Acurx Announces Presentation of a Scientific Poster at the Premier International C. difficile Symposium (ICDS) Demonstrating Superior In Vitro Kill Kinetics of Ibezapolstat vs. Vancomycin and Fidaxomicin (Standards of Care) in Clostridioides difficile and Vancomycin-Resistant Enterococcus Co-Cultures
New in vitro results and FDA feedback strengthen the case for ibezapolstat as Acurx plans pivotal CDI and recurrent CDI trials.
Rhea-AI Summary
Acurx Pharmaceuticals (ACXP) reported new in vitro data and regulatory guidance updates for its lead antibiotic ibezapolstat in Clostridioides difficile infection (CDI).
At the 9th International C. difficile Symposium, a poster showed that in C. difficile and vancomycin-resistant Enterococcus (VRE) co-cultures, ibezapolstat maintained the highest residual anti-C. difficile activity, achieving a 5.51-log reduction and significantly outperforming vancomycin (p = 0.0112). All VRE strains were highly resistant to vancomycin (MIC >128 μg/mL), while ibezapolstat and fidaxomicin had lower MIC ranges of 2–16 μg/mL and both preserved robust VRE killing where vancomycin was inactive. All treatments reduced toxin B (TcdB) gene abundance, with ibezapolstat showing statistically superior suppression of the VanA resistance cluster.
Acurx also highlighted an FDA Type C meeting, where the Agency indicated it may consider a single Phase 3 trial plus supportive data for NDA submission, and agreed that the planned 550‑patient IBZ-ASPIRE trial could, if successful, support indications for both acute CDI treatment and reduction of recurrence.
Positive
- Anti-C. difficile performance 5.51-log reduction in co-culture, significantly better than vancomycin (p = 0.0112)
- VRE susceptibility ibezapolstat and fidaxomicin MIC 2–16 μg/mL vs vancomycin MIC >128 μg/mL
- Toxin and resistance genes all drugs reduced TcdB, ibezapolstat showed superior VanA cluster reduction
- Phase 3 design IBZ-ASPIRE planned ~550 mITT subjects, 1:1 vs vancomycin, non-inferiority primary endpoint
- Regulatory path FDA is open to discussing an NDA based on a single Phase 3 trial plus supportive data
- Designations ibezapolstat holds FDA QIDP and Fast Track status and EMA SME designation
Negative
- Financing dependency advancement of the IBZ-ASPIRE international Phase 3 trial is subject to securing appropriate funding
- Additional trial risk if IBZ-ASPIRE does not meet FDA criteria, a second Phase 3 trial is recommended
News Explained
Phase 3 advancement remains funding-dependent; June 30, 2026 cash equaled 567.1 days of second-quarter operating cash use at that historical rate.
Acurx says its ibezapolstat poster was presented at the September 8–10 symposium, while planned Phase 3 advancement remains conditional on receiving appropriate funding rather than being reported as commenced.
The company also says start-up activities have begun for a 20-subject open-label PATHFINDER pilot, with first-patient enrollment expected in the fourth quarter of 2026; that is a planned milestone, not reported enrollment.
Against that funding condition,
Sources and calculations
- Acurx scientific poster and clinical-program update (2026-09-14)
- Acurx second-quarter 2026 fundamentals (2026-06-30)
- Available liquidity against the last reported quarterly operating outflow, in days at that rate $10,656,386 / ($1,709,952 / 91) = 567.1 days
Key Figures
- VAN susceptibility threshold
- MIC >128 μg/mL
- Vancomycin-resistant Enterococcus strains
- IBZ and FDX susceptibility
- MIC range: 2–16 μg/mL
- Vancomycin-resistant Enterococcus strains
- Co-culture interference
- Up to 2.90 logs
- Decrease in C. difficile killing across antibiotic arms
- IBZ residual anti-C. difficile activity
- 5.51-log reduction
- C. difficile and Enterococcus co-culture
- IBZ versus VAN performance
- p = 0.0112
- IBZ significantly outperformed vancomycin in co-culture
- IBZ versus FDX activity
- p ≥ 0.2381
- Monoculture bactericidal activity
Historical Context
-
FDA guidance supported a potential single Phase 3 NDA path subject to clinical evidence.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
co-culture technical
bactericidal medical
mic medical
non-inferiority technical
AI-generated analysis. How Rhea-AI works. Not financial advice.
