Last update 21 Nov 2024

Cephalexin

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryCephalexin, also known as KEFLEX®, is a semisynthetic cephalosporin antibacterial drug that works by inhibiting PBPs. It was first approved in 1971 in the US by Pragma Pharmaceuticals LLC for oral administration. Cephalexin is used to treat various bacterial infections such as respiratory tract infections, otitis media, skin and skin structure infections, bone infections, and genitourinary tract infections. Its molecular formula is C16H17N3O4S•H2O with a molecular weight of 365.41. KEFLEX® capsules are intended for oral administration and contain 7-(D-α-Amino-α-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid monohydrate.

Drug Type

Small molecule drug

Synonyms

Ammonia benzyl cephalosporin, Cafalexin, Cefaiexin

+ [22]

Target

PBPs

Mechanism

PBPs inhibitors(Bacterial penicillin-binding protein inhibitors), Cell wall inhibitors

Therapeutic Areas

Infectious DiseasesHemic and Lymphatic DiseasesMouth and Tooth Diseases+ [5]

Active Indication

Acute bacterial sinusitisAcute prostatitisBacterial otitis media+ [16]

Inactive Indication

AnaphylaxisUrogenital Abnormalities

Originator Organization

Pragma Pharmaceuticals LLC

Active Organization

Aspen Pharmacare Australia Pty Ltd.

Kyowa Pharmaceutical Industry Co., Ltd.Maoxiang Group (Tianjin) Pharmaceutical Co Ltd

+ [1]

Inactive Organization

Eli Lilly & Co.

Pragma Pharmaceuticals LLC

Drug Highest PhaseApproved

First Approval Date

US (04 Jan 1971),

AnaphylaxisOtitis MediaProstatitis+ [3]

Regulation-

Structure

Molecular FormulaC16H17N3O4S

InChIKeyZAIPMKNFIOOWCQ-UEKVPHQBSA-N

CAS Registry15686-71-2

View All Structures (2)

119

Clinical Trials associated with Cephalexin

NCT04401553 / WithdrawnPhase 4IIT

First Tier Versus Second Tier Antibiotics for Surgical Site Infections Following Hysterectomy In the Patients With a Beta-Lactam Allergy: A Prospective, Randomized, Single-Blinded Clinical Trial

Postoperative surgical site infection (SSI) is associated with unnecessary use of heath care resources including prolonged hospitalization and increased hospital readmission. Perioperative antibiotic prophylaxis is one of the most important strategies for prevention of SSI. If there is a beta-lactam allergy, second tier antibiotics (vancomycin and clindamycin) are recommended alternatives to first- and second-generation cephalosporins because of fears of possible allergy.
This prospective, randomized, and single-blinded clinical trial is designed to examine causality between second tier antibiotics use and surgical site infections in the subjects with a documented unverified penicillin allergy. Unverified beta-lactam allergy could be associated with antimicrobial treatment failure with second tires antibiotics during postoperative period.

Start Date16 Aug 2024

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

NCT06406114 / Not yet recruitingPhase 2IIT

Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing

Cephalosporin antibiotics are commonly used but can result in allergic reactions and anaphylaxis. There is no clear diagnostic approach for cephalosporin-allergic patients, and guidance for the use of other antibiotics in allergic patients is based on side chain chemical similarity and limited skin testing evidence. This project includes a clinical trial and mechanistic studies to optimize the approach to cephalosporin allergy and advance future diagnostics.

Start Date01 Aug 2024

Sponsor / Collaborator

The General Hospital Corp.

[+1]

NCT06336824 / RecruitingPhase 3IIT

Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia: The EVOS Randomized Controlled Trial

The Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus aureus Bacteraemia (EVOS) study is a multicentre, randomized, open-label, parallel group, phase 3, non-inferiority trial of early intravenous to oral antibiotic switch in comparison with standard intravenous antibiotic regime among patients with uncomplicated Staphylococcus aureus bacteraemia (SAB). The study is based on the hypothesis that an early switch from IV to oral antimicrobial therapy is non-inferior and safe compared to conventional minimum 14-day course of IV therapy in patients with low-risk uncomplicated SAB.

Start Date28 Jun 2024

Sponsor / Collaborator-

100 Clinical Results associated with Cephalexin

100 Translational Medicine associated with Cephalexin

100 Patents (Medical) associated with Cephalexin

3,433

Literatures (Medical) associated with Cephalexin

01 Dec 2024·Applied Microbiology and Biotechnology

Impact of Bacillus licheniformis from yaks following antibiotic therapy in mouse model

Article

Author: Quan, Chuxian ; Gong, Saisai ; Iqbal, Mudassar ; Kulyar, Muhammad Fakhar-E-Alam ; Li, Xiang ; Li, Jiakui ; Zeng, Zhibo ; Zhou, Shimeng ; Li, Yan

