zifanocycline (KBP-7072) / Sihuan Pharmaceutical - LARVOL DELTA

In vitro Activity of the Novel Tetracyclines Derivative, Zifanocycline Against Mycobacterium abscessus. (PubMed, Infect Drug Resist) - "In our study, zifanocycline (MIC50/MIC90, 0.06/0.25 mg/L) demonstrated a 2-fold lower MIC50 and MIC90 compared to tigecycline (MIC50/MIC90, 0.12/0.5 mg/L), and a 4-fold and 2-fold lower MIC50 and MIC90, respectively, compared to omadacycline (MIC50/MIC90, 0.25/0.5 mg/L). In addition to amikacin and linezolid, zifanocycline demonstrated significantly superior antibacterial activity compared with ciprofloxacin, moxifloxacin, trimethoprim-sulfamethoxazole, cefoxitin, doxycycline, imipenem, and clarithromycin. The combination of zifanocycline and the seven antibacterial drugs used for the treatment of Mycobacterium abscessus showed no significant interactions. Zifanocycline exhibits positive antibacterial activity against Mycobacterium abscessus in vitro and has potential as an alternative agent in multidrug combination therapy regimens for the treatment of this pathogen."

Journal • Preclinical

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

Study of KBP-7072 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: KBP Biosciences | Active, not recruiting ➔ Completed | Trial completion date: Jan 2024 ➔ Jun 2023

Trial completion • Trial completion date

Novel drug candidates against antibiotic-resistant microorganisms: A review. (PubMed, Iran J Basic Med Sci) - "This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus...The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small..."

Journal • Review

In vivo efficacy and PK/PD analyses of zifanocycline (KBP-7072), an aminomethylcycline antibiotic, against Acinetobacter baumannii in a neutropenic murine thigh infection model. (PubMed, J Infect Chemother) - "The in vivo efficacy results and PK/PD analyses support the design of optimal dosing regimens in clinical studies and assist with determining clinical breakpoints for zifanocycline."

Journal • PK/PD data • Preclinical • Infectious Disease

Study of KBP-7072 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: KBP Biosciences | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2023 ➔ Jan 2024 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Enrollment closed • Trial completion date • Trial primary completion date

In vivo efficacy and PK/PD analyses of KBP-7072, an aminomethylcycline antibiotic, against Acinetobacter baumannii in a neutropaenic murine thigh infection model (ECCMID 2023) - No abstract available

PK/PD data • Preclinical • Infectious Disease

Study of KBP-7072 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: KBP Biosciences

New P1 trial

In Vitro Activity of KBP-7072 against 536 Acinetobacter baumannii Complex Isolates Collected in China. (PubMed, Microbiol Spectr) - "It inhibited the growth of all isolates at 4 mg/liter, including 372 carbapenem-resistant isolates, 37 tigecycline MIC ≥ 4 mg/liter isolates, and 138 omadacycline MIC ≥ 4 mg/liter isolates...KBP-7072 was as equally active as colistin (MIC, 1 mg/liter, 99.4% susceptible). Doxycycline (33.4% susceptible), gentamicin (31.3% susceptible), meropenem (30.6%, susceptible), imipenem (30.2% susceptible), ceftazidime (27.8% susceptible), piperacillin-tazobactam (27.2% susceptible), and levofloxacin (27.2% susceptible) showed marginally poor antibacterial activity against tested isolates according to CLSI breakpoints, except for minocycline (73.7% susceptible)...KBP-7072 is a novel, expanded spectrum tetracycline antibacterial and has demonstrated good in vitro activity against recent geographically diverse A. baumannii isolates collected from North America, Europe, Latin America, and Asia-Pacific. This study has shown excellent in vitro activity of KBP-7072 against clinical A...."

Journal • Preclinical • Infectious Disease

In vitro activity of a novel aminomethylcycline antibacterial (KBP-7072), a third-generation tetracycline, against clinical isolates with molecularly characterized tetracycline resistance mechanisms. (PubMed, JAC Antimicrob Resist) - "CLSI/EUCAST breakpoints were applied, except for tigecycline and omadacycline, which used FDA criteria. The MIC for KBP-7072 (MIC, 1/4 mg/L) and tigecycline (MIC, 1/2 mg/L) increased 2- to 8-fold for tetracycline-resistant K. pneumoniae, which mostly produced Tet(A). KBP-7072 activity was minimally affected by the presence of acquired tetracycline genes."

Journal • Preclinical • Infectious Disease • Pneumococcal Infections • Pneumonia

Activity of KBP-7072 (a novel aminomethylcycline) and comparators against 1,057 geographically diverse recent clinical isolates from the SENTRY Surveillace Program (2019). (PubMed, Antimicrob Agents Chemother) - "KBP-7072 was active against Enterococcus faecalis (MIC, 0.03/0.06 mg/L) and vancomycin-susceptible and -nonsusceptible E. faecium (MIC, 0.03/0.03 mg/L); Streptococcus pneumoniae (MIC, ≤0.015/0.03 mg/L), including penicillin- and tetracycline-resistant strains; S. agalactiae (MIC, 0.03/0.06 mg/L), including macrolide-resistant strains; S. pyogenes (MIC, 0.03/0.03 mg/L); and viridans group streptococci, including S. anginosus group (MIC, ≤0.015/0.03 mg/L) isolates. Based on MIC values, KBP-7072 in vitro activity was generally superior to the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur."

Clinical • Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

A Multiple Ascending Dose Study to Investigate Safety of KBP-7072 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: KBP Biosciences; Recruiting ➔ Completed

Clinical • Trial completion

[VIRTUAL] In vitro activity of a novel aminomethylcycline antibacterial (KBP-7072) against clinical isolates with molecularly-characterised tetracycline resistance mechanisms (ECCMID 2021) - No abstract available

Preclinical

[VIRTUAL] Activity of KBP-7072, a novel aminomethylcycline antibacterial, and tetracycline class comparators against 1,057 bacterial pathogens collected worldwide during 2019 (ECCMID 2021) - No abstract available

[VIRTUAL] Assessment of resistance development to KBP-7072 by serial passage and single-step mutational selection (ECCMID 2021) - No abstract available

A Multiple Ascending Dose Study to Investigate Safety of KBP-7072 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: KBP Biosciences

Clinical • New P1 trial

Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, An Aminomethylcycline Antibiotic in Animal Models. (PubMed, Antimicrob Agents Chemother) - "Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies."

Journal • PK/PD data • Preclinical

In vitro activity of KBP-7072, a novel third-generation tetracycline, against 531 recent geographically diverse and molecularly characterized Acinetobacter baumannii species complex isolates. (PubMed, Antimicrob Agents Chemother) - P1; "KBP-7072 outperformed comparator agents, including ceftazidime (40.3%S [CLSI]), gentamicin (48.2%/48.2%S [CLSI/EUCAST]), levofloxacin (39.5%/37.9%S [CLSI/EUCAST]), meropenem (42.0%/42.0%S [CLSI/EUCAST]), piperacillin-tazobactam (33.3%S [CLSI]) and all tetracycline-class comparator agents that include doxycycline (67.3%S, [CLSI], minocycline (73.8%S [CLSI]), tetracycline (37.2%S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/L). The potent in vitro activity of KBP-7072 against recent geographically diverse, molecularly characterized and drug-resistant A. baumannii isolates supports continued clinical development for the treatment of serious infections including those caused by A. baumannii."

Journal • Preclinical