were Grade 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related.
In the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). In the first three cohorts, 90% of patients (9 of 10) achieved PSA50 and PSA90, 80% of patients (8 of 10) achieved PSA90 in less than 90 days, and 70% of patients (7 of 10) achieved PSA <0.2ng/mL. Across all dose cohorts including patients in the recently enrolled cohort four, 88% of patients (14 of 16) achieved PSA50, 69% of patients (11 of 16) achieved PSA90, 63% of patients (10 of 16) achieved PSA90 in less than 90 days, and 56% of patients (9 of 16) achieved PSA <0.2ng/mL. The randomized Phase 2 dose expansion portion of the study has been discontinued.
On October 3, 2023, the Company filed a prospectus supplement to its registration statement on Form S-3, including a base prospectus, with the SEC. Further to this, on November 6, 2023, the Company announced that it had entered into the ATM Sales Agreement with Jefferies LLC, effective as of November 3, 2023. Under the ATM Sales Agreement, ESSA may, within the period that the ATM Sales Agreement is in effect, sell its Common Shares from time to time for up to US$50.0 million in aggregate sales proceeds. No offers or sales of Common Shares will be made in Canada, to anyone known by Jefferies LLC to be a resident of Canada or on or through the facilities of any stock exchange or trading markets in Canada.
On September 18, 2023, the Company announced the initiation of the Phase 2 portion of its Phase 1/2 study evaluating its lead candidate, masofaniten (EPI-7386), in combination with Astellas and Pfizer's enzalutamide in patients with mCRPC naïve to second-generation antiandrogens.
On August 31, 2023, the Company announced the establishment of Automatic Securities Disposition Plans for its President and Chief Executive Officer, David R. Parkinson and its Executive Vice President and Chief Operating Officer, Peter Virsik.
On June 6, 2023, the Company appointed Lauren Merendino to the Board.
On April 12, 2023, the Company announced it had entered into a clinical trial support agreement with Janssen. ESSA was sponsoring and conducting a Phase 1 clinical trial evaluating the safety, pharmacokinetics, drug-drug interactions, and preliminary anti-tumor activity of masofaniten (EPI-7386) when administered in combination with either apalutamide or abiraterone acetate plus prednisone. Janssen was supplying apalutamide and abiraterone acetate.
On February 16-19, 2023, the Company presented analyses of initial clinical data from two Phase 1 studies of masofaniten (EPI-7386) in patients with mCRPC at the American Society of Clinical Oncology Genitourinary Cancers Symposium. The Company presented an update to the Phase 1 monotherapy study demonstrating that masofaniten (EPI-7386) single agent showed a favorable safety profile and was well-tolerated up to a daily dose of 1200 mg (600 mg BID), achieved target clinical exposures and showed preliminary signals of anti-tumor activity in heavily pretreated mCRPC patients. The second poster presented preliminary results to the Phase 1/2 trial of masofaniten (EPI-7386) in combination with Astellas and Pfizer’s AR inhibitor, enzalutamide. Ten patients had been enrolled in the first three cohorts: three in cohort 1 (600 mg QD masofaniten (EPI-7386) and 120 mg QD enzalutamide), four in cohort 2 (800 mg QD masofaniten (EPI-7386) and 120 mg QD enzalutamide) and three in cohort 3 (600 mg BID masofaniten (EPI-7386) and 120 mg QD enzalutamide). At that time, the DLT period had not cleared for cohort 3. For the first 2 cohorts that cleared the DLT period, no DLTs were observed, and the safety profile was consistent with second-generation antiandrogens (e.g., Grade 1 or 2 AEs of fatigue and hot flushes). Pharmacokinetic results from cohorts 1 and 2 had demonstrated that enzalutamide exposure was minimally impacted by masofaniten (EPI-7386), while, as expected, masofaniten (EPI-7386) exposure was reduced by approximately 60% by enzalutamide (a well established CYP3A4 inducer). The observed masofaniten (EPI-7386) exposures remained in the clinically relevant range suggested by pre-clinical xenograft studies. Five out of six evaluable patients enrolled in the first two cohorts showed a PSA decrease >90% regardless of the patients previous chemotherapy
status, and four out of six evaluable patients PSA levels reached < 0.2 ng/mL. All five patients that experienced biochemical responses showed stable disease by imaging.
On October 31, 2022, the Company announced that Janssen Research and Development is suspending enrollment into the Phase 1 clinical study of masofaniten (EPI-7386) with apalutamide and masofaniten (EPI-7386) with abiraterone acetate plus prednisone in mCRPC patients as a result of operational recruitment challenges. Initial clinical activity was observed in some patients, with two of the three patients achieving a PSA reduction of 90% (“PSA90”) within 12 weeks. The Company was in discussions with Janssen to supply abiraterone acetate and apalutamide for an ESSA-sponsored combination study.
On October 26, 2022, the Company announced the presentation of preclinical data for its lead first generation AR ANITen bAsed Chimera (“ANITAC”™) NTD degrader in a poster session at the 34th EORTC-NCI-AACR Annual Symposium on Molecular Targets and Cancer Therapeutics.
On October 26, 2022, the Company announced the presentation of updated clinical data from the first two cohorts of the Phase 1/2 study of ESSA's lead candidate masofaniten (EPI-7386) in combination with enzalutamide at the 2022 Prostate Cancer Foundation Scientific Retreat. In the multicenter, open-label Phase 1/2 dose escalation study, seven mCRPC patients naïve to second generation antiandrogens were enrolled in the first two cohorts, with escalating doses of masofaniten (EPI-7386) and a fixed 120 mg once a day QD dose of enzalutamide. The study permitted one prior line of chemotherapy. Pharmacokinetic results from these first two cohorts demonstrated that enzalutamide exposure was minimally impacted by masofaniten (EPI-7386) while exposures of masofaniten (EPI-7386) were reduced by coadministration with enzalutamide, but remained in the clinically relevant range as suggested by preclinical xenograft studies. The safety of the combination was favorable with a safety profile consistent with second-generation antiandrogens and no dose limiting toxicities were observed. One of the patients in the first cohort discontinued after one cycle of dosing due to a strong CYP3A inducer concomitant medication which lowered exposures to both masofaniten (EPI-7386) and enzalutamide and was therefore not evaluable for efficacy. Anti-tumor activity in the remaining six patients enrolled demonstrated that four of six of these patients achieved a PSA90 by 12 weeks of dosing and five of six patients to date have achieved a PSA90.
On September 13, 2022, the Company appointed Philip Kantoff to its Board.
On June 30, 2022, the Company announced the establishment of Automatic Securities Disposition Plans for its President and Chief Executive Officer, David R. Parkinson and its Executive Vice President and Chief Operating Officer, Peter Virsik.
On June 27, 2022, the Company presented, by conference call and webcast, a clinical update on masofaniten (EPI-7386) monotherapy and combination therapy clinical development. The update on the Phase 1a dose escalation study showed initial data from 36 patients that demonstrated that masofaniten (EPI-7386) was well-tolerated, exhibited a favorable pharmacokinetic profile, and demonstrated initial anti-tumor activity in a heavily pretreated group of patients. The Company believes the favorable safety and tolerability profile, good pharmaceutical characteristics together with both antiandrogen biological and anti-tumor activity support the Company’s decision to move into earlier lines of therapy and study masofaniten (EPI-7386) in combination with second-generation antiandrogens. The update also noted that ctDNA molecular analysis in the heavily pretreated population has provided a detailed profile of genetic alterations, which reveals the biological complexity of late-stage mCRPC patients and also allows for the continued refinement of the population of prostate cancer patients whose tumors are still primarily driven by the androgen receptor, and therefore most likely to respond to an androgen receptor inhibitor.
The update detailed that in the multi-center, open-label Phase 1a dose escalation study, 31 patients received masofaniten (EPI-7386) as oral tablets once a day QD in cohorts with 200 milligram increments from 200 milligrams up to 1000 milligrams. Patients in this QD group were heavily pretreated, with a median of seven lines of prior therapy for prostate cancer and four lines of therapy for mCRPC. Almost 60% of patients had been treated with prior chemotherapy. Patients entered the trial with rapidly progressive disease, as evidenced by a median PSA doubling time of only 2.1 months and a median ctDNA percent of 29%. Almost a third of the patients had lung, liver, or brain metastases, and an overlapping third of patients had overt neuroendocrine differentiation. The ctDNA analysis revealed that tumors in these patients had extensive non-AR associated genomic changes denoting the presence of multiple non-AR oncogenic drivers associated with late-stage prostate cancer. Subsequent to a protocol amendment, the experience was also presented for the five initial patients enrolled in a twice daily dose regimen in 400 mg and 600 mg BID cohorts. The amendment excluded patients who had been treated with more than three prior lines of therapy, excluded patients with visceral metastases, and permitted only one prior line of chemotherapy.
The key safety results from both QD and BID patients, as of June 1, 2022, showed that masofaniten (EPI-7386) was safe and well-tolerated at all dose levels and schedules tested, with no dose-limiting toxicities, treatment related adverse events were limited to Grade 1 or Grade 2, with one Grade 3 occurrence of anemia ultimately deemed unlikely to be treatment related, and that there was no apparent dose dependency in any of the side effects.
Antiandrogen response was assessed by changes in circulating PSA levels, changes in ctDNA levels, and radiographic changes in disease burden measured by both traditional RECIST criteria as well as by total lesion volumetric quantification using the AIQ Solutions platform.
The key response findings in both QD and BID patients, as of June 1, 2022, demonstrated that tumor volume decreased in five patients out of 10 patients who had measurable disease and were on therapy for more than 12 weeks. PSA decrease or PSA stabilization was observed in a clinical subset of patients with no visceral disease, fewer DNA genomic aberrations in non-AR oncogenic pathways, and fewer than 3 lines of therapy. This provided further information to support refining the monotherapy development program patient population. In 17 patients with measurable ctDNA levels at baseline, ctDNA declines were observed in patients harboring AR point mutations, AR gain/amplification and AR truncations, suggesting masofaniten’s (EPI-7386) potential activity against these tumors.
The update also described the planned Phase 1b study, the planned window of opportunity cohort and the status of the combination study of masofaniten (EPI-7386) with enzalutamide. The Phase 1b study will evaluate a patient population of mCRPC similar to the one treated under the Phase 1a BID cohort but with the additional exclusion of prior chemotherapy. Up to 12 patients per each dose/schedule (600 mg QD and either 400 mg or 600 mg BID) will be evaluated to gain additional information about safety, tolerability, exposure and anti-tumor activity of masofaniten (EPI-7386) in a less heavily pretreated patient population.
The update also described the planned window of opportunity cohort as part of the Phase 1b expansion in which a separate group of non-metastatic CRPC will be enrolled into a 12-week study with a clinical endpoint (i.e., PSA changes) to assess the anti-tumor activity of masofaniten (EPI-7386) in a patient population in which the disease is mainly AR-driven and the tumor biology has not been affected by second-generation antiandrogen therapy.
The clinical update also provided the status of the combination studies evaluating masofaniten (EPI-7386) in earlier lines of therapy in Phase 1/2 trials which combine masofaniten (EPI-7386) with approved second-generation antiandrogens. In the Phase 1/2 study being conducted by the Company of masofaniten (EPI-7386) in combination with Astellas Pharma Inc.’s and Pfizer Inc.’s AR inhibitor, enzalutamide, in patients with mCRPC who have not been treated with second-generation antiandrogens, the first cohort had cleared the 28-day DLT period with no safety issues and when reported the trial was currently enrolling the second cohort of patients. The preliminary data from the first cohort in the Phase 1/2 combination trial with enzalutamide suggests that the drugs can be combined safely and based upon clinical and preclinical data predicted to be active. The early data, in addition to preclinical studies, supported masofaniten’s (EPI-7386) potential in combination with second-generation antiandrogens to suppress androgen receptor biology and induce a potent anti-tumor response.
The Company also described the anticipated initiation later in 2022 of a Phase 2 investigator-sponsored neoadjuvant study which will evaluate darolutamide compared to masofaniten (EPI-7386) + darolutamide in patients undergoing prostatectomy for high-risk localized prostate cancer.
At the AACR annual meeting on April 10, 2022, in a poster titled “Androgen receptor (AR) N-Terminal Domain degraders can degrade AR full length and AR splice variants in CRPC preclinical models,” the Company presented preclinical data for its first generation of androgen receptor (AR) ANITen bAsed Chimera (ANITAC™) N-terminal domain (NTD) degraders. The preclinical data demonstrated the potential of ESSA’s ANITAC degraders as a new approach to AR pathway inhibition. The intrinsically disordered nature of the NTD region of the AR has meant it has generally been considered undruggable. The preclinical studies have shown that through their unique ability to bind to the NTD of AR, ANITACs have the ability to inhibit NTD-mediated AR transcription while also degrading AR protein including resistant forms of AR which are commonly associated with CRPC. The preclinical results demonstrate that ANITAC degraders utilize the ubiquitin proteasome system and can degrade many forms of AR including full length, mutant, and splice variants which are often expressed in CRPC patients. Specifically, the ANITAC degraders show robust potency in inhibiting AR transcriptional activity driven by AR-FL, AR-V7, or AR-V567es. In addition, the orally bioavailable ANITAC degraders exhibit high potency in inhibiting AR-dependent transcription and reducing viability of AR-dependent prostate cancer cells.
On January 19, 2022, the Company announced the first patient dosed in the Company-sponsored Phase 1/2 study to evaluate the safety, tolerability and preliminary efficacy of ESSA’s lead product candidate, masofaniten (EPI-7386), a first-in-class N-terminal domain androgen receptor inhibitor, in combination with Astellas and Pfizer Inc.’s ligand-binding domain androgen receptor inhibitor, enzalutamide, in patients with mCRPC. This combination trial investigated the potential clinical benefit of inhibiting the androgen receptor through two independent pathways in the treatment of patients with mCRPC who have not yet received treatment with a second-generation antiandrogen drug. In preclinical models, the combination of masofaniten (EPI-7386) with lutamides by simultaneously targeting both ends of the AR resulted in deeper and broader inhibition of androgen biology.
The Phase 1/2 clinical trial (NCT05075577) was a two part study. Phase 1 was evaluating the safety and tolerability of the drug combination to establish the recommended Phase 2 range of doses for masofaniten (EPI-7386) and enzalutamide when dosed in combination. This Phase of the study was expected to enroll up to 30 mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. As described below on June 27, 2022, the results of the initial experience with the first cohort were presented, demonstrating the safety and tolerability of the combination in this first cohort, along with the accompanying pharmacokinetic and PSA reduction information. In Phase 2, single agent enzalutamide was compared to the combination of enzalutamide and masofaniten (EPI-7386) in the same patient population. The goal of Phase 2 was to evaluate the safety, tolerability and anti-tumor activity of masofaniten (EPI-7386) in combination with a fixed dose of enzalutamide compared with enzalutamide as a single agent. This part of the study was expected to enroll 120 mCRPC patients who have not yet been treated with second-generation antiandrogen therapies.
Future Clinical Development Program
Prior to the October 2024 discontinuation of ESSA’s clinical studies, the Company planned to conduct further clinical development which would have required randomized clinical trials in earlier patient populations (potentially ranging from newly diagnosed through non-metastatic and metastatic hormone-sensitive or pre-latest generation antiandrogen CRPC populations).
As part of its efforts to focus its resources, ESSA also announced that the other remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) either as a monotherapy or in combination with other agents will be terminated. ESSA also decided to withdraw its IND and CTAs that have been submitted to date. In connection with these events, ESSA has initiated a comprehensive review process to review its strategic options to maximize shareholder value.
Competition
The competition in the prostate cancer market is very high, many of the companies against which we compete or against which we may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Several pharmaceutical therapies already have approved and many new molecules are being tested for their effect in this patient population. In addition, generic forms of Zytiga (abiraterone acetate) are now approved and commercially available in the U.S.
Currently approved therapies include:
GENERIC/PROGRAM
NAME
BRAND NAME
COMPANY NAME(S)
STAGE
Enzalutamide
Xtandi
Astellas and Pfizer
Marketed
Abiraterone acetate
Zytiga
Johnson & Johnson
Marketed
Abiraterone acetate
Yonsa
Sun Pharma
Marketed
Sipuleucel-T
Provenge
Valeant
Marketed
Docetaxel
n/a
Sanofi and various
Marketed
Cabazitaxel
Jevtana
Sanofi
Marketed
Radium-233
Xofigo
Bayer
Marketed
Apalutamide (ARN-509)
Erleada
Johnson & Johnson
Marketed
Darolutamide
Nubeqa
Bayer
Marketed
Pembrolizumab
Keytruda
Merck
Marketed
Olaparib
Lynparza
AstraZeneca
Marketed
Rucaparib
Rubraca
Clovis Oncology
Marketed
Vipivotide tetraxetan
Pluvicto
Novartis
Marketed
Niraparib/abiraterone acetate
Akeega
Johnson & Johnson
Marketed
Talazaparib (w/enzalutamide)
Talzenna
Pfizer
Marketed
In this market, ESSA believed that its competitive position was strong because its product candidate, if successful, involved a mechanistically unique, differentiated approach to prostate cancer treatment involving the therapeutic modality that has been shown to make the biggest difference to the survival of recurrent prostate cancer patients: blocking AR activation. Since Anitens have been shown to directly bind to AR-NTD and prevent AR-mediated transcription, they have the potential to bypass the AR-dependent resistance pathways (discussed above) that may develop as a result of treatment with current hormone-related therapies that target the AR LBD. If successful, ESSA believed this could have represented a significant step forward in the treatment of prostate cancer. To ESSA’s knowledge, no antagonist to the AR-NTD is currently undergoing clinical trials for prostate cancer or any other indication. Other approaches to interfering with AR signaling include potentially complementary strategies to degrade the AR such as that being pursued by Arvinas, Inc.
Collaborative Agreements
As discussed herein, in October 2024 ESSA decided to discontinue its clinical studies, including those related to collaborative agreements, and development of masofaniten (EPI-7386), and is currently conducting a review of its strategic options. ESSA is not currently engaged in any collaborations for clinical development and the Company’s plans for future collaborative agreements are dependent on the results of ESSA’s ongoing strategic evaluation.
On January 13, 2021, the Company announced a clinical collaboration with Janssen to evaluate masofaniten (EPI-7386) with abiraterone acetate with prednisone as well as the combination of masofaniten (EPI-7386) with apalutamide in patients with mCRPC. Under the terms of the agreement, Janssen could sponsor and conduct up to two Phase 1/2 studies evaluating the safety, tolerability and preliminary efficacy of the combination of masofaniten (EPI-7386) and apalutamide as well as the combination of masofaniten (EPI-7386) with abiraterone acetate plus prednisone in patients with mCRPC
who have failed a current second-generation antiandrogen therapy. Janssen would assume all costs associated with the studies, other than the manufacturing costs associated with the clinical drug supply of masofaniten (EPI-7386). The parties planned to form a joint oversight committee for the clinical studies. ESSA will retain all rights to masofaniten (EPI-7386).
The combination trial was initiated in March 2022. Enrollment was suspended by Janssen in October 2022 due to operational recruitment challenges. ESSA has announced its intention to revise the collaboration, with ESSA conducting a study of the combinations, potentially in an earlier patient population, and Janssen supplying apalutamide and abiraterone acetate.
On February 25, 2021, the Company announced a clinical collaboration with Astellas Pharma Inc. (“Astellas”) to evaluate the combination of masofaniten (EPI-7386) and Astellas/Pfizer’s androgen receptor inhibitor, enzalutamide, for patients with mCRPC. Under the terms of the agreement, ESSA was to sponsor and conduct a Phase 1/2 study to evaluate the safety, tolerability and preliminary efficacy of the combination of masofaniten (EPI-7386) and enzalutamide in mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. Astellas was to supply enzalutamide for the trial. ESSA will retain all rights to masofaniten (EPI-7386).
On April 28, 2021, the Company announced that it had entered into a clinical trial collaboration and supply agreement with Bayer Consumer Care AG (“Bayer”) to evaluate masofaniten (EPI-7386) in combination with Bayer’s androgen receptor inhibitor, darolutamide, in patients with mCRPC. Under the terms of the agreement, following review of certain clinical data, Bayer may sponsor and conduct a Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of the combination of masofaniten (EPI-7386) and darolutamide in mCRPC patients. ESSA was to supply masofaniten (EPI-7386) for the trial and will retain all rights to masofaniten (EPI-7386).
Patents and Proprietary Rights
License Agreement with UBC and the BCCA
ESSA has in-licensed intellectual property embodied in issued patents, pending patents applications and know-how relating to compounds that modulate AR activity. ESSA refers to these intellectual property rights as the “Licensed IP.”
The Company is party to a license agreement with the British Columbia Cancer Agency and the University of British Columbia (the “Licensors”) dated December 22, 2010, as amended on February 10, 2011, May 27, 2014, and May 25, 2021 (the “License Agreement”), which provides the Company with exclusive world-wide rights to develop and commercialize products based on the Licensed IP.
ESSA paid a minimum annual royalty of C$85,000 in 2017, 2018, and 2019 and must continue to pay a minimum of C$85,000 for each year thereafter. For a First Compound entering clinical development, C$50,000 was paid upon enrollment of a patient in a Phase 2 clinical trial. Additionally, C$900,000 must be paid upon enrollment of a patient in a Phase 3 clinical trial.
The Licensors may terminate the License Agreement upon ESSA’s insolvency, or the License Agreement may be terminated by either party for certain material breaches by the other party. ESSA is required to allocate reasonable time to the development and commercialization of the Licensed IP and to use reasonable efforts to promote, market and sell products covered by the Licensed IP. The terms of the License Agreement required ESSA to issue to the Licensors, 1,000,034 pre-Consolidation Common Shares, in lieu of payment of an initial license fee. If ESSA develops products covered by the Licensed IP in the future, it will be required to pay certain development and regulatory milestone payments up to an aggregate of C$2.4 million for the first drug product developed under the license and up to an aggregate of C$510,000 for each subsequent product. ESSA must also pay the Licensors low single-digit royalties based on aggregate worldwide net sales of products covered by the Licensed IP and a percentage of sublicensing revenue in the low teens. The License Agreement will expire on the later of 20 years after the date of the License Agreement or the expiry of the last issued patent included in the Licensed IP.
On December 12, 2024, ESSA provided a notice of termination of the License Agreement to the Licensors, notifying the Licensors that it terminated the License Agreement in accordance with its terms, effective as of December 12, 2024.
ESSA’s Intellectual Property Strategy
The Company currently retains all commercial rights for its Aniten series drug portfolio and believes it has developed a strong and defensive intellectual property position for the Aniten structural classes. ESSA has licensed certain patent rights, with respect to some of its compounds that modulate AR activity, from the Licensors. ESSA has the right to acquire ownership of the licensed patents and patent applications upon specified payment to the Licensors, and providing that payments required under the License Agreement continue to be made.
As of September 2024, ESSA owns rights to a patent portfolio that includes 83 issued patents, including 23 issued U.S. patents, that are in force and cover multiple EPI- and Aniten structural classes of compounds with different structural motifs/analogues. Patent applications are also pending in the United States and in contracting states to the Patent Cooperation Treaty for the Aniten next-generation NTD inhibitors, with expected expiration dates between 2036 to 2044.
The patent portfolio includes issued patents that are in force and pending patent applications that cover the masofaniten (EPI-7386) compound, pharmaceutical compositions comprising the masofaniten (EPI-7386) compound, or its methods of use, and are expected to provide protection until the expiration dates, ranging from 2036 to 2043.
Both ESSA and the broader pharmaceutical industry attach significant importance to patents for the protection of new technologies, products and processes. Accordingly, ESSA’s success depends, in part, on its ability to obtain patents or rights thereto, to protect commercial secrets and carry on activities without infringing the rights of third parties. Disputes may arise as to the inventorship of and/or ownership interest in the Company’s or the Licensors’ patents, including for example, former or current employees of the Company or the Licensors pursuing ownership rights of patents owned by or licensed to the Company. The Company may have limited ability to impact any internal disputes between the Licensors and their employees or former employees. See “Risk Factors” in this Annual Report on Form 10-K. Where appropriate, and consistent with management’s objectives, ESSA will continue to seek patents in relation to components or concepts of its technology that it perceives to be important.
Regulatory Environment
Given the decision to close the IND and CTAs for masofaniten, a current focus is the conduct of a clinical trial shutdown process that is compliant with regulatory requirements in each of the jurisdictions in which the trials were conducted. Going forward, the production and manufacture of ESSA’s potential future planned product candidates, and potential future product candidates, if any, and its R&D activities will be subject to regulation for safety, efficacy, quality and ethics by various governmental authorities around the world. In the United States, drugs and biological products are subject to regulation by the FDA. In Canada, these activities are regulated by the Food and Drugs Act and the rules and regulations thereunder, which are enforced by the TPD. Drug approval laws require registration of manufacturing facilities, carefully controlled research and testing of product candidates, government review and approval of experimental results prior to giving approval to sell drug products. Regulators also require that rigorous and specific standards such as cGMP, good laboratory practices (“GLP”) and current good clinical practices (“GCP”) are followed in the manufacture, testing and clinical development respectively of any drug product. See “Risk Factors” in this Annual Report on Form 10-K.
The process of obtaining regulatory approvals and the corresponding compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval may subject an applicant or sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of enforcement letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities. While ESSA is not currently developing any product candidates and do not have any products approved for sale, if ESSA decides to pursue any future product development efforts, it would be subject to such government regulation.
Drug Products Development Process
An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the following:
● completion of extensive nonclinical, sometimes referred to as preclinical laboratory tests, and preclinical animal trials in compliance with applicable requirements for the humane use of laboratory animals and formulation studies, including GLPs;
● submission to the FDA of an IND, which must take effect before human clinical trials may begin;
● approval by an institutional review board (“IRB”), representing each clinical site before each clinical trial may be initiated;
● performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as GCP regulations and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed drug product for its intended use;
● preparation and submission to the FDA of a New Drug Application (“NDA”);
● review of the product by an FDA advisory committee, where appropriate or if applicable;
● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to
assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;
● payment of user fees and securing FDA approval of the NDA; and
● compliance with any post-approval requirements, including Risk Evaluation and Mitigation Strategies (“REMS”) and post-approval studies required by the FDA.
Preclinical Studies
Preclinical studies are conducted in vitro and in animals to evaluate pharmacokinetics, metabolism and possible toxic effects to provide evidence of the safety of the product candidate prior to its administration to humans in clinical studies and throughout development. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations. The results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical studies, among other things, are submitted to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted.
Initiation of Human Testing
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under written trial protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to a proposed clinical trial and places the trial on clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. In Canada, this application is called a CTA. An IND/CTA application must be filed and accepted by the FDA or TPD, as applicable, before human clinical trials may begin. In addition, an IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the trial at least annually. The IRB must review and approve, among other things, the trial protocol and informed consent information to be provided to trial subjects. An IRB must operate in compliance with FDA regulations.
Two key factors influencing the rate of progression of clinical trials are the rate at which patients can be enrolled to participate in the research program and whether effective treatments are currently available for the disease that the drug is intended to treat. Patient enrollment is largely dependent upon the incidence and severity of the disease, the treatments available and the potential side effects of the drug to be tested and any restrictions for enrollment that may be imposed by regulatory agencies.
Phase 1 Clinical Trials
Phase 1 clinical trials for cancer therapeutics are typically conducted on a small number of patients to evaluate safety, dose limiting toxicities, tolerability, pharmacokinetics and to determine the dose for Phase 2 clinical trials in humans.
Phase 2 Clinical Trials
Phase 2 clinical trials typically involve a larger patient population than Phase 1 clinical trials and are conducted to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of a product candidate for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule.
Phase 3 Clinical Trials
Phase 3 clinical trials typically involve testing an experimental drug on a much larger population of patients suffering from the targeted condition or disease - in ESSA’s case, CRPC. These studies involve testing the experimental drug in an
expanded patient population at geographically dispersed test sites (multi-center trials) to establish clinical safety and effectiveness. These trials also generate information from which the overall risk-benefit relationship relating to the drug can be determined.
In most cases FDA requires two adequate and well controlled Phase 3 clinical trials to demonstrate the efficacy of the drug. A single Phase 3 trial with other confirmatory evidence may be sufficient in rare instances where the trial is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible.
New Drug Application
Assuming successful completion of required clinical testing and other requirements, the results of the preclinical and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA, or the TPD as part of a New Drug Submission (“NDS”), requesting approval to market the drug product for one or more indications. The NDS or NDA is then reviewed by the applicable regulatory body for approval to market the drug.
The FDA conducts a preliminary review of an NDA within 60 days of its receipt and informs the sponsor by the 74th day after the FDA’s receipt of the submission to determine whether the application is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA has agreed to specified performance goals in the review process of NDAs. Most such applications are meant to be reviewed within ten months from the date of filing, and most applications for “priority review” products are meant to be reviewed within nine months of filing. The review process may be extended by the FDA for three additional months to consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.
Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is or will be manufactured. These pre-approval inspections cover all facilities associated with an NDA submission, including drug component manufacturing (such as Active Pharmaceutical Ingredients), finished drug product manufacturing, and control testing laboratories. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
The cost of preparing and submitting an NDA is substantial. The submission of most NDAs is additionally subject to a substantial application user fee, currently exceeding $2,500,000 and the manufacturer or sponsor under an approved new drug application are also subject to significant annual program and establishment user fees. These fees are typically increased annually.
On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or nine months depending on the type of information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.
If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.
Post-Approval Requirements
Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, significant changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured, as well as new application fees for supplemental applications with clinical data.
In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:
● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
● fines, warning letters or holds on post-approval clinical trials;
● refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;
● product seizure or detention, or refusal to permit the import or export of products; or
● injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, which regulates the distribution of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states. Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.
Orphan Designation and Exclusivity
Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition (generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a drug product available in the United States for treatment of the disease or condition will be recovered from sales of the product). A company must request orphan product designation before submitting an NDA. If the request is granted, the FDA will disclose the identity of the therapeutic agent and its potential use. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
If a product with orphan status receives the first FDA approval for the disease or condition for which it has such designation, the product generally will receive orphan product exclusivity. Orphan product exclusivity means that the FDA may not approve any other applications for the same product for the same indication for seven years, except in certain limited circumstances. Competitors may receive approval of different products for the indication for which the orphan product has exclusivity and may obtain approval for the same product but for a different indication. If a drug or drug product designated as an orphan product ultimately receives marketing approval for an indication broader than what was designated in its orphan product application, it may not be entitled to exclusivity.
Government Regulation Outside of the United States and Canada
In addition to regulations in the United States and Canada, we are subject to a variety of regulations in other jurisdictions governing, among other things, clinical studies and any commercial sales and distribution of products.
While ESSA is not currently seeking FDA approval for a product, if it did in the future, we would need to obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical studies or marketing of the product in those countries. Certain countries outside of the United States have a similar process that requires the submission of a clinical study application much like the IND prior to the commencement of human clinical studies. In the European Union, for example, a CTA must be submitted to each country’s national health authority and an independent ethics committee, much like the FDA and IRB, respectively. Once the CTA is approved in accordance with a country’s requirements, clinical study development may proceed.
The requirements and process governing the conduct of clinical studies, product licensing, coverage, pricing and reimbursement vary from country to country. In all cases, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
Human Capital Resources
As of the date of this Annual Report, ESSA has a total of approximately 35 employees and consultants on a full-time or part-time basis. ESSA has in the past, and may in the future, retain additional expert consultants on an ad-hoc basis if required in connection with the Company’s evaluation of strategic alternatives. None of our employees is represented by a labor union, and we have never experienced a work stoppage.
Corporate Structure
The Company was incorporated under the name “ESSA Pharma Inc.” pursuant to the Business Corporations Act (British Columbia) on January 6, 2009. The Company’s registered and records office is located at Suite 3500, The Stack, 1133 Melville Street, Vancouver, British Columbia, Canada V6E 4E5. The Company’s head office is located at Suite 720, 999 West Broadway, Vancouver, British Columbia, Canada V5Z 1K5.
Since July 9, 2015, the Company’s Common Shares have traded on the Nasdaq under the symbol “EPIX.” The Company’s Common Shares traded under the symbol “EPI” on the Toronto Stock Exchange (the “TSX”) from July 28, 2015, until November 24, 2017. On November 27, 2017, the Company delisted its Common Shares from the TSX and began trading on the TSX-V under the same symbol, “EPI.” On October 26, 2020, the Company announced its decision to voluntarily delist its Common Shares from the TSX-V.
The Company has one wholly owned subsidiary:
● ESSA Pharmaceuticals Corp. (“ESSA Texas”), existing under the laws of the State of Texas. The head office of ESSA Texas is located at Suite 1300, 700 Milam Street, Houston, Texas, USA 77002.
Available Information
This Annual Report on Form 10-K, our quarterly reports on Form 10-Q, our current reports on Form 8-K, and any amendments to these reports are filed, or will be filed, as appropriate, with the SEC and the Canadian Securities Administrators (“CSA”). These reports are available free of charge on our website, www.essapharma.com, as soon as reasonably practicable after we electronically file such reports with or furnish such reports to the SEC and the Canadian regulatory authorities. Information contained on, or accessible through, our website or any other website referenced herein is not a part of this Annual Report on Form 10-K, and the inclusion of our website address or any other website address in this document is an inactive textual reference.
Additionally, our filings with the SEC may be accessed through the SEC’s website at www.sec.gov and our filings with the CSA may be accessed through SEDAR+ at www.sedarplus.com. Our annual report on Form 10-K from the year ended September 30, 2023, which includes a full discussion of the general development of our business, can be found at https://www.sec.gov/Archives/edgar/data/1633932/000155837022018570/tmb-20220930x10k.htm.