Gut microorganism (GM) is an integral component of the host microbiome and health system. Abuse of antibiotics disrupts the equilibrium of the microbiome, affecting environmental pathogens and host-associated bacteria alike. However, relatively little research on Bacillus licheniformis alleviates the adverse effects of antibiotics. To test the effect of B. licheniformis as a probiotic supplement against the effects of antibiotics, cefalexin was applied, and the recovery from cefalexin-induced jejunal community disorder and intestinal barrier damage was investigated by pathology, real-time PCR (RT-PCR), and high-throughput sequencing (HTS). The result showed that A group (antibiotic treatment) significantly reduced body weight and decreased the length of jejunal intestinal villi and the villi to crypt (V/C) value, which also caused structural damage to the jejunal mucosa. Meanwhile, antibiotic treatment suppressed the mRNA expression of tight junction proteins ZO-1, claudin, occludin, and Ki67 and elevated MUC2 expression more than the other Groups (P < 0.05 and P < 0.01). However, T group (B. licheniformis supplements after antibiotic treatment) restored the expression of the above genes, and there was no statistically significant difference compared to the control group (P > 0.05). Moreover, the antibiotic treatment increased the relative abundance of 4 bacterial phyla affiliated with 16 bacterial genera in the jejunum community, including the dominant Firmicutes, Proteobacteria, and Cyanobacteria in the jejunum. B. licheniformis supplements after antibiotic treatment reduced the relative abundance of Bacteroidetes and Proteobacteria and increased the relative abundance of Firmicutes, Epsilonbacteraeota, Lactobacillus, and Candidatus Stoquefichus. This study uses mimic real-world exposure scenarios by considering the concentration and duration of exposure relevant to environmental antibiotic contamination levels. We described the post-antibiotic treatment with B. licheniformis could restore intestinal microbiome disorders and repair the intestinal barrier. KEY POINTS: • B. licheniformis post-antibiotics restore gut balance, repair barrier, and aid health • Antibiotics harm the gut barrier, alter structure, and raise disease risk • Long-term antibiotics affect the gut and increase disease susceptibility.

01 Dec 2024·Bioorganic Chemistry

Sustainable synthesis of ZnO and FexOy nanoparticles and their nanocomposite ZnFe2O4: Comprehensive characterization and applications in antioxidant activity and antibiotics degradation efficiency

Article

Author: Salmi, Chaima ; Abdullah, Johar Amin Ahmed ; Ali Mohammed, Hamdi ; Romero, Alberto ; Eddine Laouini, Salah ; Guerrero, Antonio ; Alqarni, Zarah

This study focuses on developing and evaluating eco-friendly nanoparticles, specifically Fe_xO_y NPs, ZnO NPs, and a ZnFe₂O₄ nanocomposite (NC), for potential applications in environmental remediation and biomedicine. The nanoparticles were synthesized and characterized using X-ray diffraction (XRD), which revealed their crystalline structures with sizes of 20.3 nm for Fe_xO_y NPs, 22.1 nm for ZnO NPs, and 10.9 nm for ZnFe₂O₄ NC. Fourier-transform infrared (FTIR) spectroscopy identified functional groups, while UV-visible spectroscopy determined band gap energies of 2.35 eV, 3.38 eV, and 2.68 eV for Fe_xO_y NPs, ZnO NPs, and ZnFe₂O₄ NC, respectively. Morphological analysis via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that Fe_xO_y NPs have cubic, hexagonal, and tetragonal forms, ZnO NPs are hexagonal nanorods, and ZnFe₂O₄ NC has a hexagonal-faced cubic structure. Antioxidant activity, assessed through the DPPH assay, revealed that ZnFe₂O₄ NC had the highest potency. Additionally, under sunlight irradiation, ZnFe₂O₄ NC demonstrated superior degradation of the antibiotic cephalexin (96 % within 30 min) compared to Fe_xO_y NPs (58.2 %) and ZnO NPs (52 %), with respective kinetic rate constants of 0.109 min^-1, 0.029 min^-1, and 0.025 min^-1. These results highlight the nanoparticles' potential for environmental and biomedical applications.

01 Dec 2024·Journal of Hazardous Materials

Polyelectrolyte fabricated nanofiltration membrane with heterogeneously charged channels for high efficient cephalexin wastewater treatment

Article

Author: Jiang, Xiaobin ; Zhen, Huange ; Li, Xiangcun ; Jia, Yuandong ; Wu, Xuemei ; He, Gaohong ; Li, Zhonghua ; Li, Tiantian ; Xiao, Wu

Nanofiltration (NF) for treatments of pharmaceutical wastewater is a promising direction for water protection and resources recovery. Herein, a novel membrane with heterogeneously charged channels was constructed by modified layer-by-layer assembly methods. Within the well-designed pores, the polyanion structure excludes the cephalexin and the cationic structure slows down its diffusion, thereby rejections for cephalexin are improved. The hydrophilic property of polyelectrolytes simultaneously guarantees the water transport. Fabricated heterogeneously charged channels are shown to strengthen the electrostatic barrier and prevent monovalent cephalexin anions penetration. Optimized nanofiltration membrane exhibits rejections of 98.9 % for 3650 ppm cephalexin, maintaining steady rejection during 69 h of continuous operations. The flux recovers to 99.3 % of the original flux after water washing. Benefiting from the separation performance of fabricated membranes, multi-stage NF processes effectively enrich the cephalexin wastewater. This work offers significant prospects for achieving high-efficiency pharmaceutical wastewater treatment and amphoteric drug recovery.

