masofaniten (EPI-7386) / XenoTherapeutics - LARVOL DELTA

Phase I/II trial of oral EPI-7386 in combination with enzalutamide (enz) compared to enz alone in metastatic castration-resistant prostate cancer (mCRPC) subjects: Current phase I (PI) results (ESMO 2023) - P1/2 | "Conclusions With no safety concerns from cohorts 1-3, cohort 4 is currently enrolling at EPI-7386 BID + 160 mg QD Enz to evaluate optimal RP2Ds before the P2 component of the trial. Updated results, including cohort 4, will be presented."

Clinical • Combination therapy • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CYP3A4

Phase I/II trial of oral masofaniten (EPI-7386) in combination with enzalutamide (Enz) compared to enz alone in metastatic castration-resistant prostate cancer (mCRPC) subjects (ESMO 2024) - P1/2 | "Updated results, long term follow-up of P1 pts and a comparison to historical trials will be presented. P2 is currently enrolling in the USA, Canada, Australia, France, Belgium and Spain."

Clinical • Combination therapy • Metastases • P1/2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

EXTRA-PC: A phase II trial of masofaniten (EPI-7386) and enzalutamide with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (mHSPC). (ASCO-GU 2026) - P1/2, P2 | "They may help overcome AR resistance mechanisms at the ligand-binding domain (LBD), which is the binding site of currently approved androgen receptor pathway inhibitors (ARPIs) such as enzalutamide, apalutamide, and darolutamide. The triplet combination of masofaniten, enzalutamide, and ADT for mHSPC did show efficacy and had an acceptable safety profile. Dual inhibition of the NTD and LBD of the AR is feasible in this setting."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Small-molecule modulators of the androgen receptor N-terminal domain: Advances in medicinal chemistry for prostate cancer. (PubMed, Eur J Med Chem) - "Advances in screening platforms and the optimization of structure-activity relationships are beginning to address the challenges of targeting disordered protein domains. With agents like EPI-7386 entering clinical evaluation and others advancing through preclinical development, AR NTD-targeted therapies represent a promising avenue to overcome resistance in castration-resistant prostate cancer (CRPC), potentially in combination with existing LBD-directed treatments to achieve more durable disease control."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

EXTRA-PC: A phase II trial of masofaniten (EPI-7386) and enzalutamide for patients with treatment-naïve metastatic hormone-sensitive prostate cancer. (PubMed, Oncologist) - P2 | "The combination of masofaniten and enzalutamide for treatment-naïve mHSPC did show efficacy and had an acceptable safety profile. These results support further investigation of the dual AR blockade in mHSPC (ClinicalTrials.gov Identifier: NCT06312670)."

Journal • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Combining EPI-7386 With Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Pedro Barata, MD, MSc | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Jan 2025 | Trial primary completion date: Mar 2026 ➔ Jan 2025

Trial completion • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

EPI-7386-CS-010: EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC (clinicaltrials.gov) - P1/2 | N=77 | Terminated | Sponsor: ESSA Pharmaceuticals | N=150 ➔ 77 | Active, not recruiting ➔ Terminated; Study was terminated early due to a lack of improved efficacy.

Enrollment change • Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

EPI-7386-CS-001: Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=71 | Terminated | Sponsor: ESSA Pharmaceuticals | Active, not recruiting ➔ Terminated; Study was terminated early due to a lack of improved efficacy.

Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Faruqi & Faruqi Reminds ESSA Pharma Investors of the Pending Class Action Lawsuit with a Lead Plaintiff Deadline of March 25, 2025 - EPIX (PRNewswire) - "As detailed below, the complaint alleges that the Company and its executives violated federal securities laws by making false and/or misleading statements and/or failing to disclose that: (1) masofaniten in combination with enzalutamide had no clear efficacy benefit over enzalutamide alone; (2) accordingly, masofaniten in combination with enzalutamide was less effective in treating prostate cancer than Defendants had led investors to believe; (3) the M-E Combination Study was unlikely to meet its prespecified Phase 2 primary endpoint; (4) accordingly, Defendants had overstated masofaniten's clinical, regulatory, and commercial prospects; and (5) as a result, Defendants' public statements were materially false and misleading at all relevant times."