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ITEM 1A. RISK FACTORS
Item 1A.
Risk Factors
Risk Factor Summary
We are providing the following summary of the risk factors contained in this Annual Report on Form 10-K to enhance the readability and accessibility of our risk factor disclosures. This summary does not address all the risks that we face. We encourage you to carefully review the full risk factors contained in this Annual Report on Form 10-K in their entirety, together with our other filings with the SEC, for additional information regarding the material factors that make an investment in our securities speculative or risky, and before making an investment decision regarding our Common Shares. These risks and uncertainties include, but are not limited to, the following:
● We may fail to comply with applicable legal and regulatory requirements, which may result in administrative or judicial sanctions;
● We will have significant additional future capital needs and there are uncertainties as to the Company’s ability to raise additional funding;
● We may not be able to raise additional capital on favorable terms, which may result in dilution to our existing shareholders, restrictions on our operations or the requirement for us to relinquish rights to technologies or product candidates;
● We have incurred significant losses in every quarter since our inception and anticipate that we will continue to incur significant losses in the future and may never generate profits from operations or achieve profitability;
● We have a limited operating history, which may make it difficult for you to evaluate the success of our business to date and to assess our future viability;
● We rely on proprietary technology, the protection of which can be unpredictable and costly;
● We may not be able to protect our intellectual property rights throughout the world;
● We may be subject to claims by third parties asserting that we, or our employees, contractors or consultants have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property;
● Our business and operations would suffer in the event of computer system failures or security breaches;
● We are a smaller reporting company and a non-accelerated filer and the reduced disclosure requirements available to us may make our Common Shares less attractive to investors;
● We are and there is a risk that we may continue to be a “passive foreign investment company,” which would likely result in materially adverse U.S. federal income tax consequences for U.S. investors;
● The risk of securities class action litigation;
● The potential impact of shareholder activism on our business;
● The market price and trading volume of our Common Shares may be volatile, which could result in rapid and substantial losses for our shareholders or securities litigation; and
● Widespread health concerns, pandemics or epidemics, and other outbreaks of illness may negatively affect our ability to maintain operations and execute our business plan.
Regulatory Matters
ESSA may not be successful in its efforts to build out a pipeline of product candidates.
The Company has decided to discontinue its preclinical development programs and related work during the pendency of its strategic options review discussed further herein. Prior to October 2024, the Company was conducting preclinical work on other emerging potential clinical applications for NTD inhibitors. Even if such work was continued, ESSA may not be able to continue to identify or develop, at all or in a timely manner, new products. Even if ESSA is successful in building its pipeline, the potential product candidates that it identifies may not be suitable for clinical development or commercialization. If ESSA does not successfully identify, develop and commercialize new products based upon its approach, it will not be able to diversify its portfolio which could result in harm to ESSA’s financial position and impact the trading price of the Common Shares.
Failure to comply with applicable legal and regulatory requirements may result in administrative or judicial sanctions.
If the Company or a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, lack of efficacy, problems with the facility where the product is manufactured, or the Company or its manufacturers fail to comply with applicable regulatory requirements, the Company may be subject to the following administrative or judicial sanctions:
● restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls;
● issuance of warning letters or untitled letters;
● clinical holds;
● injunctions or the imposition of civil or criminal penalties or monetary fines;
● suspension or withdrawal of regulatory approval;
● suspension of any ongoing clinical trials;
● refusal to approve pending applications or supplements to approved applications filed by the Company, or suspension or revocation of product license approvals;
● suspension or imposition of restrictions on operations, including costly new manufacturing requirements;
● withdrawal of the product from the market and product recalls; or
● product seizure or detention or refusal to permit the import or export of product.
The occurrence of any event or penalty described above may inhibit the Company’s ability to commercialize potential products and generate revenue. Adverse regulatory action, whether pre- or post-approval, can also potentially lead to product liability claims and increase the Company’s product liability exposure.
In the future, the regulatory climate might change due to changes in the FDA and other regulatory authorities’ staffing, policies or regulations and such changes could impose additional post-marketing obligations or restrictions and related costs. While it is impossible to predict future legislative or administrative action, if the Company is not able to maintain regulatory compliance, the Company will not be able to market its drugs and its business could suffer.
Risks Related to ESSA’s Financial Position and Need for Additional Capital
ESSA will have significant additional future capital needs and there are uncertainties as to the Company’s ability to raise additional funding.
The Company has decided to discontinue its clinical and preclinical development programs and related work during the pendency of its strategic options review discussed further herein. Management has forecasted that ESSA’s working capital will be sufficient to execute its planned operating expenses and capital expenditures for the coming fiscal year. On current plans, ESSA believes it has sufficient capital resources to fund its current and planned operations through 2025, including the wind down of its clinical trials and preclinical development programs. The Company recognizes that despite a decreased cash outflow that may occur as a result of terminations to clinical trials, general and administrative and other expenses will continue to be incurred which may impact the Company’s cash runway. ESSA has based this estimate on assumptions that may prove to be wrong, and ESSA could use its capital resources sooner than it currently expects. Discontinuing the development of ESSA’s novel and proprietary therapies, or the acquisition and the development of any new products or product candidates will require considerable resources and additional access to capital. In addition, ESSA’s future cash requirements may vary materially from those now expected.
ESSA could potentially seek additional funding through strategic collaborations, alliances and licensing arrangements, through public or private equity or debt financing, or through other transactions. However, if capital market conditions in general, or with respect to life sciences companies such as ESSA’s, are unfavorable, ESSA’s ability to obtain significant additional funding on acceptable terms, if at all, will be negatively affected. There is no certainty that any such financing will be provided or provided on favorable terms.
If sufficient capital is not available, ESSA may be required to delay the discontinuance of its clinical and preclinical development programs and related work during the pendency of its strategic options review, either of which could have a material adverse effect on ESSA’s business, financial condition, prospects or results of operations.
ESSA may not be able to raise additional capital on favorable terms, which may result in dilution to ESSA’s existing shareholders, restrictions on ESSA’s operations or the requirement for ESSA to relinquish rights to technologies.
The Company expects to finance future cash needs through a combination of private and public equity offerings, debt financings, strategic collaborations and alliances and licensing arrangements, if at all. Additional financing that the Company may pursue may involve the sale of the Common Shares or financial instruments that are exchangeable for, or convertible into, the Common Shares, which could result in significant dilution to ESSA’s shareholders and the terms may include liquidation or other preferences that adversely affect the rights of existing shareholders. Additional capital may not be available on reasonable terms, if at all. Furthermore, these securities may have rights senior to those of ESSA’s Common Shares and could contain covenants that include restrictive covenants limiting ESSA’s ability to take important actions and potentially impair ESSA’s competitiveness, such as limitations on ESSA’s ability to incur additional debt, make capital expenditures, acquire, sell or license intellectual property rights or declare dividends. If ESSA raises additional funds through strategic collaborations and alliances or licensing arrangements with third parties, ESSA may have to relinquish valuable rights to technologies, or grant licenses on terms that are not favorable to ESSA. If the Company is unable to raise additional funds when needed, the Company may be required to delay the discontinuance of its clinical and preclinical development programs and related work during the pendency of its strategic options review, either of which could have a material adverse effect on ESSA’s business, financial condition, prospects or results of operations.
The Company was subject to the restrictions and conditions of the CPRIT Agreement for a period of time after receipt of the last grant payment. Failure to have complied with the CPRIT Agreement may materially and adversely affect ESSA’s financial condition.
ESSA relied on the CPRIT Grant to fund a portion of its preclinical and Phase 1 clinical development costs of clinical candidate EPI-506, which ceased development in September 2017. The total of the CPRIT Grant was US$12 million. The CPRIT Grant was subject to various requirements, including ESSA’s compliance with the scope of work outlined in the CPRIT Agreement. If ESSA was found not to have complied with the terms of the CPRIT Agreement, or found to have used any grant proceeds for purposes other than intended, or found to have failed to maintain the required level of operations in the State of Texas for three years following the final payment of grant funds, CPRIT could determine that
ESSA was in default of its obligations under the CPRIT Agreement and could, among other things, seek reimbursement of all proceeds of the CPRIT Grant received by ESSA. ESSA received and responded to a request in October 2018 for information from CPRIT regarding the nature and extent of the Company’s operations in Texas. Although the Company believes it has at all times acted in compliance with the CPRIT Agreement and believes its response to CPRIT’s request for information was satisfactory, there can be no assurance that CPRIT will agree with ESSA’s determination. If ESSA is found to be in default under the CPRIT Agreement and such default is not waived by CPRIT, the Company could be required to reimburse a portion or all of the CPRIT Grant. Being required to reimburse a portion or all of the CPRIT Grant would impact ESSA’s ongoing operations, which could materially and adversely affect its financial condition and results of operations.
The Company has incurred significant losses in every quarter since its inception and anticipates that it will continue to incur significant losses in the future and may never generate profits from operations or achieve profitability.
ESSA is a clinical stage pharmaceutical company with a limited operating history. Investment in pharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval or become commercially viable. To date, ESSA has not generated, and may not generate, any revenue from product sales, or otherwise. Furthermore, ESSA may incur expenses associated with its strategic options review, discontinuation of its research and development activities and other expenses related to its ongoing operations. As a result, ESSA is not profitable and has incurred losses in every reporting period since inception in 2009. For the years ended September 30, 2024 and September 30, 2023, ESSA reported net losses of $28,542,821 and $26,582,343, respectively. As of September 30, 2024, ESSA had an accumulated deficit since inception of $208,004,180.
The Company expects to continue to incur significant expenses and operating losses for the foreseeable future, particularly in connection with its strategic options review and the discontinuation of its research and development activities, including its clinical trials. ESSA anticipates these losses may increase as it discontinues the research and development of, and no longer seeks regulatory approvals for, its planned product candidate. ESSA may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect its financial condition. ESSA expects its financial condition and operating results to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond ESSA’s control. The Company’s prior losses and expected future losses have had and will continue to have an adverse effect on the Company’s financial condition.
Since ESSA does not currently plan to commercialize any product candidate, the Company may not generate significant revenues or achieve profitability.
The Company expects to continue to incur substantial losses for the foreseeable future, and these losses may be increasing. The Company may not be able to achieve profitability. Such failure to become profitable may impair the Company’s ability to sustain operations and adversely affect the price of the Common Shares and its ability to raise capital.
ESSA has a limited operating history, which may make it difficult for you to evaluate the success of ESSA’s business to date and to assess ESSA’s future viability.
The Company commenced operations in 2009, and its operations have been primarily limited to organizing and staffing ESSA, business planning, raising capital, establishing relationships with consultants and contract vendors with relevant expertise, acquiring the in-licensing of intellectual property, filing patent applications, discovering and developing novel small molecule product candidates, conducting preliminary preclinical research, preparing for and conducting early-stage clinical trials. ESSA is a development stage company with limited operating history and no revenue. As a development stage company ESSA may encounter unforeseen expenses, difficulties, complications, delays and other known or unknown factors. ESSA has identified a product candidate, masofaniten (EPI-7386), that it was advancing through clinical development but decided to discontinue its clinical studies and trials related to the product and does not have any other products ready for commercialization or in development. Consequently, evaluating ESSA’s performance, viability or future success will be more difficult than if ESSA had a longer operating history or approved products on the market.
Risks Related to ESSA’s Intellectual Property
ESSA relies on proprietary technology, the protection of which can be unpredictable and costly.
The Company’s activities depend, in part, on its ability to (i) obtain and maintain patents, trade secret protection and operate without infringing the intellectual proprietary rights of third parties, (ii) successfully defend these patents (including patents owned by or licensed to the Company) against third-party challenges and (iii) successfully enforce these patents against third-party competitors. There is no assurance that the Company will be granted such patents or proprietary technology or that such granted patents or proprietary technology will not be circumvented through the adoption of a competitive, though non-infringing, process or product. Failure to protect the Company’s existing and future intellectual property rights could seriously harm its business and prospects and may result in the loss of its ability to exclude others from using the Company’s technology or its own right to use the technologies. If the Company does not adequately ensure the right to use certain technologies, it may have to pay others for the right to use their intellectual property, pay damages for infringement or misappropriation or be enjoined from using such intellectual property. The Company’s patents do not guarantee the right to use the technologies if other parties own intellectual property rights that are necessary in order to use such technologies. The Company’s patent position is subject to complex factual and legal issues that may give rise to uncertainty as to the validity, scope and enforceability of a particular patent. The Company’s and the Company’s licensors’ patents and patent applications, if issued, may be challenged, invalidated or circumvented by third parties. U.S. patents and patent applications may also be subject to interference proceedings, re-examination proceedings, derivation proceedings, post-grant review or inter partes review in the United States Patent and Trademark Office (“USPTO”), challenging the Company’s or the Company’s licensors’ patent rights. Foreign patents may be subject also to opposition or comparable proceedings in the corresponding foreign patent office.
For example, in patent litigation in the United States and in some other jurisdictions, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, lack of novelty, obviousness, written description, indefiniteness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld material information from the USPTO or the applicable foreign counterpart, or made a misleading statement, during prosecution. A litigant or third party could challenge the Company’s patents on this basis even if the Company believes that it conducted its patent prosecution in accordance with the duty of candor and in good faith. The outcome following such a challenge is unpredictable.
In addition, it is possible that the Company or its licensors do not perfect ownership of all patents, patent applications or other intellectual property. This possibility includes the risk that the Company or its licensors does not identify all inventors, or identifies incorrect inventors, or that third parties pursue an ownership interest in the Company’s patents, which may lead to claims disputing inventorship or ownership of ESSA’s patents, patent applications or other intellectual property by former employees or other third parties. If ESSA fails in prosecuting or defending any such claims, in addition to paying monetary damages, ESSA may lose valuable intellectual property rights or personnel or sustain damages. ESSA may lose exclusive rights to their intellectual property rights and ESSA could be required to obtain a license from such third-party to use ESSA’s technology or products, if any. Such a license may not be available on commercially reasonable terms or at all. Even if ESSA is successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.
If a defendant were to prevail on a legal assertion of invalidity, sole or joint ownership, and/or unenforceability, the Company would lose at least part, or perhaps all, of the patent protection on a product candidate. Even if a defendant does not prevail on a legal assertion of invalidity and/or unenforceability, the Company’s patent claims may be construed in a manner that would limit its ability to enforce such claims against the defendant and others. The cost of defending such a challenge, and any resulting loss of patent protection, could have a material adverse impact on one or more of the Company’s product candidates and its business.
Certain of ESSA’s current or former employees, contractors or consultants, including senior management, were previously employed, or continue to be employed, at universities or other public institutions, or at other biotechnology or pharmaceutical companies, including ESSA’s competitors or potential competitors. Some of these employees may have executed proprietary rights, nondisclosure and noncompetition agreements, in connection with such previous employment. ESSA may be subject to claims that ESSA, or these employees, have used or disclosed confidential information or intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer.
In addition, there is a risk that improved versions of ESSA’s own planned product developed by third parties will be granted patent protection and compete with ESSA’s planned product. For example, any patents ESSA obtains may not be sufficiently broad to prevent others from utilizing its technologies or from developing competing products and technologies. Third parties may attempt to circumvent ESSA’s patents by means of alternative designs and processes or may independently develop similar products, duplicate any of ESSA’s planned products not under patent protection, or design around the inventions ESSA claims in any of its existing patents, existing patent applications or future patents or patent applications. The actual protection afforded by a patent varies on a product-by-product basis, from country to country and depends upon many factors, including the type of patent, the scope of ESSA’s coverage, the availability of regulatory related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patents. It is impossible to anticipate the breadth or degree of protection that patents will afford products developed by ESSA or their underlying technology.
In any case, there can be no assurance that:
● any rights under U.S., Canadian, or foreign patents owned by the Company or other patents that third parties license to the Company will not be curtailed;
● the Company was the first inventor of inventions covered by its issued patents or pending applications or that the Company was the first to file patent applications for such inventions;
● the Company’s pending patent applications will be issued with the breadth of claim coverage sought by the Company, or be issued at all;
● the Company’s competitors will not independently develop or patent technologies that are substantially equivalent or superior to the Company’s technologies;
● third parties will not attempt to circumvent ESSA’s patents by means of alternative designs and processes or that third parties will not also independently develop similar products, duplicate any of ESSA’s products not under patent protection, or design around the inventions ESSA claims in any of the Company’s existing patents or existing patent applications;
● any of the Company’s trade secrets will not be learned independently by its competitors; or
● the steps the Company takes to protect its intellectual property will be adequate.
In addition, effective patent, trademark, copyright and trade secret protection may be unavailable, limited or not sought in certain foreign countries. Further, countries ESSA may sell to may not protect its intellectual property to the same extent as the laws of the United States, Canada or Europe, and may lack rules and procedures required for defending ESSA’s patents.
There is a risk that any patents issued relating to ESSA’s products or any patents licensed to ESSA may be successfully challenged or that the practice of its products might infringe the patents of third parties. Disputes may arise as to the rights to know-how and inventions among ESSA’s employees and consultants who use intellectual property owned by others for the work performed for the Company. The scope and validity of patents which may be obtained by third parties, the extent to which ESSA may wish or need to obtain patent licenses and the cost and availability of such licenses are currently unknown. If such licenses are obtained, it is likely they would be royalty bearing, which could reduce ESSA’s income.
In certain instances, ESSA may elect not to seek patent protection but instead rely on the protection of the Company’s technology through confidentiality agreements or trade secrets. There can be no assurance that these agreements will not be breached, that the Company will have adequate remedies for any breach or that such persons or institutions will not assert rights to intellectual property arising out of these relationships. The value of ESSA’s assets could also be reduced to the extent that third parties are able to obtain patent protection with respect to aspects of ESSA’s technology or products or that confidential measures ESSA has in place to protect the Company’s proprietary technology are breached or become unenforceable. However, third parties may independently develop or obtain similar technology and such third parties may be able to market competing products and obtain regulatory approval through a showing of equivalency to one of ESSA’s planned products which has obtained regulatory approval, without being required to undertake the same lengthy and expensive clinical studies that ESSA would have already completed. The cost of enforcing the Company’s patent rights or defending rights against infringement charges by other patent holders may be significant and could limit operations.
Litigation may also be necessary to enforce patents issued or licensed to ESSA or to determine the scope and validity of a third party’s proprietary rights. ESSA could incur substantial costs if the Company is required to defend itself in patent suits brought by third parties, if ESSA participates in patent suits brought against or initiated by ESSA’s corporate collaborators or if ESSA initiates such suits. The Company may not have the necessary resources to participate in or defend any such activities or litigation. Even if ESSA did have the resources to vigorously pursue its interests in litigation, because of the complexity of the subject matter, it is impossible to predict whether ESSA would prevail in any such action. Any claims of patent infringement asserted by third parties may:
● divert the time and attention of the Company’s technical personnel and management;
● require the Company to cease or modify its use of the technology and/or develop non-infringing technology; or
● require the Company to enter into royalty or licensing agreements.
If third parties successfully assert their intellectual property rights against ESSA, ESSA might be barred from using certain aspects of its intellectual property portfolio. Prohibitions against using certain technologies could be imposed by a court or by a settlement agreement between the Company and a plaintiff. In addition, if ESSA is unsuccessful in defending against allegations that it has infringed, misappropriated or otherwise violated patent or other intellectual property rights of others, the Company may be forced to pay substantial damage awards to a plaintiff. If litigation leads to an outcome unfavorable to the Company or in order to avoid or settle potential claims, the Company may choose or be required to seek a license from a third-party and be required to pay license fees or royalties or both, which could be substantial. It is possible that the necessary license will not be available to the Company on commercially acceptable terms, or at all. These licenses may not be available on acceptable terms, or at all. Even if the Company or any future collaborators were able to obtain a license, the rights may be nonexclusive, which could result in the Company’s competitors gaining access to the same intellectual property. Further, the Company could be found liable for significant monetary damages as a result of claims of intellectual property infringement.
An adverse outcome in litigation, or interference or derivation proceeding to determine priority or other proceeding in a court or patent or selling office could subject ESSA to significant liabilities, require disputed rights to be licensed from third parties or require ESSA to cease using certain technology or products, any of which may have a material adverse effect on the Company’s business, financial condition and results of operations.
ESSA may not be able to protect its intellectual property rights throughout the world.
Filing, prosecuting and defending patents on ESSA’s planned product candidate and potential future product candidates throughout the world would be prohibitively expensive. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States or federal and provincial laws in Canada. Consequently, ESSA may not be able to prevent third parties from practicing its inventions in all countries outside the United States or Canada, or from selling or importing products made using its inventions in and into the United States, Canada or other jurisdictions. Competitors may use ESSA’s technologies in jurisdictions where it has not obtained patent protection to develop their own products and may export otherwise infringing products to territories where ESSA has patent protection, but where enforcement is not as strong as that in the United States or Canada. These products may compete with ESSA’s planned products in jurisdictions where it does not have any issued patents and its patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for ESSA to stop the infringement, misappropriation or violation of its patents or ESSA’s licensors patents, or marketing of competing products in violation of its proprietary rights generally. Proceedings to enforce ESSA’s patent rights in foreign jurisdictions could result in substantial cost and divert its efforts and attention from other aspects of its business, could put ESSA’s patents or the patents of ESSA’s licensors at risk of being invalidated or interpreted narrowly, could put ESSA’s patent applications or the patent applications of ESSA’s licensors at risk of not issuing and could provoke third parties to assert claims against ESSA. ESSA may not prevail in any lawsuits that it initiates and the damages or other remedies awarded, if any, may not be commercially meaningful.
The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug. In India, unlike the United States, there is no link between regulatory approval of a drug and its patent status. Furthermore, generic or biosimilar drug manufacturers or other competitors may challenge the scope, validity or enforceability of ESSA’s patents, requiring it to engage in complex, lengthy and costly litigation or other proceedings. Generic or biosimilar drug manufacturers may develop, seek approval for, and launch biosimilar versions of ESSA’s products. In addition to India, certain countries in Europe and developing countries, including China, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, ESSA may have limited remedies if patents are infringed or if it is compelled to grant a license to a third-party, which could materially diminish the value of those patents. This could limit ESSA’s potential revenue opportunities. Accordingly, ESSA’s efforts to enforce intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that it owns or licenses.
Obtaining and maintaining ESSA’s patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by regulations and governmental patent agencies, and ESSA’s patent protection could be reduced or eliminated for non-compliance with these requirements.
Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or applications will be due to the USPTO and other foreign patent agencies in several stages over the lifetime of ESSA’s patents and/or applications. ESSA has systems in place to remind the Company to pay these fees. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. ESSA employs reputable law firms to help the Company comply, and in many cases, an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules to the relevant jurisdiction. However, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If ESSA or its future potential licensors fail to maintain the patents and patent applications covering product candidates, ESSA’s competitive position would be adversely affected.
If ESSA does not obtain protection under the Hatch-Waxman Amendments and similar legislation in other countries for extending the term of patents covering each of its product candidates, ESSA’s business may be materially harmed.
Depending upon the timing, duration and conditions of FDA marketing approval of ESSA’s planned product candidates, if any, one or more of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent term extension of up to five years for a patent covering an approved product as compensation for effective patent term lost during product development and the FDA regulatory review process. However, the Company may not receive an extension if it fails to apply within applicable deadlines, fails to apply prior to expiration of relevant patents or otherwise fails to satisfy applicable requirements. Moreover, the length of the extension could be less than the Company requests. If the Company is unable to obtain patent term extension or the term of any such extension is less than it requests, the period during which the Company can enforce its patent rights for that product will be shortened and the
Company’s competitors may obtain approval to market competing products sooner. As a result, the Company’s revenue from applicable products could be reduced, possibly materially. Further, if this occurs, ESSA’s competitors may take advantage of the Company’s investment in planned development and trials by referencing the Company’s clinical and preclinical data and launch their product earlier than might otherwise be the case.
Confidentiality Agreements with employees and third parties may not prevent unauthorized disclosure of Company proprietary information, which would harm ESSA’s competitive position.
In addition to patents, ESSA relies on technical know-how and proprietary information concerning the Company’s, business strategy and planned product candidates in order to protect its competitive position. ESSA’s employees are required to sign agreements which protect the Company’s proprietary information and intellectual property rights. In the course of ESSA’s research and development activities and its business activities and operations, the Company relies on confidentiality and service agreements with its third-party service providers, consultants and contractors, to protect its proprietary information and intellectual property rights. Such assignment agreements may be breached, and the Company may be forced to bring claims against third parties, or defend claims that third parties may bring against the Company. In addition, the Company’s employees, consultants, contractors, business partners or outside scientific collaborators may intentionally or inadvertently disclose the Company’s proprietary information in breach of these agreements. Third parties working collaboratively with ESSA may have certain rights to publish data and may fail to notify ESSA of such publication and ESSA in turn may fail to apply for patent protection prior to such disclosure. It is possible that a competitor may make use of such information disclosure, and that ESSA’s competitive position could be compromised. Enforcing a claim that a third party illegally obtained and is using any of ESSA’s proprietary information is expensive and time consuming, and the outcome may be unpredictable. In addition, courts outside the U.S. sometimes may be less willing than U.S. courts to protect proprietary information and know-how. Moreover, the Company’s competitors may independently develop equivalent knowledge, methods and know-how. If the Company cannot maintain the confidentiality of its proprietary technology and other confidential information, then the Company’s ability to obtain patent protection could be jeopardized, which could adversely affect ESSA’s competitive position.
