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>>> Acurx Announces Publication in Lancet Microbe of Phase 2b Clinical Trial Data for Ibezapolstat in CDI


PR Newswire

June 17, 2025


https://finance.yahoo.com/news/acurx-announces-publication-lancet-microbe-110100523.html


As previously reported, 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population experienced Clinical Cure (CC) and all 15 of 15 (100%) remained free of C. difficile infection (CDI) recurrence through one month after EOT

In contrast, 2 of 14 (14%) patients treated with the standard of care, oral vancomycin, experienced recurrent infection within one month after EOT

When Phase 2b results are combined with Phase 2a results, 25 of 25 (100%) ibezapolstat-treated patients with CDI who had CC at EOT remained recurrence-free through 1 month after EOT; additionally, all 5 Phase 2b ibezapolstat-treated patients observed for up to 3 months following CC experienced no recurrence of infection

Adding to this Lancet Microbe publication,two recent Journal of Antimicrobial Agents and Chemotherapeutics publications regarding, respectively, favorable gut microbiome effects which differentiate IBZ from other anti-CDI antibiotics and positive results from an in-silico study predicting the microbiome-restorative potential of IBZ

The totality of ibezapolstat data-to-date further advances Acurx's robust data package and are reshaping the therapeutic landscape for future treatment of CDI with ibezapolstat's innovative and potentially transformative new class of antibiotics to treat gram-positive infections while preserving and restoring the protective gut microbiota

Acurx is well positioned to begin international Phase 3 clinical trials and has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA


STATEN ISLAND, N.Y., June 17, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company") is a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. Its lead antibiotic candidate, ibezapolstat (IBZ), is ready to advance to international Phase 3 clinical trials for treatment of patients with C. difficile infection (CDI). The Company today announced the publication of results in Lancet Microbe of its Phase 2b clinical study entitled: Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomized, double-blind, active-controlled, multicenter study. The senior author is Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, and Principal Investigator for microbiology and microbiome aspects of the IBZ clinical trial program, and a co-author of the IDSA (Infectious Diseases Society of America) C. difficile Treatment Guidelines.

Professor Garey noted that current US and European treatment guidelines for CDI recommend only two antibiotics for treatment of CDI: oral vancomycin (VAN) or fidaxomicin (FDX). VAN is most commonly used with a low CC rate of 70-92% and an SCC rate of 42-71%. FDX has fewer recurrences but low rates of CC (84%) and SCC (67%); furthermore, both FDX and VAN are associated with emerging antimicrobial resistance. Dr. Garey also stated: "The clinical need for a new antibiotic, like IBZ, to treat CDI is underscored by a study recently published in Clinical Infectious Diseases conducted in a hospital setting, documenting that C. difficile isolates with clinically relevant reduced fidaxomicin susceptibility may emerge during therapy and spread to other patients. The medical community should be aware of this alarming finding."

Acurx's Executive Chairman, Bob DeLuccia, stated: "This Lancet Microbe article complements the body of our published data to date, the totality of which establishes a comprehensive and formidable dossier to support our optimism for a successful Phase 3 clinical program and, if successful, first choice of IBZ as a front-line treatment for CDI. Our publications include data on IBZ chemistry, mechanism of action, microbiological activity, in vivo efficacy in the hamster model, human efficacy and safety, and favorable effects on the gut microbiome and bile acid metabolism." He further stated: "Data from our Phase 3 pivotal trials, if successful, will form the foundation for our continually evolving and attractive value proposition including in-market competitive advantage compared to vancomycin and fidaxomicin. Additionally, continuing optimization of our 'home-grown and made-in-America" supply chain will ensure scalability and reliability to be accessible and affordable worldwide".

This most recent publication adds important scientific information to supplement a growing list of peer-reviewed publications, including a Phase 1 study showing IBZ to be well-tolerated, localized to the gastrointestinal tract, and associated with preservation and restoration of beneficial gut microbiota. These Phase 2b study findings were supported by a Phase 2a, open-label, non-comparative study and showed 10 of 10 subjects were cured of CDI with no recurrence of infection. Based on this evidence, the Phase 2b study was initiated to assess the efficacy, safety, and associated microbiome changes of IBZ versus standard of care vancomycin (VAN).

This Phase 2b multi-site study was conducted at US medical clinics and hospitals. In the publication, Professor Garey summarized results which included high rates of CC in IBZ-treated subjects treated with no recurrence; furthermore, IBZ was found to be safe, well-tolerated, and associated with the preservation and restoration of key health-promoting bacteria responsible for bile acid homeostasis, a key component in preventing recurrent CDI. The publication establishes that IBZ shows potential as a novel antibiotic treatment for CDI with high rates of CC and SCC while minimally disturbing the protective gut microbiota, thus further supporting its clinical development.

THE ABOVE-MENTIONED PUBLICATIONS ARE ON OUR WEBSITE: www.acurxpharma.com

Lancet Microbe: Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomized, double-blind, active-controlled, multicenter study

Clinical Infectious Diseases: Emergence and Spread of Clostridioides difficile Isolates with Reduced Fidaxomicin Susceptibility in an Acute Care Hospital

About the Lancet Microbe

The Lancet Microbe is the world-leading microbiology research journal and publishes clinically relevant content on microbes at all scales, from the nature of the microbe (eg, antimicrobial resistance genes/plasmids, virulence factors) to the microbiome, to pathology (including immunology) to population level effects (eg, outbreaks, epidemiology). It also publishes early phase clinical trials and other interventional studies where the outcomes are focused on the pathogen. It is an internationally trusted source of clinical, public health, and global health knowledge.

About Clinical Infectious Diseases

Clinical Infectious Diseases (CID) is a leading journal in the field of infectious disease with a broad international readership. The Journal publishes articles on a variety of subjects of interest to practitioners and researchers. Topics range from clinical descriptions of infections, public health, microbiology, and immunology to the prevention of infection, the evaluation of current and novel treatments, and the promotion of optimal practices for diagnosis and treatment. The Journal publishes original research (as Major Articles or Brief Reports), Review Articles, Viewpoints, Editorials, Invited Commentaries, Photo Quizzes, Practice Guidelines, Correspondence, and Supplements and is among the most highly cited journals in the field of infectious diseases. Clinical Infectious Diseases is an official publication of the Infectious Diseases Society of America.

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 Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

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. 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 (10 of 10).

In the 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. In this Phase 2b trial segment, 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population experienced Clinical Cure (CC) and all 15 of 15 (100%) remained free of C. difficile infection (CDI) recurrence through one month after EOT.

When Phase 2b results are combined with Phase 2a results, the Clinical Cure rate 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. Notably, in the combined Phase 2 trial, 100% (25 of 25) ibezapolstat-treated patients) who had Clinical Cure at EOT) (End of Treatment) remained cured through one month after EOT, as compared to 86% (12 of 14) for the vancomycin patient group. Ibezapolstat was well-tolerated, with no serious adverse events assessed by the blinded investigator to be drug- related. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96%, Sustained Clinical Cure Rate of 100% and the historical vancomycin Clinical Cure Rate range of 70% to 92% and a Sustained Clinical Cure historical range of 42% to 74%, we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials, in accordance with the applicable FDA Guidance for Industry (October 2022), with favorable differentiation in both Clinical Cure and Sustained Clinical Cure.

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 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 5 of 5 IBZ patients followed for up to three months following Clinical Cure 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. 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

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, 2015, NEJM). 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, NEJM. 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 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.) 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 (Garey, 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.

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[gfp927z]

I see Acurx now has a new $12 mil equity line of credit, so that should help buy time until full funding can be found for the Phase 3, a partnership deal occurs, or M+A could be another possibility -


>>> In May 2025, we closed an equity line of credit with Lincoln Park Capital for up to $12 million of additional funding. <<<


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>>> Acurx Pharmaceuticals, Inc. Reports First Quarter Results and Provides Business Update


PR Newswire

May 13, 2025


https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-first-110100835.html


STATEN ISLAND, N.Y., May 13, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the first quarter ended March 31, 2025.

Highlights of the first quarter ended March 31, 2025, or in some cases shortly thereafter, include:

In January 2025, the Company announced it had closed a $2.5 million registered direct offering priced at the market under Nasdaq rules.

Also in January 2025, we announced that we received positive regulatory guidance from the European Medicines Agency (EMA) for the ibezapolstat (IBZ) Phase 3 clinical trial program, which is aligned with FDA on matters of manufacturing, non-clinical and clinical aspects of the Phase 3 program. The EMA guidance also confirmed ibezapolstat's regulatory pathway for a Marketing Authorization Application to be filed by the Company after successful completion of the Phase 3 clinical trials. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

In February 2025 and in March 2025, we announced new publications in the Journal of Antimicrobial Agents and Chemotherapeutics of two very important non-clinical studies which we believe we can leverage to show further positive differentiation for competitive advantage of IBZ vs all other antibiotics used for the first line therapy of C. difficile infection. And, given our clinical results to date, we're hopeful that this anti-recurrence effect of IBZ could mitigate the need for expensive microbiome therapeutic agents to prevent recurrent CDI.

In February 2025, we announced positive results from this first study, conducted by Dr. Justin McPherson from the University of Houston and funded by the National Institute of Allergy and Infectious Diseases (or NIAID). It was an in-silico study that predicted the microbiome-restorative potential of IBZ for treating CDI. Our scientific advisors consider this to be a major finding which provides a mechanistic explanation for IBZ's selectivity in that the predicted bactericidal interaction between IBZ and its target, the DNA pol IIIC enzyme, allows regrowth of gut microbes known to confer health benefits.

In March 2025, we announced the second study, conducted by Dr. Trenton Wolfe, from the University of Montana, which was funded by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI), National Center for Advancing Translational Sciences (NCATS), and the Company. This study is the first ever head-to-head comparison of gut microbiome changes associated with IBZ when compared to other anti-CDI antibiotics in a germ-free mouse model. The data showed that changes in alpha and beta microbiome diversities following IBZ treatment were less pronounced compared to those observed in vancomycin (VAN)-or metronidazole (MET)-treated groups, complementing prior Phase 2 clinical findings showing IBZ's more selective antibacterial activity. Further, and very importantly, notable differences were observed between the microbiome of IBZ- and the fidaxomicin (FDX)-treated groups, which may allow for differentiation of these two anti-CDI antibiotics in future studies.These results establish IBZ's differentiating effects on the gut microbiome, indicating a more selective spectrum of microbiome alteration compared to broader-spectrum antibiotics like VAN and MET and a narrower spectrum of microbiome alteration compared to FDX.

Also in February 2025, the Japanese Patent Office granted a new patent for our DNA polymerase IIIC inhibitors which expires in December 2039, subject to extension. This constitutes a significant building block for our ongoing development of ACX-375C, our pre-clinical antibiotic candidate targeting the treatment of MRSA, VRE and Anthrax infections.

In March 2025, we announced the closing of a registered direct offering and concurrent private placement, raising gross proceeds of $1.1 million.

In April 2025, the Indian Patent Office granted a new patent for our DNA polymerase IIIC inhibitors which expires in December 2039, subject to extension. This constitutes another significant building block for our ongoing development of ACX-375.

In May 2025, we closed an equity line of credit with Lincoln Park Capital for up to $12 million of additional funding.

First Quarter 2025 Financial Results

Cash Position:

The Company ended the quarter with cash totaling $4.6 million, compared to $3.7 million as of December 31, 2024. The Company raised a total of approximately $3.6 million of gross proceeds thru two Registered Direct Offerings.

R&D Expenses:

Research and development expenses for the three months ended March 31, 2025 were $0.6 million compared to $1.6 million for the three months ended March 31, 2024, a decrease of $1.0 million. The decrease was due primarily to a decrease in manufacturing costs of $0.4 million, and a decrease in consulting costs of $0.6 million as a result of the prior year trial related expenses.

G&A Expenses:

General and administrative expenses for the three months ended March 31, 2025 were $1.6 million compared to $2.8 million for the three months ended March 31, 2024, a decrease of $1.2 million. The decrease was primarily due to $0.7 million decrease in professional fees resulting from lower consulting expenses, and a $0.6 million decrease in share-based compensation costs.

Net Income/Loss:

The Company reported a net loss of $2.1 million or $0.11 per diluted share for the three months ended March 31, 2025 compared to a net loss of $4.4 million or $0.28 per diluted share for the three months ended March 31, 2024, for the reasons previously mentioned.

The Company had 22,397,511 shares outstanding as of March 31, 2025.

Conference Call

As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:

Date:

Tuesday, May 13, 2025

Time:

8:00 a.m. ET

Toll free (U.S.):

1-877-790-1503; Conference ID: 13753625

International:

Click here for participant international Toll-Free access numbers

https://www.incommconferencing.com/international-dial-in

About Ibezapolstat

Ibezapolstat is the Company's lead antibiotic candidate advancing 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 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, methicillinresistant 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.

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[gfp927z]

It looks like Acurx is planning for a reverse split (link below). They have a deadline of August 25 to get the share price over $1 to avoid delisting, but there might be some additional time available to comply. Anyway, the ability to reverse split was on the recent SHM voting ballot -


Reverse split - https://www.sec.gov/Archives/edgar/data/1736243/000110465925054244/tm252476d5_defa14a.htm

Delisting - https://investorshub.advfn.com/boards/read_msg.aspx?message_id=175873278



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[gfp927z]

>>> Acurx Pharmaceuticals, Inc. Reports First Quarter Results and Provides Business Update


PR Newswire

May 13, 2025


https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-first-110100835.html


STATEN ISLAND, N.Y., May 13, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the first quarter ended March 31, 2025.

Highlights of the first quarter ended March 31, 2025, or in some cases shortly thereafter, include:

In January 2025, the Company announced it had closed a $2.5 million registered direct offering priced at the market under Nasdaq rules.

Also in January 2025, we announced that we received positive regulatory guidance from the European Medicines Agency (EMA) for the ibezapolstat (IBZ) Phase 3 clinical trial program, which is aligned with FDA on matters of manufacturing, non-clinical and clinical aspects of the Phase 3 program. The EMA guidance also confirmed ibezapolstat's regulatory pathway for a Marketing Authorization Application to be filed by the Company after successful completion of the Phase 3 clinical trials. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

In February 2025 and in March 2025, we announced new publications in the Journal of Antimicrobial Agents and Chemotherapeutics of two very important non-clinical studies which we believe we can leverage to show further positive differentiation for competitive advantage of IBZ vs all other antibiotics used for the first line therapy of C. difficile infection. And, given our clinical results to date, we're hopeful that this anti-recurrence effect of IBZ could mitigate the need for expensive microbiome therapeutic agents to prevent recurrent CDI.

In February 2025, we announced positive results from this first study, conducted by Dr. Justin McPherson from the University of Houston and funded by the National Institute of Allergy and Infectious Diseases (or NIAID). It was an in-silico study that predicted the microbiome-restorative potential of IBZ for treating CDI. Our scientific advisors consider this to be a major finding which provides a mechanistic explanation for IBZ's selectivity in that the predicted bactericidal interaction between IBZ and its target, the DNA pol IIIC enzyme, allows regrowth of gut microbes known to confer health benefits.

In March 2025, we announced the second study, conducted by Dr. Trenton Wolfe, from the University of Montana, which was funded by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI), National Center for Advancing Translational Sciences (NCATS), and the Company. This study is the first ever head-to-head comparison of gut microbiome changes associated with IBZ when compared to other anti-CDI antibiotics in a germ-free mouse model. The data showed that changes in alpha and beta microbiome diversities following IBZ treatment were less pronounced compared to those observed in vancomycin (VAN)-or metronidazole (MET)-treated groups, complementing prior Phase 2 clinical findings showing IBZ's more selective antibacterial activity. Further, and very importantly, notable differences were observed between the microbiome of IBZ- and the fidaxomicin (FDX)-treated groups, which may allow for differentiation of these two anti-CDI antibiotics in future studies.These results establish IBZ's differentiating effects on the gut microbiome, indicating a more selective spectrum of microbiome alteration compared to broader-spectrum antibiotics like VAN and MET and a narrower spectrum of microbiome alteration compared to FDX.