News (Medical) associated with Cephalexin

23 Feb 2024

·www.businesswire.com

Venatorx and Melinta Provide Update on Status of U.S. New Drug Application for Cefepime-Taniborbactam

MALVERN, Pa. & PARSIPPANY, N.J.--( BUSINESS WIRE )--Venatorx Pharmaceuticals (Venatorx) and Melinta Therapeutics (Melinta) announced today that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for cefepime-taniborbactam, a beta-lactam/beta-lactamase inhibitor (BL/BLI) combination antibiotic under review as a potential treatment for adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis caused by susceptible gram-negative microorganisms. The CRL did not identify clinical safety or efficacy issues in the NDA, and the FDA did not request any new clinical trials to support the approval of cefepime-taniborbactam. The FDA requested additional chemistry, manufacturing, and controls (CMC) and related data about the drug, testing methods, and manufacturing process. “While we are disappointed with this setback, we maintain utmost confidence in cefepime-taniborbactam. We are already hard at work generating the additional requested CMC data, and we will continue to work closely with the FDA so that we can make this important new medicine available to patients as quickly as possible,” said Christopher J. Burns, Ph.D., Chief Executive Officer of Venatorx. Melinta Chief Executive Officer and President, Christine Ann Miller added, “We are committed to our plans of supporting the US commercialization of this drug, which we believe when approved, will offer healthcare providers an important therapy for adult patients suffering from complicated urinary tract infections including acute pyelonephritis caused by susceptible gram-negative microorganisms.” About Cefepime-Taniborbactam Cefepime-taniborbactam is an investigational intravenous (IV) beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotic combination being developed for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Cefepime, a fourth-generation cephalosporin, is a widely used beta-lactam (BL) antibiotic with more than two decades of proven safety and clinical utility against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a beta-lactamase inhibitor (BLI) that, in combination with cefepime, is being studied as a potential treatment option for patients with serious bacterial infections caused by antibiotic resistant gram-negative bacteria, most notably Extended Spectrum Beta-lactamase (ESBL)-expressing Enterobacterales, carbapenem-resistant Enterobacterales (CRE), and multidrug-resistant (MDR) Pseudomonas aeruginosa (MDR-PA), which can include carbapenem-resistant P. aeruginosa (CRPA). Cefepime-taniborbactam has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA). Fast Track designation is designed to facilitate the development, and to expedite the review of drugs to treat serious conditions that do not have sufficient treatment options. QIDP designation provides certain incentives for the development of new antibiotics, including priority review, as well as a five-year regulatory exclusivity extension. QIDP was authorized under the Generating Antibiotic Incentives Now (GAIN) Act of 2012, as part of the FDA Safety and Innovation Act, to underscore the urgency in development of new antibiotics. About Gram-Negative Infections and Antimicrobial Resistance (AMR) In a recent report on AMR, the U.S. Centers for Disease Control and Prevention (CDC) reported rates of resistance have increased significantly in the U.S. among bacterial pathogens including those commonly causing cUTI, pyelonephritis, and bacteremia. The CDC also cited that there are more than 2.8 million AMR infections annually in the U.S., which are directly related to more than 35,000 deaths. [1] Between 2014 and 2019, an analysis of U.S. UTI patients determined that 4.4% of cases were carbapenem resistant (CR) and 24.5% of U.S. UTI patients were bacteremic with 1.7% of cases caused by a CR pathogen. Patients with CR infections had a significantly longer hospital length of stay (LOS), were less likely to be discharged home, had a higher readmission rate, and had greater LOS-associated charges than patients with carbapenem-susceptible infections. Additionally, patients with bacteremia (urosepsis) due to CR pathogens had a significantly higher rate of mortality than those with carbapenem susceptible pathogens. [2] Gram-negative bacteria have multiple AMR mechanisms that continue to adapt in response to increases in antibiotic usage. Carbapenems are broad-spectrum antibiotics that have been widely used to treat infections caused by multidrug-resistant gram-negative bacteria, including Enterobacterales. With the increased global use of carbapenems, CRE have emerged, which have limited treatment options and are associated with increased morbidity and mortality. Resistance to carbapenems among Enterobacterales is primarily achieved by production of carbapenemases, which are enzymes capable of hydrolyzing carbapenem antibiotics and most other beta-lactams and fall into two distinct families: serine beta-lactamases and metallo-beta-lactamases (MBLs). K lebsiella pneumoniae carbapenemase (KPC), a class-A serine beta-lactamase, is one of the most prevalent carbapenemases, and New Delhi MBL (NDM) and Verona Integron-encoded MBL (VIM) are common variants of MBLs identified in gram-negative infections due to Enterobacterales and P. aeruginosa. According to an IHMA surveillance study in 2018-2019 and a JMI U.S. Surveillance study from 2021, MBLs were the most commonly identified carbapenem resistance mechanism globally among Enterobacterales isolates, with ~16 to 18% of U.S. CRE isolates