In addition, ESSA, or its licensors, may be subject to claims that former employees, collaborators or other third parties have an interest in ESSA’s owned or in-licensed patents, trade secrets, or other intellectual property as an inventor or co-inventor. For example, ESSA, or its licensors, may have inventorship disputes arise from conflicting obligations of employees, consultants or others who were involved in developing ESSA’s planned product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or ESSA’s, or its licensors’, ownership of our owned or in-licensed patents, trade secrets or other intellectual property. If ESSA, or its licensors, fail in defending against any such claims, in addition to paying monetary damages, ESSA may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to its product candidates. Even if ESSA is successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could have a material adverse effect on ESSA’s business, financial condition, results of operations and prospects.
If ESSA’s trademarks and trade names are not adequately protected, the Company may not be able to build name recognition in its markets of interest and its business, financial condition, results of operations and prospects could be significantly harmed.
The Company’s trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. The Company may not be able to protect its rights to these trademarks and trade names, which it needs to build name recognition among potential strategic partners in its markets of interest. At times, competitors may adopt trade names or trademarks similar to ESSA’s, thereby impeding its ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of the Company’s registered or unregistered trademarks or trade names. Over the long term, if the Company is unable to establish name recognition based on its trademarks and trade names, then the Company may not be able to compete effectively, and its business, financial condition, results of operations and prospects may be significantly harmed. The Company’s efforts to enforce or protect its proprietary rights related to trademarks, trade names, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could significantly harm its business, financial condition, results of operations and prospects.
Intellectual property litigation may lead to unfavorable publicity that harms ESSA’s reputation and causes the market price of the Common Shares to decline.
During the course of any intellectual property litigation, there could be public announcements of the initiation of the litigation as well as results of hearings, rulings on motions, and other interim proceedings in such litigation. If securities analysts or investors regard these announcements as negative, the perceived value of the Company’s existing products, programs or intellectual property could be diminished. Accordingly, the market price of shares of the Company’s Common Shares may decline. Such announcements could also harm ESSA’s reputation or the market for the Company’s future products, which could significantly harm the Company’s business, financial condition, results of operations and prospects.
ESSA’s intellectual property rights may not necessarily provide the Company with competitive advantages and its patent terms may be inadequate to protect the Company’s competitive position on its product candidates for an adequate amount of time.
The degree of future protection afforded by the Company’s intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect the Company’s business, or permit the Company to maintain its competitive advantage. The following examples are illustrative:
● others may be able to make compounds that are similar to the Company’s product candidates but that are not covered by the claims of the patents that the Company or the Company’s strategic partners own or have exclusively licensed;
● others may independently develop similar or alternative technologies without infringing the Company’s intellectual property rights;
● issued patents that the Company owns or has exclusively licensed may not provide the Company’s with any competitive advantages, or may be held invalid or unenforceable, as a result of legal challenges by the Company’s competitors;
● the Company may obtain patents for certain compounds many years before it obtains marketing approval for products containing such compounds, and because patents have a limited term, the term may run close to the commercial sale of the related product, the commercial value of the Company’s patents may be limited;
● the Company may fail to develop additional proprietary technologies that are patentable;
● the laws of certain countries may not protect the Company’s intellectual property rights to the same extent as the laws of the United States, or the Company may fail to apply for or obtain adequate intellectual property protection in all the jurisdictions in which it operates; and
● third-party patents may have an adverse effect on the Company’s business, for example by preventing the Company from marketing one or more of its planned product candidates for one or more indications.
Any of the aforementioned threats to the Company’s competitive advantage could have a material adverse effect on its business.
In addition, patents have a limited lifespan. In the United States, if all maintenance fees are timely paid, the expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date. Various patent term extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering the Company’s product candidates are obtained, once the patent life has expired, the Company may be open to competition from competitive products. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, the Company’s owned and licensed patents may not provide the Company with sufficient rights to exclude others from commercializing products similar or identical to the Company’s. Further, recent judicial decisions in the U.S. raised questions regarding the award of patent term adjustment (“PTA”) for patents in families where related patents have issued without PTA. Thus, it cannot be said with certainty how PTA will be viewed in the future and whether patent expiration dates may be impacted.
Changes in patent laws or patent jurisprudence could diminish the value of patents in general, thereby impairing ESSA’s ability to protect its planned products.
The patent positions of pharmaceutical and biotechnology companies can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved. Changes in either the patent laws or in the interpretations of patent laws in the United States and other countries may diminish the value of the Company’s intellectual property. The Company cannot predict the breadth of claims that may be allowed or found to be enforceable in its patents (including patents owned by or licensed to the Company), in the Company’s strategic partners’ patents or in third-party patents. Recent U.S. Supreme Court rulings have either narrowed the scope of patent protection available in certain circumstances or weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to the Company’s ability to obtain patents in the future, this has created uncertainty with respect to the validity, scope and value of patents, once obtained.
In September 2011, the Leahy-Smith America Invents Act, also known as the America Invents Act (“AIA”), was signed into law. An important change introduced by the AIA is that, as of March 16, 2013, the United States transitioned to a first inventor to file system for deciding which party should be granted a patent when two or more patent applications are filed by different parties disclosing or claiming the same invention. A third party that has filed, or files a patent application in the USPTO after March 16, 2013, but before the Company’s, could be awarded a patent covering a given invention, even if the Company had made the invention before it was made by the third party. This requires the Company to be cognizant of the time from invention to filing of a patent application.
Depending on decisions by the U.S. Congress, the U.S. federal courts, the USPTO or similar authorities in foreign jurisdictions, the laws and regulations governing patents could change in unpredictable ways that may weaken the Company’s and the Company’s licensors’ ability to obtain new patents or to enforce existing patents the Company and the Company’s licensors or partners may obtain in the future.
Risks Related to ESSA’s Business and Industry
ESSA may not be successful in identifying and implementing any strategic transaction and any strategic transaction that it may consummate in the future may not be successful.
On October 31, 2024, ESSA announced that it decided to terminate its Phase 2 clinical trial evaluating in a 2:1 randomization masofaniten (EPI-7386) combined with enzalutamide versus enzalutamide single agent in patients with mCRPC naïve to second-generation antiandrogens. This decision, mutually agreed upon by both senior management and the Board, 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 (EPI-7386) plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study.
As part of its efforts to focus its resources, ESSA also announced that the other remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) either as a monotherapy or in combination with other agents will be terminated. ESSA also decided to withdraw its IND and CTAs that have been submitted to date. In connection with these events, ESSA has initiated a comprehensive review process to review its strategic options to maximize shareholder value.
These strategic options may include, but are not limited to, a merger, amalgamation, arrangement, reverse take-over, business combination, asset sale or acquisition, shareholder distribution, wind-down, liquidation and dissolution or other strategic transaction or the operation of its business and election to seek new product candidates for development. However, there can be no assurance that ESSA will be able to successfully consummate any particular strategic transaction, or any transaction at all. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we may incur significant costs related to this continued evaluation. ESSA may also incur additional unanticipated expenses in connection with this process. A considerable portion of these costs will be incurred regardless of whether any such course of action is implemented or transaction is completed. Any such expenses will decrease the remaining cash available for use in ESSA’s business and may diminish or delay any future distributions to our shareholders.
In addition, there can be no assurances that any particular course of action, business arrangement or transaction, or series of transactions, will be pursued, successfully consummated, lead to increased shareholder value, or achieve the anticipated results. Any failure of such potential transaction to achieve the anticipated results could significantly impair ESSA’s ability to enter into any future strategic transactions and may significantly reduce or delay any future distributions to ESSA’s shareholders.
ESSA may not realize any additional value in a strategic transaction.
ESSA’s market capitalization is below the value of its current cash, cash equivalents and investments. Potential counterparties in a strategic transaction involving ESSA may place minimal or no value on our assets, including those related to masofaniten (EPI-7386). Further, the development and any potential commercialization of ESSA’s product candidate would require substantial additional cash to fund the costs associated with conducting the necessary preclinical and clinical testing and obtaining regulatory approval. Consequently, any potential counterparty in a strategic transaction involving ESSA may choose not to spend the additional resources necessary to continue developing its product candidates and may attribute little or no value, in such a transaction, to those product candidates.
If ESSA is successful in completing a strategic transaction, it may be exposed to other operational and financial risks.
Although there can be no assurance that a strategic transaction will result from the process ESSA has undertaken to assess strategic options, the negotiation and consummation of any such transaction will require significant time on the part management, and the diversion of management’s attention may disrupt the orderly operation of the Company.
The negotiation and consummation of any such transaction may also require more time or greater cash resources than ESSA anticipates and expose it to other operational and financial risks, including, but not limited to:
● increased near-term and long-term expenditures;
● exposure to unknown liabilities;
● higher than expected acquisition, disposition or integration costs;
● incurrence of substantial debt or dilutive issuances of equity securities to fund future operations;
● write-downs of assets or incurrence of non-recurring, impairment or other charges;
● inability to retain key employees of our company; and
● possibility of future litigation.
Any of the foregoing risks could have a material adverse effect on ESSA’s business, financial condition and prospects.
ESSA’s decision to discontinue development of masofaniten and any related reduction in its workforce may not result in any anticipated savings and could disrupt ESSA’s business.
In October 2024, ESSA made the decision to discontinue development of masofaniten and the Board approved a comprehensive review of strategic options to maximize shareholder value. ESSA may not realize, in full or in part, the anticipated benefits and savings in operating expenses from these decisions due to unforeseen difficulties, delays or unexpected costs. This may include higher than expected costs associated with winding down ESSA’s ongoing clinical studies. If ESSA is unable to realize the expected cost savings, its financial condition would be adversely affected and it may be more difficult to complete a potential strategic transaction. Furthermore, any reduction in ESSA’s workforce may result in weaknesses in its infrastructure and operations and may increase the risk that we become unable to comply with legal and regulatory requirements.
ESSA may decide to pursue a dissolution and liquidation. In such an event, the amount of cash available for distribution to shareholders will depend heavily on the timing of such liquidation as well as the amount of cash that will need to be distributed for outstanding liabilities.
There can be no assurance that a strategic transaction will be completed and the Board may decide to pursue a dissolution and liquidation. In such an event, the amount of cash available for distribution to ESSA’s shareholders will depend heavily on the timing of such decision, the amount of any outstanding liabilities and, as with the passage of time, the amount of cash available for distribution will be reduced as ESSA continues to fund its operations. In addition, ESSA may be subject to litigation or other claims related to a dissolution and liquidation. Accordingly, holders of ESSA’s Common Shares could lose all or a significant portion of their investment in the event of a liquidation, dissolution or winding up.
ESSA’s ability to consummate a strategic transaction depends on its ability to retain its employees required to consummate such transaction.
ESSA’s ability to consummate a strategic transaction depends upon its ability to retain its employees required to consummate such a transaction, and the loss of such employees’ services may adversely impact the ability to consummate such transaction. In November 2024, we implemented a reduction in our workforce designed to substantially reduce our operating expenses while we undertake a comprehensive review of strategic options to maximize shareholder value. ESSA’s cash conservation activities may yield unintended consequences, such as attrition beyond its planned reduction in workforce and reduced employee morale, which may cause remaining employees to seek alternative employment. ESSA’s ability to successfully complete a strategic transaction depends in large part on its ability to retain its remaining personnel. If ESSA is unable to successfully retain its remaining personnel, it is at risk of a disruption to ESSA’s exploration and consummation of strategic options as well as business operations.
ESSA may become involved in securities class action litigation that could divert management’s attention and harm ESSA’s business, and insurance coverage may not be sufficient to cover all costs and damages.
In the past, securities class action litigation has often followed the announcement of certain significant business transactions, such as the sale of a company or announcement of any other strategic transaction, or the announcement of negative events, such as negative results from clinical trials. These events may also result in or be concurrent with investigations by regulatory authorities. ESSA may be exposed to such litigation or investigation even if no wrongdoing occurred. Litigation and investigations are usually expensive and divert management’s attention and resources, which
could adversely affect ESSA’s business and cash resources and its ability to consummate a potential strategic transaction or the ultimate value ESSA’s shareholders receive in any such transaction.
ESSA and its collaborators are subject to evolving global laws and regulations relating to privacy, data protection and information security, which may require them to incur substantial compliance costs, and any failure or perceived failure by ESSA and its collaborators to comply with such laws and regulations may harm ESSA’s business and operations.
In the ordinary course of business, ESSA and its clinical research organizations (“CROs”), collaborators, contractors or consultants, among others, process personal data and other sensitive information, including its proprietary and confidential business data, trade secrets, intellectual property, data about trial participants collected in connection with clinical trials and other sensitive data. ESSA’s data processing activities subject it to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contracts and other obligations that govern the processing of personal data by ESSA and on its behalf.
In Canada, where ESSA is headquartered, federal and provincial legislation impose strict requirements for the processing of personal data of individuals, with substantial penalties for noncompliance. In the U.S., federal, state and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, and consumer protection laws. For example, the U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, imposes specific requirements relating to the privacy, security and transmission of individually identifiable health information that apply to most U.S. health care providers with which ESSA interacts, such as its U.S. clinical trial sites. At the state level, the California Consumer Privacy Act of 2018 (“CCPA”), as amended and supplemented by the California Privacy Rights Act, imposes obligations on businesses to which it applies. The CCPA allows for statutory fines for noncompliance. Although the CCPA exempts some data processed in the context of clinical trials, the CCPA, to the extent applicable to our business and operations, may increase compliance costs and potential liability with respect to other personal information ESSA maintains about California residents. Other states have also enacted data privacy laws. Additional data privacy and security laws have been proposed at the federal, state and local levels in recent years, which could further complicate compliance efforts.
Outside the U.S., the European Union’s General Data Protection Regulation, (“EU GDPR”), and the United Kingdom’s GDPR, or UK GDPR, impose strict requirements for processing the personal data of individuals. For example, under the EU GDPR, government regulators may impose temporary or definitive bans on data processing, as well as fines of up to €20 million or 4% of annual global revenue, whichever is greater. Further, individuals may initiate litigation related to ESSA’s, or its third-party collaborators’, processing of their personal data. Certain foreign jurisdictions have enacted data localization laws and cross-border personal data transfer laws, which could make it more difficult to transfer information across jurisdictions, such as transferring or receiving personal data that originates in the European Union, or EU. Additional jurisdictions continue to enact and modify their data privacy laws, which increases the complexity of the data privacy landscape.
Although ESSA endeavors to comply with all applicable data privacy and security obligations, these obligations are quickly changing in an increasingly stringent fashion, creating some uncertainty as to how to comply and potentially requiring ESSA to modify its policies and practices, which may be costly and may divert the attention of management and technical personnel. Further, ESSA or its third-party collaborators may at times fail, or be perceived to have failed, to have complied and could face significant consequences. These consequences may include, but are not limited to, government enforcement actions, investigations and other proceedings; additional reporting requirements and/or oversight; bans on processing personal data; orders to destroy or not use personal data; and imprisonment of company officials. Any of these events could have a material adverse effect on ESSA’s reputation, business or financial condition, including but not limited to: interruptions or stoppages in its business operations, including its clinical trials; inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize its products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or revision or restructuring of its operations.
ESSA’s business and operations could suffer in the event of an actual or perceived information security incident such as a cybersecurity breach, system failure, or other compromise of its systems and/or information, including information held by a third-party contractor or vendor.
ESSA relies on both internal information technology systems and networks, and those of third-party vendors and contractors including, but not limited to, ESSA’s CROs, collaborators, contractors or consultants, to acquire, transmit, store and otherwise process information in connection with its business activities. ESSA’s ability to effectively manage its business depends on the security, reliability and adequacy of its and its third-party vendors’ and collaborators’ technology systems. Any incident, whether hostile or inadvertent, that adversely impacts the confidentiality, integrity or availability of its systems and/or data, including phishing, business email compromise, social engineering, ransomware or other malware, or any security breach, security incident or other destruction, loss, or unauthorized use or other processing of data maintained or otherwise processed by ESSA or on its behalf could result in a loss of intellectual property or misappropriation of trade secrets, disruptions to its business and operations, subject it to increased costs and require it to expend time and resources to address the matter, may subject it to claims, demands, and proceedings by private parties, regulatory investigations and other proceedings, and fines, penalties, and other liability and have a material adverse effect on ESSA’s business. In addition, the loss, alteration or other damage to or other unavailability of preclinical data or clinical trial data from completed or ongoing clinical trials for ESSA’s planned product candidates could result in delays in its development and regulatory approval efforts and significantly increase its costs to recover or reproduce the data. Any cyber-attack, security breach or incident, or other destruction, loss or unauthorized processing of data maintained or otherwise processed by ESSA or on its behalf, or the perception any such matter has occurred, could result in actual or alleged violations of applicable U.S. and international privacy, data protection, information security and other laws and regulations, harm ESSA’s reputation and subject it to litigation and governmental investigations and proceedings by federal, state and local regulatory entities in the U.S. and by international regulatory entities, resulting in exposure to material civil and/or criminal proceedings and liability. In addition, ESSA may incur significant additional expense to implement further measures relating to privacy, data protection and information security, whether in response to an actual or perceived security breach or incident or otherwise.
To date, ESSA has not experienced any material impact to its business, financial position or operations resulting from cyberattacks or other information security incidents; however, because of frequently changing attack techniques, along with the increased volume and sophistication of such attacks, ESSA’s business, financial position or operations could be adversely impacted in the future. Moreover, the increasingly distributed nature of computing, including prevalent use of mobile devices to access confidential information and widespread use of cloud-based applications hosted in remote data centers, increases the risk of security breaches and incidents. These risks may be heightened due to the increasing number of ESSA’s and its third-party vendors’ and collaborators’ personnel working remotely. As cyber threats continue to evolve, ESSA may be required to expend significant additional resources to continue to modify or enhance its protective measures or to investigate and remediate information security vulnerabilities, threats and incidents. While ESSA has implemented layered security measures, its computer systems and the external systems and services used by its third-party CMOs and CROs and their vendors and contractors remain potentially vulnerable to these events and there can be no assurance that ESSA will be successful in preventing cyber-attacks or successfully mitigating their effects. ESSA’s insurance policies may not be adequate to compensate ESSA for the potential loss arising from such incidents or security breaches. In addition, such insurance may not be available to ESSA in the future on economically reasonable terms, or at all. Further ESSA’s insurance may not cover all claims made against ESSA and could have high deductibles in any event, and defending a suit, regardless of its merit, could be costly and divert management attention. While ESSA has invested in the protection of data and information technology, there can be no assurance that ESSA’s efforts, or those of ESSA’s third-party collaborators, if any, to implement adequate security and quality control measures for data processing would be sufficient to protect against data deterioration or loss in the event of a system malfunction, or to prevent data from being stolen or corrupted in the event of a security breach.
Business disruptions could seriously harm ESSA’s future revenues and financial condition and increase costs and expenses.
ESSA’s operations and the operations of third parties whom ESSA depend upon, could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics and other natural or manmade disasters or business interruptions, for which ESSA is predominantly self-insured. Although ESSA carries insurance for earthquakes and other natural disasters, ESSA may not carry sufficient
business interruption insurance to compensate the Company for all losses that may occur. The disaster recovery and business continuity plans ESSA has in place may not be adequate in the event of a serious disaster or similar event. ESSA does not carry insurance for all categories of risk that ESSA’s business may encounter. The occurrence of any of these business disruptions could seriously harm ESSA’s operations and financial condition and increase costs and expenses. Further, any significant uninsured liability may require ESSA to pay substantial amounts, which would adversely affect ESSA’s business, results of operations, financial condition and cash flows from future prospects.
The directors and officers of ESSA may be subject to conflicts of interest.
Some of the directors and officers are engaged and will continue to be engaged in the search for additional business opportunities on behalf of other corporations and situations may arise where these directors and officers will be in direct competition with the Company. Not all of the Company’s directors or officers are subject to non-competition agreements. Some of the directors and officers of the Company are or may become directors or officers of the other companies engaged in other business ventures whose operations may, from time to time, be in direct competition with ESSA’s operations. Conflicts, if any, will be dealt with in accordance with the relevant provisions of the Business Corporations Act (British Columbia) and under the Company’s articles of incorporation.
The Company may face exposure to adverse movements in foreign currency exchange rates.
ESSA’s business may expand internationally and as a result, a significant portion of its revenues, expenses, current assets and current liabilities may be preliminary denominated in foreign currencies, while its financial statements are expressed in U.S. dollars. A decrease in the value of such foreign currencies relative to the U.S. dollar could result in losses in revenues from currency exchange rate fluctuations. To date, ESSA has not hedged against risks associated with foreign exchange rate exposure. ESSA cannot be sure that any hedging techniques it may implement in the future will be successful or that its business, financial condition, and results of operations will not be materially adversely affected by exchange rate fluctuations.
The Company may acquire businesses or products or form strategic alliances in the future and the Company may not realize the benefits of such acquisitions.
The Company may acquire additional businesses or products, form strategic alliances or create joint ventures with third parties that the Company believes will complement or augment its existing business.
If the Company acquires businesses in the future, it may not be able to realize the benefit of acquiring such businesses if the Company is unable to successfully integrate them with its existing operations and company culture. The Company may encounter numerous difficulties in developing, manufacturing and marketing any new products resulting from a strategic alliance or acquisition that delay or prevent the Company from realizing their expected benefits. The potential failure of the due diligence processes to identify significant problems, liabilities or other shortcomings or challenges with respect to intellectual property, product quality, revenue recognition or other accounting practices, taxes, corporate governance and internal controls, regulatory compliance, employee, customer or partner disputes or issues and other legal and financial contingencies could decrease or eliminate the anticipated benefits and synergies of any acquisition and could negatively affect ESSA’s future business and financial results.
As part of ESSA’s business strategy, it may also acquire additional companies, products or technologies principally related to, or complementary to, ESSA’s current operations.
Also, the anticipated benefit of any joint venture or acquisition may not materialize or such strategic alliance, joint venture or acquisition may be prohibited. Additionally, future acquisitions or dispositions could result in potentially dilutive issuances of ESSA’s equity securities, the incurrence of debt, contingent liabilities or amortization expenses or write-offs of goodwill, any of which could harm ESSA’s financial condition. ESSA cannot predict the number, timing or size of future joint ventures or acquisitions, or the effect that any such transactions might have on its operating results.
ESSA may not be able to successfully overcome these risks and other problems associated with acquisitions and this may adversely affect ESSA’s business, financial condition or results of operations.
ESSA’s employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could cause significant liability for ESSA and harm ESSA’s reputation.
ESSA is exposed to the risk that its employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs suppliers and vendors may engage in misconduct or other improper activities. Misconduct by these parties could include failures to comply with FDA regulations or similar regulations of comparable foreign regulatory authorities, provide accurate information to the FDA or comparable foreign regulatory authorities, comply with manufacturing standards ESSA has established, comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and enforced by comparable foreign regulatory authorities, report financial information or data accurately or disclose unauthorized activities to ESSA. Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to ESSA’s reputation. It is not always possible to identify and deter misconduct by these parties, and the precautions ESSA takes to detect and prevent these activities may not be effective in controlling unknown or unmanaged risks or losses in protecting ESSA from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against ESSA and ESSA is not successful in defending itself or asserting ESSA’s rights, those actions could have a significant impact on ESSA’s business, including the imposition of significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from government funded healthcare programs, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings and the curtailment and restructuring of the Company’s operations.
If product liability lawsuits are brought against the Company or its strategic partners, it may incur substantial liabilities and may be required to cease or limit the sale, marketing and distribution of its product candidate and potential future products.
