taniborbactam (VNRX-5133) / VenatoRx - LARVOL DELTA

Phenotypic and biochemical characterization of the class C β-lactamase, PAC-1. (PubMed, J Antimicrob Chemother) - "PAC-1 is not inhibited by avibactam and hydrolyses a broad range of β-lactams including the novel cephalosporin cefiderocol. The combination cefiderocol/zidebactam was the most active against PAC-1. Transposon-mediated dissemination across distinct lineages warrants continued epidemiological surveillance of PAC-type β-lactamases."

Journal

Boronic Acid Inhibitors of β-Lactamases: A Promising Strategy Against Antimicrobial Resistance. (PubMed, Med Res Rev) - "Clinically approved agents such as vaborbactam, as well as investigational compounds including taniborbactam, xeruborbactam, and benzoxaboroles, are discussed in the context of their therapeutic relevance and spectrum of activity. Additionally, the review explores innovative approaches such as kinetic target-guided synthesis and fragment-based design to expand the chemical space of boronic acid pharmacophores. Together, these advances underscore the potential of boronic acid-based BLIs as powerful tools in overcoming β-lactamase-mediated resistance and developing next-generation antimicrobial therapies."

Journal • Review

Boron-Containing Drug Candidates in Clinical Trials. (PubMed, Handb Exp Pharmacol) - "The agents reviewed include borofalan, delanzomib, flovagatran, dutogliptin, talabostat, numidargistat, OATD-02, AN0128, epetraborole, ganfeborole, acoziborole, taniborbactam, xeruborbactam, and sodium borocaptate, as well as the five FDA-approved boroncontaining drugs (bortezomib, ixazomib, crisaborole, tavaborole, vaborbactam). The review also highlights how clinical success depends on matching pharmacology with unmet need, feasible administration, competitive differentiation, and durable development partnerships. Ongoing advances in scaffold design, delivery, combination therapy, and indication selection are expected to broaden the therapeutic impact of boron-containing medicines."

Journal • Cardiovascular • Head and Neck Cancer • Hematological Disorders • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombosis • Tuberculosis

A Review of β-Lactamase Inhibitors in Clinical Use and Development: Mechanisms, Spectrum, and Therapeutic Applications. (PubMed, Int J Microbiol) - "As the efficacy of conventional treatments diminishes, reliance on last-resort agents like carbapenems and colistin has increased, in turn accelerating resistance to these precious final-line options...A paramount, ongoing challenge remains the development of effective inhibitors against metallo-β-lactamases (MBLs), though promising candidates like taniborbactam and xeruborbactam are now in clinical development. This review synthesizes the current knowledge on these innovative inhibitors, from recently approved combinations like ceftazidime/avibactam and cefepime/enmetazobactam to those in advanced clinical trials, and critically examines the associated therapeutic challenges, including the emergence of resistance. By integrating mechanistic insights with clinical perspectives, this article is aimed at informing the ongoing battle against antimicrobial resistance and guiding the future development of life-saving therapeutic strategies."

Journal • Review • Infectious Disease

Overview of novel cefepime-based β-Lactam/β-lactamase inhibitor combinations. (PubMed, Expert Rev Anti Infect Ther) - "This review summarizes approved and investigational cefepime-based BL/BLI combinations, including cefepime/enmetazobactam (FEP/EMT), cefepime/taniborbactam (FTB), cefepime/zidebactam (FPZ), and cefepime/nacubactam (FEP/NAC)...FPZ combines β-lactamase inhibition and β-lactam - enhancer activity, retaining activity against XDR Enterobacterales and P. aeruginosa, including cefiderocol- or aztreonam/avibactam (ATM/AVI)-resistant strains. FEP/NAC shows promise against carbapenem- and MBL-producing strains, though clinical data remain limited. Optimal use relies on rapid molecular diagnostics, susceptibility testing, and antimicrobial stewardship to maximize efficacy and limit the emergence of resistance."

