STATEN
ISLAND, N.Y., Feb. 19,
2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage
biopharmaceutical company developing a new class of small molecule
antibiotics for difficult-to-treat bacterial infections, today
announced that a new patent has been granted by the Japanese Patent
Office (JPO) in January 2025. This patent relates to DNA
Polymerase IIIC Inhibitors, including compositions-of-matter,
surface coatings and pharmaceutical compositions for use in methods
of treating Gram-positive bacterial infection. This is the
latest in the series of granted patents and pending patent
applications that Acrux has filed to protect its proprietary
technologies in the field of antimicrobials. To date, Acurx
has obtained three U.S. patents, one Israeli patent and now one
Japanese patent, in each case, which cover the ACX-375C program,
relating to DNA Polymerase IIIC Inhibitors, with other
country-level filings in process.
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "Complementing our global patent estate
with minimally absorbed oral ibezapolstat, now Phase 3-ready for
the treatment and prevention of recurrence of C. difficile
Infection, this patent, with others to follow, is very important
and timely as we further develop our innovative, AI-supported drug
discovery platform of second-generation DNA pol IIIC inhibitors. He
added: "Other compounds in our program are systemically absorbed
for potential oral and parenteral use in multiple clinical settings
for treatment of infections caused by other gram-positive bacteria,
such as Staphylococcus aureus, including MRSA and B.
anthracis or anthrax; a Bioterrorism Category A Threat-Level
pathogen."
Acurx previously announced that it had received positive
regulatory guidance from the EMA during its Scientific Advice
Procedure which confirmed that the clinical, non-clinical and CMC
(Chemistry Manufacturing and Controls) information package
submitted to EMA supports advancement of the ibezapolstat Phase 3
program and if the Phase 3 program is successful, supports the
submission of a marketing authorization application (MAA) for
regulatory approval in Europe. The information package
submitted to EMA by the Company to which agreement has been reached
with EMA included details on Acurx's two planned Phase 3
international, 1:1 randomized clinical trials (designed as
non-inferiority trials vs vancomycin), primary and secondary
endpoints, sample size, statistical analysis plan and the overall
registration safety database. With mutually consistent
feedback from both EMA and FDA, Acurx is well positioned to
commence our international Phase 3 registration program.
The primary efficacy analysis will be performed using a Modified
Intent-To-Treat (mITT) population. This will result in an estimated
450 subjects in the mITT population, randomized in a 1:1 ratio to
either ibezapolstat or standard- of-care vancomycin, enrolled into
the initial Phase 3 trial. The trial design not only allows
determination of ibezapolstat's ability to achieve Clinical Cure of
CDI as measured 2 days after 10 days of oral treatment but also
includes assessment of ibezapolstat's potential effect on reduction
of CDI recurrence in the target population. In the event
non-inferiority of ibezapolstat to vancomycin is demonstrated,
further analysis will be conducted to test for superiority.
About the Ibezapolstat Phase
2 Clinical Trial
The completed
multicenter, open-label single-arm segment (Phase 2a) study was followed
by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase
2b) at 28 US clinical
trial sites which together comprise the Phase 2 clinical trial.
(Link to Clinicaltrials.gov/NCT042447542) This Phase 2
clinical trial was designed to evaluate the clinical efficacy of
ibezapolstat in the treatment of CDI including pharmacokinetics and
microbiome changes from baseline. from study centers in
the United States. In the Phase 2a
trial segment,10 patients with diarrhea caused by C.
difficile were treated with ibezapolstat 450 mg orally,
twice daily for 10 days. All patients were followed for recurrence
for 28± 2 days. Per protocol, after 10 patients of the projected 20
Phase 2a patients completed treatment (100% cured infection at End
of Treatment).
In the Phase 2b trial segment,
which was discontinued due to success, 32 patients with CDI were
enrolled and randomized in a 1:1 ratio to either ibezapolstat 450
mg every 12 hours or vancomycin 125 mg orally every 6 hours, in
each case, for 10 days and followed for 28 ± 2 days following the
end of treatment for recurrence of CDI. The two treatments were
identical in appearance, dosing times, and number of capsules
administered to maintain the blind.