The Company or its strategic partners could face a potential risk of product liability as a result of its potential sales, marketing and distribution activities relating to any future commercialization of any future product. For example, the Company may be sued if any product it develops allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under U.S. state or Canadian provincial or other foreign consumer protection legislation. If the Company cannot successfully defend itself against product liability claims, it may incur substantial liabilities or be required to cease or limit the sale, marketing and distribution of its products. Even successful defense against product liability claims would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims may result in:
● decreased demand for any future products that the Company may develop;
● injury to the Company’s reputation;
● withdrawal of clinical trial participants;
● costs to defend the related litigation;
● a diversion of management’s time and the Company’s resources;
● substantial monetary awards to consumers, trial participants or patients;
● product recalls, withdrawals or labeling, marketing or promotional restrictions;
● loss of revenue;
● the inability to commercialize;
● the inability to continue the sale, marketing and distribution of ESSA’s product candidate and potential future products; and
● a decline in the price of the Common Shares or other outstanding securities.
The Company currently maintains insurance that it believes has sufficient coverage to protect against the liability risks discussed above and the Company believes this coverage is consistent with industry norms for companies at a similar stage of development. However, if the Company is unable to obtain and retain sufficient product liability insurance in the future
at an acceptable cost to protect against potential product liability claims, the commercialization of potential products it develops could be hindered or prevented.
ESSA incurs significantly increased costs and devotes substantial management time as a result of operating as a public company.
As a public company, ESSA incurs significant legal, accounting and other expenses. For example, ESSA is subject to the reporting requirements of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) the Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act and the listing requirements of the Nasdaq Stock Market LLC, as well as rules and regulations subsequently implemented by the SEC and including the establishment and maintenance of effective disclosure and financial controls and changes in corporate governance practices. ESSA’s continued compliance with these requirements increase its legal and financial compliance costs and make some activities more time consuming and costly. In addition, ESSA’s management and other personnel need to divert attention from operational and other business matters to devote substantial time to these public company requirements. In particular, ESSA may or in the future incur significant expenses and devote substantial management effort toward ensuring compliance with the requirements of Section 404 of Sarbanes-Oxley, which involves annual assessments of a company’s internal controls over financial reporting. ESSA may in the future need to hire additional accounting and financial staff with appropriate public company experience and technical accounting knowledge and may need to establish an internal audit function. ESSA cannot always predict or estimate the amount of additional costs incurred as a result of being a public company or the timing of such costs.
ESSA is a smaller reporting company and a non-accelerated filer, and the reduced disclosure requirements available to ESSA may make ESSA’s Common Shares less attractive to investors.
Under the SEC rules, smaller reporting companies (“SRCs”) may choose to comply with scaled financial and non-financial disclosure requirements in their annual and quarterly reports and registration statements relative to non-SRCs. In addition, companies that are not “accelerated filers” can take advantage of additional regulatory relief. Whether a company is an accelerated filer or a SRC is determined on an annual basis. For so long as ESSA qualifies as a non-accelerated filer and/or a SRC, ESSA will be permitted to and intends to rely on some or all of the accommodations available to such companies. These accommodations include:
● not being required to provide an auditor’s attestation of management’s assessment of internal control over financial reporting required by Section 404(b) of the Sarbanes-Oxley Act of 2002;
● reduced financial disclosure obligations, including that SRCs need only provide two years of financial statements rather than three years; a maximum of two years of acquiree financial statements are required rather than three years; fewer circumstances under which pro forma financial statements are required; and less stringent age of financial statements requirements;
● reduced non-financial disclosure obligations, including regarding the description of their business, management’s discussion and analysis of financial condition and results of operations, market risk, executive compensation, transactions with related persons, and corporate governance; and
● later deadlines for the filing of annual and quarterly reports compared to accelerated filers.
ESSA will continue to qualify as a SRC and non-accelerated filer for so long as (a) ESSA’s public float is less than $75 million as of the last day of its most recently completed second fiscal quarter or (b) ESSA’s public float is $75 million or more but less than $700 million and it reported annual revenues of less than $100 million for its most recently completed fiscal year.
ESSA may choose to take advantage of some, but not all, of the available accommodations. ESSA cannot predict whether investors will find ESSA’s Common Shares less attractive if ESSA relies on these accommodations. If some investors find ESSA’s Common Shares less attractive as a result, there may be a less active trading market for ESSA’s Common Shares and the price of ESSA’s Common Shares may be more volatile.
Risks Related to Additional Legal Compliance and Regulatory Matters
ESSA is subject to risks inherent in foreign operations.
ESSA is subject to a number of risks associated with its potential international business operations, sales and marketing activities that may increase liability, costs, lengthen sales cycles and require significant management attention. These risks include:
● compliance with the laws of the United States, Canada, the European Union and other jurisdictions where ESSA may conduct business, including import and export legislation;
● increased reliance on third parties to establish and maintain foreign operations;
● the complexities and expenses of administering a business abroad;
● complications in compliance with, and unexpected changes in, foreign regulatory requirements;
● instability in economic or political conditions, including inflation, recession and actual or anticipated military conflicts, social upheaval or political uncertainty, including as a result of the conflicts between Russia and Ukraine and in the Middle East;
● foreign currency fluctuations;
● foreign exchange controls and cash repatriation restrictions;
● tariffs and other trade barriers;
● difficulties in collecting accounts receivable;
● differing tax structures and related potential adverse tax consequences;
● uncertainties of laws and enforcement relating to the protection of intellectual property or secured technology;
● litigation in foreign court systems;
● unauthorized copying or use of ESSA’s intellectual property;
● cultural and language differences;
● difficulty in managing a geographically dispersed workforce in compliance with local laws and customs that vary from country to country; and
● other factors, depending upon the country involved.
There can be no assurance that the policies and procedures ESSA implements to address or mitigate these risks will be successful, that ESSA’s personnel will comply with them or that ESSA will not experience these factors in the future or that they will not have a material adverse effect on ESSA’s business, results of operations and financial condition.
In addition, there is currently significant uncertainty about the future relationship between the United States and various other countries, most significantly China, with respect to trade policies, treaties, tariffs, taxes, and other limitations on cross-border operations. The U.S. government has made and continues to make significant additional changes in U.S. trade policy and may continue to take future actions that could negatively impact U.S. trade. For example, legislation has been introduced in Congress to limit certain U.S. biotechnology companies from using equipment or services produced or provided by select Chinese biotechnology companies, and others in Congress have advocated for the use of existing executive branch authorities to limit those Chinese service providers’ ability to engage in business in the U.S. ESSA cannot predict what actions may ultimately be taken with respect to trade relations between the United States and China or other countries, including countries which the U.S. government has identified as a foreign adversary that poses national security risks to the United States, and what products and services may be subject to such actions or what actions may be taken by the other countries in retaliation. If ESSA is unable to obtain or use services from existing or new service providers or become unable to export or sell its potential products to any of its customers or service providers, ESSA’s business, liquidity, financial condition, and/or results of operations may be materially and adversely affected.
If ESSA fails to comply with environmental, health and safety laws and regulations, ESSA could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of ESSA’s business.
ESSA is subject to numerous environmental, health and safety laws and regulations in the United States and in Canada, and may in the future involve, the handling, use, storage, treatment and disposal of hazardous materials and wastes. ESSA’s operations could involve the use of hazardous and flammable materials, including chemicals and biological materials. ESSA’s operations could also produce hazardous waste products. The Company’s general practice would be to contract with third parties for the disposal of such materials and wastes. ESSA cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from ESSA’s use of hazardous materials, it could be held liable for any resulting damages, and any liability could exceed its resources. ESSA also could incur significant costs associated with civil or criminal fines and penalties.
Although ESSA maintains workers’ compensation insurance to cover for costs and expenses ESSA may incur due to injuries to employees resulting from the use of any hazardous materials, this insurance may not provide adequate coverage against potential liabilities. ESSA does not maintain insurance for environmental liability or toxic tort claims that may be asserted against it in connection with its storage or disposal of biological or hazardous materials.
In addition, ESSA may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair any of ESSA’s planned research, development or production efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.
ESSA is and there is a risk that ESSA may continue to be a “passive foreign investment company” which would likely result in materially adverse U.S. federal income tax consequences for U.S. investors.
ESSA believes it was classified as a passive foreign investment company (“PFIC”) for the taxable year ending September 30, 2024 and believes it may be classified as a PFIC for the current taxable year and in future taxable years. However, the determination as to whether ESSA is a PFIC for any taxable year is based on the application of complex U.S. federal income tax rules that are subject to differing interpretations. If ESSA is a PFIC for any taxable year during which a U.S. Holder (as defined under “United States Income Tax Considerations”) holds the Common Shares, it would likely result in adverse U.S. federal income tax consequences for such U.S. Holder. U.S. Holders should carefully read “United States Income Tax Considerations-Passive Foreign Investment Company Rules” for more information and consult their own tax advisors regarding the consequences of ESSA being treated as a PFIC for U.S. federal income tax purposes, including the advisability of making a qualified electing fund (“QEF”) election (including a protective election), which may mitigate certain possible adverse U.S. federal income tax consequences but may result in an inclusion in gross income without receipt of such income.
It may be difficult for United States investors to effect services of process or enforcement of actions against the Company or certain of its directors and officers under U.S. federal securities laws.
The Company is incorporated under the laws of the Province of British Columbia, Canada. Its directors and officers reside in Canada or the United States. Because a number of these persons and a substantial portion of the assets of the Company are located outside the United States, it will be difficult for United States investors to effect service of process in the United States upon the Company and its directors and officers, or to enforce judgments obtained against the Company or such persons in United States courts, in any action, including actions predicated upon the civil liability provisions of the United States federal securities laws or any other United States laws. Additionally, rights predicated solely upon civil liability provisions of United States federal securities laws or any other laws of the United States may not be enforceable in original actions, or actions to enforce judgments obtained in United States courts, brought in a Canadian court including courts in the Province of British Columbia.
Risks Relating to ESSA’s Common Shares
The market price and trading volume of ESSA’s Common Shares may be volatile, which could result in rapid and substantial losses for its shareholders or securities litigation.
The market price of ESSA’s Common Shares may be highly volatile and could be subject to wide fluctuations, in response to various factors, some of which ESSA cannot control. The stock market in general, and pharmaceutical and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of ESSA’s Common Shares, regardless of ESSA’s actual operating performance. In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual report, these factors include:
● the decision to discontinue clinical trials and studies related to masofaniten (EPI-7386);
● evaluation of strategic alternatives to maximize shareholder value;
● quarterly variations in operating results;
● operating results that vary from the expectations of securities analysts and investors;
● change in valuations;
● changes in ESSA’s operations;
● expenses ESSA incurs related to future research, if any;
● regulatory approvals;
● fluctuations in the demand for ESSA’s planned product candidates;
● changes in the industry in which ESSA operates;
● announcements by ESSA or other companies of significant contracts, acquisitions, dispositions, strategic partnerships, joint ventures, capital commitments, plans, prospects, service offerings or operating results;
● results of clinical studies of our planned product candidates, including our combination studies, or those of our competitors;
● additions or departures of key personnel;
● future sales of ESSA’s securities;
● trading of ESSA’s securities by a large shareholder;
● instances of shareholder activism;
● other risk factors discussed herein; and
● other unforeseen events.
Stock markets in the United States and Canada have experienced extreme price and volume fluctuations. Market fluctuations, as well as general political and economic conditions, such as acts of terrorism, prolonged economic uncertainty, a recession or interest rate or currency rate fluctuations, could adversely affect the market price of ESSA’s Common Shares resulting in substantial losses for shareholders. Also, in the past, companies that have experienced volatility in the market price of their Common Shares have been subject to securities litigation. ESSA may be the target of this type of litigation in the future. Securities litigation against ESSA could result in substantial costs and divert management’s attention from other business concerns, which could materially harm ESSA’s business.
In recent years, shareholder activists have become involved in numerous public companies. Activists may, among other things, request one-on-one meetings with management, requisition the Board to call a special meeting of shareholders, nominate candidates for election to the Board or push ESSA to pursue a strategic combination or other transaction. Such actions may disrupt ESSA’s business and divert the attention of management and employees. In addition, any perceived uncertainties as to ESSA’s future direction resulting from such a situation could result in the loss of potential business opportunities, be exploited by its competitors, cause concern to its current or potential customers and make it more difficult to attract and retain qualified personnel and business partners, any of which could negatively impact its business. Shareholder activism could result in substantial costs and may cause significant fluctuations in the market price of ESSA’s Common Shares based on temporary or speculative market perceptions or other factors that do not necessarily reflect the underlying fundamentals of its business.
ESSA is at risk of securities class action litigation.
Securities class action litigation has often been brought against companies following a decline in the market price of their securities. This risk is especially relevant for ESSA because pharmaceutical companies have experienced significant share price volatility in recent years. ESSA is and may become in the future the target of securities litigation. The outcome of litigation is necessarily uncertain, and ESSA could be forced to expend significant resources in the defense of such suits, and it may not prevail. Monitoring and defending against legal actions is time-consuming for ESSA’s management and detracts from its ability to fully focus its internal resources on its business activities. In addition, ESSA may incur substantial legal fees and costs in connection with any such litigation. ESSA has not established any reserves for any potential liability relating to any such potential lawsuits. It is possible that ESSA could, in the future, incur judgments or enter into settlements of claims for monetary damages. ESSA currently maintains insurance coverage for some of these potential liabilities. Other potential liabilities may not be covered by insurance, insurers may dispute coverage or the amount of insurance may not be enough to cover damages awarded. In addition, certain types of damages may not be covered by insurance, and insurance coverage for all or certain forms of liability may become unavailable or prohibitively expensive in the future. A decision adverse to ESSA’s interests on one or more legal matters or litigation could result in the payment of substantial damages, or possibly fines, and could have a material adverse effect on its reputation, financial condition and results of operations.
ESSA’s management has broad discretion over the use of its cash and may not use our cash effectively, which could adversely affect ESSA’s results of operations.
ESSA’s management has broad discretion in the application of its cash resources. Shareholders may not agree with ESSA’s decisions, and ESSA’s use of its cash resources may not improve its results of operation or enhance the value of the Common Shares. ESSA’s failure to apply these funds effectively could have a material adverse effect on its business, delay the development of its product candidates and cause the market price of the Common Shares to decline. In addition, pending their use, they may be placed in investments that do not produce significant income or that may lose value.
The Company has never declared dividends and may not do so in the future.
ESSA has not declared or paid any cash dividends on Common Shares to date. The payment of dividends in the future will be dependent on ESSA’s earnings and financial condition and on such other factors as ESSA’s Board considers appropriate. Unless and until ESSA pays dividends, shareholders may not receive a return on their shares. There is no present intention by the Board to pay dividends on the Common Shares.
The Company may experience future sales or issue additional securities.
The market price of the Company’s equity securities could decline as a result of issuances of securities by the Company or sales by the Company’s existing shareholders of Common Shares in the market, or the perception that such sales could occur. Sales of Common Shares by shareholders might also make it more difficulty for the Company to sell equity securities at a time and price that the Company deems appropriate. Sales or issuances of substantial numbers of Common Shares, or the perception that such sales could occur, may adversely affect the prevailing market prices of the Common Shares. With any additional sale or issuance of Common Shares, investors will suffer dilution to their voting power and the Company may experience dilution in its earnings per share.
Additionally, as of September 30, 2024, there are 2,920,000 pre-funded warrants outstanding, which are exercisable into Common Shares at a nominal exercise price. If holders of these pre-funded warrants exercise these securities, existing shareholders will suffer dilution to their voting power and the Company may experience dilution in its earnings per share, as well as a negative impact on its share price.
An active trading market for the Common Shares may not be sustained.
Although ESSA has listed the Common Shares on the Nasdaq, an active trading market for the Common Shares may not be sustained. If an active trading market for the Common Shares is not maintained, the liquidity of the Common Shares and the prices that may be obtained for the Common Shares will be adversely affected. As of September 30, 2024, ESSA’s public float, which is defined as Common Shares outstanding minus Common Shares held by officers, directors, or beneficial holders of greater than 10% of ESSA’s outstanding Common Shares, represented approximately 60.17% of
ESSA’s outstanding Common Shares. In addition, the Company is aware of a number of significant shareholders, defined as a holding greater than 5%, who have participated in recent financings. The average number of shares traded in any given day over the past year has been relatively small compared to the public float. Thus, the actions of a few shareholders either buying or selling ESSA’s Common Shares may adversely affect the price of the Common Shares. Historically, securities similar to ESSA’s Common Shares have experienced extreme price and volume fluctuations that do not necessarily relate to operating performance and could result in rapid and substantial losses for shareholders.
General Risk Factors
Unstable market and economic conditions may have serious adverse consequences on our business and financial condition.
Global credit and financial markets have at times experienced extreme disruptions, characterized by increased market volatility, increased rates of inflation, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. Similarly, the current conflicts between Ukraine and Russia and in the Middle East, as well as recent failures in the global banking sector, have created volatility in the capital markets and are expected to have further global economic consequences. Limited liquidity, defaults, non-performance and other adverse developments affecting financial institutions or parties with which ESSA does business, or perceptions regarding these or similar risks, have in the past and may in the future lead to market-wide liquidity problems. For example, in March 2023, Silicon Valley Bank was closed and placed into receivership and, subsequently, additional financial institutions have been placed into receivership. There is no guarantee that the U.S. government or governments in other jurisdictions will intervene to provide access to uninsured funds in the future in the event of the failure of other financial institutions, or that the U.S. government or governments in other jurisdictions would do so in a timely fashion. If another such disruption in credit and financial markets and deterioration of confidence in economic conditions occurs, ESSA’s business may be adversely affected. If the equity and credit markets were to deteriorate significantly in the future, including as a result of a resurgence of a pandemic, political unrest or war or further instability of the global banking sector, it may make any necessary equity or debt financing more difficult to complete, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on ESSA’s growth strategy, financial performance and the market price of the Common Shares and could require it to delay or abandon development or commercialization plans. In addition, there is a risk that one or more of ESSA’s current collaborators, service providers, manufacturers and other partners would not survive or be able to meet their commitments to ESSA under such circumstances, which could directly affect ESSA’s ability to attain its operating goals on schedule and on budget.
Widespread health concerns, pandemics or epidemics, and other outbreaks of illness may negatively affect the Company’s ability to maintain operations and execute its business plan.
Widespread health concerns, pandemics, and other outbreaks of illness, particularly in North America but also globally, can have evolving and uncertain impacts on our business. In March 2020, the Company made the decision to transition employees to primarily remote working arrangements. This continues to the present, but the Company has taken steps to maintain internal communication, and operations have thus far continued on schedule and with minimal interruption. Although COVID-19 did not have any material adverse impact on the Company’s operations or financial condition, there can be no assurances that it, widespread health concerns, or other outbreaks of illness will not have an impact on the Company’s business, operations or financial condition going forward. The Company experienced significant delays in enrolling patients in its clinical trials, directly or indirectly related to COVID-19, resulting in resource constraints at clinical trial sites, as well as competition for patients with other studies being pursued by other entities. As a result of any widespread health concern, pandemic, or other outbreaks of illness, the Company may continue to experience disruptions that severely impact our business, commercialization, third party vendor operations, including foreign and domestic supply chains, or delays in clinical trial activities, including:
● delays or difficulties in initiating clinical trial sites;
● delays or difficulties in enrolling patients in our current and potential future clinical trials of masofaniten (EPI-7386);
● disruption to and delays in preclinical research and analysis activities due to an extended temporary closure of contract lab facilities;
● disruptions in supply, logistics or other activities related to the procurement of materials, which could have a negative impact on the Company’s ability to conduct preclinical studies, initiate or complete clinical trials or commercialize product candidates;
● diversion of healthcare resources away from conducting clinical trials;
● interruption of key preclinical studies and clinical trial activities, due to limitations on travel imposed or recommended by federal, state, provincial or municipal governments, employers and others;
● limitations in resources that would otherwise be focused on the conduct of the Company’s business or current or planned preclinical studies or clinical trials, including due to sickness, restrictions on travel, prolonged stay-at-home or shelter-in-place orders and other concerns;
● changes in regulations as part of a response to widespread health concerns, pandemics, or other outbreaks of illness, which may require the Company to change the ways in which the preclinical studies and clinical trials are conducted and incur unexpected costs, or requires the Company to discontinue our preclinical research or clinical trials altogether;
● delays in receiving regulatory approvals;
● delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or furlough of government or contractor personnel; and
● limitations on the Company’s ability to recruit preclinical research, clinical, regulatory and other professional staff on the timeframe required to support research and development programs.
Government and health authority intervention in the face of a widespread health concern, pandemic, or other outbreak of illness may vary greatly in the various geographic regions in which we operate. The extent to which a widespread health concern may impact our business, commercialization, preclinical studies, and clinical trials will depend on future developments, which are highly uncertain and cannot be predicted with confidence.
If ESSA is unable to implement and maintain effective internal control over financial reporting in the future, ESSA may not be able to report financial results accurately or prevent fraud. In that case, investors may lose confidence in the accuracy and completeness of ESSA’s financial reports and the market price of ESSA’s Common Shares may be negatively affected.
Maintaining effective internal control over financial reporting is necessary for ESSA to produce reliable financial reports and is important in helping to prevent financial fraud. If ESSA is unable to maintain adequate internal controls, ESSA’s business and operating results could be harmed.
Pursuant to Section 404(a) of the Sarbanes-Oxley Act and the related rules of the SEC, ESSA’s management is required to, among other things, assess annually the effectiveness of its internal control over financial reporting and certify that it has established effective disclosure controls and procedures and internal controls over financial reporting for the period ended September 30, 2024.
Preparing ESSA’s consolidated financial statements involves a number of complex manual and automated processes which are dependent on individual data input or review and require significant management judgment. One or more of these elements may result in errors that may not be detected and could result in a material misstatement of ESSA’s consolidated financial statements. Management’s significant estimates and judgments with respect to financial reporting are discussed and disclosed in the consolidated financial statements.
The process of designing and implementing effective internal controls and procedures, and expanding ESSA’s internal accounting capabilities, is a continuous effort that requires ESSA to anticipate and react to changes in ESSA’s business and the economic and regulatory environments and expend significant resources to establish and maintain a system of internal controls that is adequate to satisfy ESSA’s reporting obligations as a public company. The standards that must be met for management to assess the internal control over financial reporting as effective are complex, and require significant documentation, testing and possible remediation to meet the detailed standards. ESSA cannot be certain at this time whether the Company will be able to successfully complete the continuing implementation of controls and procedures or the certification and attestation requirements of Section 404(a) of Sarbanes-Oxley on a continuous basis.
If a material misstatement occurs in the future, ESSA may fail to meet its future reporting obligations, it may need to restate its financial results and the price of the Common Shares may decline. Any failure of ESSA’s internal controls could
also adversely affect the results of the periodic management evaluations and any future annual independent registered public accounting firm attestation reports regarding the effectiveness of ESSA’s internal control over financial reporting that may be required when Section 404 of Sarbanes-Oxley becomes fully applicable to ESSA. Effective internal controls are necessary for ESSA to produce reliable financial reports and are important to helping prevent financial fraud. If ESSA cannot provide reliable financial reports or prevent fraud, ESSA’s business and results of operations could be harmed, investors could lose confidence in ESSA’s reported financial information, and the trading price of ESSA’s Common Shares could drop significantly.
Provisions in ESSA's corporate charter documents and Canadian law could make an acquisition of the Company, which may be beneficial to ESSA's shareholders, more difficult and may prevent attempts by the shareholders to replace or remove ESSA's current management and/or limit the market price of the Common Shares.
Provisions in ESSA's articles, as well as certain provisions under the Business Corporations Act (British Columbia) or applicable Canadian securities laws may discourage, delay or prevent a merger, acquisition or other change in control of ESSA that shareholders may consider favorable, including transactions in which they might otherwise receive a premium for their Common Shares. These provisions could also limit the price that investors might be willing to pay in the future for ESSA’s Common Shares, thereby depressing the market price of ESSA’s Common Shares. In addition, because the Board is responsible for appointing the members of the Company's management team, these provisions may frustrate or prevent any attempts by ESSA's shareholders to replace or remove current management by making it more difficult for shareholders to replace members of the Board. Among other things, these provisions include the following:
● shareholders cannot amend ESSA's articles unless such amendment is approved by shareholders holding at least two-thirds of the votes cast on the proposal;
● the Board may, without shareholder approval, issue preferred shares having any terms, conditions, rights, preferences and privileges as the Board may determine;
● shareholders must give advance notice to nominate directors; and
● applicable Canadian securities laws generally require, subject to certain exceptions, a tender offer to remain open for a minimum of 105 days and that more than 50% of the outstanding securities not owned by the offeror be tendered before the offeror may take up the securities subject to the tender offer.
If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about ESSA’s business, its stock price and trading volume could decline.
The trading market for ESSA’s Common Shares depends in part on the research and reports that securities or industry analysts publish about it, or its business. If one or more of the securities or industry analysts who cover ESSA downgrade the Common Shares or publish inaccurate or unfavorable research about its business, its stock price would likely decline. If one or more of these analysts cease coverage of ESSA or fail to publish reports on it regularly, demand for ESSA’s stock could decrease, which might cause its stock price and trading volume to decline.

