Vancomycin Hydrochloride

REC-3964 is Recursion’s first new chemical entity developed using the RecursionOS.REC-3964 represents a novel, non-antibiotic approach with a unique mechanism of action that binds and blocks catalytic activity of the toxin's innate glucosyltransferase in order to inhibit the toxin produced by C. diff. in the gastrointestinal tract.There are up to 175,000 cases of recurrent C. diff. each year and more than 29,000 patients die in the U.S. from C. diff. annually. Rates of recurrent C. diff. have increased significantly in recent years, representing a major public health challenge. SALT LAKE CITY, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Recursion (NASDAQ: RXRX), a leading clinical stage TechBio company decoding biology to radically improve lives, today announced that the first patient has been dosed in its Phase 2 clinical trial of REC-3964, a potential first-in-class, oral small molecule and new chemical entity for the treatment of recurrent Clostridioides difficile infection. C. diff is a toxin producing bacteria that causes diarrhea and colitis, and can be life threatening. Up to 730,000 cases are estimated to occur in the U.S. and EU5 annually, and the infection is responsible for an estimated 29,000 deaths in the U.S. each year. Recursion’s study will initially address the recurrent C. diff. (up to 175,000 cases in the United States per year) population, which costs the healthcare system approximately two billion dollars per year. Increasing cases of recurrent C. diff. infections pose significant public health challenges. Antibiotics, the standard treatment for C. diff. infections, disturb the gut microbiome due to their non-selective nature. Despite initial success, antibiotics fail to prevent recurrence in 20-30% of primary cases. Further, the risk of subsequent recurrence rises to 40% after the first and 45-65% after two or more. REC-3964 is the first novel small molecule developed through Recursion’s Operating System, and selectively inhibits the glucosyltransferase activity of toxin B produced by C. diff in the gastrointestinal tract, offering a unique mechanism of action. Unlike antibiotics, which disrupt the gut microbiome, REC-3964 precisely targets the bacterial toxin while sparing healthy tissue, potentially minimizing adverse events. It is being studied as part of a treatment regimen to prevent recurrent C. diff infections, a leading cause of antibiotic-associated diarrhea that can lead to significant morbidity and mortality. Presented at the 6th Edition of World Congress on Infectious Diseases, preclinical studies demonstrated its superiority over bezlotoxumab in a human disease-relevant C. diff. hamster model. Additionally, Phase 1 studies in healthy volunteers showed REC-3964 was well tolerated with no serious adverse events (SAEs), underscoring its potential safety and tolerability. “There’s a significant unmet need for new treatment options for patients with C. diff. infection that are easier to use and more cost effective,” said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. “We are encouraged by the progress of REC-3964, the first new chemical entity from our platform to advance to Phase 2 clinical trials, and now, to the first patient dosed. We look forward to continuing to advance this trial to help patients in need and drive down billions in costs to the healthcare system for treatment.” Christian John Lillie, Co-Founder and CEO of the Peggy Lillis Foundation, shared: "We are so pleased to learn that our partner Recursion has initiated its ALDER trial. All new therapies that can be added to the known standard of care have the potential to decrease the physical and emotional suffering of recurrent C. diff. on patients and the significant burden to the health care system.” “Patients with C. diff face significant challenges, with 20-30% of initial infections recurring after standard treatment and a 40% chance of further recurrence, often leading to severe complications and a diminished quality of life,” said Najat Khan, Ph.D., Chief Commercial Officer and Chief R&D Officer at Recursion. “For these patients and their families, the need for safe, effective, non-antibiotic treatment options is critical. REC-3964 offers a novel, targeted approach by selectively inhibiting the bacterial toxin while sparing the host. With encouraging preclinical data and strong tolerability demonstrated in Phase 1 studies, it’s particularly rewarding to see the first drug developed using the RecursionOS and advancing to Phase 2 trials.” The Phase 2 ALDER clinical trial is a multi-center randomized study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 at doses of either 250 mg or 500 mg for the reduction of C. diff. and will include an observation only arm. Approximately 80 individuals will ultimately be enrolled in the study across the U.S. and Europe. About Clostridioides difficile infection Clostridioides difficile (C. diff.) infection is a bacterial disease that impacts more than 730,000 people in the U.S. and EU5 every year. Rates of recurrent C. diff. have increased significantly in recent years, representing a major public health challenge, with people 7 to 10 times more likely to get C. diff. infection while taking an antibiotic and the subsequent month. About 20-30% patients who have C. diff. infection will have it again in the subsequent 2 to 8 weeks. After the first recurrence, there’s a 40% likelihood of a second recurrence, and a 45-65% likelihood of recurrence among patients who have recurred more than twice. In total C. diff. infection is estimated to cause 29,300 deaths in the U.S. each year. More than 80% of C. diff. infection deaths occur in people aged 65 and older. On average, one in 11 patients older than 65 years diagnosed with healthcare-associated C. diff. infection will die within a month. Extended stays in healthcare settings, such as hospitals and nursing homes, also increase risk. About REC-3964REC-3964 is a potential first-in-class, orally bioavailable non-antibiotic small molecule that is being investigated for the potential treatment of recurrent Clostridioides difficile (C. diff.) infection. This selective inhibitor is Recursion’s first new chemical entity to reach the clinic, and binds and blocks catalytic activity of the toxin's innate glucosyltransferase. In preclinical studies, REC-3964 was found to be superior to bezlotoxumab in a human disease relevant C. diff. hamster model, with significant difference in probability of survival versus bezlotoxumab alone at the end of treatment. REC-3964 was also well tolerated in Phase 1 healthy volunteer studies, demonstrating potential safety and tolerability with no serious adverse events (SAEs). About the Trial Our Phase 2 ALDER clinical trial is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 (doses of either 250 mg or 500 mg PO every 12 hours) for the reduction of Clostridioides Difficile infection (C. diff.). Approximately 80 individuals will be enrolled in this open-label Phase 2 study, randomized 