Zacks Small Cap Research – EPIX: Updated Data for Phase 1 Trial of Masofaniten Shows 63% of Patients Achieved PSA – Earn Charter

By David Bautz, PhD

NASDAQ:EPIX

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Updated Phase1/2 Data for Masofaniten Presented at ASCO Genitourinary Cancers Symposium

On January 25, 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 ASCO Genitourinary Cancers Symposium. 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 naïve 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. The combination of masofaniten and Enz is 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. Lastly, there were no serious adverse events (SAEs) observed.

The following chart shows the current patient disposition. Of the 18 patients enrolled in the trial, 13 are still on treatment and five have discontinued (disease progression = 3; 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, two had a partial response, two had stable disease, and one had progressive disease.

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), 81% (13/16) 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.

While difficult to do cross-trial comparisons, the Phase 3 clinical trials of Enz show what is to be expected when treating patients either pre-chemotherapy (PREVAIL trial; Beer et al., 2014) or post-chemotherapy (AFFIRM trial; Scher et al., 2012) with single agent Enz. The following table on the left summarizes the data from those trials (along with the ENZA-p Phase 2 trial of 177Lu-PSMA-617 in combination with enzalutamide) in regards to PSA response. The figure on the right shows the current time to PSA progression (16.6 months), which while immature compares quite favorably to data from both the AFFIRM (8.3 months) and PREVAIL (11.2 months) trials.

The median PSA baseline for this study was 3.2 ng/mL, which on the surface may look like it is quite different from the other studies listed in the table above. However, this value is for all 18 patients, including the two that were not evaluable for efficacy. For the patients just listed in the waterfall plot above, the median PSA at baseline was 8.5 ng/mL. In addition, if you exclude the post-chemo patients (who had a median PSA at baseline of 2.1 ng/mL), the median PSA at baseline for the pre-chemo patients was 22.8 ng/mL, which is not far from the 33 ng/mL reported in the ENZA-p study. Lastly, the 22.8 ng/mL baseline PSA for pre-chemo patients is also in line with the ACIS study of apalutamide and abiraterone acetate in chemotherapy naïve patients with mCRPC (Saad et al., 2021). Thus, we believe the cross-trial comparisons are appropriate to help put the results seen thus far with masofaniten in context with other therapies in similar patient populations.

PSA response is an important prognosticator, as it was shown to be correlated with a number of positive outcomes from the PREVAIL study (Armstrong et al., 2019). This agrees with multiple other studies of hormone-sensitive prostate cancer (HSPC) patients that show greater PSA responses are associated with better long-term prognoses. In addition, PSA response was shown to correlated with five-year survival in the PREVAIL study:

• Armstrong et al., 2020: This was a long-term safety and efficacy analysis of the PREVAIL trial that evaluated 5-year survival and its correlation with various pretreatment prognostic factors and post-treatment PSA declines. The results showed that the 5-year survival rate for those with a best overall PSA decline of <0.2 ng/mL was 71% compared to just 11% for those with no PSA decline or < 30% confirmed decline. Even for those who achieved PSA90, the 5-year survival rate was only 42%. This exemplifies the importance of achieving PSA < 0.2 ng/mL and how that can have a positive impact on long-term survival. Approximately 11% (100/872) of patients treated with Enz in PREVAIL achieved PSA <0.2 ng/mL.

PSA responses of <0.2 ng/mL do not appear to be commonly reported in studies of mCRPC patients, however the Phase 3 ACIS study showed that 25% of mCRPC patients treated with apalutamide plus abiraterone acetate and prednisone achieved a PSA level <0.2 ng/mL at any time during treatment compared to 19% treated with just abiraterone acetate and prednisone (Saad et al., 2021).

Conclusion

The data from the ongoing Phase 1/2 clinical trial of masofaniten and Enz continues to be very encouraging, as the combination therapy is well tolerated and results in deep and durable decreases in PSA. The company is continuing to enroll patients in the dose expansion portion of the Phase 2 trial of masofaniten and Enz and we anticipate initial data from the study being reported later in 2024. With no changes to our model our valuation remains at $29 per share.

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