Journal • Review • Infectious Disease

Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms. (PubMed, Antibiotics (Basel)) - "Cefepime combined with late-generation β-lactamase inhibitors-enmetazobactam, zidebactam, and taniborbactam-represents a promising strategy to treat multidrug-resistant Gram-negative infections...It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens."

Journal • PK/PD data • Preclinical • Review • Infectious Disease • Nephrology

New-generation antibiotics and non-antibiotic strategies against carbapenemase-producing Enterobacterales: More focus on metallo-β-lactamase producers. (PubMed, Int J Antimicrob Agents) - "Continued monitoring of resistance trends and the development of innovative therapeutic strategies is warranted in the ongoing battle against CPE harboring blaMBL."

Journal • Review • Infectious Disease

Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics. (PubMed, Pharmaceuticals (Basel)) - "This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance."

Journal • PK/PD data • Review • Infectious Disease

Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase-producing Gram-negative bacteria in a neutropenic murine thigh infection model. (PubMed, J Antimicrob Chemother) - "Taniborbactam restored cefepime's activity against resistant Gram-negative bacteria in a time- and concentration-dependent manner at low and higher cefepime exposures, respectively."

Journal • PK/PD data • Preclinical • Infectious Disease • Pneumonia

NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate. (PubMed, Antimicrob Agents Chemother) - "When expressed in Escherichia coli under isogenic conditions, NDM-63 conferred a resistance profile overall similar to NDM-1, but exhibiting a lower level of resistance to carbapenems and cefepime, while remaining susceptible to inhibition by taniborbactam. Present findings expand current knowledge on the structural plasticity of NDM-type MBLs and highlight that variability in the L3 loop, which contributes to delimitation of the active site, could also tolerate amino acid deletions without loss of enzymatic activity. A virtually identical K. pneumoniae carrying a non-functional blaNDM allele entailing only the nucleotide insertion observed in blaNDM-63 (which might have played a role in the evolution of blaNDM) was also isolated from a bloodstream infection that occurred in the same patient, yielding a misleading result of molecular diagnostic testing due to the lack of enzyme activity despite the presence of the target gene."

Journal • Infectious Disease • Pneumonia

Tricyclic boronic acids as broad-spectrum serine and metallo-β-lactamase inhibitors with in vitro activity against acinetobacter baumannii: a patent evaluation (us 2025/0223303). (PubMed, Expert Opin Ther Pat) - "This article concisely reviews structurally novel xeruborbactam-inspired tricyclic boronates (reported in US 2025/0223303) with promising inhibitory activities in vitro. By introducing novel thioether-based C5 sidechains onto the previously optimized bicyclic boronate core, the inventors explored novel chemical space yielding SBL/MBL inhibitors with seemingly improved activities against carbapenem-resistant (CR) Escherichia coli, Klebsiella pneumoniae, and, importantly, Acinetobacter baumannii, when used in combination with meropenem and/or biapenem (at least with respect to taniborbactam, i.e. boronate inhibitor in late-stage clinical development). Due to the major societal importance of β-lactams for modern medicine, and the clearly demonstrated clinical potential of functionalized cyclic boronates as potent dual-acting SBL/MBL inhibitors when used in combination therapies, there is ample opportunity and scope for continued investigation of this pharmacophore,..."

Journal • Preclinical • Review • Infectious Disease • Pneumonia

APC24-7, a covalent combination of boronic acid and chelator moieties, restores β-lactam efficiency against metallo-β-lactamase-producers. (PubMed, mSphere) - "While APC24-7 demonstrated similarities in resensitization behavior to taniborbactam against a wide range of isogenic E. coli expressing single SBLs, APC24-7 reversed NDM-9- or IMP-26-mediated meropenem resistance more efficiently. Combining chelator and transition state analog technology, our hybrid compound restores the effectiveness of BL antibiotics in cases of resistance conferred by both serine β-lactamases (SBLs) and MBLs. Our approach of covalently combining a chelator with an existing SBL inhibitor scaffold offers a promising solution for managing life-threatening infections and prolonging the use of clinically available BLs."