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ITEM 1B. UNRESOLVED STAFF COMMENTS
Item 1B. Unresolved Staff Comments
None.

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ITEM 2. PROPERTIES
Item 2. Properties
Our headquarters are located in Vancouver, British Columbia, where we rent office space on a short-term lease. Our U.S. offices are located in South San Francisco, California. In March 2018, we entered into a lease for the South San Francisco office that expired on March 31, 2021, and which we have extended to July 31, 2027.
We believe that our existing facilities are adequate for our immediate needs and can accommodate our anticipated growth. We believe that, should it be needed, additional space can be leased to accommodate any future growth.

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ITEM 3. LEGAL PROCEEDINGS
Item 3. Legal Proceedings
From time to time, we may become involved in legal proceedings or be subject to claims arising in the ordinary course of our business. As of September 30, 2024, we are not a party to any legal proceedings that, in the opinion of our management, would reasonably be expected to have a material adverse effect on our business, financial condition, operating results or cash flows if determined adversely to us. Regardless of the outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors.

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ITEM 4. MINE SAFETY DISCLOSURE
Item 4. Mine Safety Disclosures
Not applicable.
PART II

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ITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY
Item 5. Market for Registrant’s Common Equity, Related Shareholder Matters and Issuer Purchases of Equity Securities Market Information
Our Common Shares began trading on the Nasdaq under the symbol “EPIX” on July 9, 2015.
Nasdaq
High
Low
Quarter Ended
September 30, 2024
7.88
4.25
June 30, 2024
8.68
4.59
March 31, 2024
11.67
5.70
December 31, 2023
7.40
2.65
September 30, 2023
3.31
2.58
June 30, 2023
3.48
2.56
March 31, 2023
3.63
2.45
December 31, 2022
5.16
1.40
On December 16, 2024, the last reported sale price of our Common Shares on the Nasdaq was $1.63 per share.
Holders
As at December 16, 2024, there were approximately 346 holders of record of ESSA’s Common Shares. This number does not include beneficial owners whose shares are held in “street name” by banks, brokers, and other financial institutions.
Dividends
We have never paid any dividends on our Common Shares or any of our other securities. We currently intend to retain any future earnings to finance the growth and development of our business, and we do not anticipate that we will declare or pay any cash dividends in the foreseeable future. Any future determination to pay cash dividends will be at the discretion of our Board and will be dependent upon our financial condition, results of operations, capital requirements, restrictions under any future indebtedness and other factors the Board deems relevant.
Certain Canadian Federal Income Tax Considerations for United States Holders
The following generally summarizes certain Canadian federal income tax consequences generally applicable under the Income Tax Act (Canada) and the regulations enacted thereunder (collectively, the “Canadian Tax Act”) and the Canada-United States Tax Convention (1980) (the “Convention”) to the holding and disposition of Common Shares. Comment is restricted to holders of Common Shares each of whom, at all material times for the purposes of the Canadian Tax Act and the Convention, (i) is resident solely in the United States for tax purposes, (ii) is a “qualifying person” under, and entitled to the benefits of, the Convention, (iii) holds all Common Shares as capital property, (iv) holds no Common Shares that are “taxable Canadian property” (as defined in the Canadian Tax Act) of the holder, (v) deals at arm’s length with and is not affiliated with ESSA, (vi) does not and is not deemed to use or hold any Common Shares in a business carried on in Canada, (vii) is not an insurer that carries on business in Canada and elsewhere, and (viii) is not an “authorized foreign bank” (as defined in the Canadian Tax Act) (each such holder, a “U.S. Resident Holder”).
Certain U.S.-resident entities that are fiscally transparent for United States federal income tax purposes (including certain limited liability companies) may not in all circumstances be entitled to the benefits of the Convention. Members of or holders of an interest in such an entity that holds Common Shares should consult their own tax advisers regarding the extent, if any, to which the benefits of the Convention will apply to the entity in respect of its Common Shares.
Generally, a U.S. Resident Holder’s Common Shares will be considered to be capital property of such holder provided that the U.S. Resident Holder is not a trader or dealer in securities, did not acquire, hold, or dispose of the Common Shares in one or more transactions considered to be an adventure or concern in the nature of trade, and does not hold the Common Shares in the course of carrying on a business.
This summary is based on the information contained in this Form 10-K, the current provisions of the Canadian Tax Act and the Convention in effect on the date hereof, all specific proposals to amend the Canadian Tax Act and Convention publicly announced by or on behalf of the Minister of Finance (Canada) on or before the date hereof, and the current published administrative and assessing policies of the Canada Revenue Agency (the “CRA”). It is assumed that all such amendments will be enacted as currently proposed, and that there will be no other material change to any applicable law or administrative or assessing practice, whether by way of judicial, legislative or governmental decision or action, although no assurance can be given in these respects. Except as otherwise expressly provided, this summary does not take into account any provincial, territorial, or foreign tax considerations, which may differ materially from those set out herein.
This summary is of a general nature only, is not exhaustive of all possible Canadian federal income tax considerations, and is not intended to be and should not be construed as legal or tax advice to any particular U.S. Resident Holder. U.S. Resident Holders are urged to consult their own tax advisers for advice with respect to their particular circumstances. The discussion below is qualified accordingly.
Generally, a U.S. Resident Holder’s Common Shares will not constitute “taxable Canadian property” of such holder at a particular time provided the Common Shares are listed on a “designated stock exchange” (which currently includes the TSX and Nasdaq) unless both of the following conditions are concurrently met:
(i)at any time during the 60-month period that ends at the particular time, 25% or more of the issued shares of any class of the capital stock of ESSA were owned by or belonged to one or any combination of:
A.the U.S. Resident Holder,
B.persons with whom the U.S. Resident Holder did not deal at arm’s length, and
C.partnerships in which the U.S. Resident Holder or a person referred to in clause (B) above holds a membership interest directly or indirectly through one or more partnerships, and
(ii)at any time during the 60-month period that ends at the particular time, more than 50% of the fair market value of the Common Shares was derived, directly or indirectly, from one or any combination of (a) real or immovable property situated in Canada; (b) “Canadian resource properties” (as defined in the Canadian Tax Act);
(c) “timber resource properties” (as defined in the Canadian Tax Act); or (d) options in respect of, interests in, or civil law rights in, such properties, whether or not the property exists.
Common Shares may also be deemed to be “taxable Canadian property” in certain circumstances set out in the Canadian Tax Act.
A U.S. Resident Holder who disposes or is deemed to dispose of one or more Common Shares generally should not thereby incur any liability for Canadian federal income tax in respect of any capital gain arising as a consequence of the disposition.
A U.S. Resident Holder to whom ESSA pays or credits or is deemed to pay or credit a dividend on such holder’s Common Shares will generally be subject to Canadian withholding tax, and ESSA will be required to withhold the tax from the dividend and remit it to the CRA for the holder’s account. The rate of withholding tax under the Canadian Tax Act is 25% of the gross amount of the dividend, but should generally be reduced under the Convention to 15% (or, if the U.S. Resident Holder is a company which is the beneficial owner of at least 10% of the voting stock of ESSA, 5%) of the gross amount of the dividend. For this purpose, a company that is a resident of the United States for purposes of the Convention and is entitled to the benefits of the Convention shall be considered to own the voting stock of ESSA owned by an entity that is considered fiscally transparent under the laws of the United States and that is not a resident of Canada, in proportion to such company’s ownership interest in that entity.
United States Income Tax Considerations
The following is a summary of the anticipated U.S. federal income tax consequences generally applicable to U.S. Holders (as defined below) of the ownership and disposition of the Company’s Common Shares. This summary addresses only holders who acquire and hold the Common Shares as “capital assets” (generally, assets held for investment purposes).
The following summary does not purport to address all U.S. federal income tax consequences that may be relevant to a U.S. Holder (as defined below) as a result of the ownership and disposition of the Common Shares, nor does it take into account the specific circumstances of any particular holder, some of which may be subject to special tax rules (including, but not limited to, brokers, dealers in securities or currencies, traders in securities that elect to use a mark-to-market method of accounting for securities holdings, tax-exempt organizations, insurance companies, banks, thrifts and other financial institutions, persons liable for alternative minimum tax, persons that hold an interest in an entity that holds the Common Shares, persons that will own, or will have owned, directly, indirectly or constructively 10% or more (by vote or value) of our stock, persons that hold the Common Shares as part of a hedging, integration, conversion or constructive sale transaction or a straddle, former citizens or permanent residents of the United States, or persons whose functional currency is not the U.S. dollar).
This summary is based on the U.S. Internal Revenue Code of 1986, as amended (the “Code”), U.S. Treasury regulations, administrative pronouncements and rulings of the United States Internal Revenue Service (the “IRS”), judicial decisions and the Canada-United States Income Tax Convention (1980), as amended, all as in effect on the date hereof, and all of which are subject to change (possibly with retroactive effect) and to differing interpretations. Except as specifically set forth below, this summary does not discuss applicable income tax reporting requirements. This summary does not describe any state, local or foreign tax law considerations, or any aspect of U.S. federal tax law other than income taxation (e.g., estate or gift tax or the Medicare contribution tax). U.S. Holders (as defined below) should consult their own tax advisers regarding such matters.
No legal opinion from U.S. legal counsel or ruling from the IRS has been requested, or will be obtained, regarding the U.S. federal income tax consequences of the ownership or disposition of the Common Shares. This summary is not binding on the IRS, and the IRS is not precluded from taking a position that is different from, and contrary to, the positions taken in this summary. In addition, because the authorities on which this summary is based are subject to different interpretations, the IRS and U.S. courts could disagree with one or more of the positions taken in this summary.
As used in this summary, a “U.S. Holder” is a beneficial owner of the Common Shares who, for U.S. federal income tax purposes, is (i) a citizen or individual resident of the United States, (ii) a corporation (or other entity that is classified as a corporation for U.S. federal income tax purposes) that is created or organized in or under the laws of the United States,
any State thereof or the District of Columbia, (iii) an estate whose income is subject to U.S. federal income tax regardless of its source, or (iv) a trust if (A) a U.S. court can exercise primary supervision over the trust’s administration and one or more U.S. persons are authorized to control all substantial decisions of the trust, or (B) the trust has a valid election in effect to be treated as a U.S. person for U.S. federal income tax purposes.
The tax treatment of a partner in a partnership (or other entity or arrangement classified as a partnership for U.S. federal income tax purposes) that holds the Common Shares may depend on both the partnership’s and the partner’s status and the activities of the partnership. Partnerships (or other entities or arrangements classified as a partnership for U.S. federal income tax purposes) that are beneficial owners of the Common Shares, and their partners and other owners, should consult their own tax advisers regarding the tax consequences of the ownership and disposition of the Common Shares.
Passive Foreign Investment Company Rules
A foreign corporation will be considered a PFIC for any taxable year in which (1) 75% or more of its gross income is “passive income” under the PFIC rules or (2) 50% or more of the average quarterly value of its assets produce (or are held for the production of) “passive income.” For this purpose, “passive income” generally includes interest, dividends, certain rents and royalties, and certain gains. Moreover, for purposes of determining if the foreign corporation is a PFIC, if the foreign corporation owns, directly or indirectly, at least 25%, by value, of the shares of another corporation, it will be treated as if it holds directly its proportionate share of the assets and receives directly its proportionate share of the income of such other corporation. If a corporation is treated as a PFIC with respect to a U.S. Holder for any taxable year, the corporation will continue to be treated as a PFIC with respect to that U.S. Holder in all succeeding taxable years, regardless of whether the corporation continues to meet the PFIC requirements in such years, unless certain elections are made.
The determination as to whether a foreign corporation is a PFIC is based on the application of complex U.S. federal income tax rules, which are subject to differing interpretations, and the determination will depend on the composition of the income, expenses and assets of the foreign corporation from time to time and the nature of the activities performed by its officers and employees. ESSA believes that it was classified as a PFIC for the taxable year ending September 30, 2024, and ESSA believes that it may be classified as a PFIC for the current taxable year and in future taxable years. However, our actual PFIC status for the current or any future taxable year is uncertain and cannot be determined until after the end of such taxable year.
If we are classified as a PFIC, a U.S. Holder that does not make any of the elections described below would be required to report any gain on the disposition of Common Shares as ordinary income, rather than as capital gain, and to compute the tax liability on the gain and any “Excess Distribution” (as defined below) received in respect of Common Shares as if such items had been earned ratably over each day in the U.S. Holder’s holding period (or a portion thereof) for the Common Shares. The amounts allocated to the taxable year during which the gain is realized or distribution is made, and to any taxable years in such U.S. Holder’s holding period that are before the first taxable year in which we are treated as a PFIC with respect to the U.S. Holder, would be included in the U.S. Holder’s gross income as ordinary income for the taxable year of the gain or distribution. The amount allocated to each other taxable year would be taxed as ordinary income in the taxable year during which the gain is realized or distribution is made at the highest tax rate in effect for the U.S. Holder in that other taxable year and would be subject to an interest charge as if the income tax liabilities had been due with respect to each such prior year. For purposes of these rules, gifts, exchanges pursuant to corporate reorganizations and use of Common Shares as security for a loan may be treated as a taxable disposition of the Common Shares. An “Excess Distribution” is the amount by which distributions during a taxable year in respect of a Common Share exceed 125% of the average amount of distributions in respect thereof during the three preceding taxable years (or, if shorter, the U.S. Holder’s holding period for the Common Shares).
Certain additional adverse tax rules will apply to a U.S. Holder for any taxable year in which we are treated as a PFIC with respect to such U.S. Holder and any of our subsidiaries is also treated as a PFIC (a “Subsidiary PFIC”). In such a case, the U.S. Holder will generally be deemed to own its proportionate interest (by value) in any Subsidiary PFIC and be subject to the PFIC rules described above with respect to the Subsidiary PFIC regardless of such U.S. Holder’s percentage ownership in us.
The adverse tax consequences described above may be mitigated if a U.S. Holder makes a timely “qualified electing fund” election (a “QEF election”) with respect to its interest in the PFIC. Consequently, if we are classified as a PFIC, it may be advantageous for a U.S. Holder to elect to treat us as a “qualified electing fund” with respect to such U.S. Holder in the first year in which it holds Common Shares. If a U.S. Holder makes a timely QEF election with respect to ESSA, the electing U.S. Holder would be required in each taxable year that we are considered a PFIC to include in gross income (i) as ordinary income, the U.S. Holder’s pro rata share of the ordinary earnings of ESSA and (ii) as capital gain, the U.S. Holder’s pro rata share of the net capital gain (if any) of ESSA, whether or not the ordinary earnings or net capital gain are distributed. An electing U.S. Holder’s basis in Common Shares will be increased to reflect the amount of any taxed but undistributed income. Distributions of income that had previously been taxed will result in a corresponding reduction of basis in the Common Shares and will not be taxed again as distributions to the U.S. Holder.
A QEF election made with respect to ESSA will not apply to any Subsidiary PFIC; a QEF election must be made separately for each Subsidiary PFIC (in which case the treatment described above would apply to such Subsidiary PFIC). If a U.S. Holder makes a timely QEF election with respect to a Subsidiary PFIC, it would be required in each taxable year to include in gross income its pro rata share of the ordinary earnings and net capital gain of such Subsidiary PFIC, but may not receive a distribution of such income. Such a U.S. Holder may, subject to certain limitations, elect to defer payment of current U.S. federal income tax on such amounts, subject to an interest charge (which would not be deductible for U.S. federal income tax purposes if the U.S. Holder were an individual).
If we determine that we, and any subsidiary in which we own, directly or indirectly, more than 50% of such subsidiary’s total aggregate voting power, is likely a PFIC in any taxable year, we intend to make available to U.S. Holders, upon request and in accordance with applicable procedures, a “PFIC Annual Information Statement” with respect to ESSA and any such subsidiary for such taxable year. The “PFIC Annual Information Statement” may be used by U.S. Holders for purposes of complying with the reporting requirements applicable to a QEF election with respect to ESSA and any Subsidiary PFIC. The U.S. federal income tax on any gain from the disposition of Common Shares or from the receipt of Excess Distributions may be greater than the tax if a timely QEF election is made.
Alternatively, if we were to be classified as a PFIC, a U.S. Holder could also avoid certain of the rules described above by making a mark-to-market election (instead of a QEF election), provided the Common Shares are treated as regularly traded on a qualified exchange or other market within the meaning of the applicable U.S. Treasury Regulations. However, a U.S. Holder will not be permitted to make a mark-to-market election with respect to a Subsidiary PFIC. U.S. Holders should consult their own tax advisers regarding the potential availability and consequences of a mark-to-market election, as well as the advisability of making a protective QEF election in case we are classified as a PFIC in any taxable year.
During any taxable year in which we or any Subsidiary PFIC is treated as a PFIC with respect to a U.S. Holder, that U.S. Holder generally must file IRS Form 8621. U.S. Holders should consult their own tax advisers concerning annual filing requirements.
The Common Shares
Distributions on the Common Shares
In general, subject to the passive foreign investment company rules discussed above, the gross amount of any distribution received by a U.S. Holder with respect to the Common Shares (including amounts withheld to pay Canadian withholding taxes) will be included in the gross income of the U.S. Holder as a dividend to the extent attributable to our current and accumulated earnings and profits, as determined under U.S. federal income tax principles. We may not calculate our earnings and profits for each year under U.S. federal income tax rules. Accordingly, U.S. Holders should expect that a distribution generally will be treated as a dividend for U.S. federal income tax purposes. Subject to the passive foreign investment company rules discussed above, distributions on the Common Shares to certain non-corporate U.S. Holders that are treated as dividends may be taxed at preferential rates provided we are not treated as a PFIC for the taxable year of the distribution or the preceding taxable year. Such dividends will not be eligible for the “dividends received” deduction ordinarily allowed to corporate shareholders with respect to dividends received from U.S. corporations.
The amount of any dividend paid in Canadian dollars (including amounts withheld to pay Canadian withholding taxes) will equal the U.S. dollar value of the Canadian dollars calculated by reference to the exchange rate in effect on the date the dividend is received by the U.S. Holder, regardless of whether the Canadian dollars are converted into U.S. dollars. A U.S. Holder will have a tax basis in the Canadian dollars equal to their U.S. dollar value on the date of receipt. If the Canadian dollars received are converted into U.S. dollars on the date of receipt, the U.S. Holder should generally not be required to recognize foreign currency gain or loss in respect of the distribution. If the Canadian dollars received are not converted into U.S. dollars on the date of receipt, a U.S. Holder may recognize foreign currency gain or loss on a subsequent conversion or other disposition of the Canadian dollars. Such gain or loss will be treated as U.S. source ordinary income or loss.
Distributions on the Common Shares that are treated as dividends generally will constitute income from sources outside the United States and generally will be categorized for U.S. foreign tax credit purposes as “passive category income.” A U.S. Holder may be eligible to elect to claim a U.S. foreign tax credit against its U.S. federal income tax liability, subject to applicable limitations and holding period requirements, for Canadian tax withheld, if any, from distributions received in respect of the Common Shares. A U.S. Holder that does not elect to claim a U.S. foreign tax credit may instead claim a deduction for Canadian tax withheld, but only for a taxable year in which the U.S. Holder elects to do so with respect to all foreign income taxes paid or accrued in such taxable year. The rules relating to U.S. foreign tax credits are complex, and each U.S. Holder should consult its own tax adviser regarding the application of such rules.