carrying MBLs. [3,4] While CRPA is also increasing in some geographies due to emergence of MBLs, MDR-PA, which may exhibit resistance to carbapenems, represents an increasing challenge for clinicians and their patients in the U.S. and globally due to the paucity of treatment options for this primarily hospital-associated pathogen. Especially outside the U.S., CRPA may carry carbapenemases including MBLs (i.e., VIM); however, non-carbapenemase resistance mechanisms (i.e., efflux pumps, porins) also contribute to the growing global resistance of MDR-PA and CRPA. [5] If AMR infections continue on this trajectory, it has been projected that an estimated 10 million people will die per year of resistant infections by 2050—a number that surpasses the projected annual number of deaths (8.2 million) caused by cancer—and the cumulative cost to the global economy could be as high as U.S. $100 trillion. [6] In the U.S., estimates have reached as high as U.S. $20 billion in excess direct healthcare costs, with an additional U.S. $35 billion associated with lost productivity. [7] By 2050, the world is at risk of losing up to 3.8% of its annual gross domestic product with an annual shortfall of up to U.S. $3.4 trillion by 2030, a figure on par with losses attributable to the 2008 global financial crisis. [8] The Infectious Disease Society of America (IDSA) maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections online at https://www.idsociety.org/practice-guideline/amr-guidance/ . [9] For those patients who do not respond to current treatment, new antibiotic therapies are needed to combat AMR. About Complicated Urinary Tract Infections Complicated UTIs, which include pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms, including fever, chills, malaise, flank pain, back pain, and/or costovertebral angle pain or tenderness, that usually occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization. Bacteremia can arise secondary to infections like cUTI and can result in substantial morbidity and mortality. [1] Annually in U.S., it is estimated that more than 3 million cUTI patients will be diagnosed and require antibiotic therapy leading to over $6 billion in annualized 30-day costs. [10] About Venatorx Pharmaceuticals Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Cefepime-taniborbactam is currently under review by the FDA for the treatment of cUTI, including acute pyelonephritis. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial. For more information about Venatorx and its anti-infectives portfolio, please visit www.venatorx.com . About Melinta Therapeutics LLC Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA ® (delafloxacin), KIMYRSA ® (oritavancin), MINOCIN ® (minocycline) for Injection, ORBACTIV ® (oritavancin), REZZAYO ® (rezafungin for injection), TOPROL-XL ® (metoprolol succinate) and VABOMERE ® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit www.melinta.com . Funding Partners and Collaborators for Cefepime-Taniborbactam This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272201300019C, and Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and has continued with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract numbers HHSO100201900007C and 75A50122C00080. In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in Greater China, South Korea, and select countries in Southeast Asia. Everest will be solely responsible for the commercialization of cefepime-taniborbactam in its territory and Venatorx will be eligible to receive royalties on net sales. In April 2020, Venatorx and the GARDP Foundation (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower-middle-income countries. In November 2023, Venatorx and Melinta entered into an exclusive License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. In December 2023, Venatorx entered into an agreement with Menarini Group, who acquired the exclusive rights to commercialize, upon approval of relevant health authorities, cefepime-taniborbactam in 96 countries in Europe, Latin America, Middle East, Turkey and North Africa and the Commonwealth of Independent States (CIS). References [1] Antibiotic Resistance Threats in the United States 2019, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [2] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infectious Diseases (2021) 21:572. [3] Estabrook et al. Epidemiology of Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Study, 2018 to 2019. Antimicrobial Agents and Chemotherapy; May 2023, Vol. 67, Issue 5 [4] Castanheira et al. Increase in the Occurrence of Carbapenem-Resistant Enterobacterales in United States Hospitals from 2019 to 2021 and Activity of Novel Beta-Lactams/Beta-Lactamase Inhibitor Combinations Against these Isolates, 2022 ID Week Abstract #664. Open Forum Infectious Diseases, Volume 9, Issue Supplement_2, December 2022, ofac492.716 [5] Jean S-S, Harnod D and Hsueh P-R (2022) Global Threat of Carbapenem Resistant Gram-Negative Bacteria. Front. Cell. Infect.Microbiol.12:823684. doi:10.3389/fcimb.2022.823684[6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. [6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. [7] Antibiotic Resistance Threats in the United States 2013, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [8] World Bank. Final Report Drug Resistant Infections: A Threat to Our Economic Future. Mar 2017. [9] Infectious Disease Society of America maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections posted online at https://www.idsociety.org/practice-guideline/amr-guidance/ accessed July 2023 [10] Carreno et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infectious Diseases. 8 October 2019