Also in February 2025, the Japanese Patent Office granted a new patent for our DNA polymerase IIIC inhibitors which expires in December 2039, subject to extension. This constitutes a significant building block for our ongoing development of ACX-375C, our pre-clinical antibiotic candidate targeting the treatment of MRSA, VRE and Anthrax infections.

In March 2025, we announced the closing of a registered direct offering and concurrent private placement, raising gross proceeds of $1.1 million.

In April 2025, the Indian Patent Office granted a new patent for our DNA polymerase IIIC inhibitors which expires in December 2039, subject to extension. This constitutes another significant building block for our ongoing development of ACX-375.

In May 2025, we closed an equity line of credit with Lincoln Park Capital for up to $12 million of additional funding.

First Quarter 2025 Financial Results

Cash Position:

The Company ended the quarter with cash totaling $4.6 million, compared to $3.7 million as of December 31, 2024. The Company raised a total of approximately $3.6 million of gross proceeds thru two Registered Direct Offerings.

R&D Expenses:

Research and development expenses for the three months ended March 31, 2025 were $0.6 million compared to $1.6 million for the three months ended March 31, 2024, a decrease of $1.0 million. The decrease was due primarily to a decrease in manufacturing costs of $0.4 million, and a decrease in consulting costs of $0.6 million as a result of the prior year trial related expenses.

G&A Expenses:

General and administrative expenses for the three months ended March 31, 2025 were $1.6 million compared to $2.8 million for the three months ended March 31, 2024, a decrease of $1.2 million. The decrease was primarily due to $0.7 million decrease in professional fees resulting from lower consulting expenses, and a $0.6 million decrease in share-based compensation costs.

Net Income/Loss:

The Company reported a net loss of $2.1 million or $0.11 per diluted share for the three months ended March 31, 2025 compared to a net loss of $4.4 million or $0.28 per diluted share for the three months ended March 31, 2024, for the reasons previously mentioned.

The Company had 22,397,511 shares outstanding as of March 31, 2025.

Conference Call

As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:

Date:

Tuesday, May 13, 2025

Time:

8:00 a.m. ET

Toll free (U.S.):

1-877-790-1503; Conference ID: 13753625

International:

Click here for participant international Toll-Free access numbers

https://www.incommconferencing.com/international-dial-in

About Ibezapolstat

Ibezapolstat is the Company's lead antibiotic candidate advancing 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 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, methicillinresistant 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.

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>>> Infant Is First To Successfully Receive Personalized Gene Therapy


iHeart

5-16-25


https://www.msn.com/en-us/science/biology/infant-is-first-to-successfully-receive-personalized-gene-therapy/ar-AA1ERcA2?ocid=TobArticle


In a groundbreaking medical achievement, an infant from Pennsylvania, referred to as KJ, has become the first person to successfully receive a personalized CRISPR gene editing therapy. The treatment was developed by a team at the Children's Hospital of Philadelphia (CHOP) and Penn Medicine to address KJ's severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare metabolic disorder.

KJ was diagnosed with CPS1 deficiency shortly after birth, a condition that prevents the conversion of ammonia to urea, leading to toxic ammonia levels in the body. Typically, such conditions are managed with liver transplants, but KJ was too young for the procedure. Instead, researchers developed a customized gene editing therapy specifically targeting KJ's genetic variant.

The therapy, administered in February 2025 when KJ was between six and seven months old, involved using lipid nanoparticles to deliver the gene editing treatment directly to the liver. Since the treatment, KJ has shown significant improvement, tolerating more dietary protein and reducing reliance on nitrogen scavenger medication. He has also been able to recover from common childhood illnesses without ammonia buildup.

Dr. Rebecca Ahrens-Nicklas and Dr. Kiran Musunuru, who led the research, hope this success will pave the way for similar treatments for other rare diseases.

"While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite promising," said Dr. Ahrens-Nicklas.

The study detailing KJ's treatment was published in the New England Journal of Medicine and presented at the American Society of Gene & Cell Therapy Annual Meeting in New Orleans. The success of this personalized therapy marks a significant step forward in the field of gene editing, offering hope to many families affected by rare genetic disorders.

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>>> Alzheimer's Could Be Linked to a Common Virus You Already Have


Health

02 May 2025

by Ruth Itzhaki, The Conversation


https://www.sciencealert.com/alzheimers-could-be-linked-to-a-common-virus-you-already-have


The common cold sore virus, which is often caught in childhood, usually stays in the body for life – quietly dormant in the nerves. Now and then, things like stress, illness or injury can trigger it, bringing on a cold sore in some people.

But this same virus – called herpes simplex virus type 1 – may also play an important role in something far more serious: Alzheimer's disease.

Over 30 years ago, my colleagues and I made a surprising discovery. We found that this cold sore virus can be present in the brains of older people.

Cold Sore

Herpes simplex virus type 1 hides out in our body from childhood – occasionally erupting as cold sores.

It was the first clear sign that a virus could be quietly living in the brain, which was long thought to be completely germ-free – protected by the so-called "blood-brain barrier".

Then we discovered something even more striking. People who have a certain version of a gene (called APOE-e4) that increases their risk of Alzheimer's, and who have been infected with this virus, have a risk that is many times greater.

To investigate further, we studied brain cells that we infected with the virus. They produced the same abnormal proteins (amyloid and tau) found in the brains of people with Alzheimer's.

We believe that the virus stays mainly dormant in the body for years – possibly decades. But later in life, as the immune system gets weaker, it can enter the brain and reactivate there. When it does, it will damage brain cells and trigger inflammation.

Over time, repeated flare-ups could gradually cause the kind of damage that leads to Alzheimer's in some people.

We later found the virus's DNA inside the sticky clumps of these proteins, which are found in the brains of Alzheimer's patients. Even more encouragingly, antiviral treatments reduced this damage in the lab, suggesting that drugs might one day help to slow or even prevent the disease.

Large population studies by others found that severe infections, specifically with the cold sore virus, was a strong predictor of Alzheimer's, and that specific antiviral treatment reduced the risk.

Our research didn't stop there. We wondered if other viruses that lie dormant in the body might have similar effects – such as the one responsible for chickenpox and shingles.

Varicella zoster virus

Shingles vaccine offers another clue

When we studied health records from hundreds of thousands of people in the UK, we saw something interesting. People who had shingles had only a slightly higher risk of developing dementia. Yet those who had the shingles vaccine were less likely to develop dementia at all.

A new Stanford University-led study gave similar results.

This supported our long-held proposal that preventing common infections could lower the risk of Alzheimer's. Consistently, studies by others showed that infections were indeed a risk and that some other vaccines were protective against Alzheimer's.

We then explored how risk factors for Alzheimer's such as infections and head injuries could trigger the hidden virus in the brain.

Using an advanced 3D model of the brain with a dormant herpes infection, we found that when we introduced other infections or simulated a brain injury, the cold sore virus reactivated and caused damage similar to that seen in Alzheimer's.

But when we used a treatment to reduce inflammation, the virus stayed inactive, and the damage didn't happen.

All of this suggests that the virus that causes cold sores could be an important contributor to Alzheimer's, especially in people with certain genetic risk factors. It also opens the door to possible new ways of preventing the disease, such as vaccines or antiviral treatments that stop the virus from waking up and harming the brain.

What began as a link between cold sores and memory loss has grown into a much bigger story – one that may help us understand, and eventually reduce, the risk of one of the most feared diseases of our time.The Conversation

Ruth Itzhaki, Professor Emeritus of Molecular Neurobiology at the University of Manchester and a Visiting Professorial Fellow, University of Oxford

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Acurx - >>> ACX-375C Program with GPSS®

Acurx’s second antibiotic program now in lead optimization stage of preclinical development seeks to develop innovative, systemic Gram-positive selective spectrum (GPSS®) bactericidal antibiotics which target all multi-drug resistant (MDR) and sensitive Gram-positive bacterial pathogens. This previously unexploited mechanism of action is the same as ibezapolstat where recent Phase 2 clinical results in CDI (Clostridioides difficile Infection) have validated the therapeutic effect of DNA pol IIIC as a bacterial target. DNA pol IIIC occurs only in low G+C Gram-positive bacteria, and not in Gram-negative bacteria or in healthy cells; inhibition is expected to be highly selective for Gram-positive bacteria and unaffected by current mechanisms of resistance.

Drug-resistant Gram-positive infections are substantial societal, public health, and economic burdens worldwide with significantly greater incidence than drug-resistant Gram-negative infections. The U.S. Centers for Disease Control (CDC) classifies methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP) as “Serious Threats” and Group A/B Streptococcus are “Concerning Threats” https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.

Metric Organism

Enterococcus / VRE Staph aureus / MRSA^ Strep pneumoniae / PRSP^^

ACX-375C MIC (µg/mL) 0.63-2.5 1.25-2.5 1.25-5.0

No. of US infections/yr* 66,000/20,000 ~2,000,000/80,500 4,000,000/1,200,000

No. of US deaths/yr* Unknown/1,300 Unknown/11,300 22,000/7,000

*Antibiotic Resistance Threats in the United States, CDC, 2013,
https://www.cdc.gov/drugresistance/biggest_threats.html, Accessed 22 January 2019;
^Estimated from Tong, Clin Microbiol Rev 2015; ^^Huang, Vaccine 2011

US Infections per Year: Selected Gram-positive Organisms

Recently published data (Jernigan, 2020) show that MRSA accounts for 52% of US inpatient infections, almost twice the incidence of carbapenem-resistant (CR) Enterobacteriaceae infections. Furthermore, VRE infections exceed CR Acinetobacter, MDR Pseudomonas aeruginosa and CR Enterobacteriaceae infections combined.

Based upon advice from our scientific advisors, we believe ACX-375C, our second antibiotic candidate, will also be eligible for FDA’s QIDP and Fast Track designations and we plan to file for these FDA designations at the appropriate time in the drug development cycle.

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Acurx infomercial -

But where's the pharma partnership to run the Phase 3?

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>>> Acurx Pharmaceuticals, Inc. Announces $1.1 Million Registered Direct Offering


PR Newswire

March 7, 2025


https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-announces-1-130000100.html


STATEN ISLAND, N.Y., March 7, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced that it has entered into a definitive agreement for the purchase and sale of an aggregate of 2,745,000 shares of its common stock (or common stock equivalents in lieu thereof) at a purchase price of $0.40 per share (or per common stock equivalent in lieu thereof) in a registered direct offering. In addition, in a concurrent private placement, the Company will issue unregistered short-term warrants to purchase up to 8,235,000 shares of common stock. The warrants will have an exercise price of $0.40 per share, will be exercisable beginning on the effective date of stockholder approval of the issuance of the shares of common stock upon exercise of the warrants (the "Stockholder Approval") and will expire twenty-four months following the date of Stockholder Approval. The closing of the offering is expected to occur on or about March 10, 2025, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the offering are expected to be approximately $1.1 million, before deducting the placement agent fees and other offering expenses payable by the Company. The Company currently intends to use the net proceeds from the offering for working capital and other general corporate purposes.

The shares of common stock (but not the warrants issued in the private placement or the shares of common stock underlying such warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-265956) filed with the Securities and Exchange Commission ("SEC") on July 1, 2022, and became effective on July 11, 2022. The registered direct offering of the shares of common stock is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the shares of common stock being offered in the registered direct offering will be filed with the SEC and be available at the SEC's website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the registered direct offering may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at [phone] or e-mail at [e-mail].

The warrants described above are being issued in a concurrent private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

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 this 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.

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>>> Acurx Pharmaceuticals to Discuss Fourth Quarter and Full Year 2024 Financial Results on March 18, 2025 Conference Call and Provide Business Update


PR Newswire

February 28, 2025


https://finance.yahoo.com/news/acurx-pharmaceuticals-discuss-fourth-quarter-130000228.html


STATEN ISLAND, N.Y., Feb. 28, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today that the Company will discuss its fourth quarter and full year 2024 financial results on Tuesday, March 18, 2025 at 8:00 am ET before the U.S. financial markets open.

David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:

Date:

Tuesday, March 18, 2025

Time:

8:00 a.m. ET

Toll free (U.S.):

1-877-790-1503;

Conference ID:

13752142

International:

Click here for participant international Toll-Free access numbers

https://www.incommconferencing.com/international-dial-in

About Ibezapolstat

Ibezapolstat is the Company's lead antibiotic candidate preparing for 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.

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 Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program

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 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).

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Acurx - >>> Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing.

On February 24, 2025, Acurx Pharmaceuticals, Inc. (the “Company”) received a letter from The Nasdaq Stock Market (“Nasdaq”) notifying the Company that for the preceding 31 consecutive business days the Company’s common stock did not maintain a minimum closing bid price of $1.00 per share as required by Nasdaq Listing Rule 5550(a)(2) (the “Minimum Bid Price Requirement”). The notice has no immediate effect on the listing or trading of the Company’s common stock, and the common stock will continue to trade on The Nasdaq Capital Market under the symbol “ACXP” at this time.

In accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company has a grace period of 180 calendar days, or until August 25, 2025, to regain compliance with Nasdaq Listing Rule 5550(a)(2). Compliance can be achieved automatically and without further action if the closing bid price of the Company’s common stock is at or above $1.00 for a minimum of 10 consecutive business days at any time during the 180-day compliance period, in which case Nasdaq will notify the Company of its compliance and the matter will be closed.

If, however, the Company does not achieve compliance with the Minimum Bid Price Requirement by August 25, 2025, the Company may be eligible for additional time to comply. In order to be eligible for such additional time, the Company will be required to meet the continued listing requirement for market value of publicly held shares and all other initial listing standards for The Nasdaq Capital Market, with the exception of the Minimum Bid Price Requirement, and must notify Nasdaq in writing of its intention to cure the deficiency during the second compliance period, by effecting a reverse stock split, if necessary. However, if it appears to Nasdaq that the Company will not be able to cure the deficiency, or if the Company is otherwise not eligible, Nasdaq will provide notice that the Company's common stock will be subject to delisting. The Company would then be entitled to appeal that determination to a Nasdaq hearings panel.

The Company intends to actively monitor the bid price of its common stock and will consider available options to regain compliance with the Minimum Bid Price Requirement. However, there can be no assurance that the Company will be able to regain compliance with the Minimum Bid Price Requirement or that Nasdaq will grant the Company a further extension of time to regain compliance, if applicable.


https://www.sec.gov/ix?doc=/Archives/edgar/data/0001736243/000110465925017437/tm257571d1_8k.htm


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>>> Acurx Announces Publication of Positive Results from an In-Silico Study Predicting the Microbiome-Restorative Potential of Ibezapolstat in the Treatment of CDI


PR Newswire

February 24, 2025


https://finance.yahoo.com/news/acurx-announces-publication-positive-results-130000199.html


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


STATEN ISLAND, N.Y., Feb. 24, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company") is 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 (IBZ), preparing to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). The Company today announced the results of a study and its publication in the Journal of Antimicrobial Agents and Chemotherapeutics entitled: "The Microbiome-restorative Potential of Ibezapolstat for the Treatment of Clostridioides difficile Infection is Predicted Through Variant PolC-type DNA Polymerase III in Lachnospiraceae and Oscillospiraceae". The primary researcher and author is Jacob K. McPherson, PharmD, a PhD Pharmacology Candidate at the University of Houston. This study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

According to co-author 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: "These studies help to explain the narrower than expected spectrum of activity of ibezapolstat in our ongoing clinical trials that helps explain regrowth of beneficial gut microbiota while patients are on ibezapolstat therapy." He added: "Genomic differences in the PolC between these species affect the binding of ibezapolstat allowing these beneficial microbes to be resistant and confer health benefits. This is distinctly different that the comparator vancomycin which kills these beneficial microbes causing high rates of C. difficile recurrence."

