Acurx Announces Publication of Positive Results from an In-Silico Study Predicting the Microbiome-Restorative Potential of Ibezapolstat in the Treatment of CDI
Acurx Pharmaceuticals (NASDAQ: ACXP) announced positive results from an in-silico study of ibezapolstat (IBZ), its lead antibiotic candidate for C. difficile Infection (CDI) treatment. The study, published in the Journal of Antimicrobial Agents and Chemotherapeutics, explains IBZ's selective antimicrobial activity.
The research revealed that IBZ's bactericidal interaction with its target DNA pol IIIC is conserved across most Bacillota phylum, including C. difficile, while beneficial gut bacteria remain naturally resistant. This mechanism explains the narrower spectrum of activity observed in human trials, where IBZ allowed the regrowth of beneficial microbiota.
The study, funded by the National Institute of Allergy and Infectious Diseases, demonstrates IBZ's advantage over vancomycin, which kills beneficial microbes and leads to higher C. difficile recurrence rates. IBZ is preparing to advance to international Phase 3 clinical trials and has received FDA QIDP, Fast-Track, and EMA SME designations.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha annunciato risultati positivi da uno studio in silico su ibezapolstat (IBZ), il suo principale candidato antibiotico per il trattamento dell'infezione da C. difficile (CDI). Lo studio, pubblicato nel Journal of Antimicrobial Agents and Chemotherapeutics, spiega l'attività antimicrobica selettiva di IBZ.
La ricerca ha rivelato che l'interazione battericida di IBZ con il suo bersaglio DNA pol IIIC è conservata nella maggior parte del phylum Bacillota, incluso C. difficile, mentre i batteri intestinali benefici rimangono naturalmente resistenti. Questo meccanismo spiega il raggio d'azione più ristretto osservato negli studi clinici umani, dove IBZ ha permesso la ricrescita della microbiota benefica.
Lo studio, finanziato dal National Institute of Allergy and Infectious Diseases, dimostra il vantaggio di IBZ rispetto alla vancomicina, che uccide i microbi benefici e porta a tassi più elevati di recidiva da C. difficile. IBZ si sta preparando per avanzare verso la fase 3 degli studi clinici internazionali e ha ricevuto le designazioni FDA QIDP, Fast-Track e EMA SME.
Acurx Pharmaceuticals (NASDAQ: ACXP) anunció resultados positivos de un estudio in silico sobre ibezapolstat (IBZ), su principal candidato a antibiótico para el tratamiento de la infección por C. difficile (CDI). El estudio, publicado en el Journal of Antimicrobial Agents and Chemotherapeutics, explica la actividad antimicrobiana selectiva de IBZ.
La investigación reveló que la interacción bactericida de IBZ con su ADN pol IIIC objetivo se conserva en la mayoría del filo Bacillota, incluyendo C. difficile, mientras que las bacterias intestinales beneficiosas permanecen naturalmente resistentes. Este mecanismo explica el espectro de actividad más estrecho observado en los ensayos clínicos humanos, donde IBZ permitió el rebrote de la microbiota beneficiosa.
El estudio, financiado por el National Institute of Allergy and Infectious Diseases, demuestra la ventaja de IBZ sobre la vancomicina, que mata microbios beneficiosos y conduce a tasas más altas de recurrencia de C. difficile. IBZ se está preparando para avanzar a ensayos clínicos internacionales de fase 3 y ha recibido las designaciones de FDA QIDP, Fast-Track y EMA SME.
Acurx Pharmaceuticals (NASDAQ: ACXP)는 C. difficile 감염(CDI) 치료를 위한 주요 항생제 후보인 ibezapolstat(IBZ)의 인 실리코 연구에서 긍정적인 결과를 발표했습니다. 이 연구는 Journal of Antimicrobial Agents and Chemotherapeutics에 게재되었으며, IBZ의 선택적인 항균 활성을 설명합니다.