Journal • Infectious Disease • Pneumonia

Classification and applicability of new beta-lactamase inhibitors. (PubMed, Rev Esp Quimioter) - "This non-exhaustive minireview describes the main characteristics of the new beta-lactamase inhibitors (enmetazobactam, avibactam, relebactam, durlobactam, zidebactam, nacubactam, vaborbactam, taniborbactam, and xeruborbactam), their spectrum of inhibition, their activity in combination with different beta-lactams, the main resistance mechanisms that can compromise their activity and the main applications of the different beta-lactam-beta-lactamase inhibitor combinations depending on the type of beta-lactamase/carbapenemase and the microorganism involved."

Journal • Review

Contribution of mutational resistance mechanisms and acquired β-lactamases to cefiderocol/xeruborbactam susceptibility in Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "Xeruborbactam was assessed in combination with cefiderocol and cefepime at 4 and 8 mg/L and compared with taniborbactam. Importantly, xeruborbactam restored susceptibility in 78% of 99 cefiderocol-resistant P. aeruginosa strains, reducing the MIC90 from 64 to 4 mg/L. Cefiderocol/xeruborbactam shows promising activity against P. aeruginosa."

Journal • PER1

Efficacy of cefiderocol in combination with xeruborbactam versus taniborbactam against cefiderocol-resistant NDM-producing Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "One isolate that was unresponsive to taniborbactam carried multiple copies of blaNDM-1. These findings highlight the species-specific limitations of xeruborbactam in P. aeruginosa."

Journal

Sporadic cefiderocol resistance in Escherichia coli from the United Arab Emirates involves multifactorial mechanisms reversible by novel beta-lactamase inhibitors. (PubMed, Sci Rep) - "Zidebactam, with intrinsic antibacterial activity, caused the most significant reduction in CFDC minimum inhibitory concentrations (MICs), while the activity of other inhibitors (taniborbactam and xeruborbactam) was dependent on the genetic makeup of the strains, especially mutations in the siderophore-iron uptake genes. Our findings underscore the importance of genomic surveillance in deciphering antibiotic resistance mechanisms. Novel BLIs and partner antibiotics could be added weapons in the fight against MDR bacteria; thus, we recommend using combinations with novel BLIs as innovative therapeutic options to combat the emerging threat of CFDC resistance, after proper validation of their in vivo efficacy."

Journal • Infectious Disease

Novel beta-lactamase inhibitors with cefepime: where do they fit in clinical practice? (PubMed, Expert Opin Pharmacother) - "We performed a literature review of articles written in English using MEDLINE, PUBMED, and EMBASE, using the search terms 'Cefepime-enmetazobactam,' 'cefepime-taniborbactam,' and 'Cefepime-zidebactam' between January of 2015 and May 2025. On balance, the in vitro activity of cefepime-zidebactam fills critical gaps for the most challenging Gram-negative pathogens, including those that harbor metallo-β-lactamases with or without mutations in penicillin-binding proteins. For each of these agents, clinical data and real-world evidence generation are needed to better define their therapeutic niche, potential for resistance selection, and potential benefits compared to currently available antibiotics."

Journal • Review • Infectious Disease

Burkholderia pseudomallei PenI β-lactamase and variants are potently inhibited by taniborbactam. (PubMed, Antimicrob Agents Chemother) - "Isogenic Escherichia coli strains producing PenI and its ceftazidime-resistance-conferring variants (C69Y and P167S) showed ceftazidime minimum inhibitory concentration (MIC) of 64 mg/L for the strain producing PenI and 1,024 mg/L for the strains producing the variants, whereas cefepime MIC was 128-256 mg/L for these three strains. Lastly, co-crystallography and molecular dynamics simulations showed that taniborbactam induced the formation of a disulfide bond between Cys77 and Cys123, which destabilizes the deacylation water and strengthens the taniborbactam-PenI complex. These results support the development of cefepime-taniborbactam as a promising agent for the treatment of infections by B. pseudomallei."