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 Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

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 (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 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). 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.

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>>> JPO Grants Acurx Pharmaceuticals Patent in Japan for DNA Polymerase IIIC Inhibitors


PR Newswire

February 19, 2025


https://finance.yahoo.com/news/jpo-grants-acurx-pharmaceuticals-patent-130000150.html


STATEN ISLAND, N.Y., Feb. 19, 2025 /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 a new patent has been granted by the Japanese Patent Office (JPO) in January 2025. This patent relates to DNA Polymerase IIIC Inhibitors, including compositions-of-matter, surface coatings and pharmaceutical compositions for use in methods of treating Gram-positive bacterial infection. This is the latest in the series of granted patents and pending patent applications that Acrux has filed to protect its proprietary technologies in the field of antimicrobials. To date, Acurx has obtained three U.S. patents, one Israeli patent and now one Japanese patent, in each case, which cover the ACX-375C program, relating to DNA Polymerase IIIC Inhibitors, with other country-level filings in process.

Robert J. DeLuccia, Executive Chairman of Acurx, stated: "Complementing our global patent estate with minimally absorbed oral ibezapolstat, now Phase 3-ready for the treatment and prevention of recurrence of C. difficile Infection, this patent, with others to follow, is very important and timely as we further develop our innovative, AI-supported drug discovery platform of second-generation DNA pol IIIC inhibitors. He added: "Other compounds in our program are systemically absorbed for potential oral and parenteral use in multiple clinical settings for treatment of infections caused by other gram-positive bacteria, such as Staphylococcus aureus, including MRSA and B. anthracis or anthrax; a Bioterrorism Category A Threat-Level pathogen."

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 Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned Phase 3 international, 1:1 randomized clinical trials (designed as non-inferiority trials vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

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 (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 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 the 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 the 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.

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>>> Elite Pharmaceuticals, Inc. (ELTP), a specialty pharmaceutical company, engages in the development, manufacture, and sale of oral, controlled-release products, and generic pharmaceuticals. The company operates through Abbreviated New Drug Applications for Generic Pharmaceuticals and New Drug Applications for Branded Pharmaceuticals segments. It owns, licenses, manufactures, and sells various generic and oral dose pharmaceuticals products, such as Phentermine HCl 37.5mg tablets, and 15mg and 30mg capsules for the treatment of bariatrics under Adipex-P brand; Phendimetrazine Tartrate 35mg tablets for bariatrics under the Bontril brand; Naltrexone HCl 50mg tablets for the treatment of pains under the Revia brand; and Isradipine 2.5mg and 5mg capsules for cardiovascular diseases. In addition, the company provides Trimipramine Maleate Immediate Release antidepressant capsules under the Surmontil brand; Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Immediate Release tablets under the Adderall brand, as well as Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine Sulfate Extended Release capsules under the Adderall XR brand for central nervous system diseases; Dantrolene Sodium capsules for muscle relaxant under the Dantrium brand; SequestOX, an immediate release Oxycodone with Naltrexone; Loxapine Succinate capsules for treating antipsychotic under the Loxapine brand; Acetaminophen and Codeine Phosphate for the management of mild to moderate pain; and antibiotic products. Further, it manufactures controlled-release products on a contract basis for third parties in the areas of pain, allergy, bariatric, attention deficit, and infection. Additionally, the company is developing a range of abuse deterrent opioid products. Elite Pharmaceuticals, Inc. was incorporated in 1997 and is headquartered in Northvale, New Jersey.

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>>> Why Axsome Therapeutics Stock Is Skyrocketing Today


by Johnny Rice

Motley Fool

February 10, 2025


https://finance.yahoo.com/news/why-axsome-therapeutics-stock-skyrocketing-194531192.html


Shares of Axsome Therapeutics (NASDAQ: AXSM) are flying higher on Monday. The company's stock is up 24.7% as of 1:10 p.m. ET, gaining as much as 25% earlier in the day. The move up comes as the S&P 500 (SNPINDEX: ^GSPC) gained 0.6% and the Nasdaq Composite (NASDAQINDEX: ^IXIC) gained 1.1% on the day.

A lawsuit reaches a settlement and gives Axsome exclusivity for the next decade

Axsome, maker of the antidepressant Auvelity, reached a settlement with fellow drugmaker Teva Pharmaceuticals. The latter, which specializes in generic drugs, had submitted an Abbreviated New Drug Application to the U.S. Food and Drug Administration (FDA) seeking to bring to market a generic version of Auvelity. Axsome sued Teva for violating its Auvelity patent, which had yet to expire.

CEO Herriot Tabuteau, MD, stated the resolution "underscores the value of [its] innovation as it relates to Auvelity, and more broadly reflects the strength of Axsome's intellectual property portfolio."

The settlement resolves all litigation and grants Teva a license to sell a generic Auvelity more than a decade from now, maintaining Axsome's right to market Auvelity exclusively until then. The win will protect Axsome's bottom line for years, sending Axsome shares higher.

What's next for Axsome?

The news comes just weeks after Axsome won full FDA approval for Symbravo, a migraine treatment, and the company has several other key drugs in the late stages of the development pipeline. While the company is still operating in the red, delivering a net loss of $64.6 million on $104.8 million in sales last quarter, the settlement with Teva, as well as the FDA's approval of Symbravo, could boost sales significantly and help Axsome turn a profit.

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In-Q-Tel funding - >>> Colossal Biosciences Inc. is an American biotechnology and genetic engineering company working to de-extinct the woolly mammoth, the Tasmanian tiger, the northern white rhinoceros, and the dodo bird.[1][3][4][5][6][7] In 2023, it stated that it wants to have woolly mammoth hybrid calves by 2028, and wants to reintroduce them to the Arctic tundra habitat.[8] Likewise, it launched the Tasmanian Thylacine Advisory Committee, a thylacine research project to release Tasmanian tiger joeys back to their original Tasmanian and broader Australian habitat after a period of observation in captivity.[9]

The company develops genetic engineering and reproductive technology for conservation biology. It was founded in 2021 by George Church and Ben Lamm,[3] and is based in Dallas, Texas.[10][11]

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https://en.wikipedia.org/wiki/Colossal_Biosciences


>>> The CIA Wants to Bring Back the Woolly Mammoth <<<

https://gizmodo.com/cia-wooly-mammoth-de-extinct-resurrect-tasmanian-tiger-1849596497



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>>> Alzheimer’s Drugs Eyed as Next Big Obesity-Like Opportunity


Bloomberg

by Lisa Pham

January 10, 2025


https://finance.yahoo.com/news/alzheimer-drugs-eyed-investors-seeking-050000316.html


(Bloomberg) -- Investors seeking the next obesity-like market opportunity will be closely watching developments related to treatments for Alzheimer’s disease in 2025.

Companies including Biogen Inc. and Eli Lilly & Co. have spent billions of dollars on developing potential treatments, while others including Novo Nordisk A/S and Roche AG are also investigating the brain-destroying disease. Any breakthroughs in trials or drug approvals could have a big impact on share prices as investors factor in potential sales for a market which Bloomberg Intelligence estimates could reach $13 billion by 2030.

“The opportunity remains huge,” said Chris Eccles, a portfolio manager at AXA Investment Managers. “If we get a strong disease-modifying drug and very positive clinical trials, numbers can go back in models and forecasts can be revised upwards quite significantly, quite quickly.”

Firms developing Alzheimer’s drugs have already seen big peaks and troughs. Biogen shares soared 44% on a single day in November 2020 after news that an experimental drug appeared to be effective, before plunging days later after failing to get support from a panel of Food and Drug Administration advisers. Despite getting approval the following year, Biogen ultimately ditched the drug after years of debate over its efficacy. Many other drugs have also failed.

Two of the newest drugs to treat the disease are currently available in the US. Lecanemab, from Biogen and Japanese partner Eisai Co., is sold under the brand name Leqembi, and donanemab from Eli Lilly is branded as Kisunla. Both drugs work by reducing the brain amyloid levels in patients in the early stages of Alzheimer’s, and act to slow the disease. Still, they don’t stop or reverse it, while both treatments have side effects that include brain bleeding and brain swelling.

“It could be a year where we also see a bit more clarity in terms of traction for the drugs that are approved so far,” said Gregoire Biollaz, senior investment manager at Pictet Asset Management.

Here are some of the stocks to watch in 2025:

Biogen and Eisai

Patients currently on Leqembi take it as an infusion, though Biogen and Eisai have also developed a version that can be administered at home. In focus for investors in 2025 will be whether the injectable formulation wins regulatory approval, which would mean patients won’t have to travel for treatment.

Another related stock to watch is Sweden’s BioArctic AB, which discovered Leqembi and is entitled to royalties for the drug. The shares have surged more than eightfold since going public in 2017, but have struggled in recent years amid a challenging launch for the treatment.

Eli Lilly

Eli Lilly’s Kisunla treatment received FDA clearance in July 2024, and investors will get more of an indication in the coming year about how adoption of the drug will fare against Leqembi.

The company is also evaluating a follow-on drug, known as remternetug, via injection as well as infusion. The late-stage trial will assess the formulations for amyloid plaque clearance and safety, which could signal whether remternetug will be a better treatment option than Kisunla, according to Bloomberg Intelligence analysts. Trial results for remternetug could be released at the end of this year or early 2026, according to BI’s Jean Rivera Irizarry.

Novo Nordisk

A study last year indicated that patients taking semaglutide were at significantly reduced risk of being diagnosed with Alzheimer’s. Novo Nordisk is currently testing whether the ingredient — which is in its diabetes and weight-loss drugs — can benefit patients with early Alzheimer’s disease. Late-stage trial results are expected in the second half. Bank of America analysts including Sachin Jain see potential for the stock to rise about 10%-15% if the data is positive, but flagged that it is “high risk.”

Roche

Roche has completed the first part of an early-stage study for trontinemab, a drug designed to clear amyloid which deploys a brain shuttle technology to slip past the protective blood-brain barrier. The company is awaiting more data before deciding whether to proceed with late-stage trials, and UBS Group AG analyst Colin White sees this data potentially being available in the first half. For Barclays Plc analyst Emily Field, it seems “far more likely than not” that Roche will go ahead with more trials. Trontinemab is a newer version of gantenerumab, Roche’s previous big bet on Alzheimer’s that ultimately failed to slow cognitive decline.

UCB

Belgian biotech firm UCB SA is expected to decide whether to continue developing bepranemab, though no timeline has been provided. A mid-stage study last year missed its primary endpoint, though showed that the experimental drug slowed cognitive decline and the rate of accumulation of tau, a protein that creates tangles within brain cells. TD Cowen analyst Stacy Ku noted that bepranemab has a “clean” safety profile that “should allow for combination treatment.”

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Yes, it looks like Luci and other management did put up some of their own money in the direct offering. Only for 167,488 shares total, plus some warrants, but I guess it demonstrates having some 'skin in the game'. Now if they would only reverse that loony Bitcoin announcement, lol..


https://www.sec.gov/Archives/edgar/data/1736243/000110465925001589/tm252141d1_424b5.htm

>>> We are offering an aggregate of 2,463,058 shares of our common stock, par value $0.001 per share (“common stock”) consisting of (i) an aggregate of 2,295,570 shares of common stock purchased by certain institutional investors (the “institutional investors”) and (ii) an aggregate of 167,488 shares of common stock purchased by David P. Luci, our President and Chief Executive Officer, Robert J. DeLuccia, our Executive Chairman, Carl V. Sailer, Jack H. Dean, James Donohue, and Joseph Scodari, each members of our Board of Directors (the “affiliate investors”). The offering price of each share of common stock is $1.015. In a concurrent private placement, we are also selling to such investors, series E warrants to purchase up to an aggregate of 2,463,058 shares of our common stock (the “warrants”). The warrants will have an exercise price of $0.90 per share, will be exercisable immediately upon issuance and will expire five years from the initial exercise date. The warrants and the shares of common stock issuable upon the exercise of the warrants are not being registered under the Securities Act of 1933, as amended (the “Securities Act”), are not being offered pursuant to this prospectus supplement and the accompanying prospectus and are being offered pursuant to the exemption provided in Section 4(a)(2) under the Securities Act and Rule 506(b) promulgated thereunder.

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More info on the registered offering -

(Note - it sounds like Luci and other Acurx management are participating in the offering, and putting up their own personal money in exchange for shares and warrants(?) Not sure, but that's what it sounds like in the 8-K) -


>>> On January 6, 2025, Acurx Pharmaceuticals, Inc., a Delaware corporation (the “Company”), entered into a Securities Purchase Agreement (the “Purchase Agreement”) with certain institutional investors named therein (the “Investors”), and with each of David P. Luci, our President and Chief Executive Officer, Robert J. DeLuccia, our Executive Chairman, Carl V. Sailer, Jack H. Dean, James Donohue, and Joseph Scodari, each a member of our board of directors (collectively, the “Affiliate Investors”), pursuant to which the Company agreed to issue and sell, in a registered direct offering by the Company directly to the Investors and to the Affiliate Investors (the “Registered Offering”), an aggregate of 2,463,058 shares (the “Shares”) of common stock, par value $0.001 per share, of the Company (the “Common Stock”) (consisting of an aggregate of 2,295,570 Shares purchased by the Investors and an aggregate of 167,488 Shares purchased by the Affiliate Investors), at an offering price of $1.015 per share, for aggregate gross proceeds from the Registered Offering of approximately $2.5 million, before deducting the placement agent fees and related offering expenses. The Company intends to use the net proceeds from the offering for working capital and other general corporate purposes.

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https://www.sec.gov/ix?doc=/Archives/edgar/data/0001736243/000110465925001586/tm252142d1_8k.htm


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Acurx --> The ATM financing approach has been suspended (see below), and instead they went with a registered direct offering (with warrants) instead. Interesting development -


https://www.sec.gov/Archives/edgar/data/1736243/000110465925001282/tm252097d1_424b3.htm


>>> The Prospectus relates to the sale of shares of our common stock, par value $0.001 per share (the “common stock”), in an “at-the-market” offering (the “ATM Program”) pursuant to the at the sales agreement, dated November 15, 2023 (the “Sales Agreement”). In accordance with the terms of the Sales Agreement, we may offer and sell from time-to-time shares of our common stock through A.G.P./Alliance Global Partners, acting as our sales agent. As of the date hereof, we have sold 2,830,328 shares of common stock under the Sales Agreement, raising net proceeds of approximately $8.8 million. The terms “Company,” “we,” “us” and “our” refer to Acurx Pharmaceuticals, Inc., a Delaware corporation.

We are filing this Prospectus Supplement to amend the Prospectus to reduce the amount of shares registered under the Prospectus to $0.00 and to suspend the ATM Program. As a result, we may not make any sales of our common stock pursuant to the Sales Agreement unless and until a new prospectus supplement is filed with the Securities and Exchange Commission; however the Sales Agreement remains in full force and effect...

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>>> Acurx Pharmaceuticals, Inc. Announces $2.5 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules


PR Newswire

January 6, 2025


https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-announces-2-223500421.html


STATEN ISLAND, N.Y., Jan. 6, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced that it has entered into a definitive agreement for the purchase and sale of an aggregate of 2,463,058 shares of its common stock at a purchase price of $1.015 per share in a registered direct offering priced at-the-market under Nasdaq rules. In addition, in a concurrent private placement, the Company will issue unregistered warrants to purchase up to 2,463,058 shares of common stock. The warrants will have an exercise price of $0.90 per share, will be exercisable upon issuance and expire five years following the date of issuance. The closing of the offering is expected to occur on or about January 7, 2025, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the offering are expected to be approximately $2.5 million, before deducting the placement agent fees and other offering expenses payable by the Company. The Company currently intends to use the net proceeds from the offering for working capital and other general corporate purposes.