Phase 3License out/inFast TrackQualified Infectious Disease ProductNDA

16 Jan 2024

·www.prnewswire.com

NRx Pharmaceuticals, Inc. (Nasdaq: NRXP) Announces FDA Qualified Infectious Disease Product (QIDP) and Fast Track Designation of NRX-101 in Complicated Urinary Tract Infection and Pyelonephritis

NRX-101 has demonstrated potent activity against resistant urinary pathogens upon FDA review QIDP designation grants Priority Review and an additional 5 years of additional product exclusivity 3 million Americans develop complicated Urinary Tract Infection (cUTI) each year at a cost that ranges from $4497 to $17,431 with a high rate of antibiotic resistance and need for inpatient hospitalization1 Unlike many advanced-generation antibiotics, NRX-101 is not contra-indicated in sulfa and penicillin allergic patients and is not believed to disrupt the normal intestinal microbiome, potentially leading to reduced risk of C. difficile infection Data have been accepted for posting on biorxiv and are under review at a peer-reviewed journal3 RADNOR, Pa., Jan. 16, 2024 /PRNewswire/ -- NRx Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals", the "Company"), a clinical-stage biopharmaceutical company, today announced that it has received Qualified Infectious Disease Product (QIDP) and Fast Track designation from the US FDA for NRX-101 in the treatment of complicated urinary tract infections (cUTI) and pyelonephritis. Receipt of QIDP designation confers Priority Review, and critically, five additional years of data-exclusivity to NRX-101's already strong Intellectual Property position. The FDA also granted NRX-101 Fast Track designation for cUTI, which additionally allows for rolling submission of the Company's New Drug Application. In addition to the marketplace protections conferred by QIDP designation in the US, NRx has composition of matter patent protection on NRX-101 through at least 2033 in all major global markets. The data that formed the basis of FDA's QIDP approval have been submitted for publication. On the basis of this advance, NRx is seeking partners with active involvement in urology, infectious disease and/or women's health for commercialization of NRX-101. The active antibiotic ingredient of NRX-101 is D-cycloserine (DCS) that was developed as an antibiotic in the 1950's and used worldwide for the treatment of tuberculosis. However, it fell out of favor with the development of trimethoprim/sulfa and various penicillins, cephalosporins, and tetracyclines, in part because of the CNS effects associated with DCS-induced blockade of the brain's NMDA receptor. In the course of its CNS research, NRx pharmaceuticals has demonstrated that small doses of lurasidone counteract those CNS effects, potentially providing a new therapeutic life to DCS as an antibiotic. Over the ensuing decades, increased antibiotic resistance has rendered standard treatments for UTI ineffective in many cases and today 3 million Americans suffer from cUTI requiring increasingly toxic antibiotics, increasingly frequent intravenous therapy, and increased need for hospital admission.1 Because DCS has the unique property of being highly concentrated, unmetabolized, in the urine with oral administration, the Company believes, and previous literature has suggested that DCS may effectively treat, and therefore help prevent, the need for intravenous and inpatient treatment of cUTI. Moreover, because DCS is rapidly absorbed and excreted in the urine, the Company is optimistic that NRX-101 will have a minimal tendency to disrupt the microbiome of the intestine and which can lead to secondary Clostridium difficile infection. C. diff associated colitis doubles hospital mortality and costs the American healthcare system up to $1.6 billion each year.2 Additionally, DCS has no known association with C. diff or with pulmonary fibrosis, a rare, lethal condition that has been associated with macrolide (tetracycline family) antibiotics. "When we embarked on the development of NRX-101 for treating bipolar depression, we did not imagine that it would develop a new utility as a potentially lifesaving antibiotic. However, the antibiotics we have relied upon for decades are increasingly failing to control resistant pathogens and those that are able to do so are increasingly toxic. NRx thanks the US FDA for its rapid award of QIDP designation for cUTI and pyelonephritis. These conditions impact 3 million Americans annually and can carry significant co-morbidities, including sepsis and death," said Dr. Jonathan Javitt, Founder, Chairman and Chief Scientist of NRx Pharmaceuticals." Whereas the 12 million Americans who contract uncomplicated UTI each year can expect rapid relief from well-known antibiotics, those who contract cUTI frequently require intravenous therapy, and hospitalization, with frequent serious side effects" Dr. Michael Manyak, noted Professor of Urology and former Global Thought Leader for Glaxo SmithKline's urology business added "As a Urologist, I am excited about the potential availability of NRX-101 for patients suffering from cUTI; this is a very serious condition in desperate need of new treatment options. Receipt of QIDP and Fast Track should make NRX-101 even more attractive to potential partners in this multi-billion-dollar market." Dr. Manyak serves as NRx's Medical Thought Leader for urology. The data presented to the FDA have now been accepted for posting on the biorxiv pre-print server and are under review by a peer-reviewed journal.3 About NRx Pharmaceuticals NRx Pharmaceuticals is a clinical-stage biopharmaceutical company developing therapeutics based on its NMDA platform for the treatment of central nervous system disorders, specifically suicidal bipolar depression, chronic pain and PTSD. The Company is developing NRX-101, an FDA-designated investigational Breakthrough Therapy for suicidal treatment-resistant bipolar depression and chronic pain. NRx has partnered with Alvogen Pharmaceuticals around the development and marketing of NRX-101 for the treatment of suicidal bipolar depression. NRX-101 additionally has potential to act as a non-opioid treatment for chronic pain, as well as a treatment for complicated UTI. NRx has recently announced plans to submit a New Drug Application for ketamine in the treatment of suicidal depression, based on results of well-controlled clinical trials conducted under the auspices of the US National Institutes of Health and newly obtained data from French health authorities, licensed under a data sharing agreement. NRx was awarded Fast Track Designation for development of ketamine (NRX-100) by the US FDA as part of a protocol to treat patients with acute suicidality. Cautionary Note Regarding Forward-Looking Statements This announcement of NRx Pharmaceuticals, Inc. includes "forward-looking statements" within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995, which may include, but are not limited to, statements regarding our financial outlook, product development, business prospects, and market and industry trends and conditions, as well as the Company's strategies, plans, objectives, and goals. These forward-looking statements are based on current beliefs, expectations, estimates, forecasts, and projections of, as well as assumptions made by, and information currently available to, the Company's management. The Company assumes no obligation to revise any forward-looking statement, whether as a result of new information, future events or otherwise. Accordingly, you should not place reliance on any forward-looking statement, and all forward-looking statements are herein qualified by reference to the cautionary statements set forth above. 1 Lodise TP, et. al. Open Forum Infectious Diseases 2 Drozd EM, et. al. Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection DOI: 10.1097/IPC.0000000000000299 3 SOURCE NRx Pharmaceuticals