연구 결과, IBZ의 표적 DNA pol IIIC와의 박테리아 살균 상호작용이 대부분의 Bacillota 문에서 보존되어 있으며, C. difficile을 포함하고 있지만 유익한 장내 세균은 자연적으로 저항성을 유지한다는 사실이 밝혀졌습니다. 이 메커니즘은 IBZ가 유익한 미생물군의 재성장을 허용한 인간 임상 시험에서 관찰된 좁은 활성 스펙트럼을 설명합니다.
이 연구는 National Institute of Allergy and Infectious Diseases의 지원을 받아 진행되었으며, IBZ가 유익한 미생물을 죽이고 C. difficile 재발률을 높이는 반코마이신보다 우수하다는 것을 입증합니다. IBZ는 국제 3상 임상 시험으로 나아갈 준비를 하고 있으며, FDA QIDP, Fast-Track 및 EMA SME 지정을 받았습니다.
Acurx Pharmaceuticals (NASDAQ: ACXP) a annoncé des résultats positifs d'une étude in silico sur ibezapolstat (IBZ), son principal candidat antibiotique pour le traitement de l'infection à C. difficile (CDI). L'étude, publiée dans le Journal of Antimicrobial Agents and Chemotherapeutics, explique l'activité antimicrobienne sélective de l'IBZ.
La recherche a révélé que l'interaction bactéricide de l'IBZ avec son ADN pol IIIC cible est conservée dans la plupart du phylum Bacillota, y compris C. difficile, tandis que les bactéries intestinales bénéfiques restent naturellement résistantes. Ce mécanisme explique le spectre d'activité plus étroit observé dans les essais cliniques chez l'homme, où l'IBZ a permis la régénération de la microbiote bénéfique.
L'étude, financée par le National Institute of Allergy and Infectious Diseases, démontre l'avantage de l'IBZ par rapport à la vancomycine, qui tue les microbes bénéfiques et entraîne des taux de récidive plus élevés de C. difficile. L'IBZ se prépare à avancer vers des essais cliniques internationaux de phase 3 et a reçu les désignations FDA QIDP, Fast-Track et EMA SME.
Acurx Pharmaceuticals (NASDAQ: ACXP) hat positive Ergebnisse aus einer in-silico-Studie zu ibezapolstat (IBZ), dem führenden Antibiotikum-Kandidaten zur Behandlung von C. difficile-Infektionen (CDI), bekannt gegeben. Die Studie, die im Journal of Antimicrobial Agents and Chemotherapeutics veröffentlicht wurde, erklärt die selektive antimikrobielle Aktivität von IBZ.
Die Forschung ergab, dass die bakterizide Wechselwirkung von IBZ mit seiner Ziel-DNA-Pol IIIC im gesamten Bacillota-Stamm erhalten bleibt, einschließlich C. difficile, während nützliche Darmbakterien von Natur aus resistent bleiben. Dieser Mechanismus erklärt das engere Wirkungsspektrum, das in klinischen Studien am Menschen beobachtet wurde, bei denen IBZ das Nachwachsen der nützlichen Mikrobiota ermöglichte.
Die Studie, die vom National Institute of Allergy and Infectious Diseases finanziert wurde, zeigt den Vorteil von IBZ gegenüber Vancomycin, das nützliche Mikroben abtötet und zu höheren Rückfallraten von C. difficile führt. IBZ bereitet sich darauf vor, in internationale Phase-3-Studien einzutreten und hat die FDA-QIDP-, Fast-Track- und EMA-SME-Auszeichnungen erhalten.
- Ibezapolstat shows selective antimicrobial activity, preserving beneficial gut bacteria unlike competitor vancomycin
- Advancing to international Phase 3 clinical trials for CDI treatment
- Received multiple regulatory designations (FDA QIDP, Fast-Track, EMA SME)
- None.
Insights
The newly published in-silico study results for ibezapolstat (IBZ) reveal a important scientific breakthrough that could significantly impact Acurx Pharmaceuticals' market position in the $1.5 billion CDI treatment market. The study demonstrates IBZ's unique ability to selectively target C. difficile while preserving beneficial gut bacteria - a characteristic that addresses one of the major limitations of current treatments.
