Clostridium difficile colitis

As previously announced, planning is underway with FDA to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI) As anticipated, an End of Phase 2 Meeting (EOP2) with FDA is now confirmed to occur in late April 2024 to finalize the Phase 3 development plan Per FDA Guidance, Acurx also announced it has submitted the required pre-meeting Briefing Document to FDA yesterday, February 26, 2024 SME (Small and Medium-sized Enterprise) designation has been granted by the EMA (European Medicines Agency) which allows Acurx to benefit from fee incentives and other support from the EMA for EU Marketing Authorization Ibezapolstat has previously received FDA QIDP and Fast-Track Designation STATEN ISLAND, N.Y., Feb. 27, 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, today announced that an EOP2 meeting has been granted by FDA to discuss the overall Phase 3 clinical and non-clinical development plan to support an NDA (New Drug Application) filing for ibezapolstat for the treatment of CDI. The Company submitted its Meeting Request earlier this month following successful completion of ibezapolstat's Phase 2 clinical trial. On February 14, 2024, the FDA granted an EOP2 meeting which confirms adequate information was provided to warrant this type of meeting. In accordance with FDA Guidance (September 2023, REV1), the Company submitted its pre-meeting information Meeting Package (or Briefing Document) yesterday, February 26, 2024, which includes detailed information on the clinical development plan, including clinical pharmacology and clinical microbiology studies, to support the NDA filing, study design and statistical analysis plan for the Phase 3 studies. Additionally, the Company was granted SME designation by the European Medicines Agency on February 15, 2024 which allows Acurx to benefit from fee incentives and other support from the EMA for conduct of required clinical trials for ultimate EU Marketing Authorization. The SME designation was established by EMA to promote innovation and the development of new medicinal products by smaller companies. Companies with SME status are eligible to receive financial incentives as well as administrative and regulatory support through national and regional level programs. These benefits include access to dedicated EMA personnel during the clinical development process as well as reductions in fees associated with regulatory procedures such as Scientific Advice, Marketing Authorizations, and inspections. Robert J. DeLuccia, Executive Chairman of Acurx, stated: "We are very pleased to have our FDA EOP2 Meeting granted which confirms that our Meeting Request information package was acceptable since FDA could deny such a meeting for sponsors if it is premature for the stage of development or because the meeting information package provided is not adequate. He further stated: "Having SME status granted by EMA will allow us to leverage the outcome our EOP2 FDA meeting to seek EMA guidance for requirements of a Marketing Authorization in the EU which is consistent with our plan to conduct international Phase 3 clinical trials." David P. Luci, President & CEO of Acurx, stated: "We are pleased to have the opportunity to meet with FDA to confirm readiness for, and design of, our Phase 3 program which includes international clinical study sites and to have SME designation, allowing us to benefit from financial incentives and support from the EMA as we aim to ultimately bring ibezapolstat to the global pharmaceutical marketplace. Throughout 2024 we anticipate further regulatory developments internationally to leverage our success with U.S. clinical trials to date." 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 ). 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 Company's Scientific Advisory Board concurred with this recommendation. 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. 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). The Phase 2b clinical trial segment was 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 and its aftermath. The Company had 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 was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously. The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI. In the Phase 2 clinical trial, the Company 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. 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. 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 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 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 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+ 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 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: [email protected] SOURCE Acurx Pharmaceuticals, Inc.