The shares of common stock (but not the warrants issued in the private placement or the shares of common stock underlying such warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-265956) filed with the Securities and Exchange Commission ("SEC") on July 1, 2022 and became effective on July 11, 2022. The registered direct offering of the shares of common stock is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the shares of common stock being offered in the registered direct offering will be filed with the SEC and be available at the SEC's website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the registered direct offering may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at [phone] or e-mail at [e-mail].

The warrants described above are being issued in a concurrent private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

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 this 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.

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>>> Acurx Receives Positive Regulatory Guidance from EMA for Ibezapolstat Phase 3 Program for C. Difficile Infection (CDI)


PR Newswire

January 6, 2025


https://finance.yahoo.com/news/acurx-receives-positive-regulatory-guidance-133000707.html


Acurx has now received positive written responses from the EMA (European Medicines Agency) under its Scientific Advice Procedure that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted supports advancement of the ibezapolstat Phase 3 program

The responses also included guidance on ibezapolstat's regulatory pathway for a Marketing Authorization Application for ibezapolstat in CDI

With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program

Acurx is also preparing to request regulatory guidance to initiate clinical trials in Japan, Canada and the United Kingdom

Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designation from FDA and Acurx has received SME (Small and Medium-sized Enterprise) designation by the EMA to benefit from fee incentives and other support from the EMA for EU Marketing Authorization


STATEN ISLAND, N.Y., Jan. 6, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company") is 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 that it has received positive regulatory guidance from the EMA during its Scientific Advice Procedure that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted supports advancement of the ibezapolstat Phase 3 program. The information package supporting the Phase 3 program included details on Acurx's two planned Phase 3 clinical trials (designed as non-inferiority trials vs vancomycin), the patient population, primary endpoint of Clinical Cure, sample size, statistical analysis plan and the overall registration safety database.

Acurx's Executive Chairman, Bob DeLuccia, stated: "We are appreciative of the EMA's constructive suggestions, and we will proactively incorporate them into our global registration plan. He further stated: "We are very pleased with the latest favorable communications from both regulatory agencies which provide a straightforward international roadmap for conduct of our Phase 3 program and ultimate requirements for a US NDA (New Drug Application) submission and EU Marketing Authorization Application."

Written communications are used by both regulatory agencies in lieu of face-to-face or teleconference/video conferences when these agencies determine that a written response to the sponsor's questions would be the most appropriate means for providing feedback and advice to the sponsor. (FDA Guidance on Formal Meetings, EMA Guidance on Centralised Procedure)

Acurx previously announced it had a successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, including written positive feedback regarding acceptability of its CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program. In addition, Acurx had initiated the Scientific Advice procedure with the EMA to discuss the readiness for initiation of the Phase 3 clinical program in the EU. Acurx is 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. 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 (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 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.

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Thanks for the info. I was wondering if MNMD is using some type of micro-dosing of their LSD? I couldn't find specific info on their website about the dosing levels used, but I assume they aren't putting these patients into full blown LSD trips.

Also, while using a proprietary version of LSD has enabled a new patent for the company, competitors and docs might be able to use regular old LSD and achieve similar clinical results (?) MNMD has 'tweaked' something in order to get the new patent, but does that tweak enable a better clinical outcome than ordinary LSD would produce, when similarly dosed?

But sounds interesting, and MNMD must be doing something right to be able to raise nearly $300 mil recently. Thanks for any additional info :o)



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[MomsSpaghetti]

Thanks for the response. I will add some ideas here and on your board as well.

They have a cash runway through completing their Phase 3 trials. For which they have two. I suggest everyone look at their latest Corporate Presentation - December 2024:

https://d1io3yog0oux5.cloudfront.net/_25951dd8646049733b7a9ba6d9a4c850/mindmed/db/2265/21500/pdf/MindMed+Investor+Presentation+December+2024+.pdf

Also, since they have received FDA Breakthrough Status they also interacted with the FDA. See Docket Number: FDA-2023-D-1987: Psychedelic Drugs: Considerations for Clinical Investigations; Draft Guidance for Industry; Availability

https://downloads.regulations.gov/FDA-2023-D-1987-0197/attachment_1.pdf

They have also added an Ex-FDA person to their already stellar staff. He recently gave a presentation that is notable:

Psychedelic Clinical Trials: Regulatory Consideration from the FDA - Javier Muniz, MD - https://www.nationalacademies.org/documents/embed/link/LF2255DA3DD1C41C0A42D3BEF0989ACAECE3053A6A9B/file/DC13F898D77B1738F10CD41B1FB160CB84D5802C8F6F?noSaveAs=1

The stars are aligning and MindMed has a very high chance of being bought out or better yet actually bringing their main drug candidates to market.

I know the hype is around mushrooms, but they will likely become a commodity like cannabis. The money will be in true pharmaceuticals that will be hard to reproduce at the street level. I am not against the naturalists. But MindMed has the lock on LSD.

ATAI is a good contender as well maybe lagging behind but is still a strong leader in the space. MindMed will hit the market first though.

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>>> Scientists warn of ‘unprecedented’ risks of research into mirror life


by Katie Hunt

CNN

12-17-24


https://www.msn.com/en-us/news/technology/scientists-warn-of-unprecedented-risks-of-research-into-mirror-life/ar-AA1vXH2Z?ocid=BingHp01&cvid=aa103681ee904d2580ca9d66412a5a0e&ei=31


A group of 38 scientists working in nine countries has sounded an alarm about the potential creation of mirror bacteria — synthetic organisms in which the molecular structure found in nature is reversed and could put humans, animals and plants at risk of exposure to dangerous pathogens.

While the science and technology necessary to create mirror bacteria in a laboratory is a decade or more away, the scientists argued that the possibly lethal risks posed by this new field of research are “unprecedented” and “overlooked.”

“Driven by curiosity and plausible applications, some researchers had begun work toward creating lifeforms composed entirely of mirror-image biological molecules,” the researchers wrote in a report published December 12 by the journal Science.

“Such mirror organisms would constitute a radical departure from known life, and their creation warrants careful consideration.”

A fundamental feature of all known life is a uniform chirality, or handedness. For example, DNA and RNA are made from “right-handed” nucleotides, and proteins are made from “left-handed” amino acids. Just as a right-handed glove cannot fit a left hand, interactions between molecules often depend on chirality.

While the authors, who included experts in immunology, plant pathology, ecology, evolutionary biology, biosecurity and planetary sciences, had initially been skeptical that mirror bacteria could pose major risks, the experts said they had now become “deeply concerned.”

“It’s a genie you don’t want to let out of the bottle,” said report coauthor Jonathan Jones, a group leader at The Sainsbury Laboratory in Norwich, United Kingdom.

“The risk of something bad happening is low, but the consequences of something bad happening are really awful,” he added.

Unless compelling evidence were to emerge that mirror life would not pose extraordinary dangers, research with the goal of creating mirror bacteria should not be permitted, and funders should make clear that they will not support such work, the scientists recommended.

Risks of mirror bacteria

The authors based the Science paper on a 300-page technical report by Adamala et al. that detailed the feasibility and risks of mirror bacteria.

The report said that creating mirror life was a longer-term aspiration of multiple laboratories and major funders of research as part of efforts to better understand life and potentially aid in the development of drugs and other therapeutics.

Many synthetic biologists seek to understand how cells could be created from their constituent molecules with the aim of shedding light on how life first arose and understanding what other kinds of life might be possible. The report said that if a cell with natural chirality can be created from lifeless molecules, then, in theory, a mirror-image cell could be created from mirror-image molecules using the same methods.

No imminent threat exists, the report stressed, and there are currently sizable technical hurdles to creating mirror bacteria. Doing so within a decade would require substantial, coordinated efforts similar in scale and budget to the Human Genome Project, which mapped 92% of the human genome over the span of 12 ½ years.

Organisms vulnerable to infection

Immune systems rely on recognizing specific molecular shapes found in invading bacteria. If these shapes were reflected — as they would be in mirror bacteria — recognition would be impaired and immune defenses could fail, potentially leaving organisms vulnerable to infection.

“We cannot rule out a scenario in which a mirror bacterium acts as an invasive species across many ecosystems, causing pervasive lethal infections in a substantial fraction of plant and animal species, including humans,” the scientists argued in the Science report.

“Even a mirror bacterium with a narrower host range and the ability to invade only a limited set of ecosystems could still cause unprecedented and irreversible harm.”

Transmission via animals and humans could enable the spread of such bacteria into different ecosystems. Jones, an expert in plant immune systems, said that mirror bacteria would be extremely difficult to detect in plants.

“Even if it didn’t grow very well initially, mutations would kick in and there’d be selection for something that grew better. That’s the way evolution works,” Jones explained.

Tom Ellis, a professor of synthetic genome engineering at Imperial College’s Centre for Synthetic Biology and department of bioengineering, said that mirror life was still very much science fiction rather than science fact.

“Broadly I agree with the concerns, although they are very speculative considering research is currently at a very early stage and a long way from being any threat,” said Ellis, who wasn’t involved in the research.

Scientists had been trying to create synthetic life using non-mirror molecules for more than a decade, Ellis said, but they were still a “long way” from having self-sustaining cells that can divide, replicate and evolve.

“This ‘synthetic cell’ work is challenging enough already when (scientists) use normal molecules, enzymes and chemicals. When they have to do all that but only with mirror molecules, that all need to be made and invented, then it makes it … 1000x harder,” he said via email.

“The scale of difficulty is akin to humans preparing to land on Mars, and people starting to talk about flying to other stars and galaxies,” he said. “There’s such a leap in difference of the achievement needed, and the basic initial goal isn’t even done yet.”

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>>> Novo Nordisk Stock Crashes on Obesity Drug Data. It’s a Win for Eli Lilly.


Barron's

by Josh Nathan-Kazis

Dec 20, 2024


https://www.barrons.com/articles/novo-nordisk-stock-data-eli-lilly-9c83e0d5?siteid=yhoof2


For more than a year, Novo Nordisk NOVO.B has told the world it expects patients to lose “at least 25%” of their body weight on its experimental drug CagriSema.

It turns out the company was wrong.

On Friday, Novo released the results of a large Phase 3 trial of the drug. Patients lost only 22.7% of their body weight, on average, after about a year and a half.

There were some wrinkles in the data that suggest the drug could be better than it looks, and Novo says it still plans to ask regulators to approve the medicine. But that 22.7% rate is about the same efficacy as Zepbound, the Eli Lilly
LLY weight-loss drug that is already on the market, analysts wrote early Friday.

That is severely undermining expectations for sales of CagriSema, which analysts had expected would be a step up from Zepbound. While Wall Street had been anticipating CagriSema sales would hit $15.6 billion a year by 2029, according to FactSet, those estimates are now very much in question.

There were complexities in the study results. Under the design of the trial, patients had control over the size of their CagriSema dosage, and only 57.3% of patients on the drug chose to escalate to the highest dose.

Still, investors weren’t interested in the nuances. Novo’s American depositary receipt was down 20.5% early Friday. Lilly shares were up 6.7%.

Investors were also buying shares of obesity-focused biotechs, under the apparent theory that they would benefit from CagriSema’s results. Shares of Viking Therapeutics were up 8.8%, while the American depositary receipts of Structure Therapeutics rose 1.2%.

More than anything, the result appears to solidify Lilly’s lead position in the obesity market. Lilly’s Zepbound has already shown better efficacy than Novo’s currently available drug Wegovy in a head-to-head trial. In addition to Zepbound, Lilly has a pipeline of promising weight-loss assets that includes the pill orfoglipron, and retatrutide.

In a statement to Barron’s, Novo said it still plans to submit CagriSema for regulatory approval “towards the end of 2025.”

The company also said that it plans to start a new trial of CagriSema in the first half of next year. In that trial, the company would work to improve how the dosage of CagriSema that patients take is ramped up, it said.

“The 22.7% weight loss is significantly higher than Wegovy and on par with best-in-class treatments,” Novo said. “The trial permitted dose reductions, and statistically significant results were achieved even though only 57% of patients on CagriSema reached the highest dose.”

CagriSema is a combination of semaglutide—the medicine sold under the brand names Ozempic and Wegovy—and cagrilintide, another medicine. The two ingredients work differently from each other, and their action was thought to be complimentary.

In the trial, patients who received semaglutide alone lost 16.1% of their body weight, according to one statistical method of analysis, while patients on cagrilintide alone lost 11.8%. But the whole turned out to be less than the sum of its parts: Patients who received CagriSema, the combination of the two drugs, lost 22.7% of their body weight on average.

Novo said that 40.4% of the patients on CagriSema did lose 25% of their body weight or more over the 68-week duration of the trial.

The results come days after Novo closed on the complex and controversial $11 billion purchase of three factories it can use to ramp up its GLP-1 drug manufacturing over the coming years.

They also come just a day after the Food and Drug Administration officially declared an end to the yearslong shortage of tirzepatide, the drug Lilly sells as Zepbound and Mounjaro. Novo’s semaglutide remains in shortage.

In recent months, investors have gone wobbly on the weight-loss trade as complexities and uncertainties mount. What had once seemed a simple bet on highly effective obesity treatments has grown trickier in the face of an aggressive legal copycat market, amid other troubles. Before Friday’s selloff, Novo’s ADR had been down nearly 28% since the start of July.

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>>> Why Novo Nordisk Stock Got Destroyed Today, but Eli Lilly and Viking Stocks Are Up


by Rich Smith

Motley Fool

December 20, 2024


https://finance.yahoo.com/news/why-novo-nordisk-stock-got-172025713.html


Bad news for Novo Nordisk (NYSE: NVO) Friday was good news for Eli Lilly (NYSE: LLY) and Viking Therapeutics (NASDAQ: VKTX), its two main rivals in the field of weight loss drugs. This morning, Novo reported headline results from its phase 3 trial of a new weight loss drug, CagriSema, and while objectively not bad, the results were less great than Novo was shooting for.

As of 11:05 a.m. ET, Novo Nordisk stock is down a disheartening 20.8%, while both Lilly and Viking stocks are up 4.4% apiece.

Novo Nordisk's no good, very bad day

Originally designed to treat patients with diabetes, GLP-1 drugs like Novo's Ozempic and Lilly's Zepbound have taken on a new role in society as the go-to treatment for obesity, and for easy weight loss, generally. Novo was hoping to expand its lead in this market with its new offering, CagriSema, which fortifies the semaglutide ingredient in Ozempic with an amylin-focused drug that also aims to decrease food cravings.

The goal: to beat Ozempic's record for 16.1% weight loss among patients taking the drug over 68 weeks, by hitting a new target of 25% weight loss over the same period.

I won't keep you in suspense. Novo missed that target. The company's Redefine 1 phase 3 trial of CagriSema, containing both cagrilintide and semaglutide "achieved its primary endpoint by demonstrating a statistically significant and superior weight loss" relative to a placebo. However, average weight loss over the course of the 68-week trial was only 22.7% -- not the targeted 25%.

So that's the bad news. The good news is that CagriSema does appear to have resulted in greater weight loss than Novo's original recipe Ozempic and better weight loss than Lilly's Zepbound. (Viking's own weight loss drug, VK2735, is still in trials.)

How bad is this news for Novo Nordisk stock?

Investors in Novo Nordisk seem very unhappy with these results while investors in Lilly and Viking seem much happier, but should they be?

While you'd expect Novo to try to put a happy face on these results, management honestly doesn't seem too upset.

"We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy in the REDEFINE 1 trial," said Novo's Executive Vice President for Development Martin Lange, noting that the company plans to "further explore the additional weight loss potential of CagriSema." And when you consider that 40.4% of the patients participating in the REDEFINE 1 study actually did achieve 25% or greater weight loss after 68 weeks (it's only the average that fell short of the mark), it would seem at least possible that further tweaking of the drug combination might eventually yield the results Novo is looking for.

