Results are from Acurx's ongoing scientific collaboration
with Leiden University Medical Center (LUMC) partially under a
grant from Health Holland to further study the mechanism of action
of DNA pol IIIC inhibitors
LUMC highlighted Acurx's new class of promising
antimicrobials, ibezapolstat and related analogues Novel
chemotype specifically targeting gram-positive bacteria through an
unexploited target Ibezapolstat ready to enter pivotal Phase
3 clinical trials for C. difficile Infection (CDI), with no cross
resistance reported to date
Ibezapolstat has previously been granted FDA QIDP and
Fast-Track Designations and has received SME (Small and
Medium-sized Enterprise) designation by the EMA
STATEN ISLAND, N.Y.,
June 9,
2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company") is a late-stage
biopharmaceutical company developing a new class of small molecule
antibiotics for difficult-to-treat bacterial infections.
Its lead antibiotic candidate, ibezapolstat
(IBZ), is ready to advance
to international pivotal Phase 3
clinical trials for treatment
of patients with C. difficile infection (CDI).
The Company today announced that a presentation of a
poster and an oral presentation regarding Acurx's overall DNA pol
IIIC inhibitor platform was presented at a scientific conference on
May 21 by Mia
Urem, PhD, from Leiden University Medical Center in
the Netherlands entitled: "A
Unique Inhibitor Conformation Selectively Targets the DNA
Polymerase PolC of Gram-Positive Priority Pathogens".
This scientific conference is sponsored by the Federation of
American Societies for Experimental Biology and is the premier
venue for the newest research and technological trends in molecular
"machines" inside the human body that ensure DNA replication and
expression of genes to create proteins that make up a cell. The
distinctive non-planar conformation of ACX-801 and IBZ, together
with high conservation of the induced binding pocket in PolC,
suggests that this is a general mechanism for this class of
inhibitor and is conserved in Gram-positive bacteria.
According to Dr. Wiep Klaas Smits, Associate
Professor/Principal Investigator, Leiden University Medical Center:
"Our findings with regards to the structural biology of DNA pol
IIIC in complex with inhibitors have important implications for the
development of this novel class of antibiotics to treat high
priority, multi-drug resistant, gram-positive infections."
Acurx's Executive Chairman, Bob DeLuccia, stated: "This
research outcome provides a deeper understanding of the mechanism
of action and selectivity of ibezapolstat in the gut. These data
will guide the rational design of new compounds with improved
inhibitory activity and drug-like characteristics that will be
crucial in addressing the pandemic of antimicrobial
resistance."
POSTER AND PRESENTATION ARE ON ACURX
WEBSITE www.acurxpharma.com
About the Federation of American Societies for Experimental
Biology
Since its inception 20 years ago, this conference
has been the premier venue for the newest research and
technological trends that aid in studying the molecular "machines"
inside the human body. These biological elements ensure faithful
DNA replication and expression of genes to create the many proteins
that make up a cell. The Machines on Genes scientific conference
covers all aspects that govern the central building blocks of life,
DNA replication, transcription, and translation, as well as
activities that impact these processes such as DNA repair, DNA
editing, and RNA editing. There is special emphasis on how they
work, how they interact with one another, and how they may be used
as diagnostic tools or as targets for novel therapies.
About Leiden University Medical
Center
Antimicrobial resistant microorganisms are a major
threat to global health and pose a significant economic burden.
Increasing resistance to multiple agents and resistance to so
called last-resort antibiotics underscore the necessity to develop
therapeutics that have a novel mode of action. DNA replication is a
process that can be successfully targeted by small molecules.
Ibezapolstat, an inhibitor of the replicative DNA polymerase pol
IIIC from Gram-positive bacteria identified by screening library of
dGTP analogues, has shown promising results for the treatment
of Clostridioides difficile Infection in a recent
Phase 2a clinical trial, but the molecular basis of selective
inhibition is not fully characterized as no structural information
is available on pol IIIC proteins from pathogens. Ongoing research
project will determine the structure of pol IIIC from the
multidrug-resistant organisms methicillin resistant
Staphylococcus aureus (MRSA), vancomycin resistant
Enterococci (VRE) and/or penicillin resistant Streptococcus
pneumoniae (PRSP) in the absence and presence of lead
compounds. These results will reveal the structural space of
inhibitor-binding and guide the rational design of inhibitors with
optimal pharmacological properties and organism-specificity that
will be demonstrated by in vitro polymerase inhibition
assays and in vivo minimal inhibitory concentration
determination.
Leiden University was the first university to be established in
the Netherlands. Its motto is
praesidium libertatis – bastion of freedom. The University
wishes to create an increasingly attractive and challenging working
climate for top academics and young researchers that is guided by
quality and excellence. Leiden University Medical Center (LUMC)
research aims to meet the highest international standards of
quality and academic integrity. LUMC promotes excellent research
through greater collaboration, both disciplinary and
interdisciplinary; stronger positioning and greater scope for top
talent; and better supervision and more support for young
researchers.
The presented research was performed in part as a public-private
partnership that includes the Dutch Top Sector Life Sciences and
Health ('Topconsortium voor Kennis en Innovatie' or 'TKI' Life
Sciences and Health) and is represented by Stichting Life Sciences
Health – TKI (aka, Health~Holland). This foundation is tasked by
the Dutch government to promote and stimulate public-private
partnerships (PPPs) to undertake R&D projects in the life
sciences. To promote such partnerships, the Minister of Economic
Affairs and Climate Policy has allocated certain funds to Stichting
LSH-TKI, to grant allowances to projects under the TKI-programme
Life Sciences & Health. Stichting LSH-TKI has designated the
Board of Directors of LUMC as delegated grantor for the PPP
allowance allocated to the LUMC.
Together with Acurx Pharmaceuticals the PPP has led to the
research project entitled "Bad bugs, new drugs: elucidation of the
structure of DNA polymerase C of multidrug resistant bacteria in
complex with novel classes of antimicrobials." The collaboration
project was co-funded by the PPS Allowance made available by
Health~Holland, Top Sector Life Sciences & Health, to stimulate
public-private partnerships.
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 international
Phase 3 clinical trials, 1:1 randomized (designed as
non-inferiority 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.
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 (10 of 10).
In the Phase 2b trial segment, 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.
In the Phase 2b trial, the
Clinical Cure rate 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.
Notably, in the combined Phase 2 trial, 100% (25 of 25)
ibezapolstat-treated patients ) who had Clinical Cure at EOT) (End
of Treatment) remained cured through one month after EOT,
as compared to 86% (12 of 14) for the vancomycin patient
group. Ibezapolstat was well-tolerated, with no serious
adverse events assessed by the blinded investigator to be drug-
related. The Company is confident that based on the pooled Phase 2
ibezapolstat Clinical Cure rate of 96%, Sustained Clinical Cure
Rate of 100% and the historical vancomycin Clinical Cure Rate
range of 70% to 92% and a Sustained Clinical Cure historical range
of 42% to 74%, we will demonstrate non-inferiority of ibezapolstat
to vancomycin in Phase 3 trials, in accordance with the applicable
FDA Guidance for Industry (October
2022), with favorable differentiation in both Clinical Cure
and Sustained Clinical Cure.
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 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 5 of 5 IBZ patients followed for
up to three months following Clinical Cure 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. 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
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, 2015, NEJM). 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, NEJM. 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 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.)
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 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 (Garey, 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
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, 2024, 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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