10 Oct 2023

·www.biospace.com

Venatorx Pharmaceuticals Awarded a Third Antibiotic BARDA Contract

Total award of up to $167 million for development of novel oral antibiotic ceftibuten-ledaborbactam etzadroxil for treatment of complicated urinary tract infection (cUTI), including pyelonephritis MALVERN, Pa.--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections, today announced the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), has awarded the company a contract to support the development of oral ceftibuten-ledaborbactam etzadroxil for the treatment of complicated urinary tract infection (cUTI), including pyelonephritis. Venatorx has recently completed multiple Phase 1 clinical studies with ceftibuten-ledaborbactam etzadroxil and will advance directly to global Phase 3 clinical trial testing under this contract. The contract will provide funding and technical support for the development activities required for submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing authorization of ceftibuten-ledaborbactam etzadroxil for the treatment of cUTI, including pyelonephritis. The contract will also cover a pediatric program as a post-marketing commitment. “We thank BARDA, ASPR, and HHS for their dedication to scientific innovation and commitment to this private-public partnership. This contract supports Venatorx’s mission to address the devastating impact on patient lives from the growing number of bacterial infections in the U.S. and the urgent need for oral antibiotics to combat drug-resistant gram-negative pathogens,” said Christopher J. Burns, Ph.D., President and CEO of Venatorx. “Currently, there are no approved oral antibiotics that are effective in the treatment of drug-resistant gram-negative bacterial infections to help address increasing drug-resistant bacterial infections globally. We believe that oral ceftibuten-ledaborbactam etzadroxil could play an important role in treating drug-resistant gram-negative infections, preventing unnecessary hospitalizations, and saving lives.” Terms of the Award BARDA will provide a firm initial commitment of up to $20.3 million with options to provide up to a total of $167 million over six years. BARDA and Venatorx will share the costs of all studies needed to bring the drug to market, including a planned pivotal global Phase 3 clinical trial to treat cUTI. Venatorx will lead all regulatory activities necessary to seek FDA approval of ceftibuten-ledaborbactam etzadroxil under the contract. This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50123C00050. About Complicated Urinary Tract Infections (cUTI) and Antimicrobial Resistance (AMR) Complicated UTIs, which include pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms and are one of the most common bacterial infections in hospital and community settings. Bacteremia can arise secondary to infections like cUTI and can result in substantial morbidity and mortality.[1] Annually in the U.S., it is estimated that more than 2.8 million cUTI patients will be diagnosed and require antibiotic therapy leading to over $6 billion in annualized 30-day costs.[2] Between 1998 and 2011, incidence of US UTI hospitalizations increased 52%, while severity of UTI admissions decreased, indicating that patients previously treated with oral agents as outpatients in the community may now be admitted to the hospital due to increasing antimicrobial resistance to oral agents.[3] In a study of US patients hospitalized with an infection between 2012 and 2017, 83% of infections in the hospital cohort originated in the community with 32% of those infections caused by bacterial pathogens carrying extended spectrum beta-lactamases (ESBLs). During that time, the incidence of ESBL-associated infections increased by ~53%, a change that investigators believed was driven by an increase in community-onset cases.[4] Treatment of cUTIs in the community has been compromised by increasing drug resistance to commonly used oral antibiotics such as fluoroquinolones, cephalosporins and trimethoprim-sulfamethoxazole.[5] In a study tracking resistance of E. coli isolates from US UTI patients in 2017, high co-resistance among oral antibiotics was observed suggesting diminishing utility of currently available oral antibiotics due to increasing antimicrobial resistance.