EPI-7386 was safe and well-tolerated at all
dose levels and schedules tested with plasma target concentrations
achieved and clinically important efficacy signals
Conference Call and Webcast Today at
5:00 p.m. ET
SOUTH
SAN FRANCISCO, California and VANCOUVER, Canada, June 27,
2022 /CNW/ - 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 presented clinical results from the Phase 1a dose
escalation study of EPI-7386, ESSA's first-in-class N-terminal
domain ("NTD") androgen receptor ("AR") inhibitor, as a monotherapy
for the treatment of patients with metastatic castration-resistant
prostate cancer ("mCRPC") resistant to current standard-of-care
therapies. The initial data from 36 patients demonstrate that
EPI-7386 was well-tolerated, exhibited a favorable pharmacokinetic
profile, and demonstrated initial anti-tumor activity in a heavily
pretreated group of patients. ESSA expects to initiate the Phase
1b expansion study in Q3 2022.
"We are pleased with the progress in advancing our novel
prostate cancer candidate EPI-7386 as a monotherapy in patients
with advanced mCRPC. EPI-7386's favorable safety and tolerability
profile, good pharmaceutical characteristics together with both
antiandrogen biological and anti-tumor activity support our
decision to move into earlier lines of therapy and, importantly,
study EPI-7386 in combination with second-generation
antiandrogens," said Dr. David R.
Parkinson, President and Chief Executive Officer of ESSA
Pharma Inc. "Further, ctDNA molecular analysis in this heavily
pretreated population has given us a detailed profile of genetic
alterations, revealing the biological complexity of late-stage
mCRPC patients but also allowing us to continue to refine 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."
In the multi-center, open-label Phase 1a dose escalation study,
31 patients received 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 metastatic mCRPC. Almost 60% of
patients had been treated with prior chemotherapy. Patients entered
the trial with rapidly progressive disease, as evidenced by a
median prostate-specific antigen ("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. Following a protocol amendment, five patients were enrolled
in a twice-daily (BID) 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.
Key safety results from both QD and BID patients as of
June 1, 2022:
- 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.
- 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.
Key response findings in both QD and BID patients as of
June 1, 2022:
- In five patients who had measurable disease and were on therapy
for more than 12 weeks, tumor volume decreased in all five
patients.
- PSA decreases 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, providing further information to refine 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 EPI-7386's
potential activity against these tumors.
The Company expects to initiate the Phase 1b monotherapy expansion study in Q3 2022 and
will plan to enroll two dose cohorts into this study following
recent guidance from the FDA from Project Optimus. The study will
evaluate a patient population of mCRPC similar to the one treated
under the BID dose regimen 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 EPI-7386 in a less heavily pretreated
patient population. In addition, a separate cohort of patients with
non-metastatic CRPC will be enrolled into a 12-week Window of
Opportunity study with a clinical endpoint (i.e. PSA changes) to
assess the anti-tumor activity of 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.
Lastly, we anticipate initiating later this year a Phase 2
investigator-sponsored neoadjuvant study which will evaluate
darolutamide compared to EPI-7386 + darolutamide in patients
undergoing prostatectomy for high-risk localized prostate
cancer.
In addition to these studies, EPI-7386 is under evaluation in
earlier lines of therapy in Phase 1/2 trials combining EPI-7386
with approved second-generation antiandrogens. The Company has
completed dosing of the first cohort of patients past the 28-Day
dose-limiting toxicity period with no safety issues and is
currently enrolling the second cohort of patients into the Phase
1/2 study of 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.
"We continue to be excited by our combination trials evaluating
EPI-7386 with the four leading, commercially available
antiandrogens in earlier line patient populations," said Dr.
Parkinson. "Preliminary data from the first cohort in the Phase 1/2
combination trial with enzalutamide suggests that the drugs can be
combined safely and result in drug levels of both drugs which are
predicted to be active based upon clinical and preclinical data.
The early data, in addition to preclinical studies, support
EPI-7386's potential in combination with second-generation
antiandrogens to suppress androgen receptor biology and induce a
potent anti-tumor response."
Webcast and Conference Call
Management will host a conference call and live audio webcast to
discuss the clinical updates at 5:00 p.m.
ET today. To participate in the conference call, please dial
1-877-405-1224 (domestic) or 1-201-389-0848 (international). The
live webcast can be accessed in the Events & Presentations
section of the Company's website at
www.investors.essapharma.com. The archived webcast will be
available for replay following the event.