Sale, Exchange or Other Taxable Disposition of the Common Shares
A U.S. Holder generally will recognize gain or loss on the sale, exchange or other taxable disposition of Common Shares in an amount equal to the difference, if any, between the amount realized on the sale, exchange or other taxable disposition and the U.S. Holder’s adjusted tax basis in the Common Shares exchanged therefor. Subject to the passive foreign investment company rules discussed above, such gain or loss will be capital gain or loss and will be long-term capital gain (currently taxable at a reduced rate for non-corporate U.S. Holders) or loss if, on the date of the sale, exchange or other taxable disposition, the Common Shares have been held by such U.S. Holder for more than one year. The deductibility of capital losses is subject to limitations. Such gain or loss generally will be sourced within the United States for U.S. foreign tax credit purposes.
Required Disclosure with Respect to Foreign Financial Assets
Certain U.S. Holders are required to report information relating to an interest in the Common Shares, subject to certain exceptions (including an exception for common shares held in accounts maintained by certain financial institutions), by attaching a completed IRS Form 8938, Statement of Specified Foreign Financial Assets, with their tax return for each year in which they hold an interest in Common Shares. U.S. Holders should consult their own tax advisers regarding information reporting requirements relating to their ownership of the Common Shares.
Recent Sales of Unregistered Securities
None.
Issuer Repurchases of Equity Securities
None.

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ITEM 6. SELECTED FINANCIAL DATA
Item 6. [Reserved.]

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ITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion should be read in conjunction with the attached financial statements and notes thereto. This Annual Report on Form 10-K, including the following sections, contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those expressed or implied by such forward-looking statements. For a detailed discussion of these risks and uncertainties, see Item 1A, “Risk Factors” of this Annual Report on Form 10-K. We caution the reader not to place undue reliance on these forward -looking statements, which reflect management’s analysis only as of the date of this Annual Report on Form 10-K. We undertake no obligation to update forward-looking statements to reflect events or circumstances occurring after the date of this Annual Report on Form 10-K. Throughout this discussion, unless the context specifies or implies otherwise, the terms “ESSA,” “the Company,” “we,” “us,” and “our” refer to ESSA Pharma Inc. and its subsidiaries. For a discussion regarding our financial condition and results of operations for fiscal 2024 as compared to fiscals 2023 and 2022 see Item 7 of our Annual Report on Form 10-K for the fiscal year ended September 30, 2023, filed with the SEC on December 13, 2023.
Overview
ESSA is a clinical stage pharmaceutical company that, prior to the discontinuation of its clinical trials and preclinical and other development programs, has been focused on developing novel and proprietary therapies for the treatment of prostate cancer with an initial focus on patients whose disease is progressing despite treatment with current standard of care therapies, including second-generation antiandrogen drugs such as abiraterone, enzalutamide, apalutamide, and darolutamide. The Company believed its latest series of investigational compounds, including its planned product candidate masofaniten (EPI-7386), had the potential to significantly expand the interval of time in which patients with castration-resistant prostate cancer can benefit from anti-hormone-based therapies. Specifically, the compounds were designed to disrupt the AR signaling pathway, the primary pathway that drives prostate cancer growth and prevent AR activation through selective binding to the N-terminal domain of the AR. In this respect, the Company’s compounds are designed to differ from classical non-steroid antiandrogens. These antiandrogens interfere either with androgen synthesis (i.e., abiraterone), or with the binding of androgens to the ligand-binding domain, located at the opposite end of the receptor from the NTD (i.e., lutamides). A functional NTD is essential for activation of the AR; blocking the NTD inhibits AR-driven transcription and therefore androgen-driven biology.
As discussed further herein, on October 31, 2024, ESSA announced that it decided to terminate its clinical studies evaluating masofaniten (EPI-7386) and has also decided to withdraw its IND and CTAs that have been submitted to date. ESSA has initiated a comprehensive review process to review its strategic options.
General Development of the Business
Termination of Clinical Studies and Evaluation of Strategic Options
On October 31, 2024, ESSA announced that it decided to terminate its Phase 2 clinical trial evaluating in a 2:1 randomization masofaniten (EPI-7386) combined with enzalutamide versus enzalutamide single agent in patients with mCRPC naïve to second-generation antiandrogens. This decision, mutually agreed upon by both senior management and the Board, 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 (EPI-7386) plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study.
As part of its efforts to focus its resources, ESSA also announced that the other remaining company-sponsored and investigator-sponsored clinical studies evaluating masofaniten (EPI-7386) either as a monotherapy or in combination with other agents will be terminated, including those discussed below and elsewhere in this Annual Report on Form 10-K. ESSA also decided to withdraw its IND and CTAs that have been submitted to date.
In connection with these events, ESSA has initiated a comprehensive review process to review its strategic options to maximize shareholder value. ESSA expects to devote significant time and resources to its review of strategic options. There can be no assurances that the strategic review process will deliver the anticipated benefits thereof or enhance shareholder value. Strategic options may include, but are not limited to, a merger, amalgamation, arrangement, reverse take-over, business combination, asset sale or acquisition, shareholder distribution, wind-down, liquidation and dissolution or other strategic transaction or the operation of its business and election to seek new product candidates for development.
There can also be no assurance that ESSA will be able to successfully consummate any particular strategic transaction, or any transaction at all. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we may incur significant costs related to this continued evaluation. ESSA may also incur additional unanticipated expenses in connection with this process. A considerable portion of these costs will be incurred regardless of whether any such course of action is implemented or transaction is completed. Any such expenses will decrease the remaining cash available for use in ESSA’s business and may diminish or delay any future distributions to our shareholders.
Significant Business Developments for the Year Ended September 30, 2024
On September 13-17, 2024, the Company updated dose escalation data from its Phase 1/2 study evaluating masofaniten (formerly EPI-7386) in combination with enzalutamide at the 2024 European Society for Medical Oncology (ESMO).
The updated dose escalation data included that in patients evaluable for safety (n=18), masofaniten combined with enzalutamide, was well-tolerated at the dose levels tested through 32 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities (DLTs) were observed, therefore the maximum tolerated dose (MTD) was not reached. The recommended Phase 2 combination doses (RP2CDs) were identified as masofaniten 600 mg twice daily (BID) in combination with enzalutamide 160 mg once daily (QD).
At such time, in the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). Across all dose cohorts, 88% of patients (14 of 16) achieved PSA50, 88% of patients (14 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 63% of patients (10 of 16) achieved PSA <0.2ng/mL. With a median follow up of 15.2 months, the median time to PSA progression and radiographic progression free survival had not yet been reached.
The randomized, open-label, two arm, Phase 2 dose expansion portion of the study was underway and designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naïve to second generation anti-androgens. The study planned to enroll patients at approximately 33 sites in the USA, Canada and Australia, and an additional 22 sites in Europe.
On January 25-27, 2024, the Company presented updated dose escalation data from its Phase 1/2 study evaluating masofaniten (EPI-7386) in combination with enzalutamide at the 2024 ASCO Genitourinary Cancers Symposium.
The data included that in patients evaluable for safety (n=18), masofaniten combined with enzalutamide, was well-tolerated at the dose levels tested through 25 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities were observed, therefore the maximum tolerated dose was not reached. The recommended Phase 2 combination doses were identified as masofaniten 600 mg BID in combination with enzalutamide 160 QD.
In the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). Across all dose cohorts, 88% of patients (14 of 16) achieved PSA50, 81% of patients (13 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 63% of patients (10 of 16) achieved PSA <0.2ng/mL. While the data for disease PSA progression were maturing with a median follow up of 11.1 months, the median time to PSA progression was at 16.6 months.
The randomized, open-label, two arm, Phase 2 dose expansion portion of the study was underway and designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naïve to second generation anti-androgens. The study planned to enroll patients in the U.S., Canada, certain countries in Europe, and Australia.
Financing and Capital
On November 6, 2023, the Company announced that it had entered into the ATM Sales Agreement with Jefferies LLC, effective as of November 3, 2023. Under the ATM Sales Agreement, ESSA may, within the period that the ATM Sales Agreement is in effect, sell its Common Shares from time to time for up to US$50.0 million in aggregate sales proceeds.
No offers or sales of Common Shares will be made in Canada, to anyone known by Jefferies LLC to be a resident of Canada or on or through the facilities of any stock exchange or trading markets in Canada.
ESSA has never been profitable and has incurred net losses since inception. ESSA’s net losses were $28,542,821 and $26,582,343 for the years ended September 30, 2024 and 2023, respectively. ESSA expects to incur losses for the foreseeable future, and it expects these losses to increase as it progresses its comprehensive review of strategic options, winds down its clinical and preclinical development programs and/or continues the development of, and seek regulatory approvals for, potential product candidates. Because of the numerous risks and uncertainties associated with its strategic options review, the wind down of such programs and product development, ESSA is unable to predict the timing or amount of increased expenses or when, or if, it will be able to achieve or maintain profitability.
Results of Operations
The following table sets forth ESSA’s consolidated statements of financial position and consolidated statements of loss and comprehensive loss as at and for the fiscal years ended September 30, 2024 and 2023:
(US$)
Year Ended
Year Ended
Income Statement Data
September 30, 2024
September 30, 2023
Revenue
-
-
Research and development, net of recoveries
21,206,824
21,322,530
Financing costs
-
6,942
General and administration, net of recoveries
13,214,193
10,811,574
Total operating expenses
(34,421,017)
(32,141,046)
Net loss for the year
(28,542,821)
(26,582,343)
Loss and comprehensive loss
(28,485,690)
(26,567,596)
Balance Sheet Data
Cash and cash equivalents
103,709,537
33,701,912
Short term investments and other current assets
23,850,018
115,094,966
Deposits
256,977
257,245
Right-of-use assets
295,471
68,008
Total assets
128,112,003
149,122,131
Accounts payable and accrued liabilities
3,176,973
3,414,743
Income tax payable
-
-
Lease liabilities
329,260
80,328
Shareholders’ equity
124,605,770
145,627,060
Total liabilities and shareholders’ equity
128,112,003
149,122,131
Results of Operations for the Fiscal Years Ended September 30, 2024 and 2023
There was no revenue in any of the fiscal years as reported. The Company incurred a comprehensive loss of $28,542,821 for the year ended September 30, 2024 compared to a comprehensive loss of $26,582,343 for the year ended September 30, 2023. Variations in ESSA’s expenses and net loss for the periods resulted primarily from the following factors described below.
Research and Development Expenditures
R&D expense included the following major expenses by nature:
Year ended
September 30, 2024
September 30, 2023
Clinical
$
9,374,882
$
5,780,660
Preclinical and data analysis
2,900,433
6,081,575
Salaries and benefits
2,896,757
2,712,168
Share-based payments
1,823,076
2,627,505
Manufacturing
1,674,299
2,356,472
Legal patents and license fees
1,141,325
919,859
Other
538,723
213,972
Consulting
595,159
430,260
Travel and other
162,931
137,285
Royalties
99,239
62,774
Total
$
21,206,824
$
21,322,530
The overall R&D expense for the year ended September 30, 2024 was $21,206,824 compared to $21,322,530 for the year ended September 30, 2023 and includes non-cash expense related to share-based payments expense, net of recoveries for
stock options forfeit, of $1,823,076 (2023 - $2,627,505). R&D expense in 2024 reflects the then-ongoing clinical trial of masofaniten (EPI-7386) which commenced in July 2020.
Clinical costs of $9,374,882 (2023 - $5,780,660) were generated in relation to expenditures associated with the Company’s clinical research organizations conducting the clinical trials of masofaniten (EPI-7386). Expenditures in the year ended September 30, 2024 have increased over the prior period as the clinical sites and participants have expanded in the combination studies. Associated variable costs for the resulting data have increased concurrently.
Preclinical and data analysis costs of $2,900,433 (2023 - $6,081,575) have been generated in relation to expenditures for pharmacokinetic data analysis on data from the clinical trials and previously work on preclinical pipeline and Anitac compounds. Costs have decreased as the Company’s focus concentrated on supporting the clinical studies and continued work on mechanism of action.
Salaries and benefits have increased to $2,896,757 (2023 - $2,712,168) as preclinical and clinical staff counts have remained relatively stable with some compensation adjustments over the periods presented.
The share-based payments expense of $1,823,076 (2023 - $2,627,505), which is a non-cash expense, relates to the value assigned to stock options and employee share purchase rights granted to key management personnel and consultants of the Company. The expense is recognized in relation to the grant and vesting of these equity instruments, net of expiries and forfeitures, and allocated to research and development, general and administration and financing expenditures relative to the activity of the underlying optionee.
Manufacturing costs of $1,674,299 (2023 - $2,356,472) includes amount for cGMP manufacturing of masofaniten (EPI-7386) drug supply to support the ongoing clinical trials as well as costs incurred in formulation and chemistry work around the Company’s pharmaceutical characteristics of masofaniten (EPI-7386). Manufacturing costs were reduced in the current period from the prior period as the manufactured drug is now being supplied to clinical trials. These costs also include the shipment, international specifications and site audit work for drug management.
Legal patents and license fees decreased to $1,141,325 (2023 - $919,859). The Company has adopted a tiered patent strategy to protect its intellectual property as the pharmaceutical industry places significant importance on patents for the protection of new technologies, products and processes. The costs reflect that ongoing investment and the timing of associated maintenance costs.
Consulting costs were $595,159 (2023 - $430,260) for the year ended September 30, 2024 relating to contract project management services as well as data quality audit support resulting in a small increase in the current period.
General and Administration Expenditures
General and administrative expenses include the following major expenses by nature:
Year ended
September 30, 2024
September 30, 2023
Salaries and benefits
$
4,830,220
$
4,303,570
Share-based payments
4,715,814
2,379,965
Insurance
1,437,845
1,724,746
Professional fees
1,036,088
1,019,989
Investor relations
502,615
602,645
Office, IT and communications
498,764
529,301
Director fees
447,750
392,667
Regulatory fees and transfer agent
249,426
202,525
Travel and other
215,733
179,302
Operating lease liabilities and rent
134,095
22,567
Consulting and subcontractor fees
63,267
8,700
Accretion of short-term investments
(917,424)
(554,403)
Total
$
13,214,193
$
10,811,574
General and administration expenses increased to $13,214,193 for the year ended September 30, 2024 from $10,811,574 in the year ended September 30, 2023 and included non-cash expense related to share-based payments of $4,715,814 (2023 - $2,379,965). This non-cash expense relates to the value assigned to stock options and employee share purchase rights granted to key management and consultants of the Company. The expense is recognized in relation to the grant and vesting of these equity instruments, net of expiries and forfeitures, and allocated to research and development, general and administration and financing expenditures relative to the activity of the underlying optionee.
Salaries and benefits expense increased to $4,830,220 (2023 - $4,303,570) as a result of an increased number of corporate staff to support administrative functions and relative wage adjustments.
Insurance expense of $1,437,845 (2023 - $1,724,746) relates to the cost of insurance coverage for directors and officers of the Company. The Company realized a decrease in annual premiums for its directors and officers insurance package for the current year.
Professional fees of $1,036,088 (2023 - $1,019,989) were incurred for legal and accounting services in conjunction with ongoing corporate activities. In the current year, the Company refreshed its ATM Sales Agreement and filed a prospectus supplement to its registration statement and base shelf prospectus resulting in an overall increased expense for the period.
Director fees of $447,750 (2023 - $392,667) were incurred for remuneration paid to directors for their membership on the Board based on an annual fee structure. The Board was awarded base increases effective April 2024 and has an additional member compared to the previous period.
Amortization/(Accretion) recognized varies relative to the Company’s investment holdings and market conditions for expected investment returns. Over the periods presented, the Company had a larger investment holding and had benefited from higher interest rates.
Liquidity and Capital Resources
As at September 30, 2024, the Company had working capital of $124,258,528 (2023 - $145,301,807). Operational activities during the year ended September 30, 2024 were financed mainly by proceeds from financings in July 2020 and February 2021. At September 30, 2024, the Company had available cash reserves and short-term investments of $126,760,119 (2023 - $148,076,401) to settle current liabilities of $3,301,027 (2023 - $3,495,071). At September 30, 2024, the Company believed that it had sufficient capital to satisfy its obligations as they became due and execute its planned expenditures for more than twelve months. The Company expects its current cash runway to fund its operations through 2025, including the wind down of its clinical trials and preclinical development programs, as well as the Company’s review and evaluation of strategic alternatives to maximize shareholder value.
ESSA’s future cash requirements may vary materially from those now expected due to a number of factors, including the costs associated with discontinuing clinical and preclinical work and to explore and take advantage of strategic opportunities, such as partnering collaborations or mergers and acquisitions activities. In the future, it may be necessary to raise additional funds. These funds may come from sources such as entering into strategic collaboration arrangements, the issuance of shares from treasury, or alternative sources of financing. However, there can be no assurance that ESSA will successfully raise funds to continue its operational activities. See “Risk Factors” in Item 1A. elsewhere in this Annual Report.
Critical Accounting Policies and Estimates
The Company makes estimates and assumptions about the future that affect the reported amounts of assets and liabilities. Estimates and judgments are continually evaluated based on historical experience and other factors, including expectations of future events that are believed to be reasonable under the circumstances. In the future, actual experience may differ from these estimates and assumptions.
The effect of a change in an accounting estimate is recognized prospectively by including it in comprehensive income in the period of the change, if the change affects that period only, or in the period of the change and future periods, if the change affects both. Significant assumptions about the future and other sources of estimation uncertainty that management has made at the statement of financial position date, that could result in a material adjustment to the carrying amounts of assets and liabilities, in the event that actual results differ from assumptions that have been made that relate to the following key estimates:
Income tax
The determination of income tax is inherently complex and requires making certain estimates and assumptions about future events. Changes in facts and circumstances as a result of income tax audits, reassessments, changes to corporate structure and associated domiciling, jurisprudence and any new legislation may result in an increase or decrease the provision for income taxes. The value of deferred tax assets is evaluated based on the probability of realization; the Company has assessed that it is improbable that such assets will be realized and has accordingly not recognized a value for deferred taxes.
Share-based payments and compensation
The Company has applied estimates with respect to the valuation of shares issued for non-cash consideration. Shares are valued at the fair value of the equity instruments granted at the date of grant and the cost is recorded when the Company receives the goods or services.
The Company measures the cost of equity-settled transactions with employees by reference to the fair value of the equity instruments at the date at which they are granted. Estimating fair value for share-based payment transactions requires determining the most appropriate valuation model, which is dependent on the terms and conditions of the grant. This estimate also requires determining the most appropriate inputs to the valuation model including the fair value of the underlying Common Shares, the expected life of the share option, volatility and dividend yield and making assumptions about them. The fair value of the underlying Common Shares is assessed as the most recent issuance price per common share for cash proceeds.
Trend Information
ESSA is a clinical stage pharmaceutical company and does not currently generate revenue. The Company was focused on the development of small molecule drugs for the treatment of prostate cancer. The Company has acquired a license to certain Licensed IP. As at the date of this Annual Report, no products are in commercial production or use. The Company’s financial success will be dependent upon its ability to efficiently wind down its clinical trials and preclinical development programs and studies and identify strategic alternatives that maximize shareholder value.
Safe Harbor
See “Cautionary Note Regarding Forward-Looking Statements” in the introduction to this Annual Report.