Journal • Infectious Disease

Establishing the reference broth microdilution MIC method for cefepime-taniborbactam. (PubMed, J Clin Microbiol) - P3 | "It also held up well under different testing conditions, showing that it is a dependable tool for guiding treatment decisions. This is an important step in meeting the challenge of antibiotic-resistant infections since it will help clinicians evaluate cefepime-taniborbactam as a potential treatment option as they strive to improve the care of patients suffering from serious infections."

Journal • Infectious Disease

Antibiotics and non-traditional antimicrobial agents for pseudomonas aeruginosa in clinical phases 1, 2, and 3 trials. (PubMed, Expert Opin Investig Drugs) - "Traditional agents in clinical development include β-lactam/β-lactamase inhibitors (funobactam, taniborbactam, QPX2014-xeruborbactam), aminoglycosides (apramycin), polymyxin derivatives (upleganan, MRX-8, and SPR741), fluoroquinolones (MP-376), and lipopolysaccharide transport inhibitors (murepavadin). Non-traditional antibiotics in clinical development include anti-virulence agents (fluorothiazinone), monoclonal antibodies (INFEX-702, TRL-1068, and CMTX-101), bacteriophages (AP-PA02, YPT-01, BX004-A, and WRAIR-PAM-CF1), and miscellaneous agents (AR-501, PLG-0206, SNSP-113, OligoG CF-5/20, and ALX-009). A considerable number of antimicrobial agents, some with novel mechanisms of action, are in clinical phases of development for treating Pseudomonas aeruginosa infections. The urgent need for more therapeutic options necessitates the rapid optimization of progress to introduce new agents into clinical practice."

Journal • Review • Infectious Disease

Development and in vitro evaluation of 1,4,7-triazacyclononane-coupled β-lactams against metallo-β-lactamase producing bacteria. (PubMed, RSC Adv) - "Unlike serine-β-lactamases (SBLs), for which inhibitors exist, there are no clinically approved MBL inhibitors; only taniborbactam is in pre-registration. These inhibitors restored the efficacy of meropenem, reducing its minimum inhibitory concentration (MIC) against MBL-expressing pathogens to <2 mg L-1. Time-kill assays confirmed bactericidal activity, with this series being non-toxic and highly specific, these compounds hold promising potential as MBL inhibitors."

Journal • Preclinical

Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review. (PubMed, JAC Antimicrob Resist) - "A total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included...In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria. Although there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed."

Journal • PK/PD data • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Challenges of Carbapenem-Resistant Enterobacteriaceae in the Development of New β-Lactamase Inhibitors and Antibiotics. (PubMed, Antibiotics (Basel)) - "However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates."

Journal • Review

Genetic Basis of Cefiderocol Heteroresistance in Pseudomonas aeruginosa and Impact of New β-Lactamase Inhibitors (ASM Microbe 2025) - "Background: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that frequently causes drug-resistant infections in immunocompromised patients. Understanding the mechanisms underlying heteroresistant P. aeruginosa isolates can enable the development of therapeutic strategies to preserve the activity of FDC."

Infectious Disease

The Emerging Concern of IMP Variants Being Resistant to the Only IMP-Type Metallo-ß-Lactamase Inhibitor, Xeruborbactam (ASM Microbe 2025) - "Background: Metallo-β-lactamases (MBLs) of IMP-type hydrolyze almost all β-lactams and are not inactivated by currently commercialized ß-lactamase inhibitors, including taniborbactam (TAN) which inhibit other MBLs of the NDM- and VIM-types...Susceptibility testing of cefepime, meropenem in combination with TAN or XER at 4 mg/L or 8mg/L, was performed by broth microdilution... The production of IMP-6, IMP-10, IMP-14, IMP-26 conferred resistance to XER and, therefore, to the combination MER-XER under clinical development. On the other hand, this study highlighted IMP-59, as the only IMP variant sensitive to both TAN and XER."

Infectious Disease