[6] Currently, there are no approved oral beta-lactam or beta-lactam/beta-lactamase inhibitor combinations that are effective against Enterobacterales expressing Ambler class A ESBLs, class C cephalosporinases, and class A& D serine carbapenemases (KPC and OXA-48). About Ceftibuten-Ledaborbactam etzadroxil Ceftibuten, an oral third-generation, highly bioavailable cephalosporin antibiotic, is approved in the US for the treatment of upper and lower respiratory tract infections and for urinary tract infections outside the US. Ledaborbactam etzadroxil is a novel broad-spectrum boronic acid beta-lactamase inhibitor (BLI). In vitro and in vivo studies demonstrated that ledaborbactam restores the activity of ceftibuten against strains of Enterobacterales expressing Ambler class A ESBLs, class C cephalosporinases, and class A & D serine carbapenemases (KPC and OXA-48, respectively) as well as multidrug-resistant (MDR) Enterobacterales. Ceftibuten-ledaborbactam etzadroxil may offer a new treatment option for outpatient therapy to treat serious bacterial infections caused by MDR Enterobacterales that are resistant to current standard-of-care oral and intravenous antibiotics, including fluoroquinolones, trimethoprim-sulfamethoxazole, cephalosporins and carbapenems. Ceftibuten-ledaborbactam etzadroxil has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA) for cUTI and uncomplicated urinary tract infections. Venatorx has recently completed multiple Phase 1 clinical studies with ceftibuten-ledaborbactam etzadroxil and will advance directly to global Phase 3 clinical trial testing under this new BARDA contract. Funding Partners and Collaborators for Ceftibuten-Ledaborbactam etzadroxil This project has also been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201600029C. About Venatorx Pharmaceuticals, Inc. Venatorx is a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections. Venatorx’s lead asset, cefepime-taniborbactam, is an investigational antibiotic that completed a Phase 3 study (NCT03840148) in adults with complicated urinary tract infections (cUTI), including pyelonephritis and an NDA is under FDA review with a PDUFA action date of February 22, 2024. In October 2022, BARDA awarded a contract of up to $318 million to Venatorx for development and procurement of cefepime-taniborbactam for the treatment of melioidosis. As part of its broader pipeline, Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam etzadroxil, that will advance directly to a global Phase 3 cUTI clinical trial under its BARDA contract. For more information about Venatorx and its anti-infectives portfolio, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical development of Venatorx Pharmaceuticals’ product candidates. References [1] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infect Dis (2021) 21:572. [2] Carreno et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect Dis. 8 October 2019 [3] Simmering, J.E., et al. The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998-2011 Open Forum Infect Dis. 2017 Feb 24;4(1):ofw281. [4] Jernigan et al. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012–2017 N Engl J Med 2020;382:1309-19. [5] Zilberberg MD et al. Antimicrobial susceptibility and cross-resistance patterns among common complicated urinary tract infections in U.S. hospitals, 2013 to 2019. Antimicrob Agents Chemother 2020;64(8):e00346-20 [6] Critchley, I.A., et al. (2019) The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS One 14(12): e0220265 (2019).

Phase 3Phase 1Fast TrackQualified Infectious Disease ProductDrug Approval

100 Deals associated with Cephalexin

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KEGG	Wiki	ATC	Drug Bank
D00906	Cephalexin	J01DB01	DB00567

R&D Status

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Indication	Country/Location	Organization	Date
Acute bacterial sinusitis	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Acute prostatitis	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Bacterial otitis media	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Beta-hemolytic Streptococcus infection	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Complicated skin and soft tissue infection	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Pneumococcal Infections	AU	Aspen Pharmacare Australia Pty Ltd.	24 Feb 2004
Bacterial Infections	CN	Maoxiang Group (Tianjin) Pharmaceutical Co Ltd	01 Jan 1981
Acute Bronchitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Cystitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Lymphadenitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Otitis Externa	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Pharyngolaryngitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Pneumonia	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Pyoderma	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Secondary infection	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Sinusitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Skin and skin structure infections	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Tonsillitis	JP	Kyowa Pharmaceutical Industry Co., Ltd.	01 Aug 1978
Inflammation	JP	FUJIFILM Toyama Chemical Co., Ltd.	04 Apr 1972

