taniborbactam (VNRX-5133) / VenatoRx - LARVOL DELTA

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

Structure and mechanism of taniborbactam inhibition of the cefepime-hydrolyzing, partial R2-loop deletion Pseudomonas-derived cephalosporinase variant PDC-88. (PubMed, Antimicrob Agents Chemother) - "Structurally, taniborbactam positioned very similarly in the PDC-3 and PDC-88 active sites, interacting with many nearby residues. Based upon these data, cefepime-taniborbactam may represent an important alternative to ceftazidime-avibactam and ceftolozane-tazobactam for P. aeruginosa infections."

Journal • Infectious Disease

The emerging concern of IMP variants being resistant to the only IMP-type metallo-β-lactamase inhibitor, xeruborbactam. (PubMed, Antimicrob Agents Chemother) - "Metallo-β-lactamases (MBLs) of IMP type are not inhibited by currently commercialized β-lactamase inhibitors, including taniborbactam (TAN), which inhibits only NDM- and VIM-type enzymes. However, the development of xeruborbactam (XER), which additionally inhibits IMP enzymes, may provide effective drug combinations such as meropenem-XER (MEM-XER) against most MBL producers...Finally, structural analyses and molecular modeling simulations indicated that the Ser262Gly mutation in IMP-6 may alter the electronic properties of the active site, whereas the Phe residue in IMP-10 may exert a steric effect counteracting XER binding. Resistance to XER in IMP-6, IMP-10, IMP-14, and IMP-26 variants, conferring resistance to MEM-XER, might be considered a serious concern since MEM-XER will be supposed to be a salvage therapy for MBL-, and especially IMP-producing Enterobacterales infections."

Journal • Infectious Disease

Plasma and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult participants. (PubMed, Antimicrob Agents Chemother) - P1 | "The highest and lowest values of AUC0-8 values for ELF and DPRELF/plasma for cefepime and taniborbactam were observed with aspirate 1 and aspirate 4, respectively. These results support further consideration of cefepime-taniborbactam as a potential treatment for bacterial pneumonia caused by susceptible MDR Gram-negative pathogens.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04951505."

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

Discovery of 3-methacylic acid substituted benzoxaboroles as dual metallo- and serine-β-lactamase inhibitors. (PubMed, Eur J Med Chem) - "Co-crystallographic analyses revealed their binding modes with VIM-2 and OXA-48, which are similar as those of taniborbactam and xeruborbactam. Bacterial assays demonstrated that compound 10 can potentiate meropenem against multidrug-resistant Gram-negative strains. This work provides new lead compounds and structural basis for developing new drug candidates against MBL/SBL-mediated carbapenem resistance."

Journal • Infectious Disease

The NitroSpeed Taniborbactam NP test as a rapid test for detection of β-lactamase-mediated susceptibility to taniborbactam. (PubMed, FEMS Microbiol Lett) - "Taniborbactam (TAN) is an investigational β-lactamase inhibitor in clinical development combined with cefepime for the treatment of bacterial infections caused by broad-spectrum β-lactamase-expressing bacteria...The test is based on the hydrolysis of (i) nitrocefin (to determine the presence or absence of β-lactamase), (ii) ertapenem (to confirm the presence or the absence of carbapenemase), and (iii) TAN (to assess whether the carbapenemase is inhibited by TAN)...The NitroSpeed Taniborbactam NP test is simple, easy to perform, and provides results within ≤ 15 minutes. When evaluated against a broad set of β-lactamases, the test demonstrated 100% sensitivity, specificity, and accuracy."

Journal • Infectious Disease

Decreased porin transcription promotes resistance to taniborbactam when combined with meropenem (ESCMID Global 2025) - No abstract available

The NitroSpeed Taniborbactam NP test; easy detection of β-lactamase sensitivity to taniborbactam (ESCMID Global 2025) - No abstract available

The Triple Combination of Meropenem, Avibactam, and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers. (PubMed, Engineering (Beijing)) - "This work explores the potential of a triple combination of meropenem (MEM), a novel metallo-β-lactamase (MBL) inhibitor (indole-2-carboxylate 58 (InC58)), and a serine-β-lactamase (SBL) inhibitor (avibactam (AVI)) for broad-spectrum activity against carbapenemase-producing bacteria. The mutants manifested a fitness cost, a decreased level of resistance during passage without antibiotic pressure, and cross resistance to another carbapenem (imipenem) and a β-lactamase inhibitor (taniborbactam). In conclusion, compared with the dual combinations, the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemase-producing bacteria, revealing a new strategy to combat β-lactamase-mediated antimicrobial resistance."

Journal • Infectious Disease • Pneumonia

In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-β-lactamase producers. (PubMed, Eur J Clin Microbiol Infect Dis) - "Cefiderocol and aztreonam/avibactam are already clinically available and recommended by international guidelines. In addition, two new classes of β-lactam/ β-lactamase combinations are under clinical evaluation: (i) combination of β-lactam with novel boronic-derived inhibitors (e.g. taniborbactam and xeruborbactam), (ii) combination of β-lactam with last generation diazabicyclooctane β-lactamase inhibitors (e.g. zidebactam and nacubactam), active on most of serine-β-lactamases but also showing strong intrinsic activity on PBP-2. This review aims to provide up-to-date data on the characteristics, activity and emerging resistance mechanisms of the armamentarium of clinically available or soon-to-be introduced drugs for the treatment of MβL-producing Gram-negative organisms."

Journal • Preclinical • Review • Infectious Disease

Cefepime-taniborbactam and ceftibuten-ledaborbactam maintain activity against KPC variants that lead to ceftazidime-avibactam resistance. (PubMed, Antimicrob Agents Chemother) - "K2/K was less affected for D179Y-containing KPC-3 variants, and robust inhibition was observed by TAN, LED, and AVI. Together, the findings illustrate a biochemical basis for FEP-TAN and CTB-LED efficacy in KPC variant-mediated CAZ-AVI resistance backgrounds, whereby the boronate inhibitors have sufficient inhibitory activity, while FEP and CTB are poor substrates and bind to the variant enzymes with reduced affinity."

Journal • Infectious Disease • Pneumonia