Is Novo Nordisk stock a sell?

Meanwhile, today's massive sell-off in Novo Nordisk stock may be giving investors an unexpected second bite at the GLP-1 apple -- a chance to buy Novo stock at a price-to-earnings ratio of barely 29. On a stock expected to grow earnings at better than 21% annually over the next five years, and paying a modest 1.3% dividend yield to boot, that's not too much more than what I'd call a fair valuation for Novo Nordisk shares.

When you consider further that Lilly shares are selling for closer to 82 times earnings (i.e., twice as expensive), while Viking Therapeutics stock has no earnings at all, and therefore no P/E ratio on which to value it, this all kind of makes Novo Nordisk look like the value investor's choice for investing in weight loss drugs.

Crazy as it may sound to say it, today just might be good day to buy Novo Nordisk stock.

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[gfp927z]

>>> J&J’s comeback kid Spravato heads for blockbuster status


Yahoo Finance

by Meagan Parrish

October 25, 2024


https://finance.yahoo.com/news/j-j-comeback-kid-spravato-074632633.html


This story was originally published on PharmaVoice. To receive daily news and insights, subscribe to our free daily PharmaVoice newsletter.

Johnson & Johnson’s esketamine nasal spray Spravato didn’t look like a sure-fire win after it hit the market in 2019. Despite blazing a new trail as the first psychedelic-based treatment to score an FDA nod, the depression medication got off to a sluggish start, and the company didn’t even report sales figures for the first few years. Times have changed.

J&J reported that Spravato reached worldwide sales of $780 million in the first nine months of 2024 — 62% higher than the same period the year before. The story was the same in 2023 when Spravato sales spiked 89% in the first three quarters compared to 2022.

What’s been driving that growth?

Following the initial launch, critics took aim at Spravato’s efficacy and pricing, and the treatment was ultimately rejected for coverage in the U.K.

And then pandemic-related challenges further stymied the launch by complicating arrangements for the drug’s necessary medical supervision. After in-person doctor visits were once again the norm, J&J began to market the drug more heavily and raise its profile.

“We always knew it would take time to see significant uptake — new models of care always do — but the overwhelming patient need continues to drive treatment center expansion,” Bill Martin, global neuroscience therapeutic area head at Johnson & Johnson Innovative Medicine, said in an email.

J&J’s neuroscience darling

$780 million

Global Spravato sales in the first three quarters of 2024.

$483 million

Global Spravato sales in the first three quarters of 2023.

2,800

Treatment centers currently administering Spravato, according to J&J.

Martin pointed to the accumulation of safety and efficacy data over time as another contributor to its gradual acceptance — five years of real-world data and a head-to-head study demonstrating superior efficacy gave physicians higher confidence in the treatment, he said.

Now J&J’s fastest growing drug, Spravato could become a blockbuster, according to both analysts and the company, with forecasts for $1 billion to $5 billion in peak sales.

Winning expanded indications could help Spravato surpass that threshold. Spravato is currently approved as an adjunctive therapy alongside oral medications in treatment resistant depression and major depressive disorder, and in July, J&J asked the FDA to also greenlight the drug to be prescribed on its own.

“The filing is based on phase 4 data which showed rapid improvement in depressive symptoms at around 24 hours and was sustained through the four weeks endpoint,” Martin said. “If approved, it will be the first monotherapy treatment option available for adults with TRD.”

While J&J currently has a lock on the current market for esketamine, emerging companies are targeting a similar approach but in much earlier stages. Mira Pharmaceuticals, for example, is in preclinical development with a ketamine-based treatment for neuropathic pain and depression and aims to start clinical trials early next year.

For J&J, keeping Spravato’s momentum will be crucial for its plans to become a neuroscience powerhouse.

“Spravato is the foundation for our growing neuroscience portfolio in [major depressive disorder] and a growth driver for J&J,” Martin said.

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>>> MindMed Announces First Patient Dosed in Phase 3 Voyage Study of MM120 in Generalized Anxiety Disorder (GAD)


- Voyage is the first-ever Phase 3 study of lysergide D-tartrate (LSD) with the primary endpoint measuring the change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) score at week 12 for MM120 Orally Disintegrating Tablet (ODT) 100 µg vs placebo -

- Study builds on positive Phase 2b study results presented at the American Psychiatric Association’s Annual Meeting in May 2024 -

- Topline data from the 12-week double-blind period anticipated in the first half of 2026 -


December 16, 2024


https://www.businesswire.com/news/home/20241216046321/en/


NEW YORK--(BUSINESS WIRE)--Mind Medicine (MindMed) Inc. (NASDAQ: MNMD), (the "Company" or "MindMed"), a clinical-stage biopharmaceutical company developing novel product candidates to treat brain health disorders, today announced that the first patient has been dosed in its Phase 3 Voyage study of MM120 ODT, a pharmaceutically optimized form of lysergide D-tartrate (LSD) for the treatment of GAD. Voyage is the first of two Phase 3 studies in GAD evaluating the efficacy and safety of MM120 ODT versus placebo and is expected to enroll approximately 200 participants in the United States. The Panorama study, the second Phase 3 trial, will be conducted in the U.S. and Europe and is on track to initiate in the first half of 2025.

“Management's Discussion and Analysis of Financial Condition and Results of Operations”

“Today marks a pivotal moment in our journey towards advancing a novel treatment option for the 20 million people1 in the U.S. living with GAD. Building on our scientifically rigorous Phase 2b study, which demonstrated efficacy that far exceeds today’s standard of care and a favorable tolerability profile, our Phase 3 studies are designed to adhere to the highest clinical and ethical standards and are in alignment with guidance from the U.S. Food and Drug Administration,” said Daniel R. Karlin, M.D., M.A., Chief Medical Officer of MindMed.

The 52-week Voyage study will be conducted in two parts: Part A, a 12-week, randomized, double-blind, placebo-controlled, parallel group period; and Part B, a 40-week extension period during which participants will be eligible for open-label treatment with MM120 ODT based on symptom severity. The primary endpoint of Voyage will measure the change from baseline in HAM-A at Week 12, which is consistent with the durable clinical effect observed in the Phase 2b study.

“It is critical to continue to develop new and effective treatment options for patients with GAD, a debilitating condition where there is an urgent need for transformational innovation,” said David Feifel, M.D., Ph.D., Professor Emeritus of Psychiatry at the University of California, San Diego and Director of the Kadima Neuropsychiatry Institute in La Jolla, California and an investigator in the Voyage study. “The design of the MM120 ODT Phase 3 clinical program directly builds on the robust Phase 2b study results and incorporates best-in-class methodologies to mitigate the impact of functional unblinding, including the use of independent central raters blinded to both treatment assignment and visit number. The studies have also been designed to isolate the standalone drug effect of MM120 ODT from other psychotherapeutic intervention and follow industry best practices for safety monitoring.”

About Generalized Anxiety Disorder (GAD)

GAD is a common condition associated with significant impairment that adversely affects millions of people. GAD results in fear, continuing anxiety, and a constant feeling of being overwhelmed. It is characterized by excessive, persistent, and unrealistic worry about everyday things. Approximately 10% of U.S. adults, representing around 20 million people1, currently suffer from GAD. This underdiagnosed and underserved mental health disorder is associated with less accomplishment at work and reduced labor force participation. Despite the significant personal and societal burden of GAD, there has been little innovation in the treatment of GAD in the past several decades, with the last new drug approval occurring in 2007.

About MM120 Orally Disintegrating Tablet (ODT)

MM120 ODT (lysergide D-tartrate or LSD) is a synthetic ergotamine belonging to the group of classic, or serotonergic, psychedelics which acts as a partial agonist at human serotonin-2A (5-HT2A) receptors. MM120 ODT is MindMed’s proprietary and pharmaceutically optimized form of LSD. MM120 ODT is an advanced formulation incorporating Catalent’s Zydis® ODT fast-dissolve technology which has a unique clinical profile with more rapid absorption, improved bioavailability and reduced gastrointestinal side effects.

The MM120 ODT Phase 3 clinical development program includes the Voyage and Panaroma studies in generalized anxiety disorder (GAD) and the Emerge study in major depressive disorder (MDD). Additional clinical indications are under consideration. MindMed’s Phase 2b study, MMED008, met its primary and key secondary endpoints and demonstrated rapid, clinically meaningful, and statistically significant improvements on the Hamilton Anxiety Rating Scale (HAM-A) at Week 4 and Week 12, with a 65% clinical response rate and 48% clinical remission rate sustained to Week 12 in the MM120 100 µg cohort. MM120 was generally well-tolerated in this study, with most adverse events rated as mild to moderate, transient, and occurring on the dosing day and being consistent with the expected acute effects of the trial drug.

Based on the significant unmet medical need in the treatment of GAD along with the initial clinical data from the Phase 2b study and other research conducted by MindMed, the U.S. Food & Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for the MM120 program in GAD.

About MindMed

MindMed is a clinical-stage biopharmaceutical company developing novel product candidates to treat brain health disorders. Our mission is to be the global leader in the development and delivery of treatments that unlock new opportunities to improve patient outcomes. We are developing a pipeline of innovative product candidates, with and without acute perceptual effects, targeting neurotransmitter pathways that play key roles in brain health. MindMed trades on NASDAQ under the symbol MNMD.

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[gfp927z]

I see MindMed has plenty of cash now, and will be starting phase 3. I haven't been following the sector too much lately, but looks like MNMD has emerged as the most promising company? Just curious if ATAI still has the backing from Thiel? Also any other promising psych-med companies on your radar? Thanks for any insights :o)

Btw, my main Psych Med board is here (link below), but feel free to post on the Biotech Ideas board also :o)

https://investorshub.advfn.com/Psychedelic-Medicine-Sector-37972



>>> MindMed to Be Added to the Nasdaq Biotechnology Index


Business Wire

December 19, 2024


https://finance.yahoo.com/news/mindmed-added-nasdaq-biotechnology-index-120000637.html


NEW YORK, December 19, 2024--(BUSINESS WIRE)--Mind Medicine (MindMed) Inc. (Nasdaq: MNMD), (the "Company" or "MindMed"), a clinical-stage biopharmaceutical company developing novel product candidates to treat brain health disorders, today announced that it will be added to the Nasdaq Biotechnology Index (NBI), effective at market open on Monday, December 23, 2024.

"2024 has been a transformational year for MindMed. We’ve successfully executed many important milestones, including raising approximately $250 million through two equity financings, obtaining a newly issued patent covering MM120 orally disintegrating tablet (ODT) and extending intellectual property protection through 2041, expanding our pipeline to include MM120 ODT for major depressive disorder, and most recently, launching Voyage, our Phase 3 study of MM120 ODT in generalized anxiety disorder," said Rob Barrow, Chief Executive Officer of MindMed. "We are in a pivotal phase in our growth and the addition to the NBI further validates our potential in delivering long-term value to shareholders as we progress our pipeline and aim to deliver transformational innovation for people living with brain health disorders."

The NBI is designed to track the performance of a set of securities listed on The Nasdaq Stock Market® (Nasdaq®) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The NBI is calculated under a modified capitalization-weighted methodology. Companies in the NBI must meet eligibility requirements, including minimum market capitalization, average daily trading volume, and seasoning as a public company, among other criteria. Nasdaq selects constituents once annually in December.

For more information about the NBI, please visit https://indexes.nasdaqomx.com/Index/Overview/NBI.

About MindMed

MindMed is a clinical-stage biopharmaceutical company developing novel product candidates to treat brain health disorders. Our mission is to be the global leader in the development and delivery of treatments that unlock new opportunities to improve patient outcomes. We are developing a pipeline of innovative product candidates, with and without acute perceptual effects, targeting neurotransmitter pathways that play key roles in brain health. MindMed trades on Nasdaq under the symbol MNMD.

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[MomsSpaghetti]

MindMed Announces First Patient Dosed in Phase 3 Voyage Study of MM120 in Generalized Anxiety Disorder (GAD)

https://www.businesswire.com/news/home/20241216046321/en/

MindMed to Be Added to the Nasdaq Biotechnology Index

https://www.businesswire.com/news/home/20241219955108/en/

Corporate Presentation December 2024

https://d1io3yog0oux5.cloudfront.net/_80b2b065dd756bcc65a56ab23eb57ef8/mindmed/db/2265/21500/pdf/MindMed+Investor+Presentation+December+2024+.pdf

[XenaLives]

From my effort to understand... Blood tests for gadolinium are negative because it has been absorbed by the bone. That is why chelation is the only option.

[gfp927z]

Xena, Yes, Covid is just one more in a long list of toxic crap we're exposed to daily. We're living in a chemical soup, and compounds used in medicine just compound the problem. As boomers we grew up breathing the lead from leaded gasoline, got mercury in our vaccines and dental fillings, constantly breath in zillions of VOCs outgassed from our furniture, flooring, fabrics, etc, and then there's the chemical laden water supply, food sprayed with herbicides, pesticides, and now the big revelations on nanoplastics (see below). It's never ending. Americans spends the most on heathcare, but have the worst health on the planet.

All we can really do is try to minimize the exposure as best we can. I've taken steps with the food and water, and a key step is to avoid glyphosate (Roundup) since it wipes out the intestinal microbiome, as does the sweetener sucralose (Splenda).

With gadolinium, assuming the tests confirm its presence in your body, then chelation might be the only solution. I remember chelation from decades ago, and there were apparently risks associated with the chelation process itself. But I know very little about it. In one of his videos Dr. Gundry mentioned chelation therapy as a way to correct mercury exposure, so it must be a reasonably safe approach if he would recommend it. But there are undoubtedly different types of chelation, some safe, some not (?) And chelation for gadolinium could be totally different than chelation for mercury or lead. So it's essential to get fully up to speed on it before having it done.

One thing Gundry mentioned about mercury is that it ends up stored in the body's fat cells, and as long as it's in there it actually doesn't cause much problem. Putting it in fat cells is the body's own mechanism to neutralize its ability to cause damage. Gundry said the problem comes when people lose a lot of weight, and the mercury then has to leave the fats cells and is floating around in the bloodsteam again (concentrating in the brain, etc). So an unintended negative consequence of weight loss. Gadolinium might be totally different however (?) Gundry, or someone like him, would be the one to consult with to get the scoop on gadolinium toxicity and how to detect and reverse it.


>>> Micro- and Nanoplastics Breach the Blood–Brain Barrier (BBB): Biomolecular Corona’s Role Revealed


https://pmc.ncbi.nlm.nih.gov/articles/PMC10141840/


Verena Kopatz 1,2,3,4, Kevin Wen 5, Tibor Kovács 6, Alison S Keimowitz 5, Verena Pichler 3,7, Joachim Widder 2,4, A Dick Vethaak 8,9, Oldamur Hollóczki 6,*,†, Lukas Kenner 1,3,4,10,11,*,†

PMCID: PMC10141840 PMID: 37110989

Abstract

Humans are continuously exposed to polymeric materials such as in textiles, car tires and packaging. Unfortunately, their break down products pollute our environment, leading to widespread contamination with micro- and nanoplastics (MNPs). The blood–brain barrier (BBB) is an important biological barrier that protects the brain from harmful substances. In our study we performed short term uptake studies in mice with orally administered polystyrene micro-/nanoparticles (9.55 µm, 1.14 µm, 0.293 µm). We show that nanometer sized particles—but not bigger particles—reach the brain within only 2 h after gavage. To understand the transport mechanism, we performed coarse-grained molecular dynamics simulations on the interaction of DOPC bilayers with a polystyrene nanoparticle in the presence and absence of various coronae. We found that the composition of the biomolecular corona surrounding the plastic particles was critical for passage through the BBB. Cholesterol molecules enhanced the uptake of these contaminants into the membrane of the BBB, whereas the protein model inhibited it. These opposing effects could explain the passive transport of the particles into the brain.