- The microbiome of patients experiencing recurrent CDI is frequently dominated by overgrowths of Enterococcus species
- This study evaluated the in vitro bactericidal and molecular efficacy of ibezapolstat (IBZ), vancomycin (VAN), and fidaxomicin (FDX) against C. difficile and Enterococcus in standalone and complex co-culture environments
- These findings demonstrate that Enterococcus creates a protective microenvironment that actively impairs C. difficile killing using standard of care antibiotic regimens
- IBZ maintained superior bactericidal activity under co-culture conditions, including further decreasing Clostridioides difficile toxin B (TcdB) expression while simultaneously eradicating vancomycin-resistant bacterial overgrowth
- Acurx has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA
All vancomycin-resistant Enterococcus (VRE) strains demonstrated high-level resistance to VAN (MIC >128 μg/mL), whereas IBZ and FDX exhibited equivalent lower susceptibility thresholds (MIC range: 2–16 μg/mL). In monoculture, IBZ displayed potent bactericidal activity against C. difficile non-inferior to FDX (p ≥ 0.2381). Enterococcus co-culture with C. difficile created severe microbial interference that impaired C. difficile killing across all antibiotic arms, decreasing killing by up to 2.90 logs; however, IBZ maintained the highest residual anti-C. difficile performance (5.51-log reduction), significantly outperforming VAN (p = 0.0112). Conversely, C. difficile presence exerted negligible interference on VRE killing, where IBZ and FDX maintained robust anti-VRE killing while VAN remained inactive. At the transcriptional level, all treatments significantly suppressed TcdB gene abundance compared to the experimental laboratory control while IBZ showed statistically significant superiority over the other two antibiotics in decreasing the VanA cluster (ibezapolstat, vancomycin and fidaxomicin)
The study was performed at the University of
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "If these results are validated in our Phase 3 registration program, and ultimately in clinical practice, for the treatment of patients with CDI, ibezapolstat's activity has the potential to reduce the nosocomial emergence of the critical pathogen VRE while treating CDI." He further stated: "Adding to the totality of data on ibezapolstat from studies such as this increase our confidence in a successful outcome of our clinical trial program and continue to elevate our favorable product profile and attractive value proposition, including in-market competitive advantage compared to vancomycin and fidaxomicin, the current standards of care for acute CDI, particularly for the reduction of recurrence".
The poster is available on Acurx Pharmaceuticals' website: www.acurxpharma.com
Acurx previously reported the successful outcome of a Type C Meeting conducted with FDA on July 13, 2026 to discuss ibezapolstat's Phase 3 clinical program and scope of its planned NDA. The Agency stated that it is open to further discussion at a Pre-NDA Meeting regarding the possibility of submitting an NDA with only a single Phase 3 trial, depending on the totality of the clinical data plus any other supportive data that Acurx may generate by that milestone. The Agency noted that determination of acceptability of one Phase 3 clinical trial for an NDA is made on a case-by-case basis, taking into consideration such factors as the magnitude, consistency, and overall robustness of the efficacy results; generalizability of the results to the US population; relevance of the results to US patient care and clinical practice guidelines; Phase 2 data; and an adequate safety database. The Agency acknowledged Acurx's planned clinical trial in recurrent CDI (rCDI) and noted the data from this rCDI trial, if successful, will support an NDA submission. If the IBZ-ASPIRE trial does not meet these criteria, then a second trial consistent with the agreement reached at the end of Phase 2 (EOP2) meeting on April 27, 2024 is recommended.
The currently planned IBZ-ASPIRE trial is of non-inferiority design with the primary efficacy analysis in the Modified Intent-To-Treat (mITT) population. This will result in approximately 550 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin. The Agency also agreed with the overall trial design and evaluation criteria and further agreed that the trial testing criteria, if successful, could support indications for both the acute treatment and the reduction of recurrence of CDI. In the event non-inferiority of ibezapolstat to vancomycin for Clinical Cure of CDI is demonstrated, further analyses will be conducted to test for superiority for reduction of recurrence and for clinical cure of CDI.
Acurx also previously announced that it is conducting a new clinical trial (IBZ-PATHFINDER) in patients with multiply recurrent C. difficile Infection (rCDI) while its program in the broader CDI patient population is ready to advance to Phase 3 international clinical trials (IBZ-ASPIRE), subject to receiving appropriate funding. This new IBZ-PATHFINDER clinical trial in rCDI involves an open-label pilot trial to gain experience with IBZ in patients with multiply-recurrent CDI with at least 3 episodes of CDI within the past 12 months.