The Company previously reported that the overall observed
Clinical Cure rate in the combined Phase 2 trials in patients with
CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients
(100%) in Phase 2a in the Modified Intent to Treat Population, plus
15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who
experienced Clinical Cure during treatment with
ibezapolstat. Ibezapolstat was well-tolerated, with three
patients each experiencing one mild adverse event assessed by the
blinded investigator to be drug- related. All three events were
gastrointestinal in nature and resolved without treatment. There
were no drug-related treatment withdrawals or no drug-related
serious adverse events, or other safety findings of concern. In the
Phase 2b vancomycin control arm, 14 out of 14 patients
experienced Clinical Cure. The Company is confident that based on
the pooled Phase 2 ibezapolstat Clinical
Cure rate of 96% and the historical vancomycin cure
rate of approximately 81% (Vancocin® Prescribing Information,
January 2021), we will demonstrate
non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in
accordance with the applicable FDA Guidance for Industry
(October 2022).
In the Phase 2 clinical trial (both trial segments), the Company
also evaluated pharmacokinetics (PK) and microbiome changes and
test for anti-recurrence microbiome properties, including the
change from baseline in alpha diversity and bacterial abundance,
especially overgrowth of healthy gut microbiota Actinobacteria
and Firmicute phylum species during and after
therapy. Phase 2a data demonstrated complete eradication of colonic
C. difficile by day three of treatment with ibezapolstat as
well as the observed overgrowth of healthy gut microbiota,
Actinobacteria and Firmicute phyla species, during and after
therapy. Very importantly, emerging data show an increased
concentration of secondary bile acids during and following
ibezapolstat therapy which is known to correlate with colonization
resistance against C. difficile. A decrease in primary
bile acids and the favorable increase in the ratio of
secondary-to-primary bile acids suggest that ibezapolstat may
reduce the likelihood of CDI recurrence when compared to
vancomycin. The company also recently reported positive extended
clinical cure (ECC) data for ibezapolstat (IBZ), its lead
antibiotic candidate, from the Company's recently completed Phase
2b clinical trial in patients with
CDI. This exploratory endpoint showed that 12 patients who agreed
to be followed up to three months following Clinical Cure of their
infection, 5 of 5 IBZ patients experienced no recurrence of
infection. In the vancomycin control arm of the
trial, 7 of 7 patients experienced no recurrence of
infection. ECC success is defined as a clinical cure at the
TOC visit (i.e., at least 48 hours post EOT) and no recurrence of
CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post
EOT (ECC84) in patients who consented to extended observation. In
the Phase 2b trial, 100% (5 of 5) of
ibezapolstat-treated patients who agreed to observation for up to
three months following Clinical Cure of CDI experienced no
recurrence of infection. Furthermore, ibezapolstat-treated patients
showed lower concentrations of fecal primary bile acids, and higher
beneficial ratio of secondary to primary bile acids than
vancomycin-treated patients.
About Ibezapolstat
Ibezapolstat is the Company's
lead antibiotic candidate planning to advance to international
Phase 3 clinical trials to treat patients with C.
difficile Infection (CDI). Ibezapolstat is a novel, orally
administered antibiotic, being developed as a Gram-Positive
Selective Spectrum (GPSS®) antibacterial. It is the first of a new
class of DNA polymerase IIIC inhibitors under development by Acurx
to treat bacterial infections. Ibezapolstat's unique spectrum of
activity, which includes C. difficile but spares other
Firmicutes and the important Actinobacteria phyla, appears to
contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was
designated by the U.S. Food and Drug Administration (FDA) as a
Qualified Infectious Disease Product (QIDP) for the treatment of
patients with CDI and will be eligible to benefit from the
incentives for the development of new antibiotics established under
the Generating New Antibiotic Incentives Now (GAIN) Act. In 2019,
FDA granted "Fast Track" designation to ibezapolstat for the
treatment of patients with CDI. The CDC has designated C.
difficile as an urgent threat highlighting the need for
new antibiotics to treat CDI.
About Clostridioides difficile
Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice
Guidelines for C. difficile Infection by the Infectious Diseases
Society of America (IDSA) and Society or Healthcare
Epidemiology of America (SHEA), CDI remains a significant medical
problem in hospitals, in long-term care facilities and in the
community. C. difficile is one of the most common
causes of health care- associated infections in U.S. hospitals
(Lessa, et al, 2015,
New England Journal of Medicine). Recent estimates suggest C.
difficile approaches 500,000 infections annually in the U.S.
and is associated with approximately 20,000 deaths annually. (Guh,
2020, New England Journal of Medicine). Based on internal
estimates, the recurrence rate for the antibiotics currently used
to treat CDI is between 20% and 40% among approximately 150,000
patients treated. We believe the annual incidence of CDI in the
U.S. approaches 600,000 infections and a mortality rate of
approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI)
and Bile Acid Metabolism
C. difficile can be a
normal component of the healthy gut microbiome, but when the
microbiome is thrown out of balance, the C.
difficile can thrive and cause an infection. After
colonization with C. difficile, the organism
produces and releases the main virulence factors, the two
large clostridial toxins A (TcdA) and B (TcdB).