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[XenaLives]

Yeah but what it isn't "COVID" ...

What if it's all about the S#IT they gave people in the MRI?

"Abstract
The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T1-weighted images taken prior to and after CA injection. This MR method is useful for investigating BBB permeability in in vivo mouse models and can be easily applied in a number of experimental disease conditions including neuroinflammation disorders, or to assess (un)wanted drug effects."

https://pubmed.ncbi.nlm.nih.gov/29341021

[gfp927z]

>>> Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

Nature - Neuroscience

Feb 22, 2024


https://www.nature.com/articles/s41593-024-01576-9


Chris Greene, Ruairi Connolly, Declan Brennan, Aoife Laffan, Eoin O’Keeffe, Lilia Zaporojan, Jeffrey O’Callaghan, Bennett Thomson, Emma Connolly, Ruth Argue, James F. M. Meaney, Ignacio Martin-Loeches, Aideen Long, Cliona Ni Cheallaigh, Niall Conlon, Colin P. Doherty & Matthew Campbell

Nature Neuroscience volume 27, pages421–432 (2024)Cite this article

Abstract

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog.

Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

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>>> Acurx Updates Phase 3 Readiness for Ibezapolstat in C. difficile Infection Based on Recent FDA and EMA Communications


PR Newswire

December 9, 2024


https://finance.yahoo.com/news/acurx-updates-phase-3-readiness-130000907.html


Following the previously announced successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, Acurx has now also received written positive feedback from FDA regarding acceptability of our CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program

Acurx has initiated the Scientific Advice procedure with the European Medicines Agency (EMA) to discuss the readiness for initiation of the Phase 3 clinical program in the European Union (EU). Acurx has been notified that we should expect to receive the final written advice letter in the coming few weeks

Acurx is also in the process of discussing the pediatric development plans for ibezapolstat in C. difficile Infection with FDA and EU health authorities, per regulatory requirements.

Phase 3 international trial planning continues to advance, using AI and other state-of-the-art techniques to identify and qualify clinical trial sites with the highest potential for patient enrollment

Acurx is also preparing to request regulatory guidance to initiate clinical trials in Japan, Canada and the United Kingdom

Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designation from FDA and Acurx has received SME (Small and Medium-sized Enterprise) designation by the EMA to benefit from fee incentives and other support from the EMA for EU Marketing Authorization


STATEN ISLAND, N.Y., Dec. 9, 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 updates on Phase 3 Readiness for Ibezapolstat in C. difficile Infection based on recent FDA and EMA Communications.

Written communications are used by both regulatory agencies in lieu of face-to-face or teleconference/video conferences when these agencies determine that a written response to the sponsor's questions would be the most appropriate means for providing feedback and advice to the sponsor. (FDA Guidance on Formal Meetings, EMA Guidance on Centralised Procedure)

Acurx's Executive Chairman, Bob DeLuccia, stated: "We are very pleased with these latest favorable communications from both regulatory agencies and in our opinion are a testament to the strength of our clinical data to date, our robust regulatory submissions, and adherence to current regulatory guidance." He further added: "We anticipate, and are confident, that with final EMA advice for our ibezapolstat Phase 3 trials for adult patients with CDI and the pediatric development plans from both regulatory agencies, Acurx will have a clear international roadmap for conduct of our Phase 3 program and, if successful, requirements for US NDA submission and EU Marketing Authorization."

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-reat (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 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 (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 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: 0.3390/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.

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Acurx - >>> MicroStrategy Copycats Are Buying Bitcoin as Price Nears $100,000


Barron's

by Paul R. La Monica

Nov 22, 2024


https://www.barrons.com/articles/microstrategy-copycats-companies-buy-bitcoin-0032c5ff?siteid=yhoof2


As Bitcoin heads toward $100,000, it looks like three tiny biotechs are hoping to emulate the success of MicroStrategy, the software company whose stock has gone into orbit as it plows money into the cryptocurrency.

In just the past week, Acurx Pharmaceuticals, Hoth Therapeutics, and Enlivex Therapeutics have announced plans to invest up to $1 million each in Bitcoin. That is, of course, an infinitesimal amount compared with MicroStrategy, whose balance-sheet holdings of 331,200 coins are now worth about $32.8 billion, one-third of its more than $95 billion market capitalization.

MicroStrategy stock is up nearly 600% so far this year.

The three biotech companies all said in news releases that they were taking the crypto plunge due to increased support for Bitcoin among institutional investors. They suggested that Bitcoin could be a good hedge against inflation.

“As demand for Bitcoin grows, and so does its acceptance as a major and primary asset class, we believe that Bitcoin will serve as a strong treasury reserve asset for cash not needed over the next 12 to 18 months” said David Luci, president and CEO of Acurx, in a press release, echoing similar statements made by Enlivex CEO Oren Hershkovitz and Hoth CEO Robb Knie.

It is true that big money-management firms, such as BlackRock, Fidelity, Invesco, and Cathie Wood’s ARK Invest have all jumped into the Bitcoin pool with crypto exchange-traded funds. But whether Bitcoin actually is the new “digital gold” and can hold its value during times of dollar weakness and rising inflation over the long haul remains to be seen.

Regardless of where Bitcoin heads next, investors shouldn’t expect any of these penny stock biotechs to take off. For one, they are all early-stage microcap companies that are thinly traded, volatile, and unprofitable.

Acurx, worth about $20 million, is the largest of the trio. To say that they were already risky investments before they announced plans to buy Bitcoin is an understatement.

Investors seem to realize that none of them are the next MicroStrategy. Only Hoth’s shares got a modest pop this week, rising about 6% following its Bitcoin announcement. And all three stocks are down sharply this year, with Hoth tumbling 40% and Enlivex and Acurx each plunging more than 65%.

Still, it will be worth watching to see whether other larger and more recognizable publicly traded companies decide to buy and hold Bitcoin for their corporate treasuries.

Besides MicroStrategy, only a handful of other companies have Bitcoin on their balance sheets. Many of them are in the crypto sector, such as Coinbase; Block, owner of Square and Cash App; and Bitcoin miners MARA Holdings, Hut 8, and Riot Platforms. Elon Musk’s Tesla is also a Bitcoin investor.

But who knows? Though the price is surging now, with a gain of almost 50% in the past four weeks, this could wind up being a short-term speculative top for Bitcoin. It is a little reminiscent of late 2017, when Bitcoin surged to nearly $20,000, and non-crypto companies flocked to the business.

A company named Long Island Iced Tea Corp., which made a nonalcoholic version of the popular beverage, changed its name to Long Blockchain. It was delisted in 2021. Penny stocks Rich Cigars and e-cigarette maker Vapetek also announced plans to become blockchain firms.

Bitcoin tumbled to below $4,000 by December 2018 and took about two years to recover to its 2017 levels. This doesn’t mean history will repeat itself and that Bitcoin will plunge precipitously.

But investors should remember that any time there is a speculative mania like the one occurring now, more volatility, at the very least, is highly likely.

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>>> RFK Jr. Leaves Dr. Phil Stunned As He Explains Huge Kickbacks Fauci and NIH Have Earned From Moderna Vaccines (VIDEO)


by Ben Kew

Jun. 30, 2024

TruthTweetShareGettrGab


https://www.thegatewaypundit.com/2024/06/rfk-jr-leaves-dr-phil-stunned-as-he/


Robert F. Kennedy Jr. left Dr. Phil McGraw stunned by the amount of kickbacks Dr. Anthony Fauci and other high-level deputies at the National Institute for Health received from Moderna and other major pharmaceuticals.

Kennedy, who is running as an independent presidential candidate, explained the situation during an in-depth interview with Dr. Phil, who recently interviewed Donald Trump in similar circumstances.

As long reported by The Gateway Pundit, the pharmaceutical industry has pocketed many billions of dollars off their dodgy COVID “vaccines,” and some of that money is going toward health officials such as Anthony Fauci.

Here is a transcript of the exchange:

DR. PHIL: The government regulators have been bought off by Big Pharma. I think that is what you are saying when you say that this entanglement has occurred. You say agency employees are actually getting royalties, getting payments on vaccines and drugs that they approve. Is that true?

KENNEDY: Yes, there is a couple of things happening with FDA. About 50 percent of the FDA’s budget comes from regulated industries, mainly the pharmaceutical industry. So you have agency capture on steroids. The principal objective of FDA today is to serve the mercantile interests of pharmaceutical companies. For example, the Moderna vaccine, NIH owns half of that vaccine, 50 percent. So the billions of dollars that vaccines makes, half of that goes to NIH the agency, but there is also individuals at least four, maybe six, who work for NIH who are high-level deputies under Anthony Fauci who get to collect 150,000 dollars a year forever, not just for their life but their children, as long as that mRNA technology is on the market and they’re going to be making money. That is a conflict.

DR. PHIL: Hang on a minute now, I don’t want to blow by this too fast. So the National Institute for Health is getting a kick, a bribe, a royalty, a share, whatever you want to call it, is this not a clear conflict of interest? That is what you are pointing out, right?

KENNEDY: Yes, it is. People are shocked.

DR. PHIL: Why are you the only one talking about this?

KENNEDY: If you talk about this kind of thing, you get censored on YouTube. You will not be allowed on the mainstream media to talk about these issues. It used to be that you could, but nowadays, you cannot.

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>>> A Systematic Review Of Autopsy Findings In Deaths After COVID-19 Vaccination


https://publichealthpolicyjournal.com/a-systematic-review-of-autopsy-findings-in-deaths-after-covid-19-vaccination/



Nicolas Hulscher *
Paul E. Alexander
Richard Amerling
Heather Gessling
Roger Hodkinson
William Makis
Harvey A. Risch
Mark Trozzi
Peter A. McCullough
Peer Reviewed, Public Health, Science
11/17/2024
v5.2019-2024

Abstract

Background: The rapid development of COVID-19 vaccines, combined with a high number of adverse event reports, have led to concerns over possible mechanisms of injury including systemic lipid nanoparticle (LNP) and mRNA distribution, Spike protein-associated tissue damage, thrombogenicity, immune system dysfunction, and carcinogenicity. The aim of this systematic review is to investigate possible causal links between COVID-19 vaccine administration and death using autopsies and post-mortem analysis.

Methods: We searched PubMed and ScienceDirect for all published autopsy and organ-restricted autopsy reports relating to COVID-19 vaccination up until May 18th, 2023. All autopsy and organ-restricted autopsy studies that included COVID-19 vaccination as an antecedent exposure were included. Because the state of knowledge has advanced since the time of the original publications, three physicians independently reviewed each case and adjudicated whether or not COVID-19 vaccination was the direct cause or contributed significantly to death.

Results: We initially identified 678 studies and, after screening for our inclusion criteria, included 44 papers that contained 325 autopsy cases and one organ-restricted autopsy case (heart). The mean age of death was 70.4 years. The most implicated organ system among cases was the cardiovascular (49%), followed by hematological (17%), respiratory (11%), and multiple organ systems (7%). Three or more organ systems were affected in 21 cases. The mean time from vaccination to death was 14.3 days. Most deaths occurred within a week from last vaccine administration. A total of 240 deaths (73.9%) were independently adjudicated as directly due to or significantly contributed to by COVID-19 vaccination, of which the primary causes of death include sudden cardiac death (35%), pulmonary embolism (12.5%), myocardial infarction (12%), VITT (7.9%), myocarditis (7.1%), multisystem inflammatory syndrome (4.6%), and cerebral hemorrhage (3.8%).

Conclusions: The consistency seen among cases in this review with known COVID-19 vaccine mechanisms of injury and death, coupled with autopsy confirmation by physician adjudication, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death. Further urgent investigation is required for the purpose of clarifying our findings.

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Stupid - >>> Acurx Board of Directors Approves Bitcoin as Treasury Reserve Asset


PR Newswire

November 20, 2024


https://finance.yahoo.com/news/acurx-board-directors-approves-bitcoin-120100338.html


STATEN ISLAND, N.Y., Nov. 20, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today that the Company's Board of Directors approved the purchase of up to $1 million in Bitcoin to hold as a treasury reserve asset.

"As demand for Bitcoin grows, and so does its acceptance as a major and primary asset class, we believe that Bitcoin will serve as a strong treasury reserve asset for cash not needed over the next 12 to 18 months" said David P. Luci, President & CEO of Acurx. "With the recent approval of Bitcoin ETFs and the growing support from government agencies and institutional investors, it is a great addition to our treasury strategy. Its limited supply and inflation-resistant characteristics provide a functional store of value. This new treasury strategy is a finance strategy and has no impact on our overarching drug development plans."

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).

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>>> The Microbiome’s Forgotten Cousin Could Be Key to Solving America’s Gut Issues

Human innards are teeming with viruses that infect bacteria. What are they up to?


Inverse

by Amber Dance and Knowable Magazine

Aug. 18, 2024




3d render of inner intestine with plica and villi. human digestive anatomy



You’ve probably heard of the microbiome — the hordes of bacteria and other tiny life forms that live in our guts. Well, it turns out those bacteria have viruses that exist in and around them — with important consequences for both them and us.

Meet the phagosome.

There are billions, perhaps even trillions, of these viruses, known as bacteriophages (“bacteria eaters” in Greek) or just “phages” to their friends, inside the human digestive system. Phageome science has skyrocketed recently, says Breck Duerkop, a bacteriologist at the University of Colorado Anschutz School of Medicine, and researchers are struggling to come to grips with their enormous diversity. Researchers suspect that if physicians could harness or target the right phages, they might be able to improve human health.

“There will turn out to be good and bad phages,” says Paul Bollyky, an infectious disease physician and researcher at Stanford Medicine. But for now, it’s still unclear how many phages occupy the gut — perhaps one for each bacterial cell or even fewer. There are also bacteria that contain phage genes but aren’t actively producing viruses; the bacteria are just living their lives with phage DNA tagging along in their genomes.

And there are lots of phages still unidentified; scientists call them the “dark matter” of the phagosome. A big part of current phage research is to identify these viruses and their host bacteria. The Gut Phage Database contains more than 140,000 phages, but that’s surely an underestimate. “Their variety is just extraordinary,” says Colin Hill, a microbiologist at University College Cork in Ireland.

Scientists find phages by sifting through genetic sequences culled from human fecal samples. That’s where researchers found the most common gut phage group, called crAssphage. (Get your mind out of the gutter — they were named for the “cross-assembly” technique that plucked their genes out of the genetic mishmash.) In a recent study, Hill and colleagues detailed a light-bulb shape for crAssphages, with a 20-sided body and a stalk to inject DNA into host bacteria.

It’s not clear whether crAssphages make a difference to human health, but given that they infect one of the most common groups of gut bacteria, Bacteroides, Hill wouldn’t be surprised if they did. Other common groups that also infect Bacteroides include the Gubaphage (gut Bacteroides phage) and the LoVEphage (lots of viral genetic elements).

Phageomes vary widely from person to person. They also change depending on age, sex, diet and lifestyle, as Hill and colleagues described in the 2023 Annual Review of Microbiology.

Though phages infect bacteria and sometimes kill them, the relationship is more complicated than that. “We used to think that phage and bacteria are fighting,” says Hill, “but now we know that they’re actually dancing; they’re partners.”

Phages can benefit bacteria by bringing in new genes. When a phage particle is assembled inside an infected bacterium, it can sometimes stuff bacterial genes into its protein shell along with its own genetic material. Later, it squirts those genes into a new host, and those accidentally transferred genes could be helpful, says Duerkop. They might provide resistance to antibiotics or the ability to digest a new substance.

Phages keep bacterial populations fit by constantly nipping at their heels, says Hill. Bacteroides bacteria can display up to a dozen types of sugary coats on their outer surfaces. Different coats have different advantages: to evade the immune system, say, or to occupy a different corner of the digestive system. But when crAssphages are around, Hill says, the Bacteroides must constantly change coats to evade the phages that recognize one coat or another. The result: At any given time, there are Bacteroides with different coat types present, enabling the population as a whole to occupy a variety of niches or handle new challenges.