About the International C. difficile Symposium (ICDS)
The International C. difficile Symposium (ICDS) is established as the premier venue for the review of Clostridium difficile research. The first meeting was held in
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. (Data published in Lancet, August 2025 https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(25)00054-0/fulltext).
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
About Clostridioides difficile Infection (CDI) and Recurrent CDI (rCDI)
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 the Society of 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
In recent studies, rCDI ranges from
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 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 preparing to advance into international Phase 3 trials.
Additionally, the Company has initiated start-up activities for a ground-breaking clinical trial in patients with rCDI with the first patient expected to enroll in the fourth quarter this year. This trial is a 20-patient, open-label pilot trial in patients with multiply-recurrent CDI with at least 3 episodes of CDI in the past year and will inform elements of a planned active-controlled, Phase 3 registration trial in the rCDI. Upon subsequent successful completion of a Ph3 pivotal rCDI trial, and per the operative FDA procedure, Acurx plans to request FDA approval for treatment and prevention of rCDI under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs (Guidance for Industry, 2020). Successful trial outcome has the potential to shift the paradigm of treatment and prevention of rCDI from two agents to one.
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 post-exposure prophylaxis of inhalation anthrax is being planned in parallel.
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 described in the Company's annual report on Form 10-K for the year ended December 31, 2025 as filed with the Securities and Exchange Commission on March 12 2026, 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
View original content:SOURCE Acurx Pharmaceuticals, Inc.
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What were the key findings of the ibezapolstat co-culture study with C. difficile and VRE?
In monoculture, ibezapolstat showed potent bactericidal activity against C. difficile that was non-inferior to fidaxomicin (p ≥ 0.2381). In co-culture with Enterococcus, microbial interference reduced C. difficile killing by up to 2.90 logs across all antibiotics, but ibezapolstat retained the highest residual activity with a 5.51-log reduction. Vancomycin-resistant Enterococcus strains were highly resistant to vancomycin, while ibezapolstat and fidaxomicin maintained robust anti-VRE killing where vancomycin was inactive.
How did ibezapolstat affect toxin and resistance gene expression in the study?
At the transcriptional level, all three antibiotics significantly suppressed C. difficile toxin B (TcdB) gene abundance versus the experimental control. Ibezapolstat also showed statistically significant superiority over vancomycin and fidaxomicin in reducing expression of the VanA resistance gene cluster, which is associated with vancomycin resistance.
What did the FDA communicate regarding the ibezapolstat Phase 3 program and NDA strategy?
In a Type C meeting, the FDA stated it is open to further discussion at a Pre-NDA meeting about accepting an NDA supported by a single Phase 3 trial, depending on the totality of clinical and supportive data. The Agency emphasized that acceptability of one trial is case-by-case, based on the magnitude, consistency and robustness of efficacy, generalizability to the US population, relevance to US clinical practice, Phase 2 data and an adequate safety database.
What is the design of the planned IBZ-ASPIRE Phase 3 CDI trial?
IBZ-ASPIRE is planned as a non-inferiority Phase 3 trial with the primary efficacy analysis in the modified intent-to-treat (mITT) population. Approximately 550 subjects with CDI will be randomized 1:1 to ibezapolstat or standard-of-care vancomycin. The FDA agreed with the overall design and stated that, if successful, the trial could support indications for both acute treatment of CDI and reduction of recurrence, with additional analyses planned to test for superiority on recurrence and clinical cure.
What is the IBZ-PATHFINDER trial and which patients will it enroll?
IBZ-PATHFINDER is an open-label pilot clinical trial in patients with multiply recurrent C. difficile infection (rCDI). It is planned to enroll 20 patients who have experienced at least three CDI episodes within the previous 12 months. The trial is intended to gain clinical experience with ibezapolstat in this high-risk population and to inform design elements of a future active-controlled, Phase 3 registration trial in rCDI.
What prior ibezapolstat Phase 2 data are referenced in this announcement?
The completed Phase 2 program included an open-label Phase 2a segment and a double-blind, randomized, active-controlled non-inferiority Phase 2b segment at 28 US sites. These trials evaluated clinical efficacy, pharmacokinetics and microbiome changes, including bile acid metabolism. Reported data showed that ibezapolstat-treated patients had lower fecal primary bile acids and a higher ratio of secondary to primary bile acids than vancomycin-treated patients, findings that may be associated with reduced CDI recurrence.