DUBLIN , Feb. 12, 2024 /PRNewswire/ -- The "Antimicrobial Resistance Diagnostic Markets, Strategies and Trends by Pathogen and Technology, With Executive Guides and Customization 2023 to 2027" report has been added to ResearchAndMarkets.com's offering. Diagnostics are leading the charge in reducing the threat posed by antimicrobial resistance. Will these technologies solve the problem before new antibiotics come along? New diagnostic technologies, beyond gene sequencing, are under development to capture this growing market. The publisher has looked at the technology picture, giving you a plain language understanding of the different ways pathogens, and infections can be diagnosed. The report has identified the 6 Key Large Pathogen Opportunities in this space and developed market forecasts. The report profiles over 30 companies, large and small, working in this area. Antibiotic Resistance Diagnostics Recent Developments FDA Clears New bioMerieux Diagnostic System and Panel Selux Diagnostics Phenotyping System Gets FDA Approval New diagnostics to tackle drug resistant infections Takara Bio USA, Inc. and BioExcel Diagnostics Partner for Infectious Disease Panels Three companies join forces to tackle antimicrobial resistance (AMR) T2 Biosystems Exercises BARDA Option OpGen to Ramp up Use of Acuitas AMR Gene Panel BD Partners With Pfizer, Wellcome to Study AMR Dx Sepsis Test Developers Accelerate Plans OpGen Receives FDA Clearance for AMR Panel Visby Medical - Rapid Uptake of Handheld PCR Test for STIs MicroGenDx, OrthoKey Clinic and OrthoKey Surgery BioMerieux Receives CE Mark for Vitek Clinical Microbiology System Hologic to Acquire Mobidiag Campylobacter strains exchange genes Disinfection spreads antimicrobial resistance Molzym, Fraunhofer Developing Rapid Sepsis Dx Illumina, IDbyDNA Build NGS-Based Respiratory Panel Accelerate Diagnostics Expands AMR Testing Rapid diagnostics linked to optimal antibiotics Visby Medical Wins AMR Diagnostic Competition DNAe Technology SARS-CoV-2 Sequences Infections with foodborne bacteria becoming harder to treat Dust is sharing antibiotic resistance genes Key AMR Diagnostics Companies 1928 Diagnostics Abacus Diagnostica Abbott Laboratories Accelerate Diagnostics ADT Biotech Beckman Coulter Diagnostics Becton, Dickinson Binx Health bioMérieux Diagnostics Bio-Rad Laboratories Cepheid (Danaher) Curetis N.V. / Curetis Day Zero Diagnostics. Enzo Biochem Eurofins Scientific Fusion Genomics. GeneFluidics Genetic Signatures Great Basin Corporation Hologic Hutman Diagnostics Inflammatix Linear Diagnostics. Lumos Diagnostics Millipore Sigma OpGen Ortho Clinical Diagnostics Perkin Elmer Qiagen Roche Molecular Diagnostics SeLux Diagnostics Sense Biodetection Siemens Healthineers Sysmex Thermo Fisher Scientific Visby Medical Key Topics Covered: 1 Market Guides 1.1 Antimicrobial Resistance - Strategic Situation Analysis 1.2 Guide for Executives and Business Development Staff 1.3 Guide for Management Consultants and Investment Advisors 2 Introduction and Market Definition 2.1 The Threat and Opportunity of Antimicrobial Resistance 2.2 Defining the Opportunity 2.3 Methods and Sources 2.4 Perspective: Healthcare and the IVD Industry 2.5 Spending on Diagnostics 3 Overview of a Dynamic Market 3.1 Players in a Dynamic Market 3.1.1 Diagnostic Test Developer 3.1.2 Instrumentation Supplier 3.1.3 Chemical/Reagent Supplier 3.1.4 Pathology Supplier 3.1.5 Independent Clinical Laboratory 3.1.6 Public National/regional Laboratory 3.1.7 Hospital Laboratory 3.1.8 Physicians Office Lab (POLS) 3.1.9 Audit Body 3.1.10 Certification Body 3.2 Understanding Antimicrobial Resistance 3.3 The Changing Road to New Antibiotics & Technologies 3.4 The Key Role of Diagnostics in AMR 4 The Market Opportunity of AMR 4.1 The Key Large Market Opportunities in AMR 4.1.1 Streptococcus Pneumoniae (DRSP) 4.1.2 Campylobacter (DRC) 4.1.3 Clostridium Difficile (CD) 4.1.4 Staphylococcus aureus (MRSA) 4.1.5 Neisseria gonorrhoeae (DRNG) 4.1.6 Salmonella (DRNTS) 4.2 Diagnostic Technology Development Opportunities 4.2.1 What's Wrong with Microbiology 4.2.2 The Features Battleground of Infectious Disease Diagnostics 4.2.3 Multiplex vs. POC/Rapid 4.2.4 The Miracle of Genetics 4.2.5 From Multiple Pathogens to All Pathogens - The Next Next Generation 4.2.6 Gene Sequence Diagnostics WITHOUT the Sequencing. 4.2.7 Markers of Resistance. 4.2.8 What Happens to the Microbiology Lab? 5 Antibiotic Resistance Diagnostics Recent Developments 6 Key AMR Diagnostics Companies 7 The Global Market for Antimicrobial Resistance Diagnostics 7.1 Global Market Overview by Country. 7.2 Global Market by Technology 8 Global Antibiotic Resistance Diagnostic Markets - By Pathogen 8.1 Drug Resistant Streptococcus Pneumoniae - DRSP 8.2 Drug Resistant Campylobacter - DRC 8.3 Clostridium Difficile - CD 8.4 Methicillin Resistant Staphylococcus Aureus - MRSA 8.5 Drug Resistant Neisseria Gonorrhoeae - DRNG 8.6 Drug Resistant Salmonella - DRNTS 9 Global Antibiotic Resistance Diagnostic Markets - by Technology 9.1 Microbiology Culture 9.2 Immunoassay 9.3 PCR 9.4 NGS 9.5 Mass Spectrometry - MS 9.6 Rapid and Point of Care - Rapid/POC 10 Vision of the Future of AMR Diagnostics For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

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 Further analyses will be forthcoming as data become available regarding effects on bile acid metabolism and pharmacokinetic data Preparation is underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials Ibezapolstat has previously received FDA QIDP and Fast-Track Designation STATEN ISLAND, N.Y., Jan. 29, 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, today announced 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. According to Dr. Garey: "CDI has long-term consequences including poor quality of life for the patient. It's exciting to see that the ibezapolstat Phase 2b study followed patients for an extended time period to assure that the ibezapolstat cure and anti-recurrence effects are long-lasting and durable. This adds to the exciting microbiome data showing replenishment of healthy microbiota that we have seen in our prior studies." Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This Extended Clinical Cure data showing that no ibezapolstat-treated patient who achieved Clinical Cure and consented to three months of post-treatment observation experienced a recurrence of CDI during this period further strengthens the ibezapolstat lineage of clinical success building on our previously reported Phase 2 results of 96% Clinical Cure and 100% Sustained Clinical Cure along with favorable preservation of the microbiome and no safety signals." He further stated: "We look forward to advancing to Phase 3 clinical trials and are optimistic about achieving non-inferiority versus vancomycin which is the regulatory clinical development hurdle for marketing registration". David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate continued favorable differentiation between the two therapeutic options in 2024. We expect to leverage this success in a $1 billion plus US CDI global market as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also anticipates its price point for ibezapolstat, if approved, could meet or beat other antibiotics recommended for use in treating patients with CDI, thereby providing the whole package of clinical comparability with microbiome health, safety and cost for patients with this life-threatening disease." 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 ). 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 Company's Scientific Advisory Board concurred with this recommendation. 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. 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). The Phase 2b clinical trial segment was 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 and its aftermath. The Company had 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 was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously. The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI. In the Phase 2 clinical trial, the Company 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. 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 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 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 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 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+ 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 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: [email protected] SOURCE Acurx Pharmaceuticals, Inc.