NASDAQ:EPIX
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Business Update
Masofaniten plus Enzalutamide Results in Increased rPFS
On September 13, 2024, ESSA Pharma, Inc. (NASDAQ:EPIX) announced that updated Phase 1/2 clinical trial data for masofaniten (formerly EPI-7386) in combination with enzalutamide (Enz) was presented at the 2024 European Society for Medical Oncology (ESMO) Congress. A copy of the poster presentation can be found here. The Phase 1/2 trial is enrolling patients with metastatic castration-resistant prostate cancer (mCRPC) who are naĂ¯ve to second-generation antiandrogens. The Phase 1 portion of the study enrolled 18 patients in four dose cohorts, with 16 patients evaluable for efficacy as per protocol.
After 15.2 months of follow-up, median progression has not yet been reached for various outcomes. Currently, 11 of 18 patients are still on treatment. While cross trial comparisons are difficult and have a number of limitations, at this point it is fair to say that the data compares quite well to other 1st line mCRPC trials testing Enz as a single agent, with the values for time to PSA progression (TTPP) and radiographic progression free survival (rPFS) depicted for those other studies in the following graphs: ENZA-P (Emmett et al., 2024; AFFIRM Scher et al., 2012; PREVAIL Beer et al., 2014).
Of the following data, the radiographic progression-free survival (rPFS) graph is where we believe investors should focus their attention. rPFS is an approvable endpoint, as demonstrated by the approval of olaparib with abiraterone acetate and prednisone based on results of the PROpel Phase 3 trial (FDA). The data compiled thus far for masofaniten clearly show a substantial improvement in rPFS when used in combination with Enz and it will likely be some time before an estimated median rPFS can be calculated, however it is likely it will be well beyond that seen in PREVAIL. For reference, the rPFS seen in the PREVAIL trial (20.0 months) is similar to rPFS results for Enz monotherapy from other Phase 3 trials in mCRPC such as ALLIANCE (rPFS 21.3 months; Morris et al., 2023) and TALAPRO-2 (rPFS 21.9 months; Agarwal et al., 2023).
Importantly, the combination of masofaniten and Enz continues to be safe and well tolerated, with an adverse event profile that is consistent with single-agent Enz. The following table shows adverse events (AEs) occurring in ≥10% of patients, with most either related to androgen receptor inhibition or gastrointestinal tract irritation and were Grade 1 or 2 in severity. In Cohort 4, there was a report of a Grade 3 rash that was deemed to be probably related to study drug. It was observed after administration of masofaniten and Enz in combination during the dose-limiting toxicity period. The patient has since discontinued the study due to disease progression. It should be noted that the monotherapy study of masofaniten did not report a similar rash, while Enz’s Phase 1 dose escalation study had a rash as a dose limiting toxicity at higher Enz exposures. There was no greater probability of treatment-related AEs observed at higher EPI-7386 or Enz exposures and AEs are not increasing in frequency over time. There have been two dose modifications: Grade 2 fatigue (Enz 120 mg to 80 mg) and Grade 3 rash (masofaniten 600 mg BID to QD + Enz 160 mg to 120 mg). Lastly, there were no serious adverse events (SAEs) observed.
The following chart on the left shows the current patient disposition with a median follow up of 15.2 months. Of the 18 patients enrolled in the trial, 11 are still on treatment and seven have discontinued (disease progression = 5; brain abscess = 1 (non-related event); non-cancer related death = 1). Of the 18 enrolled patients, 13 have non-measurable disease while five have measurable disease. Of the five with measurable disease, three had a partial response and two had stable disease, as shown in the figure on the right.
Across all dosing cohorts, patients showed a rapid, deep, and durable decrease in prostate-specific antigen (PSA). The following chart on the left shows the PSA outcomes for all enrolled patients. The current response rates in evaluable patients show that 88% (14/16) have achieved PSA50 (a 50% decrease in PSA levels from baseline), 88% (14/16) have achieved PSA90 (a 90% decrease in PSA levels from baseline), 69% (11/16) achieved PSA90 within 90 days, and 63% (10/16) have achieved PSA <0.2 ng/mL. The graph on the right shows the best % PSA change from baseline for each patient.
Conclusion
Overall, we continue to be impressed by the combination data of masofaniten and Enz as it compares quite favorably to single agent Enz treatment from previous Phase 3 studies. We are particularly intrigued by the rPFS data as it is likely to surpass the results of the PREVAIL trial based on how the graph looks now and the continued low PSA values for patients in the trial. The Phase 2 portion of the trial is continuing to enroll patients and the company is in the process of opening an additional 22 sites in Europe. We anticipate updates from the Phase 2 portion of the trial in 2025. We have increased the probability of approval for masofaniten based on the rPFS results, which has increased our valuation to $33 per share.
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