- Three scientific posters highlighting novel anti-virulence
pharmacologic properties of oral ibezapolstat for C.
difficile Infection; effects on toxin production, biofilm and
the gut microbiome
- A podium presentation entitled First of a New Class of
Antibiotics (pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority
Pathogens; Preparing for the Next Pandemic: Antimicrobial
Resistance in Gram-positive Bacterial Infections
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation
STATEN
ISLAND, N.Y., Oct. 19,
2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage
biopharmaceutical company developing a new class of antibiotics for
difficult-to-treat bacterial infections, today announced three
scientific posters were presented during the 13th
International Conference on Molecular Biology and Pathogenesis of
Clostridia (ClostPath) held in Banff,
Canada from September 19 to 23,
2023. Additionally, two podium presentations were made at
the Infectious Disease Society of America (IDSA) IDWeek™ 2023
Conference held October 11-15, 2023
in Boston, MA. Highlights of each
are shown below.
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "In light of our recent decision to
discontinue the Phase 2b ibezapolstat
clinical trial earlier than planned and prepare for Phase 3
clinical trials, the new information contained in these scientific
posters and presentations at these conferences will add to our
evidence-based briefing package for an End of Phase 2 FDA meeting
planned for in the first half of next year." He also added: "We are
currently compiling and verifying all data from the Phase
2b trial and we will report topline
clinical efficacy for the primary clinical endpoint and safety data
in the coming weeks, with other outcome data available later this
year".
ClostPath:
- Ibezapolstat modulates Clostridioides difficile virulence
factors in vitro
- Presented by Eugenie Basseres, et al;
University of Houston College of
Pharmacy
- Ibezapolstat reduces toxin production by C.
difficile
- C. difficile In Vitro Biofilm Studies of Ibezapolstat And
Comparator Antibiotics
- Presented by M. Jahangir
Alam et al; University of
Houston College of Pharmacy
- Ibezapolstat was as effective as the
currently-used anti-C. difficile agents
fidaxomicin, vancomycin and metronidazole
to reduce biofilm-embedded C. difficile
quantity and biofilm biomass
- Metagenomic Evaluation of Ibezapolstat Compared to Other
Anti-Clostridioides difficile Agents
- Presented by Jinhee Jo, University
of Houston College of Pharmacy
- Ibezapolstat and fidaxomicin caused
proportional increases in Bacteroidetes distinct
from vancomycin and metronidazole, which
caused proportional increases in Proteobacteria
IDWeek:
- First of a New Class of Antibiotics (pol IIIC Inhibitors)
Targeting CDC/FDA/WHO Priority Pathogens
- Presented by Michael
Silverman, MD, FACP, Acurx's
Medical Director; at the New Antimicrobials in
the Pipeline session
- Among the promising data for ibezapolstat in the
treatment of C. difficile are in vitro potency,
anti-virulence activities, high human fecal concentrations, 100%
Clinical Cure rate in a 10-patient open-label trial, favorable
safety profile to date, and potentially beneficial effects on the
gut microbiome
- Elucidating the Gram-Positive Selective Spectrum Activity
of Ibezapolstat; Secondary Analysis from the Phase 2a
trial; Presented by Kevin Garey,
PharmD, MS, Professor& Chair, University
of Houston, School of Pharmacy
- Ibezapolstat showed variable selectivity against
Firmicutes helping to elucidate its narrow spectrum of
activity against certain pathogenic Firmicutes
including C. difficile
The posters and presentations are available on the Company's
website www.acurxpharma.com.
About Ibezapolstat
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
January 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 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 (see
https://clinicaltrials.gov/ct2/show/NCT04247542). 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 and continue to test for
anti-recurrence microbiome properties seen in the Phase 2a trial,
including the treatment-related changes in alpha diversity and
bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label
cohort of up to 20 subjects from study centers in the United States. In this cohort, 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), the Trial Oversight
Committee assessed the safety and tolerability and made its
recommendation regarding early termination of the Phase 2a study
and advancement to the Ph2b segment.
The Phase 2b clinical trial
segment has been discontinued due to success. The Company made this
decision in consultation with its medical and scientific advisors
and statisticians based on observed aggregate blinded data and
other factors, including the cost to maintain clinical trial sites
and slow enrollment due to COVID-19. The Company has determined
that the trial performed as anticipated for both treatments,
ibezapolstat and the control antibiotic vancomycin (a standard of
care to treat patients with CDI), with high rates of clinical cure
observed across the trial without any emerging safety concerns.
Accordingly, an Independent Data Monitoring Committee will not be
required to perform an interim analysis of this Phase 2b trial data as originally planned. Acurx will
analyze the data and report topline efficacy results promptly. The
Company anticipates that this decision will allow the Company to
advance this first-in-class, FDA QIDP/Fast Track-designated
antibiotic product candidate to Phase 3 clinical trials more
expeditiously.
In the now completed 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.
This Phase 2 clinical trial will also evaluate 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. In the event noninferiority of ibezapolstat to
vancomycin is demonstrated, further analysis will be conducted to
test for superiority. 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.
About ClostPath
The ClostPath conferences, which
began in 1995, have been a leading venue to bring together top
scientists and clinicians studying the molecular biology of
clostridia and their role in health and disease. The scientific
program of ClostPath 13 included lectures by
internationally recognized leaders in clostridial research and
clinical practice. In addition to state-of-the-art invited talks on
the most recent and exciting discoveries in the field, short oral
contributions were selected from submitted abstracts. Poster
presentations gave attendees the opportunity to discuss their
ongoing work with a broad audience in line with the goal to bring
together basic science with clinical and translational research
issues.
About the IDSA and
IDWeek
The Infectious Diseases Society of America
(IDSA) is a community of over 12,000 physicians, scientists
and public health experts who specialize in infectious diseases.
Our mission is to improve the health of individuals, communities,
and society by promoting excellence in patient care, education,
research, public health, and prevention relating to infectious
diseases. IDWeek is the joint annual meeting of the Infectious
Diseases Society of America (IDSA), Society for Healthcare
Epidemiology of America (SHEA), the HIV Medicine Association
(HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the
Society of Infectious Diseases Pharmacists (SIDP). Over 9,500
participants attended this conference in October 2022.
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 of two of the
three 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 Clostridioides 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
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)
About Acurx
Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage
biopharmaceutical company focused on developing new
antibiotics for difficult to treat infections. The Company's
approach is to develop antibiotic candidates that target the DNA
polymerase IIIC enzyme and 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) and
drug-resistant Streptococcus pneumoniae (DRSP).
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, 2022, 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.