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ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk
We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item.

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ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
Item 8. Financial Statements and Supplementary Data
ESSA Pharma Inc.
CONSOLIDATED FINANCIAL STATEMENTS
(Expressed in United States dollars)
FOR THE YEARS ENDED SEPTEMBER 30, 2024 and 2023
Report of Independent Registered Public Accounting Firm
To the Shareholders and Directors of
ESSA Pharma Inc.
Opinion on the Consolidated Financial Statements
We have audited the accompanying consolidated balance sheets of ESSA Pharma Inc. (the “Company”) as of September 30, 2024 and 2023, and the related consolidated statements of operations and comprehensive loss, cash flows, changes in shareholders’ equity for the years ended September 30, 2024 and 2023, and the related notes (collectively referred to as the “financial statements”). In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company as of September 30, 2024 and 2023, and the results of its operations and its cash flows for the years ended September 30, 2024 and 2023, in conformity with accounting principles generally accepted in the United States of America.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on these financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) ("PCAOB") and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the entity’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.
Critical Audit Matters
The critical audit matters communicated below are matters arising from the current period audit of the financial statements that were communicated or required to be communicated to the audit committee and that: (1) relate to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the financial statements, taken as a whole, and we are not, by communicating the critical audit matters below, providing separate opinions on the critical audit matters or on the accounts or disclosures to which they relate.
We have not identified any critical audit matters for the year ended September 30, 2024.
We have served as the Company’s auditor since 2012.
/s/ DAVIDSON & COMPANY LLP
Vancouver, Canada Chartered Professional Accountants
December 17, 2024
ESSA PHARMA INC.
CONSOLIDATED BALANCE SHEETS
(Expressed in United States dollars)
AS AT SEPTEMBER 30
ASSETS
Current
Cash and cash equivalents
$
103,709,537
$
33,701,912
Short-term investments (Note 4)
23,050,582
114,374,489
Receivables
162,973
135,057
Prepaids (Note 5)
636,463
585,420
127,559,555
148,796,878
Deposits
256,977
257,245
Operating lease right-of-use asset (Note 7)
295,471
68,008
Total assets
$
128,112,003
$
149,122,131
LIABILITIES AND SHAREHOLDERS’ EQUITY
Current
Accounts payable and accrued liabilities (Note 6)
$
3,176,973
$
3,414,743
Current portion of operating lease liability (Note 7)
124,054
80,328
3,301,027
3,495,071
Operating lease liability (Note 7)
205,206
-
Total liabilities
3,506,233
3,495,071
Shareholders’ equity
Authorized
Unlimited common shares, without par value
Unlimited preferred shares, without par value
Common shares 44,388,550 issued and outstanding (September 30, 2023 - 44,100,838) (Note 8)
279,862,420
278,161,537
Additional paid-in capital (Note 8)
54,810,797
49,047,280
Accumulated other comprehensive loss
(2,063,267)
(2,120,398)
Accumulated deficit
(208,004,180)
(179,461,359)
124,605,770
145,627,060
Total liabilities and shareholders’ equity
$
128,112,003
$
149,122,131
Nature of operations (Note 1)
Commitments (Note 13)
The accompanying notes are an integral part of these consolidated financial statements.
ESSA PHARMA INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(Expressed in United States dollars)
FOR THE YEARS ENDED SEPTEMBER 30
OPERATING EXPENSES
Research and development
$
21,206,824
$
21,322,530
Financing costs
-
6,942
General and administration
13,214,193
10,811,574
Total operating expenses
(34,421,017)
(32,141,046)
Foreign exchange
3,432
6,529
Investment and other income
5,874,764
5,553,774
Loss for the year before taxes
(28,542,821)
(26,580,743)
Income tax expense (Note 10)
-
(1,600)
Net loss for the year
(28,542,821)
(26,582,343)
OTHER COMPREHENSIVE INCOME
Unrealized gain on short-term investments (Note 4)
57,131
14,747
Loss and comprehensive loss for the year
$
(28,485,690)
$
(26,567,596)
Basic and diluted loss per common share
$
(0.64)
$
(0.60)
Weighted average number of common shares outstanding
- basic and diluted
44,277,050
44,089,557
The accompanying notes are an integral part of these consolidated financial statements.
ESSA PHARMA INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
(Expressed in United States dollars)
FOR THE YEARS ENDED SEPTEMBER 30
CASH FLOWS FROM OPERATING ACTIVITIES
Net loss for the year
$
(28,542,821)
$
(26,582,343)
Items not affecting cash and cash equivalents:
Amortization of right-of-use asset
90,681
118,491
Accretion of premiums/discounts on short-term investments, net
(917,424)
(671,268)
Accretion of lease liability
33,139
6,942
Accrued investment income
500,148
Unrealized foreign exchange
-
(528)
Share-based payments
6,538,890
5,007,469
Changes in non-cash working capital items:
Receivables
(27,916)
(128,846)
Prepaids
(50,775)
1,232,416
Accounts payable and accrued liabilities
(237,770)
1,235,577
Operating lease liabilities
(102,351)
-
Net cash used in operating activities
(22,716,199)
(19,781,716)
CASH FLOWS FROM INVESTING ACTIVITIES
Purchase of short-term investments
(39,234,545)
(365,203,691)
Proceeds from short-term investments sold
131,023,755
361,676,542
Net cash provided by (used in) investing activities
91,789,210
(3,527,149)
CASH FLOWS FROM FINANCING ACTIVITIES
Options exercised
879,997
-
Shares purchased through employee share purchase plan
45,513
68,709
Lease payments
-
(136,866)
Net cash provided by (used in) financing activities
925,510
(68,157)
Effect of foreign exchange on cash and cash equivalents
9,104
2,459
Change in cash and cash equivalents for the year
70,007,625
(23,374,563)
Cash and cash equivalents, beginning of year
33,701,912
57,076,475
Cash and cash equivalents, end of year
$
103,709,537
$
33,701,912
Supplemental disclosure of non-cash investing and finance items:
Leased assets obtained in exchange for operating lease liabilities
$
318,144
$
-
There were no amounts paid for taxes and interest in the year ended September 30, 2024 and 2023.
The accompanying notes are an integral part of these consolidated financial statements.
ESSA PHARMA INC.
CONSOLIDATED STATEMENT OF CHANGES IN SHAREHOLDERS’ EQUITY
(Expressed in United States dollars)
Accumulated
Additional
other
Number
Common
paid-in
comprehensive
of shares
shares
capital
loss
Deficit
Total
Balance, September 30, 2022
44,073,076
$
278,089,136
$
44,043,503
$
(2,135,145)
$
(152,879,016)
$
167,118,478
Shares issued through employee share purchase plan
27,762
72,401
(3,692)
-
-
68,709
Share-based payments
-
-
5,007,469
-
-
5,007,469
Loss and comprehensive loss for the year
-
-
-
14,747
(26,582,343)
(26,567,596)
Balance, September 30, 2023
44,100,838
$
278,161,537
$
49,047,280
$
(2,120,398)
$
(179,461,359)
$
145,627,060
Options exercised
271,018
1,631,693
(751,696)
-
-
879,997
Shares issued through employee share purchase plan
16,694
69,190
(23,677)
-
-
45,513
Share-based payments
-
-
6,538,890
-
-
6,538,890
Loss and comprehensive loss for the year
-
-
-
57,131
(28,542,821)
(28,485,690)
Balance, September 30, 2024
44,388,550
$
279,862,420
$
54,810,797
$
(2,063,267)
$
(208,004,180)
$
124,605,770
The accompanying notes are an integral part of these consolidated financial statements.
1. NATURE OF OPERATIONS
Nature of Operations
ESSA Pharma Inc. (the “Company”) was incorporated under the laws of the Province of British Columbia on January 6, 2009. The Company’s head office address is Suite 720 - 999 West Broadway, Vancouver, British Columbia, Canada V5Z 1K5. The registered and records office address is Suite 3500, The Stack, 1133 Melville Street, Vancouver, British Columbia, V6E 4E5. The Company is listed on the Nasdaq Capital Market (“Nasdaq”) under the symbol “EPIX.”
The Company has been focused on the development of small molecule drugs for the treatment of prostate cancer. The Company has a license to certain patents (the “NTD Technology”) which were the joint property of the British Columbia Cancer Agency and the University of British Columbia. As at September 30, 2024, no products are in commercial production or use.
2. BASIS OF PRESENTATION
Basis of Presentation
These accompanying consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the United States of America (“U.S. GAAP”) on a going concern basis.
The accompanying consolidated financial statements have been prepared on a historical cost basis except for certain financial assets measured at fair value using the accrual basis of accounting.
All amounts expressed in these accompanying consolidated financial statements and the accompanying notes are expressed in United States dollars, except per share data and where otherwise indicated. References to “$” are to United States dollars and references to “C$” are to Canadian dollars.
Basis of Consolidation and Functional Currency
Consolidation
The accounts of subsidiaries are prepared for the same reporting period as the parent company, using consistent accounting policies. Inter-company transactions, balances and unrealized gains or losses on transactions are eliminated upon consolidation. The consolidated financial statements comprise the accounts of ESSA Pharma Inc., the parent company, and its wholly owned subsidiary.
Functional Currency
The functional currency of an entity is the currency of the primary economic environment in which the entity operates.
The functional currency of the Company and its subsidiary have been determined as follows:
Country of
Effective
Functional
Incorporation
Interest
Currency
ESSA Pharma Inc.
Canada
-
US Dollar
ESSA Pharmaceuticals Corp.
USA
%
US Dollar
Use of Estimates
The preparation of the accompanying consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions about future events that affect the reported amounts of assets, liabilities, expenses, contingent assets and contingent liabilities as at the end of, or during, the reporting period. Actual results could significantly differ from those estimates. Significant areas requiring management to make estimates include the valuation of equity instruments issued for services and income taxes. Further details of the nature of these assumptions and conditions may be found in the relevant notes to these consolidated financial statements.
The effect of a change in an accounting estimate is recognized prospectively by including it in comprehensive income in the period of the change, if the change affects that period only, or in the period of the change and future periods, if the change affects both. Significant assumptions about the future and other sources of estimation uncertainty that management has made at the statement of financial position date, that could result in a material adjustment to the carrying amounts of assets and liabilities, in the event that actual results differ from assumptions that have been made, relate to the following key estimates:
Income tax
The determination of income tax is inherently complex and requires making certain estimates and assumptions about future events. Changes in facts and circumstances as a result of income tax audits, reassessments, changes to corporate structure and associated domiciling, jurisprudence and any new legislation may result in an increase or decrease the provision for income taxes. The value of deferred tax assets is evaluated based on the probability of realization; the Company has assessed that it is improbable that such assets will be realized and has accordingly not recognized a value for deferred taxes.
Share-based payments and compensation
The Company has applied estimates with respect to the valuation of shares issued for non-cash consideration. Shares are valued at the fair value of the equity instruments granted at the date the Company receives the goods or services.
The Company measures the cost of equity-settled transactions with employees by reference to the fair value of the equity instruments at the date at which they are granted. Estimating fair value for share-based payment transactions requires determining the most appropriate valuation model, which is dependent on the terms and conditions of the grant. This estimate also requires determining the most appropriate inputs to the valuation model including the fair value of the underlying Common Shares, the expected life of the share option, volatility and dividend yield and making assumptions about them. The assumptions and models used for estimating fair value for share-based payment transactions are discussed in Note 8.
3. SIGNIFICANT ACCOUNTING POLICIES
Cash and cash equivalents
Cash and cash equivalents consist primarily of cash in banks, high-interest savings accounts, guaranteed investment certificates and term deposits, with original maturities of three months, or less and cash collateral which are recorded at cost plus accrued interest, which approximates fair value.
Short-term investments
The Company’s short-term investments consist of guaranteed investment certificates, U.S. treasury securities, and term deposits with original maturities exceeding three months and less than one year. The investments are carried at fair value plus accrued interest.
Foreign exchange
Transactions in currencies other than the United States dollar are recorded at exchange rates prevailing on the dates of the transactions. At the end of each reporting period, monetary assets and liabilities of the Company that are denominated in foreign currencies are translated at the period end exchange rate while non-monetary assets and liabilities are translated at historical rates. Revenues and expenses are translated at the exchange rates approximating those in effect on the date of the transactions. Exchange gains and losses arising on translation are included in comprehensive loss.
On translation of the entities whose functional currency is other than the United States dollar, revenues and expenses are translated at the exchange rates approximating those in effect on the date of the transactions. Assets and liabilities are translated at the rate of exchange at the reporting date.
Translation gains and losses are recorded in other comprehensive income (loss) as the cumulative translation adjustment along with the historical effects of a change in the functional currency.
Research and development costs
Expenditures on research and development activities, undertaken with the prospect of gaining new scientific or technical knowledge and understanding, are recognized in profit or loss as incurred. Investment tax credits related to current expenditures are included in the determination of net income as the expenditures are incurred when there is reasonable assurance they will be realized.
Fair value of financial instruments
The Company’s financial instruments consist of cash and cash equivalents, short-term investments, receivables, and accounts payable and accrued liabilities.
The Company provides disclosures that enable users to evaluate (a) the significance of financial instruments for the entity’s financial position and performance; and (b) the nature and extent of risks arising from financial instruments to which the entity is exposed during the period and at the date of the statement of financial position, and how the entity manages these risks.
The Company provides information about its financial instruments measured at fair value at one of three levels according to the relative reliability of the inputs used to estimate the fair value:
Level 1 - quoted prices (unadjusted) in active markets for identical assets or liabilities;
Level 2 - inputs other than quoted prices included in Level 1 that are observable for the asset or liability, either
directly (i.e., as prices) or indirectly (i.e., derived from prices); and
Level 3 - inputs for the asset or liability that are not based on observable market data (unobservable inputs).
Share-based payments
Share based payment arrangements in which the Company receives goods or services as consideration for its own equity instruments are accounted for as equity settled share-based payment transactions and measured at the fair value of at grant date.
Share-based compensation
The Company grants stock options to acquire Common Shares of the Company to directors, officers, employees and consultants.
The fair value of stock options is measured on the date of grant, using the Black-Scholes option pricing model, and is recognized over the requisite service or vesting period as applicable. Consideration paid for the shares on the exercise of stock options is credited to share capital. Such value is recognized as expense over the requisite service period, net of actual forfeitures, using the accelerated attribution method. The Company recognizes forfeitures as they occur. The estimation of stock awards that will ultimately vest requires judgment, and to the extent actual results, or updated estimates, differ from current estimates, such amounts are recorded as a cumulative adjustment in the period estimates are revised.
Basic and diluted loss per share
Basic loss per share is computed by dividing the loss available to common shareholders by the weighted average number of Common Shares outstanding during the year. The computation of diluted earnings per share assumes the conversion, exercise or contingent issuance of securities only when such conversion, exercise or issuance would have a dilutive effect on earnings per share. The dilutive effect of convertible securities is reflected in diluted earnings per share by application of the “if converted” method. The dilutive effect of outstanding options and warrants and their equivalents is reflected in diluted earnings per share by application of the weighted-average method. Since the Company has losses, the exercise of outstanding options and warrants has not been included in this calculation as it would be anti-dilutive.
Leases
At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on the unique facts and circumstances present in the arrangement. Leases with a term greater than one year are recognized on the balance sheet as ROU assets and short-term and long-term lease liabilities, as applicable. ROU assets represent the Company’s right to use an underlying asset for the lease term and lease liabilities represent its obligation to make lease payments arising from the lease. The Company typically only includes an initial lease term in its assessment of a lease arrangement. It also considers termination options and factors those into the determination of lease payments. Options to renew a lease are not included in the assessment unless there is reasonable certainty that the Company will renew.
Operating lease liabilities and their corresponding ROU assets are recorded based on the present value of lease payments over the expected remaining lease term. Certain adjustments to the ROU asset may be required for items such as incentives received. The interest rate implicit in lease contracts is typically not readily determinable. As a result, the Company utilizes its incremental borrowing rate, which reflects the fixed rate at which it could borrow on a collateralized basis the amount of the lease payments in the same currency, for a similar term, in a similar economic environment. Lease expense for lease payments is recognized on a straight-line basis over the lease term.
The Company elected the short-term lease exemption for all leases that qualify; as a result, we will not recognize right-of-use assets or lease liabilities for leases with a term of less than 12 months at inception.
Income taxes
Income tax is recognized in profit or loss except to the extent that it relates to items recognized directly in equity, in which case it is recognized in equity. Current tax expense is the expected tax payable on the taxable income for the year, using tax rates enacted at period end.
Deferred tax is recognized in respect of temporary differences, between the carrying amounts of assets and liabilities for financial reporting purposes and the amounts used for taxation purposes. The following temporary differences are not provided for: goodwill not deductible for tax purposes and an excess of the amount for financial reporting over the tax basis of an investment in a foreign subsidiary that is essentially permanent in duration. The amount of deferred tax provided is based on the expected manner of realization or settlement of the carrying amount of assets and liabilities, using tax rates enacted at the financial position reporting date.
A valuation allowance is recognized for deferred tax assets if, based on the weight of available evidence, it is more likely than not that some portion or all of the deferred tax assets will not be realized. Deferred tax assets are reviewed at each reporting date and a valuation allowance is recorded to the extent that it is no longer more likely than not that the related tax benefit will be realized.
Deferred tax assets and liabilities are offset when there is a legally enforceable right to set off current tax assets against current tax liabilities and when they relate to income taxes levied by the same taxation authority and the Company intends to settle its current tax assets and liabilities on a net basis.
Recently accounting pronouncements adopted
During the year ended September 30, 2024, there have been no new, or existing, recently issued accounting pronouncements that are of significance, or potential significance, that impact the Company’s consolidated financial statements.
Recently accounting pronouncements not yet adopted
In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740) - Improvements to Income Tax Disclosures (ASU 2023-09), which is intended to enhance the transparency and decision usefulness of income tax disclosures. Public business entities are required to adopt this standard for annual fiscal periods beginning after December 31, 2024, and early adoption is permitted. The Company is evaluating the impact the adoption of this guidance will have on its consolidated financial statements and related disclosures.
The Company evaluates all Accounting Standards Updates (ASUs) issued by the FASB for consideration for their applicability to the consolidated financial statements. Management assesses ASUs issued but not yet adopted and concluded that those not disclosed are not relevant to the Company or not expected to have a material impact.
4. SHORT-TERM INVESTMENTS
Short-term investments consist of U.S. treasury securities. The Company has classified these investments as available-for-sale, as the sale of such investments may be required prior to maturity to implement management strategies, and therefore has classified all investment securities as current assets. Investments in guaranteed investment certificates with maturity dates of three months or less at the date of purchase are presented as cash equivalents in the accompanying balance sheets. Short-term investments are carried at fair value with the unrealized gains and losses included in accumulated other comprehensive loss as a component of shareholders’ equity until realized. The Company records an allowance for credit losses when unrealized losses are due to credit-related factors. Realized gains and losses are calculated using the specific identification method and recorded as interest income.
Guaranteed investment certificates are held at financial institutions, have maturities of up to 12 months and purchased in accordance with the Company’s treasury policy.
As of September 30, 2024
Amortized
Unrealized
Accrued
Estimated
Cost
Gains
Losses
Investment Income
Fair Value
U.S. Treasury securities
$
23,015,247
$
11,284
$
-
$
24,051
$
23,050,582
GICs and Term deposits
-
-
-
-
-
Balance, end of year
$
23,015,247
$
11,284
$
-
$
24,051
$
23,050,582
As of September 30, 2023
Amortized
Unrealized
Accrued
Estimated
Cost
Gains
Losses
Investment Income
Fair Value
U.S. Treasury securities
$
72,802,531
$
-
$
(43,248)
$
301,738
$
73,061,021
GICs and Term deposits
41,141,314
-
-
172,154
41,313,468
Balance, end of year
$
113,943,845
$
-
$
(43,248)
$
473,892
$
114,374,489
As of September 30, 2024, short-term investments have an aggregate fair market value of $23.1 million (2023 - $114.4 million) were in an aggregate gross unrealized gain position of $11,284 (2023 - loss of $43,248).
5. PREPAIDS
September 30,
September 30,
Prepaid insurance
$
75,841
$
24,839
Prepaid CMC and clinical expenses and deposits
226,005
181,835
Other deposits and prepaid expenses
334,617
378,746
Balance, end of year
$
636,463
$
585,420
6. ACCOUNTS PAYABLE AND ACCRUED LIABILITIES
September 30,
September 30,
Accounts payable
$
2,403,519
$
2,028,265
Accrued expenses
171,690
845,730
Employee compensation and vacation accruals
601,764
540,748
Balance, end of year
$
3,176,973
$
3,414,743
7. OPERATING LEASE
The Company’s operating leases included on the balance sheet are as follows:
Operating lease right-of-use assets
Balance, September 30, 2022
$
186,499
Amortization
(118,491)
Balance, September 30, 2023
$
68,008
Addition
318,144
Amortization
(90,681)
Balance, September 30, 2024
$
295,471
Operating lease liabilities
Balance, September 30, 2022
$
210,252
Accretion
6,942
Lease payments
(136,866)
Balance, September 30, 2023
$
80,328
Addition
318,144
Cost of operating lease
(69,212)
Balance, September 30, 2024
$
329,260
Operating lease liabilities with expected life of less than one year
$
124,054
Operating lease liabilities with expected life greater than one year
$
205,206
The Company recognizes a right-of-use asset for the right to use the underlying asset for the lease term, and a lease liability, which represents the present value of the Company’s obligation to make payments over the lease term. The present value of the lease payments is calculated using an incremental borrowing rate as the Company’s leases do not provide an implicit interest rate. The incremental borrowing rate applied to the lease liability was 10.25%. As at September 30, 2024, the remaining lease term for the South Francisco office was 34 months.
As at September 30, 2024, the maturity of the Company’s operating lease liability was as follows:
Operating lease
Within 1 year
$
129,982
1 to 2 years
133,881
2 to 3 years
114,459
378,322
Less:
Imputed interest
(49,062)
Operating lease liability
$
329,260
8. SHAREHOLDERS’ EQUITY
Authorized
Unlimited common shares, without par value.
Unlimited preferred shares, without par value.
Omnibus incentive plan
On February 25, 2021, the Company adopted an omnibus incentive plan (“Omnibus Plan”), as subsequently amended, consistent with the policies and rules of Nasdaq. Pursuant to the Omnibus Plan, the Company may issue stock options, share appreciation rights, restricted shares, restricted share units and other share-based awards. As of June 30, 2024, the Company has not issued any instruments other than stock options under the Omnibus Plan.
Prior to the adoption of the Omnibus Plan, the Company issued equity compensation pursuant to the Company’s amended and restated stock option plan (the “Legacy Option Plan”), Amended and Restated Restricted Share Unit Plan (the “RSU Plan”) and Employee Stock Purchase Plan. Since the adoption of the Omnibus Plan, no further grants have been made under the Legacy Option Plan or RSU Plan, though existing grants under the Legacy Option Plan will continue in effect in accordance with their terms.
As of September 30, 2024, the Omnibus Plan has a maximum of 10,810,907 common shares which may be reserved for issuance.
Employee Share Purchase Plan
The Company has adopted an Employee Share Purchase Plan (“ESPP”) under which qualifying employees may be granted purchase rights (“Purchase Rights”) to the Company’s Common Shares at not less of 85% of the market price at the lesser of the date the Purchase Right is granted or exercisable. The Company currently holds offerings consisting of six-month periods commencing on January 1 and July 1 and ending on June 30 and December 31 of each calendar year. As at September 30, 2024, the ESPP has a maximum of 192,142 (2023 - 208,836) Common Shares reserved for issuance.
Eligible employees are able to contribute up to 15% of their gross base earnings for purchases under the ESPP through regular payroll deductions. Purchase of shares under the ESPP are limited for each employee at $25,000 worth of the Company’s Common Shares (determined using the lesser of (i) the market price of a common share on the first day of an applicable purchase period and (ii) the market price of a common share on the purchase date) for each calendar year in which a purchase right is outstanding.
During the year ended September 30, 2024, the Company issued a total of 16,694 (2023 -27,762) Common Shares upon the exercise of Purchase Rights. The Company recognizes compensation expense for purchase rights on a straight-line basis over the service period.
For the year ended
September 30,
Research and development expense
$
26,575
$
4,517
General and administrative
17,529
7,031
$
44,104
$
11,548
The Company measures the purchase rights based on their estimated grant date fair value using the Black-Scholes option pricing model and the estimated number of shares that can be purchased. The following weighted average assumptions were used for the valuation of purchase rights:
Risk-free interest rate
5.01%
%
4.90
%
Expected life of share purchase rights
6 months
6 months
Expected annualized volatility
77.53%
%
72.45
%
Dividend yield
-
-
Stock options
Pursuant to the Legacy Option Plan and Omnibus Plan, options were previously or may be granted, respectively, with expiry terms of up to 10 years, and vesting criteria and periods are approved by the Board at its discretion. The options issued under the Legacy Option Plan and Omnibus Plan are accounted for as equity-settled share-based payments.
Stock option transactions are summarized as follows:
Weighted
Number
Average
of Options
Exercise Price*
Balance, September 30, 2022
7,902,061
$
5.13
Options granted
300,000
2.97
Options expired/forfeited
(89,287)
(12.27)
Balance, September 30, 2023
8,112,774
$
4.97
Options granted
1,728,750
8.81
Options exercised
(271,018)
(3.25)
Options expired/forfeited
(358,232)
(11.68)
Balance outstanding, September 30, 2024
9,212,274
$
5.48
Balance exercisable, September 30, 2024
6,986,024
$
4.84
* Options exercisable in Canadian dollars as at September 30, 2024 are translated at current rates to reflect the current weighted average exercise price in U.S. dollars for all outstanding options.
The aggregate intrinsic value of stock options outstanding at September 30, 2024, was $14,669,988 (2023 - $85,700).
At September 30, 2024, options were outstanding enabling holders to acquire Common Shares as follows:
Weighted average remaining
Exercise price
Number of options
contractual life (years)
$
2.39 - 3.23
3,592,900
5.15
$
3.59 - 3.75
936,667
7.54
$
3.81 - 4.67
922,311
3.97
$
5.99 - 7.00
1,648,646
6.36
$
8.47 - 9.76
1,750,000
9.05
$
13.96
190,000
6.28
$
31.62
50,000
6.67
C$
4.90
106,750
2.85
C$
5.06
15,000
4.36
9,212,274
6.27
Share-based compensation
During the year ended September 30, 2024, the Company granted a total of 1,728,750 (2023 - 300,000) stock options with a weighted average fair value of $8.80 per option (2023 - $2.82).
The Company recognized share-based payments expense for options granted and vesting, net of recoveries on cancellations of unvested options, during the years ended September 30, 2024 and 2023 with allocations to its functional expense as follows:
For the year ended
September 30,
Research and development expense
$
1,796,501
$
2,622,987
General and administrative
4,698,285
2,372,934
$
6,494,786
$
4,995,921
The following weighted average assumptions were used for the Black-Scholes option-pricing model valuation of stock options granted:
Risk-free interest rate
4.20
%
3.78
%
Expected life of options
10.0
years
10.0
years
Expected annualized volatility
228.62
%
186.50
%
Dividend yield
-
-
Warrants
Warrant transactions are summarized as follows:
Weighted
Number
Average
of Warrants
Exercise Price
Balance, September 30, 2022
3,234,750
$
4.84
Warrants expired
(307,273)
(49.86)
Balance, September 30, 2023
2,927,477
$
0.11
Warrants expired
(7,477)
(42.80)
Balance outstanding and exercisable, September 30, 2024
2,920,000
$
0.00
In the year ended September 30, 2024, the Company amended the terms of the outstanding warrants to remove the expiry date. At September 30, 2024, warrants were outstanding enabling holders to acquire Common Shares as follows:
Number
of Warrants
Exercise Price
2,920,000
$
0.0001
2,920,000
9. RELATED PARTY TRANSACTIONS
Included in accounts payable and accrued liabilities at September 30, 2024, is $98,023 (2023 - $98,360) due to related parties with respect to key management personnel compensation and expense reimbursements. Amounts due to related parties are non-interest bearing, with no fixed terms of repayment.
10. INCOME TAXES
The following is a reconciliation of income taxes calculated at the combined Canadian federal and provincial income statutory corporate tax rate of 27.0% (2023 - 27.0%) to the tax expense:
For the years ended September 30
Loss for the year before income tax
$
(28,542,821)
$
(26,580,743)
Tax recovery at statutory income tax rates
$
(7,700,000)
$
(7,177,000)
Non-deductible share-based payments
1,274,000
643,000
Other permanent differences including foreign exchange
(10,000)
(4,000)
Change in statutory, foreign tax, foreign exchange rates and other
1,157,000
1,212,000
Adjustment to prior years provision versus statutory tax returns and expiry of non-capital losses
196,000
325,000
Change in valuation allowance
5,083,000
5,002,600
Total income tax expense
$
-
$
1,600
Tax attributes are subject to review, and potential adjustment, by tax authorities. The Company has recorded an income tax expense of $nil for the year ended September 30, 2024 (2023 - $1,600) in relation to taxable income generated by its U.S. subsidiary.
For the years ended September 30, 2024 and 2023, the Company did not record a provision for income taxes due to a full valuation allowance against our deferred tax assets. The significant components of the Company’s deferred tax assets that have not been included on the consolidated statement of financial position are as follows:
Deferred tax assets
Operating losses carried forward
$
49,750,000
$
43,726,000
Equipment and intangible assets
77,000
77,000
Investment tax credits
29,000
29,000
Financing costs
499,000
1,191,000
Federal R&D credit
210,000
210,000
Other
(303,000)
(54,000)
50,262,000
45,179,000
Valuation allowance
(50,262,000)
(45,179,000)
Net future tax assets
$
-
$
-
As at September 30, 2024, the Company has non-capital loss carry-forwards of approximately $95,100,000 (2023 - $90,502,000) available to offset future taxable income in Canada and approximately $114,633,000 (2023 - $91,858,000) available to offset future taxable income in the US. These non-capital loss carryforwards begin to expire in 2031.
11. SEGMENTED INFORMATION
The Company works in one industry being the development of small molecule drugs for prostate cancer. The Company’s right of use asset is located in the USA.
12. FINANCIAL INSTRUMENTS AND RISK
The Company’s financial instruments consist of cash and cash equivalents, short-term investments, receivables, and accounts payable and accrued liabilities. The fair value of cash and cash equivalents, GICs and term deposits included in short-term investments, receivables, accounts payable and accrued liabilities approximates their carrying values due to their short term to maturity. The fair value of U.S. treasury securities included in short-term investments are measured using Level 2 inputs based on standard observable inputs, including reported trades, broker/dealer quotes, and bids and/or offers (Note 4).
Fair value estimates of financial instruments are made at a specific point in time, based on relevant information about financial markets and specific financial instruments. As these estimates are subjective in nature, involving uncertainties and matters of judgment, they cannot be determined with precision. Changes in assumptions can significantly affect estimated fair values.
Financial risk factors
The Company’s risk exposures and the impact on the Company’s financial instruments are summarized below:
Credit risk
Financial instruments that potentially subject the Company to a significant concentration of credit risk consist primarily of cash and cash equivalents, short-term investments and receivables. The Company limits its exposure to credit loss by placing its cash with major financial institutions. The Company considers highly liquid investments with a maturity of up
to twelve months when purchased to be short-term investments. The Company maintains an investment policy which requires certain minimum investment grades over its investment instruments.
As of September 30, 2024, cash and cash equivalents consisted of cash in Canada and the United States and term deposits in Canada and investments in certain instruments which have a maturity of less than three months at the date of purchase. Balances in cash accounts exceed amounts insured by the Canada Deposit Insurance Corporation for up to C$100,000 and by the Federal Deposit Insurance Corporation for up to $250,000. Amounts due from government agencies are considered to have minimal credit risk.
Liquidity risk
As at September 30, 2024, the Company had working capital of $124,258,528 which will fund budgeted operations past the horizon of the coming year. The Company does not generate revenue and will use available financing options when required to pursue its business objectives.
Market risk
Market risk is the risk of loss that may arise from changes in market factors such as interest rates, and foreign exchange rates.
(a)Interest rate risk
As of June 30, 2024, the Company has cash and cash equivalents balances and short-term investments which are interest bearing. Interest income is not central to the Company’s capital management strategy and not significant to the Company’s projected operational budget. Interest rate fluctuations are not significant to the Company’s risk assessment.
(b)Foreign currency risk
The Company’s foreign currency risk exposure relates to net monetary assets denominated in Canadian dollars and Euro. The Company maintains its cash and cash equivalents in U.S. dollars and converts on an as needed basis to discharge Canadian and Euro denominated expenditures. The Company’s exposure to foreign exchange is not currently significant and may increase with clinical activities in the future. The Company does not currently engage in hedging activities.
13. COMMITMENTS
License Agreement
The NTD Technology is held under a license agreement signed in fiscal 2010 (the “License Agreement”). As consideration for the License Agreement, the Company issued Common Shares of the Company. The License Agreement contains an annual royalty as a percentage of annual net revenue and a percentage of any annual sublicensing revenue earned with respect to the NTD Technology. The License Agreement stipulates annual minimum advance royalty payments of C$85,000. In addition, there are certain milestone payments for the first compound, to be paid in stages as to C$900,000 at the start of a Phase 3 clinical trial, C$1,450,000 at application for marketing approval, and with further milestone payments on the second and additional compounds.
14. SUBSEQUENT EVENT
Subsequent to September 30, 2024, the Company announced the termination of its going clinical trial of masofaniten, its primary molecule. The Company has not incurred any immediate financial obligations with respect to the termination of the study and is evaluating its future operations.