Phages also keep bacterial populations from getting out of hand. The gut is an ecosystem, like the woods, and phages are bacteria predators, like wolves are deer predators. The gut needs phages like the woods need wolves. When those predator-prey relationships are altered, disease can result. Researchers have observed phagosome changes in inflammatory bowel syndrome (IBS), irritable bowel disease, and colorectal cancer — the viral ecosystem of someone with IBS is often low in diversity, for example.

People try to re-balance the gut microbiome with diets or, in extreme medical cases, fecal transplants. Tackling phages might provide a more fine-tuned approach, Hill says. As a case in point, scientists are seeking phages that could be used therapeutically to infect the bacteria that cause ulcers.

Be grateful for the trillions of phages managing your gut’s ecosystem. Without them, Hill suggests, a few kinds of bacteria might quickly come to dominate — potentially leaving you unable to digest some foods and subject to gas and bloating.

The wild and wondrous phagosome is a dance partner for bacteria and humans alike.

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>>> Acurx Pharmaceuticals, Inc. Reports Third Quarter 2024 Results and Provides Business Update


PR Newswire

November 13, 2024


https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-third-120000114.html


STATEN ISLAND, N.Y., Nov. 13, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the third quarter ended September 30, 2024.

Highlights of the third quarter ended September 30, 2024, or in some cases shortly thereafter, include:

In July 2024, results from the ibezapolstat (IBZ) Phase 2 clinical trial in patients with C. difficile Infection (CDI) were presented at the 17th Biennial Congress of the Anaerobe Society of the Americas by Taryn A. Eubank, PharmD, BCIDP, Research Assistant Professor, University of Houston College of Pharmacy delivered an oral presentation entitled: "Clinical Efficacy of Ibezapolstat in CDI: Results from Phase 2 trials."

Also in July 2024, and very timely given our late-stage development progress, the USPTO (United States Patent and Trademark Office) granted Acurx a new patent for ibezapolstat which specifically encompasses the "treatment of C. difficile Infection while reducing recurrence of infection and improving the health of the gut microbiome". This patent expires in June 2042 and we believe will provide an important downstream competitive advantage.

In August 2024, we submitted our request to FDA for a meeting to review our manufacturing processes and specifications for drug substance and final product and packaging (a "CMC Meeting") in order to commence Phase 3 clinical trials. This FDA submission is customary and follows our successful End of Ph2 clinical meeting with FDA which confirmed our Ph3 clinical trial readiness. We anticipate convening a meeting with FDA regarding CMC in the fourth quarter.

In September 2024, a presentation was given by Executive Chairman, Bob DeLuccia, at the World Antimicrobial Resistance Scientific Congress held in Philadelphia. In his presentation at the Innovation Showcase session, he highlighted that we have a complete roadmap, not only for the required components of our phase 3 clinical program, but also what's required for ultimate filing of an NDA (or New Drug Application) which is to be followed by submissions for Marketing Authorizations in other countries around the world. He also presented an update on the Company's preclinical GPSS® (Gram Positive Selective Spectrum) program for systemic oral and IV treatment of other gram-positive infections including, MRSA, VRE and DRSP.

Also in September 2024, we participated at the 8th Annual C. Difficile Symposium (or ICDS) in Bled, Slovenia, which is the premier global scientific venue for the review of C. Difficile research. At the ICDS Meeting, two presentations were made on behalf of the Company.

Additionally in September 2024, we announced that selected ACX-375 DNA pol IIIC analogues demonstrated in vitro activity against B. anthracis (or Anthrax), which is a Bioterrorism Category A pathogen, including activity against ciprofloxacin-resistant Anthrax. This work was performed at two independent qualified laboratories including the University of Florida. Planning is underway for an Anthrax bioterrorism development program.

In October 2024, we participated at IDWeek in Los Angeles, the annual scientific conference of the Infectious Diseases Society of America. Drs. Kevin Garey and Taryn Eubank presented a scientific poster showing that 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. Ibezapolstat-treated patients showed decreased concentrations of fecal primary bile acids, and higher ratios of secondary to primary bile acids than vancomycin-treated patients.

International regulatory filing initiatives will continue in Q4 2024.

Third Quarter 2024 Financial Results

Cash Position:

The Company ended the quarter with cash totaling $5.8 million, compared to $7.5 million as of December 31, 2023. During the third quarter, the Company raised additional proceeds under its ATM financing program, with gross proceeds of approximately $1.6 million.

R&D Expenses:

Research and development expenses for the three months ended September 30, 2024 were $1.2 million compared to $1.3 million for the three months ended September 30, 2023. The decrease was due primarily to an increase in manufacturing related costs during the quarter of $0.1 million, offset by a reduction in consulting fees of $0.2 million. For the nine months ended September 30, 2024 research & development expenses were $4.6 million compared to $4.1 million for the nine months ended September 30, 2023, an increase of $0.5 million primarily due to $0.9 million increase in manufacturing related costs, offset by $0.4 million decrease in consulting fees.

G&A Expenses:

General and administrative expenses for the three months ended September 30, 2024 were $1.6 million compared to $1.8 million for the three months ended September 30, 2023, a decrease of $0.2 million. The decrease was primarily due to $0.2 million increase in professional fees, a $0.1 million increase in compensation costs, offset by a $0.5 million decrease in non cash share-based compensation related costs. For the nine months ended September 30, 2024, general and administrative expenses were $6.7 million compared to $5.4 million for the nine months ended September 30, 2023, an increase of $1.3 million. The increase was primarily due to $1.1 million increase in professional fees and a $0.2 million increase in legal costs.

Net Income/Loss:

The Company reported a net loss of $2.8 million or $0.17 per diluted share for the three months ended September 30, 2024 compared to a net loss of $3.1 million or $0.24 per diluted share for the three months ended September 30, 2023, and a net loss of $11.3 million or $0.71 per share for the nine months ended September 30, 2024, compared to a net loss of $9.5 million or $0.77 per share for the nine months ended September 30, 2023 for the reasons previously mentioned. The Company had 16,770,378 shares outstanding as of September 30, 2024.

Conference Call

As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:

Date:

Wednesday, November 13, 2024

Time:

8:00 a.m. ET

Toll free (U.S. and International):

877-790-1503

Conference ID:

13749688

About Ibezapolstat

Ibezapolstat is the Company's lead antibiotic candidate preparing 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 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).

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Acurx - CEO update -

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>>> Acurx Announces Additional Ibezapolstat Ph2b Results in CDI as well as Anthrax (B. anthracis) Susceptibility to ACX-375 Analogues


PR Newswire

September 26, 2024


https://finance.yahoo.com/news/acurx-announces-additional-ibezapolstat-ph2b-110000237.html


New analyses extend data on beneficial effects of ibezapolstat on the gut microbiome

Confirmed ibezapolstat's favorable pharmacokinetics showing low systemic exposure and high colonic concentrations

Selected ACX-375 analogues demonstrated in vitro activity against Anthrax (B. anthracis), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant Anthrax. Planning is underway for an Anthrax bioterrorism development program

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, the United Kingdom, Japan and Canada

Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA


STATEN ISLAND, N.Y., Sept. 26, 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 results from new analyses that extend data on the beneficial effects of ibezapolstat on the gut microbiome. The data show an increased proportion of Actinobacteriota and increased quantity of beneficial Bacillota (Firmicutes) leading to reversal of dysbiosis and contributing to the CDI anti-recurrence effect of ibezapolstat.

Additionally, ibezapolstat's favorable pharmacokinetics properties were confirmed showing mean systemic exposure below 1mcg/mL and fecal concentrations well in excess of the minimal inhibitory concentration (MIC) for C. difficile.

Microbiological testing of certain ACX-375 DNA pol IIIC analogues in independent qualified laboratories, including the University of Florida, demonstrated in vitro activity with MICs of 0.5-2mcg/mL against B. anthracis (Anthrax), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant B. anthracis.

The above results were presented at the premier International C. difficile Symposium (ICDS) held in Bled, Slovenia on September 17-19, 2024. 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 of ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides Difficile Infection.

According to Dr. Garey: "The microbiome data also show an unexpected finding of a unique microbiome signature in two vancomycin-treated patients in the Ph2b trial who experienced recurrence of CDI. Since these changes were evident and observed early during treatment and then consistently until the end of therapy, they may be predictive of pending CDI recurrence and suggest the need to modify therapy."

Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new data add to and reinforce ibezapolstat's emerging overall distinctive product profile, particularly the favorable microbiome-related unexpected findings." He added: "Furthermore, the initial in vitro activity shown against the Bioterrorism Category A pathogen B. anthracis (Anthrax) with some of our earlier-stage compounds included a ciprofloxacin-resistant strain. Selective microbiome effects will be tested with these new compounds as they proceed through development to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other critical gram-positive pathogens in parallel with planning for the Anthrax bioterrorism program. The presentation is available on the Acurx Pharmaceuticals website 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, 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 C. difficile Symposium (ICDS)

The International C. difficile Symposium (ICDS) is now established as the premier venue for the review of Clostridium difficile research.

The 1st meeting was held in Kranjska Gora in 2004, the 2nd in Maribor in 2007, while all earlier meetings were in Bled in 2010, 2012, 2015 and in 2018. ICDS in 2020 was held virtually. The 2024 meeting will provide the ideal opportunity to review progress in epidemiology, diagnostics, clinical trials, basic research and in understanding C. difficile pathogenesis and controlling the devastating disease it causes.

About the Ibezapolstat Phase 2 Clinical Trial

The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. 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).

In the now completed 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, 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 www.acurxpharma.com

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>>> FDA Approves the First New Schizophrenia Drug in Decades


Time

by Alice Park

9-28-24


https://www.msn.com/en-us/health/other/fda-approves-the-first-new-schizophrenia-drug-in-decades/ar-AA1rjUAB?ocid=BingNewsSerp


No new treatments for schizophrenia have been approved in nearly three decades, but that changed on Sept. 26, when the U.S. Food and Drug Administration (FDA) approved Cobenfy for the psychiatric disorder.

Developed by Karuna Therapeutics, which was subsequently acquired by Bristol Myers Squibb, the drug works in an entirely different way from existing medications for schizophrenia, which is building excitement and enthusiasm among doctors and patients alike.

How scientists developed the new drug

While schizophrenia treatments primarily target the dopamine neurotransmitter system in the brain, Cobenfy goes after a different one, the cholinergic system, through muscarinic receptors. Decades ago, scientists at Eli Lilly had studied the muscarinic system as a possible treatment for Alzheimer’s disease, since manipulating it seemed to reduce some of the symptoms of Alzheimer’s-related psychosis that some patients develop. The company's researchers also serendipitously learned that a compound they developed to activate the system also improved symptoms of schizophrenia. But cells in many parts of the body—the brain, but also the bladder, gut, salivary glands, eyes, and heart—contain receptors for the muscarinic system, which meant it was challenging to selectively target just those in the brain and not elsewhere. Because the compound, called xanomeline, caused wide-ranging side effects, Lilly's researchers shelved further study on it.

Andrew Miller, co-founder of Karuna, became intrigued by this research and tried to figure out how to activate the muscarinic system in the brain while tamping it down elsewhere in the body. He and his team tested 7,000 compounds and eventually combined xanomeline with a drug that had been approved by the FDA in the 1970s for treating overactive bladder, to suppress muscarinic activity elsewhere in the body. "It's a pretty out-of-the-box approach," says Miller. The overactive bladder drug "has nothing to do with psychiatry," he said. Combining it with a serendipitous discovery of xanomeline "didn't fit the traditional model of innovative drug discovery." But it worked.

What studies have found

In a study the company published last December in the journal Lancet, the researchers reported that the combination—now called Cobenfy but then called KarXT—helped to significantly reduce symptoms of schizophrenia such as hallucinations, delusions, paranoia, social withdrawal, and a loss of motivation compared to a placebo. Those data were part of the application that the company submitted to the FDA for approval.

Bristol Myers Squibb acquired Karuna in 2023 largely based on these encouraging results. “When we looked at the available neuroscience and neuropsychiatric assets out there, we didn’t want the next dopamine agonist or antagonist in the marketplace, which all of the physicians have [already] seen,” says Adam Lenkowsky, chief commercialization officer for Bristol Myers Squibb. “We wanted a truly revolutionary asset, one with a different mechanism: a first-in-class, best-in-category asset we think could transform the space.”

Samit Hirawat, chief medical officer at Bristol Myers Squibb, says that not only does Cobenfy address schizophrenia in an entirely new way, but its approach could be used for other neurological conditions as well. "The breadth of applicability of this medicine is what attracted us.”

Dr. Rishi Kakar, chief scientific officer at Segal Trials who led several studies on Cobenfy, says that “the uniqueness of the mechanism of action differentiated this medication from everything else we had so far, and truly caught my eye right off the bat.” Kakar—a psychiatrist who treats patients as well as conducts research—says that historically, only about 40% of people with schizophrenia respond to dopamine-based treatments, and the other 60% who may respond often stop taking their medications because of intolerable side effects, which can include uncontrolled muscle movements, dizziness, fainting, and weight gain.

The trials included patients who were hospitalized for acute schizophrenia and randomly assigned to receive Cobenfy—as a pill taken twice a day—or a placebo for five weeks. In order to reflect the real-world population of patients, some had been taking existing medications but stopped because of the side effects, or weren’t compliant. All patients went through a wash-out period of up to two weeks to ensure any measurements of their outcomes during the study were due solely to Cobenfy or placebo. Patients received escalating doses of the drug, and prescribing doctors were able to adjust dosages for their patients depending on their symptoms.

The studies documented a significant reduction in overall symptoms of schizophrenia in the patients receiving Cobenfy compared to placebo. “My viewpoint is that [this difference] can mean someone can potentially carry on a better life by having symptom control,” says Kakar.

What else to know about Cobenfy

The FDA approved Cobenfy as a monotherapy—meaning it is meant to be taken alone, without other medications—but more studies will be needed to see how the medication works in combination with existing treatments, and what the benefits and risks are of combining them. “I think many clinicians are going to try this as a first-time pharmacological option, because they will find that the reduction in symptoms is fairly robust,” says Kakar. “From what I saw, it has true value for the unmet need we have.” Lenkowsky says Bristol Myers Squibb is conducting a trial studying Cobenfy in combination with dopamine-based medications that will yield results in about a year.

In contrast to the existing dopamine-based treatments, the side effects of Cobenfy reported by the volunteers in the studies were mostly mild to moderate, involving nausea and gastrointestinal distress, and tended to lessen with time. The label also alerts patients that the drug is associated with urinary retention, increased heart rate and swelling in the face in rare cases; the medication is not recommended for people with a history of liver or kidney disorders.

Bristol Myers Squibb is continuing to study the drug for its longer term effects, as well as to understand and potentially guide doctors on how to adjust doses for patients as their symptoms change over time. The success in schizophrenia patients may lead to other uses of the drug in other conditions as well. “Neuropsychiatry is at the cusp of bringing an explosion of new medicines, and Cobenfy is the start of a pipeline of potential products,” says Hirawat. The company is currently studying the drug in Alzheimer’s-related psychosis, and next year plans to start late-stage trials investigating whether it can improve bipolar mania, Alzheimer’s-associated agitation, and Alzheimer’s-associated cognitive impairment. In 2027, the company hopes to begin trials in people with autism.

How much will Cobenfy cost?

According to a Bristol Myers Squibb spokesperson, the wholesale cost for a month's supply will be $1,850. Depending on people's insurance coverage, that cost could be lower for individual patients. Bristol Myers Squibb estimates that 80% of people with schizophrenia in the U.S. have insurance coverage either through Medicare or Medicaid.