About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small
molecule inhibitor of the N-terminal domain of the androgen
receptor. EPI-7386 is currently being studied in a Phase 1 clinical
trial (NCT04421222) in men with mCRPC whose tumors have progressed
on current standard-of-care therapies. The Phase I clinical trial
of EPI-7386 began in calendar Q3 of 2020 following FDA allowance of
the Investigational New Drug application and Health Canada
acceptance. The U.S. FDA has granted Fast Track designation to
EPI-7386 for the treatment of adult male patients with mCRPC
resistant to standard-of-care treatment. ESSA is also conducting a
Phase 1/2 study to evaluate the safety, tolerability and
preliminary efficacy of the combination of EPI-7386 and the
antiandrogen enzalutamide in mCRPC patients who have not yet been
treated with second-generation antiandrogen therapies. ESSA retains
all rights to EPI-7386 worldwide.
About ESSA Pharma Inc.
ESSA is a clinical-stage pharmaceutical company focused on
developing novel and proprietary therapies for the treatment of
patients with prostate cancer. For more information, please visit
www.essapharma.com and follow us on Twitter under
@ESSAPharma.
About Prostate Cancer
Prostate cancer is the second-most commonly diagnosed cancer
among men and the fifth most common cause of male cancer death
worldwide (Globocan, 2018). Adenocarcinoma of the prostate is
dependent on androgen for tumor progression and depleting or
blocking androgen action has been a mainstay of hormonal treatment
for over six decades. Although tumors are often initially sensitive
to medical or surgical therapies that decrease levels of
testosterone, disease progression despite castrate levels of
testosterone can lead to mCRPC. The treatment of mCRPC patients has
evolved rapidly over the past ten years. Despite these advances,
many patients with mCRPC fail or develop resistance to existing
treatments, leading to continued disease progression and limited
survival rates.
Forward-Looking Statement Disclaimer
This release contains certain information which, as presented,
constitutes "forward-looking information" within the meaning of the
Private Securities Litigation Reform Act of 1995 and/or applicable
Canadian securities laws. Forward-looking information involves
statements that relate to future events and often addresses
expected future business and financial performance, containing
words such as "anticipate", "believe", "plan", "estimate",
"expect", and "intend", statements that an action or event "may",
"might", "could", "should", or "will" be taken or occur, or other
similar expressions and includes, but is not limited to, statements
regarding: the results of the initial clinical data, including the
favorable pharmaceutical properties of EPI-7386; the commencement
and timing of a Phase 1b expansion
study and other milestones; the design and success of EPI-7386's
Phase 1a/1b monotherapy study and
questions addressed thereby; the design and timing of
Window-of-Opportunity and Investigator-Sponsored neoadjuvant
studies; the possibility of greater AR suppression from EPI-7386's
combination with antiandrogen therapies; planned studies under the
EPI-7386 Combination Development Program; EPI-7386's drug-drug
interactions and safety in combination with other therapies;
and other statements surrounding the Company's clinical
evaluation of EPI-7386.
Forward-looking statements and information are subject to
various known and unknown risks and uncertainties, many of which
are beyond the ability of ESSA to control or predict, and which may
cause ESSA's actual results, performance or achievements to be
materially different from those expressed or implied thereby. Such
statements reflect ESSA's current views with respect to future
events, are subject to risks and uncertainties and are necessarily
based upon a number of estimates and assumptions that, while
considered reasonable by ESSA as of the date of such statements,
are inherently subject to significant medical, scientific,
business, economic, competitive, political and social uncertainties
and contingencies. In making forward looking statements, ESSA may
make various material assumptions, including but not limited to (i)
the accuracy of ESSA's financial projections; (ii) obtaining
positive results of clinical trials; (iii) securing partner
participation in combination clinical trials; (iv) obtaining
necessary regulatory approvals; and (v) general business, market
and economic conditions.
Forward-looking information is developed based on assumptions
about such risks, uncertainties and other factors set out herein
and in ESSA's Annual Report on Form 10-K dated November 18, 2021 under the heading "Risk
Factors", a copy of which is available on ESSA's profile on
EDGAR at www.sec.gov, and as otherwise disclosed from time to time
on ESSA's SEDAR profile www.sedar.com.Forward-looking statements
are made based on management's beliefs, estimates and opinions on
the date that statements are made and ESSA undertakes no obligation
to update forward-looking statements if these beliefs, estimates
and opinions or other circumstances should change, except as may be
required by applicable Canadian and United States securities laws. Readers are
cautioned against attributing undue certainty to forward-looking
statements.
View original
content:https://www.prnewswire.com/news-releases/essa-pharma-presents-clinical-update-on-epi-7386-monotherapy-and-combination-therapy-clinical-development-301576138.html
SOURCE ESSA Pharma Inc