The mechanism's significance lies in its potential to reduce disease recurrence rates, a critical metric in CDI treatment. Current standard-of-care treatments like vancomycin often lead to high recurrence rates (20-30%) because they indiscriminately kill both harmful and beneficial bacteria. IBZ's selective action could potentially lower these rates substantially, offering a compelling value proposition for healthcare providers and payers.
The study also validates IBZ's broader potential beyond CDI treatment. The insights gained about the drug's interaction with DNA pol IIIC could accelerate the development of Acurx's pipeline, particularly their MRSA and anti-anthrax programs. This scientific validation strengthens the company's platform technology and could attract partnership opportunities or additional funding for pipeline expansion.
The combination of FDA Fast-Track Designation, QIDP status, and advancing Phase 3 trials positions IBZ as a serious contender in the antibiotics market. The drug's novel mechanism of action and potential for reduced recurrence rates could lead to favorable pricing and reimbursement decisions, potentially driving significant revenue growth for Acurx if approved.
- Major finding provides mechanistic explanation for ibezapolstat's (IBZ) selectivity in that the predicted bactericidal interaction between IBZ and its target DNA pol IIIC is conserved across most of the Bacillota phylum, including C. difficile, while certain beneficial taxa are naturally resistant to IBZ, allowing regrowth of resistant microbes known to confer health benefits
- This study used in silico methods to better interpret the narrower than expected ibezapolstat (IBZ) spectrum of activity observed in human trials, which included increased proportion of certain key gut microbiota of the Bacillota phylum
- IBZ susceptibility of human commensal (nonpathogenic) microbiota was predicted using genomic analysis and a phylogenetic tree construction of the IBZ target enzyme, pol IIIC
- Preparation continues to advance IBZ into international Ph3 clinical trials for treatment of CDI
- IBZ has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA
According to co-author Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of
Acurx's Executive Chairman, Bob DeLuccia, stated: "This in silico genomic analysis complements the structural biology data emerging from our scientific collaboration with Leiden University Medical Center." He further stated: "We're confident that these results can be leveraged to advance not only the ibezapolstat program but also our systemic Gram-positive antibiotic discovery program in lead optimization for an oral pol IIIC inhibitor for methicillin-resistant Staphylococcus aureus (MRSA) and in parallel planning for our anti-anthrax bioterrorism program."
During clinical trials with IBZ, a narrower than expected spectrum of activity was observed that included increased proportion of certain key microbiota of the Bacillota phylum known to confer health benefits, specifically Lachnospiraceae, Oscillospiraceae (formerly Ruminococcaceae), and Coprobacillaceae within Erysipelotrichales. The purpose of this study was to utilize in silico approaches to better interpret the narrower than expected IBZ spectrum of activity observed in human trials. IBZ susceptibility to human commensal microbiota was predicted using genomic analysis and PolC phylogenetic tree construction in relation to C. difficile and commensal low G + C bacteria. An amino acid phylogenetic tree identified certain residues that were phylogenetically variant in Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales but conserved in C. difficile. The major finding of this study was that the predicted interactions between IBZ and pol IIIC is conserved across the majority of the Bacillota phylum except for Lachnospiraceae and Oscillospiraceae, and Erysipelotrichales (including Erysipelotrichaceae and Coprobacillaceae), taxa that were not killed or regrown in IBZ-treated subjects while on therapy.
THE PUBLICATION IS ON OUR WEBSITE: www.acurxpharma.com
About the AAC Journal:
Antimicrobial Agents and Chemotherapy (AAC) is an interdisciplinary journal devoted to the dissemination of knowledge relating to all aspects of antimicrobial and antiparasitic agents and chemotherapy. Generally, any report involving studies on or with antimicrobial, antiviral (including antiretroviral), or antiparasitic agents is within the purview of AAC. Studies involving animal models, pharmacological characterization, and clinical trials are appropriate for consideration.
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
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 (
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
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
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,
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
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
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 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, 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
View original content:SOURCE Acurx Pharmaceuticals, Inc.
FAQ
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