Acurx Sponsored and Participated in the Peggy Lillis Foundation Inaugural CDI Scientific Symposium and Presented Ibezapolstat Ph2b Clinical Data Update

Acurx is proud to sponsor this inaugural Scientific Symposium of the Peggy Lillis Foundation (PLF) for C. Diff Education & Advocacy
An update of ibezapolstat Ph2b clinical and microbiome results was presented
Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)
Acurx continues preparation to submit requests for regulatory guidance to initiate clinical trials in the European Union to be followed by Japan, Canada and the United Kingdom
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA

STATEN ISLAND, N.Y., Nov. 18, 2024 /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, with its lead antibiotic candidate, ibezapolstat, preparing to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). The Company today announced its support and participation in the Inaugural Peggy Lillis Foundation (virtual) Scientific Symposium, held on Friday, November 15, 2024.

Acurx’s Executive Chairman, Bob DeLuccia, delivered opening remarks for the symposium which assembled experts and thought leaders from around the world to present state-of-the art updates regarding C difficile Infection and therapeutic options. Topics covered included epidemiology, bacterial physiology, risk factors for infections, and new and emerging treatment modalities. The Symposium also included testimonials from patients who survived CDI.

Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program, and Acurx Scientific Advisory Board member, delivered a presentation entitled: “Ibezapolstat Preserves Key Clostridium Leptum Species: Microbiome Results from the Phase 2, Randomized, Double-Blind Study.”

According to Dr. Garey: “In contrast to patients dosed with vancomycin, ibezapolstat has consistently shown in the phase 1 and 2 studies that it promotes the growth of beneficial Actinobacteria important for short chain fatty acid production and Clostridiales important for bile acid homeostasis. At the same time, it does not promote the overgrowth of potentially harmful Proteobacteria.” He further added: “Ibezapolstat showed a favorable secondary to primary ratio of bile acids which is linked to a lower recurrence rate of CDI. I’m excited to see this new antibiotic advance to phase 3 clinical trials for the treatment of acute C. difficile Infection, particularly considering the favorable effects on bile acid homeostasis, which could lead to a reduction in CDI recurrence, a current unmet medical need with currently marketed antibiotics.”

Robert J. DeLuccia, Executive Chairman of Acurx, stated: “As a leader in the field with the first new class of antibiotics in decades now preparing to enter Ph3 international trials for the treatment of acute CDI and reduction of recurrence, we are very excited to have sponsored this event to support the PLF and to present an update on ibezapolsat’s Ph2b data, particularly during November being CDC-designated as Cdiff Awareness month.” Dr. Garey’s presentation is available on the Acurx Pharmaceuticals website at www.acurxpharma.com.

Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, to be followed by requests to be submitted in the United Kingdom, Japan and Canada.

Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population consistent with EMA requirements. 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 Peggy Lillis Foundation
The Peggy Lillis Foundation (PFL) is building a nationwide C. DIFF (Clostridioides difficile) awareness movement by educating the public, empowering advocates and shaping public policy. Currently, PLF is going beyond its early beginnings as a patient advocacy group to raise awareness of Cdiff, but now is building a broader foundation by uniting researchers, clinicians, and the medical community, along with all advocates to share groundbreaking research findings, foster collaboration and ultimately enhance cdiff patient outcomes.
For more information about PLF please visit: https://cdiff.org/

About the Ibezapolstat Phase 2 Clinical TrialThe 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. 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 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 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 MetabolismC. 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) and drug-resistant Streptococcus pneumoniae (DRSP). To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com.

Forward-Looking StatementsAny 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: [email protected]

SOURCE Acurx Pharmaceuticals, Inc.