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>>> Acurx Announces Results of Its Pioneering Research with Ibezapolstat in Collaboration with Leiden University Medical Center at the Premier International C. difficile Symposium


PR Newswire

September 24, 2024


https://finance.yahoo.com/news/acurx-announces-results-pioneering-research-110000976.html


Results feature high-resolution elucidation of interaction of ibezapolstat with its molecular target

Mechanistic findings explain ibezapolstat's properties of lacking cross resistance with other antibiotics and not fostering the emergence of Enterococcus, including vancomycin-resistant strains, a unique differentiation among anti-CDI antibiotics

Molecular structure data will be used to guide rational design of new systemic therapeutic compounds with improved inhibitory activity and PK characteristics

Planning continues to prepare to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)

Acurx is also preparing requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada

Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA


STATEN ISLAND, N.Y., Sept. 24, 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 results from its pioneering research with ibezapolstat in collaboration with Leiden University Medical Center (LUMC). These results were presented at the premier International C. difficile Symposium (ICDS) held in Bled, Slovenia on September 17-19, 2024. Dr. Wiep Klaas Smits, PhD, Associate Professor, LUMC, delivered a presentation entitled: Structure of the Replicative Polymerase PolC Reveals Mode of Action and Mechanism of Resistance of the Anti-CDI Agent Ibezapolstat and Related Inhibitors.

According to Dr. Smits: "Our findings with ibezapolstat regarding the structural biology of DNA pol IIIC inhibitors have important implications for the development of a new family of antibiotics to treat high priority, multi-drug resistant, gram-positive infections". He further stated: "I believe that DNA replication is a promising but underexplored target, and this novel class of DNA pol IIIC inhibitors could be an important new tool to address the pandemic of antimicrobial resistance"

Robert J. DeLuccia, Executive Chairman of Acurx, stated: "We are very pleased with the outcome of our collaboration with LUMC which has been exceptionally productive." He added: "This detailed demonstration of the mode of action of DNA pol IIIC inhibitors in general, and for ibezapolstat specifically, is critically important to support our scientific foundation and our regulatory filings as we advance into this late-stage of ibezapolstat's development pathway toward commercialization".

The presentation is available on the Acurx Pharmaceuticals website 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 now preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.

Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement with FDA 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 Research Project, Leiden University Medical Center, the Research Consortium

Health Holland awarded a grant of approximately $500,000 USD to Leiden University Medical Center which was co-funded by a PPP (Public Private Partnership) allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships and to further study the mechanism of action of DNA pol IIIC inhibitors in scientific collaboration with Acurx Pharmaceuticals. https://www.health-holland.com/

This innovative research included study of 3-dimensional structures of DNA polymerases and their binding interactions with Acurx inhibitors. The antibacterial action of Acurx's pipeline of novel DNA pol IIIC inhibitors has been clinically validated by ibezapolstat's completion of a Ph2 clinical trial for treatment of C. difficile Infection (CDI). https://www.lumc.nl/en/research/.

The research outcome is intended to accelerate lead product candidate selection for Acurx's pre-clinical program for other WHO, CDC and FDA high-priority, multi-drug resistant Gram-positive pathogens where new classes of antibiotics are needed.

Together with Acurx Pharmaceuticals the PPP initiated the research project entitled "Bad bugs, new drugs: elucidation of the structure of DNA polymerase C of multidrug resistant bacteria in complex with novel classes of antimicrobials."

About the C. difficile Symposium (ICDS)

The International C. difficile Symposium (ICDS) is now established as the premier venue for the review of Clostridium difficile research.

The 1st meeting was held in Kranjska Gora in 2004, the 2nd in Maribor in 2007, while all earlier meetings were in Bled in 2010, 2012, 2015 and in 2018. ICDS in 2020 was held virtually. The 2024 meeting will provide the ideal opportunity to review progress in epidemiology, diagnostics, clinical trials, basic research and in understanding C. difficile pathogenesis and controlling the devastating disease it causes.

About the Ibezapolstat Phase 2 Clinical Trial

The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.

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, 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).

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.

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 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).

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AstraZeneca -- >>> AstraZeneca is an international drugmaker that doesn't get much attention from U.S.-based investors. That's because its dividend payouts are a little unusual.

https://www.fool.com/investing/2024/09/19/2-unstoppable-sp-500-stocks-that-keep-beating-the/

Instead of four equal quarterly distributions, AstraZeneca insists on two payments per year, with a greater portion announced alongside fourth-quarter results and payable in March. In July, the company raised its first interim distribution by 7.5% to $0.50 per American depository receipt (ADR).

At recent prices, the stock offers a 1.9% dividend yield. That isn't particularly tempting now, but the distribution could grow at the same pace as the company's bottom line. AstraZeneca generated $7 billion in free cash flow over the past year and only needed 64% of this sum to meet its dividend commitment.

AstraZeneca has multiple growth drivers that could push up profits and its dividend payout in the years ahead. In the first half of 2024, sales of Farxiga -- a treatment for diabetes, heart failure, and chronic kidney disease -- surged 35% year over year to $3.8 billion. Sales of Calquence, a blood cancer drug, surged 27% to $1.5 billion, and Ultomiris, a rare disease drug, shot 32% higher to $1.8 billion.

Free cash flow has surged since 2020 and could continue rising, thanks to an extremely successful product line. In the first half of 2024, AstraZeneca reported sales that grew more than 10% year over year for 21 different drugs.

With heaps of growth drivers to push earnings higher and a lack of significant patent cliffs to offset, AstraZeneca expects earnings to grow by a percentage in the middle teens this year. Adding some shares to a diversified portfolio now looks like a smart move.

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AbbVie -- >>> AbbVie raised its dividend payout by a stunning 270% over the past 10 years but isn't trading like a stock that rapidly raises its quarterly payout. At recent prices, it offers a 3.2% yield.

https://www.fool.com/investing/2024/09/19/2-unstoppable-sp-500-stocks-that-keep-beating-the/

Shares of AbbVie have been under pressure because its former lead drug Humira lost patent-protected market exclusivity in the U.S. in 2023. In the first half of 2024, Humira sales decreased 33% year over year to $5.1 billion.

Declining Humira sales are a challenge, but AbbVie has done a pretty good job reinvesting the profits it produced. In 2019, the company launched Skyrizi for psoriasis and Rinvoq for arthritis, and these two drugs are offsetting Humira losses on their own.

Combined sales of the pair reached $7.3 billion in the first half of 2024 and are a long way from being finished. In February, management told investors it expects Rinvoq and Skyrizi to generate more than $27 billion in combined annual sales by 2027.

Investors will be glad to learn that Rinvoq and Skyrizi aren't the only blockbuster drugs that AbbVie's launched in recent years. For example, its oral treatments for migraine headaches, Ubrelvy and Qulipta, are expected to produce more than $3 billion in combined annual sales at their peaks.

AbbVie shares have been trading for around 17.9x the midpoint of management's earnings expectations for 2024. That's a historically high multiple for this company, but pressure from Humira's competition is already beginning to subside. With plenty of growth drivers to push earnings higher, investors who buy at recent prices have a great chance to come out miles ahead over the long run.

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>>> Pfizer, joining Lilly, enters the direct-to-consumer market with a telehealth and prescription platform


Yahoo Finance

by Anjalee Khemlani

Aug 27, 2024


https://finance.yahoo.com/news/pfizer-joining-lilly-enters-the-direct-to-consumer-market-with-a-telehealth-and-prescription-platform-120250691.html


On Tuesday, Pfizer (PFE) said it will enter the direct-to-consumer business, following the lead of a Big Pharma rival, Eli Lilly (LLY), which launched a similar plan in January.

The new website and patient platform, called PfizerForAll, aims to help patients more quickly access migraine treatments as well as vaccines and treatments for respiratory viruses like COVID-19 and the flu. While these are all products of Pfizer, the company contends that patients will not be forced to choose a Pfizer drug. That decision, they say, will remain in the hands of clinicians.

Pfizer chief US commercial officer Aamir Malik told Yahoo Finance the company is hoping to make access to medicines easier. "Navigating our healthcare system is time-consuming. It's complicated. It's overwhelming. And the last thing that anybody needs when they're trying to get the care that they need for themselves or a loved one is to have to navigate that complex, painful, difficult system," Malik said.

Malik and others point out that patients often have to search for doctors who can write the prescriptions they need quickly — or even find a doctor who will see them in a timely manner, Malik said.

Adding to the complexity is the insurance process, which involves various coverage hurdles, such as pre-authorization requests and the hunt for a pharmacy that can dispense the drug at a lower co-pay cost.

But Pfizer's goal isn't to eradicate that complex system. Instead, Malik emphasized that the new portal will simply serve as an additional avenue for patients to get the drugs they are already familiar with, and also introduce new patients to the drugs. (It won't be able to help with drug shortages, as that issue rests with drug manufacturers.)

In addition, the site will have a customer helpline for patients if they run into any of the usual hurdles. That includes contacting the insurer to remove any access barriers or guiding the patients on how to contact the insurers themselves if needed.

How it works

Pfizer will use social media ads to find patients and funnel them to the new portal. The entry point will be whatever health problem the patient is trying to resolve, such as addressing migraine pain. That will lead to a specific landing page, which will offer a telehealth visit through a third-party vendor, UpScript, for $35 or an in-person visit with the booking portal Zocdoc.

At that point, the patient is outside of the Pfizer portal and has a visit with a clinician who can prescribe an appropriate drug. This could be a Pfizer drug — or not, Malik said.

There is no revenue sharing from the clinical visits or the prescriptions, which means that clinicians aren't getting paid or sharing in profits of the sales if they prescribe a Pfizer drug.

Patients can then get the drug mailed or pick it up at their regular pharmacy. In the case of vaccines, Pfizer will help book appointments at major retail pharmacies CVS (CVS) or Walgreens (WBA), which have more than 17,000 locations combined across the country — and more pharmacies anticipated in the future. Under respiratory care, Pfizer will also offer access to at-home tests through Instacart (CART) the same day or via two-day shipping from Amazon (AMZN).

Pfizer said that the company doesn't see this as a profit-focused business. "We're not building this as a standalone business with a revenue and a profit objective to it," Malik told Yahoo Finance. "We're not holding revenue targets to PfizerForAll." Instead, the company will measure success on how popular the site is.

The market

Eli Lilly launched its site, LillyDirect, earlier this year to help patients with diabetes, obesity, and migraines.

Lilly CEO David Ricks noted that the telehealth solution helps obesity patients the most — especially those hunting for its blockbuster drug, Zepbound. He told Yahoo Finance in January that "patients report doctor shopping" for someone who will write their prescription. That's why the site, in addition to offering telehealth, can also help find an obesity specialist by zip code.

LillyDirect is similar to PfizerForAll in that it relies on replicating the traditional pathway to get a prescription. But the clinicians are different. Whereas Pfizer is using one platform for telehealth and ZocDoc for doctor's visits, Lilly is using three different telehealth platforms.

For diabetes and obesity, Lilly is using 9amHealth, which accepts a limited number of insurance plans only in Texas and California. It is unclear if patients in other states have access. Lilly is also using FormHealth for obesity, which accepts most major insurers and Medicare. For migraine treatments, the company partnered with Cove, which accepts insurers and has a $30 copay or costs $99 for a visit without insurance.

Compare that to the $35 flat fee through Pfizer for UpScript.

In the eight months since its launch, it is unclear how well LillyDirect is doing. Lilly declined to provide Yahoo Finance with updates on traffic to the site.

In a first quarter earnings call in April, Lilly USA Diabetes and Obesity president Patrik Jonsson said that the site was "gaining traction by weeks." But in response to a question about tracking prescriptions for GLP-1 weight loss drug Zepbound, Jonsson said, "It's relatively low volume that goes through LillyDirect."

But new patients, who are filling prescriptions for the drug for the first time in their lives through the site, was slightly higher, he said. No specific numbers were provided.

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>>> Ozempic Could Have a Terrible Side Effect. Is Novo Nordisk in Trouble?


by Prosper Junior Bakiny

Motley Fool

Aug 27, 2024


https://finance.yahoo.com/news/ozempic-could-terrible-side-effect-100000193.html


The diabetes medicine Ozempic has been a veritable cash cow for Novo Nordisk (NYSE: NVO). The company's revenue, earnings, and stock price have been on a tear in recent years -- and no single drug has contributed more to its performance than Ozempic.

However, various potential headwinds have popped up that could disrupt Ozempic's progress. One of them is competition. Novo Nordisk's longtime foe in the diabetes market, Eli Lilly, developed Mounjaro, a diabetes medicine whose sales are growing incredibly fast.

Elsewhere, the side effects of Novo Nordisk's crown jewel have come under increased scrutiny, and a recent study suggests that Ozempic could have a dangerous safety issue. Let's look at what it could mean for Novo Nordisk.

Could Ozempic cause suicidal thoughts?

One of Ozempic's side effects that has generated quite a bit of attention is muscle loss. However, an even more dangerous potential drawback that some researchers have warned about is the possibility that Ozempic could increase suicidal thoughts.

A recent study claims to shed more light on this topic. The study looked at two medicines in the GLP-1 receptor agonist class, to which semaglutide, the active ingredient in Ozempic, belongs. The other GLP-1 medicine featured was liraglutide, the generic name for Victoza and Saxenda, which treat diabetes and obesity, respectively.

Liraglutide was another one of Novo Nordisk's discoveries. Through a database from the World Health Organization that tracks suspected adverse reactions from medicines and vaccines, the researchers found that Ozempic was associated with a higher rate of reported suicidal thoughts compared to other drugs. Liraglutide did not seem to be linked with higher rates of suicidal thoughts.

What should investors make of these findings? Should you sell the healthcare stock?

No reason to hit the panic button

Regulatory authorities are already aware of the potential association between Ozempic -- or at least its active ingredient, semaglutide -- and suicidal thoughts. Wegovy, an obesity medicine that shares this same active ingredient, has a warning for precisely that in the U.S.

Researchers sometimes learn even more about a therapy and its side effects after years of use in real-life settings. If studies establish a robust causal link between Ozempic or Wegovy and suicidal thoughts, that could cause regulators to take action. Perhaps they would add additional warnings or, in the worst-case scenario, take the medicine off the market. Either way, it would mean lower (or nonexistent) sales for Novo Nordisk's biggest growth driver, dragging down its revenue, earnings, and stock price.

But there's no reason to think this study will lead to that morbid scenario. Other studies have reached different conclusions. One published in Nature Medicine, one of the world's most prestigious science journals, found that semaglutide had a lower risk of producing suicidal thoughts than other non-GLP-1 anti-obesity medicines in real-life settings. This study, unlike the previous one, compared patients based on factors that can influence suicidal behavior, including sex, socioeconomic status, ethnicity, and mental health.

It would take a lot to reverse these findings. So, for now, investors can continue focusing on how Novo Nordisk is performing. And on that front, there aren't too many complaints.

Financial results continue to be strong. In the first half of the year, the company's net sales grew by 24% year over year to 133.4 billion Danish kroner ($19.8 billion). Ozempic's sales increased 36% year over year, while Wegovy's jumped 74%. Notably, Novo Nordisk continues to lead the GLP-1 market -- its share was 56% as of May, compared to 54% a year before.

Ozempic could win several label expansions, including in the exciting area of nonalcoholic steatohepatitis, where it's being investigated in a phase 3 study. Novo Nordisk has many more promising candidates. CagriSema, a next-gen GLP-1 drug, could be yet another multibillion-dollar medicine. The drugmaker is also looking to diversify, with several programs across a range of therapeutic areas.

Though various challenges to Ozempic will continue to appear, the recent study doesn't pose too much of a problem for the medicine and its maker. Novo Nordisk should continue delivering strong financial results and stock-market performance for the foreseeable future. I believe the stock is still worth buying.

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