QPX9003 / Monash University, Brii Biosci, Shionogi - LARVOL DELTA

Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants. (PubMed, Antimicrob Agents Chemother) - P1 | "PK exposure was statistically equivalent between non-Chinese and Chinese participants. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of BRII-693 in healthy non-Chinese and Chinese participants.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04808414."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease

Potentially effective antimicrobial treatment for pneumonia caused by isolates of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii complex species: what can we expect in the future? (PubMed, Expert Rev Anti Infect Ther) - "Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases

"We need Antibiotics for CRAB , but Polymyxins, again ? 🆕️⚡️ @antibioticsmdpi @AbdullahTarikA1 @davidantibiotic et Al Next-Generation Polymyxin Class of Antibiotics: A Ray of Hope Illuminating a Dark Road SPR206, MRX-8, and 📍QPX9003📍,others ? https://t.co/zUVaJK4Ffa" (@ABsteward)

Pharmacodynamics (PD) of the lipopeptide QPX9003 Against Acinetobacter baumannii and Pseudomonas aeruginosa in the Neutropenic Mouse Thigh Infection Model (IDWeek 2022) - No abstract available

PK/PD data • Preclinical • Infectious Disease

A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of the Lipopeptide QPX9003 in Healthy Adult Subjects (IDWeek 2022) - No abstract available

Clinical • P1 data • PK/PD data • Infectious Disease

SAD/MAD Safety and PK Study of QPX9003 (Novel Polymyxin) in Normal Healthy Volunteers (clinicaltrials.gov) - P1 | N=104 | Completed | Sponsor: Qpex Biopharma, Inc. | Recruiting ➔ Completed

Trial completion • Infectious Disease

A phase I study of the safety, tolerability, and pharmacokinetics of the Novomixin QPX9003 in healthy adult subjects (ECCMID 2022) - No abstract available

Clinical • P1 data • PK/PD data

A synthetic lipopeptide targeting top-priority multidrug-resistant Gram-negative pathogens. (PubMed, Nat Commun) - "Here we employ chemical biology to systematically optimize multiple non-conserved positions in the polymyxin scaffold, and successfully disconnect the therapeutic efficacy from the toxicity to develop a new synthetic lipopeptide, structurally and pharmacologically distinct from polymyxin B and colistin. This resulted in the clinical candidate F365 (QPX9003) with superior safety and efficacy against lung infections caused by top-priority MDR pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

SAD/MAD Safety and PK Study of QPX9003 (Novel Polymyxin) in Normal Healthy Volunteers (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Trial completion date: Mar 2022 ➔ Aug 2022

Trial completion date • Infectious Disease

SAD/MAD Safety and PK Study of QPX9003 (Novel Polymyxin) in Normal Healthy Volunteers (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: Qpex Biopharma, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease

SAD/MAD Safety and PK Study of QPX9003 (Novel Polymyxin) in Normal Healthy Volunteers (clinicaltrials.gov) - P1; N=80; Not yet recruiting; Sponsor: Qpex Biopharma, Inc.

Clinical • New P1 trial • Infectious Disease

QPX9003: Pharmacology of a Novel Polymyxin in Mice and Rats (IDWeek 2019) - "QPX9003 showed better bacterial killing of A. baumannii than PMB at similar plasma exposures in both the mouse thigh model (-0.41 vs. +0.83 log CFU/thigh) and rat lung infection model (-1.10 vs. +1.44 log CFU/lung).Conclusion : QPX9003 was less acutely toxic, less nephrotoxic, and was more efficacious in mouse and rat infection models compared to PMB. QPX9003 is a promising new polymyxin.(This work was supported in part by federal funds from the National Institutes of Allergy and Infectious Diseases [R01AI098771], and the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under OTA number HHSO100201600026C)."

Preclinical

Activity of a Novel Polymyxin Analog, QPX9003, Tested against Resistant Gram-Negative Pathogens, including Carbapenem-Resistant Acinetobacter, Enterobacterales, and Pseudomonas  (IDWeek 2019) - "We evaluated the activity of QPX9003, a novel polymyxin analog with an improved safety profile over current polymyxins, against a large collection of resistant GN isolates collected worldwide.Methods : Susceptibility testing was performed by reference microbroth dilution against 2,518 GN organisms for QPX9003, colistin (COL), levofloxacin, tigecycline, gentamicin, amikacin, meropenem, cefepime, piperacillin-tazobactam, and ceftazidime-avibactam. Other comparator agents had limited activity against PSA, CRAB, and CRE isolates.Conclusion : QPX9003 had activity against this collection of highly resistant GN isolates and was particularly active against the PSA and CRAB isolates. QPX9003 is a promising new-generation polymyxin agent."