Corporate lawsuit • Castration-Resistant Prostate Cancer

A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Janssen Research & Development, LLC | Phase classification: P1b ➔ P1

Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Combining EPI-7386 with Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=13 | Active, not recruiting | Sponsor: Pedro Barata, MD, MSc | Recruiting ➔ Active, not recruiting | N=35 ➔ 13

Enrollment change • Enrollment closed • Metastases • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EPI-7386-CS-010: EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC (clinicaltrials.gov) - P1/2 | N=150 | Active, not recruiting | Sponsor: ESSA Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Jan 2025 | Trial primary completion date: Aug 2025 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EPI-7386-CS-001: Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=99 | Active, not recruiting | Sponsor: ESSA Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Jan 2025 | Trial primary completion date: Apr 2026 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Announces Termination of Phase 2 Study Evaluating Masofaniten Combined with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer (Canada Newswire) - "Efficacy signals observed will not achieve ESSA's target product profile in patients with metastatic castration-resistant prostate cancer naïve to second-generation antiandrogens; A futility analysis conducted as part of a protocol-specified interim review of the safety, PK and efficacy data showed the single-agent enzalutamide control arm performing better than historical controls and similar to the combination of masofaniten and enzalutamide and therefore, unlikely to achieve the primary endpoint of the study; Additional clinical studies with masofaniten including the combination study with abiraterone acetate and apalutamide as well as the remaining investigator sponsored trials will also be terminated and the IND and CTAs in different geographies will be withdrawn."

Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1/2 Trial of Oral Masofaniten (EPI-7386) in Combination with Enzalutamide (Enz) Compared to Enz Alone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Subjects (PCF 2024) - P1/2 | "Updated results, long term follow-up of P1 pts and a comparison to historical trials will be presented. P2 is currently enrolling in the USA, Canada, Australia, France, Belgium and Spain."

Clinical • Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Presents Updated Phase 1/2 Masofaniten (EPI-7386) Clinical Data at the 2024 ESMO Congress (PRNewswire) - P1/2 | N=150 | NCT05075577 | Sponsor: ESSA Pharmaceuticals | "ESSA Pharma...announced the presentation of updated dose escalation data from its Phase 1/2 study evaluating masofaniten (formerly EPI-7386) in combination with enzalutamide at the 2024...ESMO Congress....'We look forward to providing further updates in 2025'....In patients evaluable for safety (n=18), masofaniten combined with enzalutamide, continues to be well-tolerated at the dose levels tested through 32 cycles of dosing in some patients....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)....Across all dosing cohorts, 88% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 63% of patients achieved PSA <0.2ng/mL. After 15.2 months of follow up, median time to PSA progression and radiographic progression free survival have not yet been reached."

P1/2 data • Metastatic Castration-Resistant Prostate Cancer

ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal Third Quarter Ended June 30, 2024 (PRNewswire) - "Phase 1/2 study is still ongoing evaluating masofaniten in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer ('mCRPC') naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting...ESSA plans to report updated data from the Phase 1 dose escalation study at the European Society for Medical Oncology (ESMO) 2024 congress...Enrollment in the Phase 2 portion of this Phase 1/2 study is expected to be completed during the first quarter of 2025...Expansion to European clinical sites is in progress with an additional 14 clinical sites planned to be activated by the third quarter of 2024. ESSA is on track to report preliminary data from the Phase 2 dose expansion portion of the study in mid-2025."