(Kachrimanidou, Microorganisms 2020, 8, 200;
doi:10.3390/microorganisms8020200.) TcdA and TcdB
are exotoxins that bind to human intestinal epithelial
cells and are responsible for inflammation, fluid and mucous
secretion, as well as damage to the intestinal mucosa. Bile acids
perform many functional roles in the GI tract, with one of the most
important being the maintenance of a healthy microbiome by
inhibiting C. difficile growth. Primary bile acids,
which are secreted by the liver into the intestines, promote
germination of C. difficile spores and thereby increase
the risk of recurrent CDI after successful treatment of an initial
episode. On the other hand, secondary bile acids, which are
produced by normal gut microbiota through metabolism of primary
bile acids, do not induce C. difficile sporulation and
therefore protect against recurrent disease. Since ibezapolstat
treatment leads to minimal disruption of the gut microbiome,
bacterial production of secondary bile acids continues which may
contribute to an anti-recurrence effect. Beneficial effects of bile
acids include a decrease in primary bile acids and an increase in
secondary bile acids in patients with CDI, which was observed in
the Company's Ph2a trial results and previously reported (CID,
2022). In the Ph2b trial, ibezapolstat-treated patients showed
lower concentrations of fecal primary bile acids, and higher
beneficial ratio of secondary to primary bile acids than
vancomycin-treated patients.
About Acurx Pharmaceuticals, Inc.
Acurx
Pharmaceuticals is a late-stage biopharmaceutical company focused
on developing a new class of small molecule antibiotics for
difficult-to-treat bacterial infections. The Company's approach is
to develop antibiotic candidates with a Gram-positive selective
spectrum (GPSS®) that blocks the active site of the Gram-positive
specific bacterial enzyme DNA polymerase IIIC (pol IIIC),
inhibiting DNA replication and leading to Gram-positive bacterial
cell death. Its R&D pipeline includes antibiotic product
candidates that target Gram-positive bacteria, including
Clostridioides difficile, methicillin- resistant
Staphylococcus aureus (MRSA), vancomycin resistant
Enterococcus (VRE), drug- resistant Streptococcus pneumoniae (DRSP)
and B. anthracis (anthrax; a Bioterrorism Category A
Threat-Level pathogen). Acurx's lead product candidate,
ibezapolstat, for the treatment of C. difficile Infection is
Phase 3 ready with plans in progress to begin international
clinical trials next year. The Company's preclinical pipeline
includes the development of an oral product candidate for treatment
of ABSSSI (Acute Bacterial Skin and Skin Structure Infections),
upon which a development program for treatment of inhaled anthrax
is being planned in parallel.
To learn more about
Acurx Pharmaceuticals and its product
pipeline, please visit www.acurxpharma.com.
Forward-Looking Statements
Any statements in this press release about our future expectations,
plans and prospects, including statements regarding our strategy,
future operations, prospects, plans and objectives, and other
statements containing the words "believes," "anticipates," "plans,"
"expects," and similar expressions, constitute forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. Actual results may differ materially from those
indicated by such forward-looking statements as a result of various
important factors, including: whether ibezapolstat will benefit
from the QIDP designation; whether ibezapolstat will advance
through the clinical trial process on a timely basis; whether the
results of the clinical trials of ibezapolstat will warrant the
submission of applications for marketing approval, and if so,
whether ibezapolstat will receive approval from the FDA or
equivalent foreign regulatory agencies where approval is sought;
whether, if ibezapolstat obtains approval, it will be successfully
distributed and marketed; and other risks and uncertainties
described in the Company's annual report filed with the Securities
and Exchange Commission on Form 10-K for the year ended
December 31, 2023, and in the
Company's subsequent filings with the Securities and Exchange
Commission. Such forward- looking statements speak only as of the
date of this press release, and Acurx disclaims any intent or
obligation to update these forward-looking statements to reflect
events or circumstances after the date of such statements, except
as may be required by law.
Investor Contact: Acurx
Pharmaceuticals, Inc.
David P. Luci, President &
CEO Tel: 917-533-1469
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.