1:2:1 to receive oral doses of REC-3964, 250 mg, 500 mg or observation. The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 for the reduction of recurrent Clostridioides difficile infection (rCDI) after initial cure with vancomycin. Participants will receive treatment with REC-3964 for 28 days. About RecursionRecursion (NASDAQ: RXRX) is a clinical stage TechBio company leading the space by decoding biology to radically improve lives. Enabling its mission is the Recursion OS, a platform built across diverse technologies that continuously generate one of the world’s largest proprietary biological and chemical datasets. Recursion leverages sophisticated machine-learning algorithms to distill from its dataset a collection of trillions of searchable relationships across biology and chemistry unconstrained by human bias. By commanding massive experimental scale — up to millions of wet lab experiments weekly — and massive computational scale — owning and operating one of the most powerful supercomputers in the world, Recursion is uniting technology, biology and chemistry to advance the future of medicine. Recursion is headquartered in Salt Lake City, where it is a founding member of BioHive, the Utah life sciences industry collective. Recursion also has offices in Toronto, Montréal, London, and the San Francisco Bay Area. Learn more at www.Recursion.com, or connect on X (formerly Twitter) and LinkedIn. Media ContactMedia@Recursion.com Investor ContactInvestor@Recursion.com Forward-Looking Statements This document contains information that includes or is based upon “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including, without limitation, those regarding the potential efficacy of REC-3964; timing of the Phase 2 clinical trial of REC-3964; early and late stage discovery, preclinical, and clinical programs; licenses and collaborations; prospective products and their potential future indications and market opportunities; Recursion OS and other technologies; business and financial plans and performance; and all other statements that are not historical facts. Forward-looking statements may or may not include identifying words such as “plan,” “will,” “expect,” “anticipate,” “intend,” “believe,” “potential,” “continue,” and similar terms. These statements are subject to known or unknown risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements, including but not limited to: challenges inherent in pharmaceutical research and development, including the timing and results of preclinical and clinical programs, where the risk of failure is high and failure can occur at any stage prior to or after regulatory approval due to lack of sufficient efficacy, safety considerations, or other factors; our ability to leverage and enhance our drug discovery platform; our ability to obtain financing for development activities and other corporate purposes; the success of our collaboration activities; our ability to obtain regulatory approval of, and ultimately commercialize, drug candidates; our ability to obtain, maintain, and enforce intellectual property protections; cyberattacks or other disruptions to our technology systems; our ability to attract, motivate, and retain key employees and manage our growth; inflation and other macroeconomic issues; and other risks and uncertainties such as those described under the heading “Risk Factors” in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. All forward-looking statements are based on management’s current estimates, projections, and assumptions, and Recursion undertakes no obligation to correct or update any such statements, whether as a result of new information, future developments, or otherwise, except to the extent required by applicable law.

The data presented indicate a favorable gut bile acid profile which may contribute to ibezapostat's beneficial anti-recurrence effect in patients with C. difficile Infection (CDI) Ibezapolstat treatment of patients with CDI is associated with the restoration of beneficial bacterial classes in the gut Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI) Preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union to be followed by the United Kingdom, Japan and Canada Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA STATEN ISLAND, N.Y., Oct. 21, 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 the presentation of a scientific poster at the Infectious Diseases Society of America (IDSA) IDWeek™ 2024 Conference held October 16-19, 2024 in Los Angeles, CA. 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, and Taryn A. Eubank, PharmD, BCIDP, Research Assistant Professor, University of Houston College of Pharmacy presented a scientific poster entitled: A phase 2, randomized double-blind study of ibezapolstat compared with vancomycin for the treatment of C. difficile infection: clinical and microbiome evaluation. In the Phase 2b clinical trial, ibezapolstat had comparable clinical cure and sustained clinical cure rates and safety profile to vancomycin. Also, 5 of 5 ibezapolstat patients who were followed for 3 months after end of treatment (EOT) experienced no recurrence. Favorable microbiome results were observed in ibezapolsat-treated patients who had increased proportion of Actinobacteriota and beneficial Bacillota. Furthermore, ibezapolstat-treated patients showed decreased concentrations of fecal primary bile acids, and higher ratios of secondary to primary bile acids than vancomycin-treated patients. According to Dr. Garey: "These exciting results demonstrate two properties of ibezapolstat which may contribute to the anti-recurrence effect. First, the preservation and restoration of beneficial bacterial classes in the gut provide resistance to recolonization by C. difficile. Second, these data, presented for the first time, indicate that these beneficial bacteria known to metabolize primary to secondary bile acids persist in ibezapolstat-treated patients providing another important mechanism to prevent recurrent CDI". Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This new impressive bile acid and microbiome data compliment and extend our knowledge of ibezapolstat's pharmacologic profile. These results, when added to previous work showing anti-virulence properties, preclinically, give us a high level of confidence that our excellent Phase 2 clinical results will be confirmed in our Phase 3 studies". The scientific poster is available on the Acurx Pharmaceuticals website at . 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 IDSA and IDWeek The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). 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. 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. 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 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-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 . 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: [email protected] SOURCE Acurx Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED