Masofaniten +Enzalutamide This could be a game changer...Science is coming to our aid

[Scout4answers]

This is a company that I was turned on to by Nalkrantz before he was removed from this board. He told me that he was in touch with a doctor that was involved with this drug. Reportedly the early testing on a single patient had been phenomenal. These are pretty amazing #s

NEWS PROVIDED BY

ESSA Pharma Inc

21 Oct, 2023, 09:00 ET

Combination of masofaniten plus enzalutamide continues to be well tolerated with deep and durable reductions in PSA in patients with mCRPC

Across all cohorts of patients including those recently enrolled into cohort four, 69% of patients achieved PSA90, 63% of patients achieved PSA90 in less than 90 days, and 56% of patients achieved PSA <0.2mg/mL

SOUTH SAN FRANCISCO, Calif. and VANCOUVER, Canada, Oct. 21, 2023 /PRNewswire/ - ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, today 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 European Society of Medical Oncology (ESMO) 2023 Congress, taking place October 20-24, 2023, in Madrid, Spain. Masofaniten is a first-in-class N-terminal domain androgen receptor ("AR") inhibitor that suppresses androgen activity through a novel mechanism of action and is being developed for the treatment of prostate cancer. The poster presentation is available on the ESMO Digital Program and in the "Publications" section of the Company's website at essapharma.com.

"The dose escalation data presented at ESMO this year continue to demonstrate that the combination of masofaniten and enzalutamide is well tolerated and results in deep and durable reductions in prostrate-specific antigen ("PSA") in patients with metastatic castration-resistant prostate cancer ("mCRPC")," said David Parkinson, MD, President and CEO of ESSA. "While the data for patients in cohort four are not yet mature, we are highly encouraged by the PSA responses seen thus far in the cohort and in the study as a whole. We look forward to further elucidating the potential clinical benefit of this combination in the randomized Phase 2 portion of the study which is currently underway."

Poster presentation details:

Title: Phase 1/2 Trial of Oral EPI-7386 (masofaniten) in Combination with Enzalutamide (Enz) Compared with Enz Alone in Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC): Current Phase 1 (P1) results

Presenting Author: Andrew Laccetti, MD, MS, Memorial Sloan Kettering Cancer Center

Abstract # 1813P

Date: Sunday, October 22, 2023

Data summary: This Phase 1/2 multicenter, open-label clinical trial is enrolling patients with mCRPC who have received androgen deprivation therapy and who are naïve to second-generation antiandrogens but may have been treated previously with one line of prior chemotherapy in the metastatic hormone-sensitive prostate cancer setting. The data presented today are from the first four cohorts of patients in the Phase 1 dose escalation portion of the study. Masofaniten has no effect on enzalutamide exposure, thus allowing the use of full dose per label (160mg) of enzalutamide in combination. Enzalutamide reduces masofaniten exposure but twice daily dosing of masofaniten appears to mitigate the reduction and maintains clinically relevant drug exposures.

In patients evaluable for safety (n=18), masofaniten combined with enzalutamide, continues to be 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 <0.2mg/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 <0.2mg/mL. The randomized Phase 2 dose expansion portion of the study is currently enrolling.

About Masofaniten

Masofaniten (formerly known as EPI-7386) is a first-in-class investigational, highly selective, oral, small molecule inhibitor of the N-terminal domain ("NTD") of the androgen receptor ("AR"). Masofaniten's unique mechanism of action disrupts the AR signaling pathway, the primary pathway that drives prostate cancer growth, by selectively binding to the NTD, a region of the AR that is not currently targeted by other therapies. Masofaniten is currently being studied in an open-label, randomized Phase 2 clinical trial (NCT05075577) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) naïve to second-generation antiandrogens. ESSA is also conducting a Phase 1 monotherapy study (NCT04421222) in patients with mCRPC whose tumors have progressed on standard-of-care therapies. The U.S. Food and Drug Administration has granted Fast Track designation to masofaniten for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to masofaniten worldwide.

[Maxone73]

Posted it today as well! Very interesting !

[Scout4answers in reply to Maxone73]

Great minds think alike... maybe curious minds

[Maxone73 in reply to Scout4answers]

Ahahah!! Right!!

[Ramp7]

More information from your thoughts. ncbi.nlm.nih.gov/pmc/articl...

[Maxone73]

not prostate related (yet) but keep an eye on this for the future: blogs.bcm.edu/2023/10/26/fr...

[Garbonzeaux]

Scout,

Thanks for this. Any idea what Masofaniten is, other than "small molecule"? As a chemist, it's always something I like to know. Nalakrats (note spelling) is also a chemist, so he might know, but I have no idea how to contact him anymore.

[Scout4answers in reply to Garbonzeaux]

My background is in Finance not Science so I do not know .

[GP24]

Here is a report of the presentation of Masofaniten at the ESMO 2023: urotoday.com/conference-hig...

[j-o-h-n]

Note: You can't contact Good ole Nal...... he's in the Witness Protection Program.

BTW "Masofaniten" sounds like something that should be served on German Pumpernickel Bread and is fattening.

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 10/28/2023 1:18 PM DST

[addicted2cycling in reply to j-o-h-n]

j-o-h-n wrote -- " ... BTW "Masofaniten" sounds like something that should be served on German Pumpernickel Bread and is fattening ... "

Sounds to me like a HUGE canine that's ready to bite my arse off.

[j-o-h-n in reply to addicted2cycling]

Come to think of it, that too...........

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 10/29/2023 11:32 AM DST

[GP24]

Let me try to explain how Masofaniten or EPI-7386 works. Zachary Klaassen writes in Uroday:

The androgen receptor is activated by androgen binding to the ligand binding domain which induces the dimerization and nuclear translocation of the androgen receptor. Current androgen receptor targeted therapies work directly or indirectly through the ligand binding domain of the androgen receptor either by competing with androgen binding to the ligand binding domain or by inhibiting the androgen production (centrally through CYP17 inhibition).

EPI-7386 is a next generation antiandrogen designed to inhibit androgen receptor activity by binding the N-terminal domain and blocking transcription despite resistance driven by point mutations and splice variants in the ligand-binding domain.

Below is a schema of the androgen receptor. At the top there is the full AR, which already amplified to several ligand-binding domains, which bind to testosterone. All hormone therapy drugs block or address these ligand-binding domains. In CRPC the androgen receptor of many PCa cells mutates by loosing the ligand binding domains and is able to work without testosterone. As you can see, all of these mutations still have an N-terminal domain (in blue).

Masofaniten works by blocking this N-terminal domain and therefore works for those mutated cells where all other drugs are no longer effective.

Androgen receptor splice variants

[Scout4answers in reply to GP24]

Does this mean cancer can not progress? or will it still have work arounds so it can metastasize.

[GP24 in reply to Scout4answers]

This a logical consequence. However, so far cancer has always found a workaround.

[Maxone73 in reply to Scout4answers]

I think at the end of the day a solution could come by crossing different fields of research. I am in close contact with some dear friends who work with CRISPR/Cas9 keeping me updated (during a great dinner like yesterday evening!). That's another very promising field.