---

ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.

---

ITEM 9A. CONTROLS AND PROCEDURES
Item 9A. Controls and Procedures
Evaluation of Disclosure Controls and Procedures
As of end of the period covered by this Annual Report on Form 10-K, our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated the design and operating effectiveness of our disclosure controls and procedures as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act of 1934 as amended (the “Exchange Act”). Our disclosure controls and procedures are designed to ensure that information required to be disclosed in the reports that the Company files or submits under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Any such information is accumulated and communicated to the company’s management, including its principal executive and principal financial officers, as appropriate, to allow timely decisions regarding required disclosure.
Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on our evaluation of our disclosure controls and procedures as of the end of the period covered by this report, our Chief Executive Officer and Chief Financial Officer concluded that, as of such date, our disclosure controls and procedures were, in design and operation, effective at the reasonable assurance level.
Management’s Annual Report on Internal Control over Financial Reporting
Our management, with the participation of our Chief Executive Officer and our Chief Financial Officer, is responsible for establishing and maintaining adequate internal control over our financial reporting, defined in Rule 13a-15(f) and Rule 15d-15(f) of the Exchange Act.
The effectiveness of any system of internal control over financial reporting, including ours, is subject to inherent limitations, including the exercise of judgment in designing, implementing, operating, and evaluating the controls and procedures, and the inability to eliminate misconduct completely. Accordingly, any system of internal control over financial reporting, including ours, no matter how well designed and operated, can only provide reasonable, not absolute, assurances. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions or that the degree of compliance with the policies or procedures may deteriorate. Management has assessed the effectiveness of our internal control over financial reporting as at September 30, 2024. In making its assessment, management used the criteria set forth in the internal control - integrated framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 COSO framework) to evaluate the effectiveness of our internal control over financial reporting. Based on this evaluation, management has concluded that our internal control over financial reporting was effective as of September 30, 2024.
Changes in Internal Control Over Financial Reporting
There were no changes in our internal control over financial reporting during the quarter ended September 30, 2024 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

---

ITEM 9B. OTHER INFORMATION
Item 9B. Other Information
None.

---

ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
Item 10. Directors, Executive Officers and Corporate Governance
The information required by Item 10. of Form 10-K is incorporated by reference to our proxy statement for the 2024 annual meeting of shareholders (the “2024 Proxy Statement”), to be filed with the SEC within 120 days after the end of the fiscal year ended September 30, 2024.
We have a disclosure and insider trading policy which governs the purchase, sale and/or other dispositions of our securities by our directors, executive officers and employees that we believe is reasonably designed to promote compliance with insider trading laws, rules and regulations, and the exchange listing standards applicable to us. A copy of our disclosure and insider trading policy is filed as Exhibit 19.1 to this Annual Report on Form10-K.

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ITEM 11. EXECUTIVE COMPENSATION
Item 11. Executive Compensation
The information required by Item 11. of Form 10-K is incorporated by reference to our 2024 Proxy Statement (excluding the information under the subheading “Pay versus Performance”), to be filed with the SEC within 120 days after the end of the fiscal year ended September 30, 2024.

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ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Shareholder Matters
The information required by Item 12. of Form 10-K is incorporated by reference to our 2024 Proxy Statement, to be filed with the SEC within 120 days after the end of the fiscal year ended September 30, 2024.

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ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by Item 13. of Form 10-K is incorporated by reference to our 2024 Proxy Statement, to be filed with the SEC within 120 days after the end of the fiscal year ended September 30, 2024.

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ITEM 14. PRINCIPAL ACCOUNTING FEES AND SERVICES
Item 14. Principal Accountant Fees and Services
The information required by Item 14. of Form 10-K is incorporated by reference to our 2024 Proxy Statement, to be filed with the SEC within 120 days after the end of the fiscal year ended September 30, 2024.
PART IV

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ITEM 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES
Item 15. Exhibits and Financial Statement Schedules
(a)(1) Financial Statements-The financial statements included in Item 8 are filed as part of this Annual Report on Form 10-K.
(a)(2) Financial Statement Schedules-All schedules have been omitted because they are not applicable or required, or the information required to be set forth therein is included in the consolidated Financial Statements or notes thereto included in Item 8 of this Annual Report on Form 10-K.
(a)(3) Exhibits-The exhibits required by Item 601 of Regulation S-K are listed in paragraph (b) below.
(b) Exhibits-The exhibits listed on the Exhibit Index below are filed herewith or are incorporated by reference to exhibits previously filed with the SEC.
EXHIBITS INDEX
Exhibit No.
3.1
Amended Articles of Incorporation of ESSA Pharma Inc. (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K (File No. 001-37410), originally filed with the SEC on September 18, 2023)
4.1
Specimen common share certificate (incorporated by reference to Exhibit 4.1 to the Company’s Registration Statement on Form S-8 (File No. 333-225056), originally filed with the SEC on May 18, 2018)
4.2
Description of Capital Stock (incorporated by reference to Exhibit 4.2 to the Company’s Annual Report on Form 10-K (File No. 001-37410), originally filed with the SEC on December 13, 2022)
10.1
Cancer Research Contract between CPRIT and the Company, dated July 9, 2014 (incorporated by reference to Exhibit 4.1 to the Company’s Registration Statement on Form 20-F (File No. 377-00939), originally filed with the SEC on February 24, 2015)
10.2
License Agreement between the BC Cancer Agency, UBC and the Company, dated December 22, 2010, as amended on February 10, 2011 and May 27, 2014 (incorporated by reference to Exhibit 4.2 to the Company’s Registration Statement on Form 20-F (File No. 377-00939), originally filed with the SEC on February 24, 2015)
10.3
Amendment to License Agreement between the BC Cancer Agency, UBC and the Company, dated May 25, 2021 (Schedules have been omitted pursuant to Item 601(b)(10) of Regulation S-K. The Company agrees to furnish supplementally to the SEC a copy of any omitted schedule upon request)*
10.4
Employment Agreement for David Wood (incorporated by reference to Exhibit 4.9 to the Company’s Registration Statement on Form 20-F (File No. 377-00939), originally filed with the SEC on April 7, 2015)
10.5
Employment Agreement for David Parkinson (incorporated by reference to Exhibit 4.9 to the Company’s Annual Report on Form 20-F (File No. 001-37410), originally filed with the SEC on December 14, 2016)
10.6
Employment Agreement for Peter Virsik (incorporated by reference to Exhibit 4.10 to the Company’s Annual Report on Form 20-F File (No. 001-37410), originally filed with the SEC on December 14, 2016)
10.7
Employment Agreement for Alessandra Cesano (incorporated by reference to Exhibit 4.7 to the Company’s Annual Report on Form 20-F (File No. 001-37410), originally filed with the SEC on December 20, 2019)
10.11
Lease for 400 Oyster Point Boulevard, South San Francisco, California, United States dated March 5, 2018 (incorporated by reference to Exhibit 4.12 to the Company’s Annual Report on Form 20-F (File No. 001-37410), originally filed with the SEC on December 13, 2018)
10.12
ESSA Pharma Inc. 2022 Omnibus Incentive Plan (incorporated by reference to Exhibit 99.1 to the Company’s Current Report on Form 8-K (File No. 001-37410), originally filed with the SEC on March 10, 2022)
10.13
ESSA Pharma Inc. Severance Plan*
19.1
ESSA Pharma Inc. Disclosure and Insider Trading Policy*
21.1
List of Subsidiaries*
23.1
Consent of Davidson & Company LLP, an Independent Registered Public Accounting Firm*
31.1
Certification of the Chief Executive Officer pursuant to Rule 13a-14(a) of the Securities and Exchange Act of 1934, as amended*
31.2
Certification of the Chief Financial Officer pursuant to Rule 13a-14(a) of the Securities and Exchange Act of 1934, as amended*
32.1
Certification by the Chief Executive Officer and Chief Financial Officer pursuant to 18 U.S.C. Section 1350 as added by Section 906 of the Sarbanes-Oxley Act of 2002**
The ESSA Pharma Inc. Clawback Policy*
101.INS
Inline XBRL Instance Document - The instance document does not appear in the interactive data file because its XBRL tags are embedded within the Inline XBRL document. *
101.SCH
Inline XBRL Taxonomy Extension Schema Document *
101.CAL
Inline XBRL Taxonomy Extension Calculation Linkbase Document *
101.LAB
Inline XBRL Taxonomy Extension Label Linkbase Document *
101.PRE
Inline XBRL Taxonomy Extension Presentation Linkbase Document *
101.DEF
Inline XBRL Taxonomy Extension Definition Linkbase Document *
Cover page from the Company’s Annual Report on Form 10-K for the year ended September 30, 2024 formatted in Inline XBRL (included in Exhibit 101).
* Filed herewith.
** Furnished herewith