P1 data • P2 data • Trial status • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal Third Quarter Ended June 30, 2024 (PRNewswire) - "ESSA remains on track to complete the Phase 1b masofaniten monotherapy study evaluating masofaniten in patients with mCRPC resistant to second-generation antiandrogens....ESSA plans to present the complete Phase 1b monotherapy results in the second half of 2024 at a medical conference....R&D expenditures for the third quarter ended June 30, 2024, were $5.5 million compared to $6.3 million for the third quarter ended June 30, 2023, and include non-cash costs related to share-based payments of $851,971 for the third quarter ended 2024 compared to $599,621 for the third quarter ended 2023. The decrease is largely attributable to reductions in preclinical work with the focus on ongoing clinical trials."

Commercial • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Combining EPI-7386 With Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Pedro Barata, MD, MSc | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal Second Quarter Ended March 31, 2024 (PRNewswire) - "Masofaniten is currently being evaluated in combination with enzalutamide compared to enzalutamide monotherapy in a Phase 2 dose randomized study in patients with mCRPC naïve to second-generation antiandrogens but who may have been treated with chemotherapy in the metastatic castration-sensitive setting. Enrollment in the Phase 2 portion of this Phase 1/2 study is expected to be completed during the first quarter of 2025....The study is currently enrolling at approximately 25 sites in the USA, Canada, and Australia. Expansion to European clinical sites is in progress with an additional 15 clinical sites planned to be activated by 3Q24. ESSA expects to report preliminary data from the Phase 2 dose expansion portion of the study in mid-2025."

P2 data • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Combining EPI-7386 w/ Enzalutamide & Androgen Deprivation Therapy for Newly Diagnosed Prostate Cancer (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: Pedro Barata, MD, MSc

Metastases • New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal First Quarter Ended December 31, 2023 (PRNewswire) - "On track to complete the Phase 1b masofaniten monotherapy study evaluating masofaniten in patients with late-line mCRPC, which is currently ongoing....ESSA plans to present the complete Phase 1a and 1b monotherapy results in 2024 at a medical conference."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal First Quarter Ended December 31, 2023 (PRNewswire) - "Reported Phase 1 dose escalation data at multiple medical meetings from the four cohorts of its ongoing Phase 1/2 study evaluating masofaniten in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer ('mCRPC') naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting....ESSA expects to report updated data from the Phase 1 dose escalation study during the second half of 2024. Initiated two additional masofaniten combination arms as part of the ongoing Phase 1 masofaniten study. One arm will evaluate masofaniten in combination with abiraterone acetate and prednisone in patients with either metastatic castration-sensitive prostate cancer or mCRPC while the second arm will evaluate masofaniten in combination with apalutamide in patients with non-metastatic castration-resistant prostate cancer after 12 weeks of masofaniten single agent. ESSA..."

P1 data • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1/2 trial of oral EPI-7386 (masofaniten) in combination with enzalutamide (Enz) compared to Enz alone in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase 1 (P1) results and phase 2 (P2) design. (ASCO-GU 2024) - P1/2 | "The RP2CD for P2 was established at masofaniten 600 mg BID + Enz 160 mg QD. Updated results, including long term follow-up of the dose escalation patients, and P2 study design, will be presented. Clinical trial information: NCT05075577."

Clinical • Combination therapy • Metastases • P1/2 data • P2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • CYP3A4

ESSA Pharma Presents Updated Phase 1 Masofaniten (EPI-7386) Clinical Data at the 2024 ASCO Genitourinary Cancers Symposium (PRNewswire) - P1/2 | N=150 | NCT05075577 | Sponsor: ESSA Pharmaceuticals | "The data presented today include 18 patients across four cohorts in the Phase 1 dose escalation portion of the study....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 are still maturing with a current median follow up of 11.1 months, the median time to PSA progression is at 16.6 months....The study is currently enrolling at approximately 25 sites in the USA, Canada and Australia. Expansion to European sites is in progress."

P1 data • Trial status • Metastatic Castration-Resistant Prostate Cancer