OMNIvance (xeruborbactam) / Brii Biosci, Shionogi - 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

Susceptibilities of cefiderocol, meropenem-xeruborbactam, cefepime-taniborbactam, aztreonam-avibactam, and sulbactam-durlobactam against imipenem-non-susceptible Gram-negative bacilli in Taiwan. (PubMed, Int J Infect Dis) - " Cefiderocol was highly effective, whereas novel β-lactam/β-lactamase inhibitors activity varied by species and carbapenemase types. PBP3 alterations reduced FTB and AZA activity in INS-EC."

Journal • Infectious Disease • Pneumonia

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Qpex Biopharma, Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors. (PubMed, Chem Sci) - "Crucially, the resulting 3D architectures mimic structural motifs found in the potent β-lactamase inhibitor Xeruborbactam. The biological relevance of these frameworks was validated by NMR titration, pK a analysis, and co-crystallisation with serine β-lactamase CTX-M-14, revealing enantiospecific binding and a well-defined hydrogen bonding network. These results establish a versatile platform for the synthesis of functionalised boron heterocycles with direct translational potential in medicinal chemistry."

Journal

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Qpex Biopharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease

P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants (clinicaltrials.gov) - P1 | N=71 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial primary completion date • Infectious Disease

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

Structural Insights into the Role of the Stereochemistry of the Cyclopropyl Ring in the Inhibitory Activity of Xeruborbactam against SME-1 Class A Carbapenemase. (PubMed, Biochemistry) - "In the molecular dynamics, xeruborbactam stabilized SME-1 more than its isomer, which is consistent with our experimental findings. These results together show the strong inhibitory profile of xeruborbactam and highlight the importance of stereochemistry in the design of next-generation β-lactamase inhibitors and diagnostics for AMR."

Journal

A Study to Investigate Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Renal Disease

Phase 1, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the safety, tolerability, and pharmacokinetics of intravenous xeruborbactam (QPX7728) in healthy adult subjects. (PubMed, Antimicrob Agents Chemother) - "Significant accumulation was noted with 8-hourly dosing. Xeruborbactam at doses up to 1,000 mg daily for 7-10 days was well tolerated, with no serious or life-threatening AEs."

Clinical • Journal • P1 data • PK/PD data • Pain

Pharmacodynamic Assessment of Combination of Cefiderocol with Xeruborbactam in Murine Thigh Infection Model (IDWeek 2025) - No abstract available

PK/PD data • Preclinical • Infectious Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Qpex Biopharma, Inc. | Active, not recruiting ➔ Completed

Trial completion

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc.

New P1 trial

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Qpex Biopharma, Inc. | N=40 ➔ 60

Enrollment change • Infectious Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc.

New P1 trial • Infectious Disease • Renal Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Qpex Biopharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Amphiphilic nebramine analogs synergize with β-lactam/β-lactamase inhibitor combinations, including cefepime-taniborbactam and meropenem-xeruborbactam against metallo-β-lactamase-carrying Pseudomonas aeruginosa. (PubMed, RSC Med Chem) - "Cefepime-taniborbactam (FEP-TAN) and meropenem-xeruborbactam (MEM-XER) are β-lactam-β-lactamase inhibitor (BL-BLI) combinations currently in development and both projected to treat metallo-β-lactamase (MBL)-producing Gram-negative pathogens. Compound 4 was found to be less toxic than both polymyxin B and its corresponding amphiphilic tobramycin counterpart (compound 7) in human renal cell lines, RPTEC and HK-2. Overall, our study suggests that addition of compound 4 alongside next-generation BL-BLIs such as FEP-TAN, MEM-XER as well as the recently approved ATM-AVI combination can overcome intrinsic and acquired in vitro P. aeruginosa resistance determinants that confer high-level resistance to β-lactam antibiotics."

Journal • Infectious Disease

Broad spectrum of β-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new β-lactam/β-lactamase inhibitor combinations. (PubMed, Antimicrob Agents Chemother) - "The MICs of meropenem, meropenem/xeruborbactam, meropenem/vaborbactam, imipenem, imipenem/relebactam, cefepime, cefepime/taniborbactam, ceftazidime, ceftazidime/avibactam, aztreonam, and aztreonam/avibactam were determined by reference broth microdilution and interpreted following the European Committee on Antimicrobial Susceptibility Testing guidelines, using the breakpoint of the β-lactam alone for not yet approved combinations. Xeruborbactam restored meropenem activity against the strains carrying resistance mechanisms to β-lactam/β-lactamase inhibitor combinations, including strains producing KPC variants or MBLs in combination with additional chromosomal alterations (MIC range: ≤0.06-0.25 and ≤0.06-4 mg/L, respectively). Our findings highlight the potential of xeruborbactam in combination with meropenem as a promising treatment against carbapenemase-producing Enterobacterales, including strains with emerging resistance to other β-lactam/β-lactamase inhibitor..."

Journal

Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation. (PubMed, JAC Antimicrob Resist) - "Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution...The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging...Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms."

Journal • Infectious Disease • Pneumonia • Transplantation

Clinical and microbiological analysis of bloodstream infections by four cefiderocol-resistant and not previously exposed NDM-producing Klebsiella pneumoniae. (PubMed, J Antimicrob Chemother) - "This case series highlights the urgent need of new therapeutic agents that will overcome the diffusion of NDM-KP resistant to FDC. The emergence of NDM-KP with an acquired fec operon in nosocomial settings, even without a previous drug exposure, may further compromise cefiderocol efficacy. Further studies will be necessary to assess the in vivo activity of xeruborbactam, a new cyclic boronate β-lactamase inhibitor, which may restore cefiderocol susceptibility in NDM-KP isolates."

Journal • CNS Disorders • Infectious Disease • Pneumonia • Psychiatry • ST14