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAAAI2024	Not Applicable	Anaphylaxis	-	Cefazolin	ixftlcjlkw(isutvikfsp) = ljcmwsewqz shryjibdlq (kmfwikuapg )	-	23 Feb 2024
				Cefoxitin	ixftlcjlkw(isutvikfsp) = erxpamvipe shryjibdlq (kmfwikuapg )
NCT02579161 (CTgov)	Phase 3	Kidney Calculi	98	Fluoroquinolones+cephalosporins+Gentamicin+Ampicillin+Clindamycin (Antibiotics for a 24 Hour Period)	(fgmmegzcuc) = gjdhcmzoso fkwgabqlwd (vsrdsprofl, ycuzjrqonj - wjjpkfxsgr) View more	-	14 Mar 2023
				Fluoroquinolones+cephalosporins+Gentamicin+Ampicillin+Clindamycin (Continued Antibiotics)	(fgmmegzcuc) = litpsknywm fkwgabqlwd (vsrdsprofl, arrnuvdzus - sddoseohmd) View more
AAAAI2023	Not Applicable	Allergy to penicillin	-	Cephalosporins	funxijijku(ruuzmvkvoy) = dmixipwdet ruroxmeiok (zcgystfder )	-	01 Feb 2023
AAAAI2023	Not Applicable	Anaphylaxis	220	Cephalosporins	xxvbmgtyef(zinqwosbbk) = wkuexmwaoe lpqhwteakt (isxxujxked ) View more	-	01 Feb 2023
NCT04471246 (Pubmed)	Phase 4	Cellulitis	69	High-dose cephalexin (1000 mg)	smmnnyjgef(nyjueuumec) = nizprftizv mxfdledxzs (oitylfdswy, 43.1 - 59.8)	-	02 Jan 2023
IRCT20200608047685N2 (Pubmed)	Phase 3	Obesity	-	Oral cephalexin and metronidazole	(hwedtxgpfj) = jsqzzwbrgg ahkuoeblpq (wsfjajnojn ) View more	Positive	05 Dec 2022
				Cephalexin and placebo	(hwedtxgpfj) = tahqtdmfiq ahkuoeblpq (wsfjajnojn ) View more
NCT01595529 (SCOUT, CTgov)	Phase 2	Urinary Tract Infections	717	Cephalexin+Trimethoprim-sulfamethoxazole (TMP-SMX)+Sulfamethoxazole+Trimethoprim+Cefdinir+Cefixime (Standard Course Treatment)	njmnqzwiqi(lccxxpcngt) = hbtfcinijz swmusdvirp (zhlrcfqnud, njytafdezo - cqkuijgyps) View more	-	13 Jul 2020
				placebo (Short Course Treatment)	njmnqzwiqi(lccxxpcngt) = bcyvpwrdji swmusdvirp (zhlrcfqnud, epxvxurgjm - dqfoloczpa) View more
P0300 (ERA2020)	Not Applicable	PMRG-producing bacteria \| extended spectrum beta-lactamases producers (ESBLs) \| PMQR	105	Cephalosporins	(humnleqgyk) = vbwwwqxhcm hnljvjliyu (dukzxxswao, 0.495%CI[0 - 21;0 to 75]) View more	Negative	06 Jun 2020
				Fluoroquinolones	(humnleqgyk) = covjqyizwx hnljvjliyu (dukzxxswao, 0.495%CI[0 - 21;0 to 75]) View more
NCT00957827 (CTgov)	Not Applicable	Lacerations	4	keflex (Keflex)	xyheshrbxn(jacmptweev) = ordquqjjla nplbkgtepm (ejeurovwtr, cvjzdfdujx - vrvsxilwpn) View more	-	16 Apr 2019
				placebo (Placebo)	xyheshrbxn(jacmptweev) = ryztztpddk nplbkgtepm (ejeurovwtr, cdtppkzrqt - zrunbxnbcn) View more
NCT01029782 (CTgov)	Phase 2	Cellulitis	206	cephalexin+cefazolin+probenecid (IV Cefazolin Plus Oral Probenecid and Placebo Cephalexin)	tebobktrqj(lveymnuavf) = migkgbltxr vejaxrzkrr (uckmudqoqf, ftirvjwvbf - agrtdytvbi) View more	-	13 Aug 2018
				Oral cephalexin (Oral Cephalexin and Saline IV Plus Probenecid Placebo)	tebobktrqj(lveymnuavf) = rnslqmpvdl vejaxrzkrr (uckmudqoqf, rucguixxdd - ghqomfvnmc) View more

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