NOSO-502 / Nosopharm - LARVOL DELTA

The magnitude of the pharmacodynamic index for NOSO-502: pathogen clearance, emergence of resistance and human dose predictions. (PubMed, J Antimicrob Chemother) - "A combination of the use of PDI targets and prediction of human pharmacokinetics allowed effective doses of NOSO-502 in man to be estimated."

Journal • PK/PD data • Infectious Disease • Pneumonia • GDF15

In vitro activity of NOSO-502, a novel-action antimicrobial, against clinical strains of Enterobacterales including MDR strains. (PubMed, J Antimicrob Chemother) - "NOSO-502 showed potent in vitro inhibitory and bactericidal activity against a panel of Enterobacterales enriched for resistant phenotypes for which there are few therapeutic choices. These findings need to be placed in context with the appropriate pharmacokinetic and dynamic characteristics of NOSO-502."

Journal • Preclinical • Infectious Disease • Pneumonia

Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver. (PubMed, J Antimicrob Chemother) - "NOSO-502 exhibits both dose- and time-dependent in vitro and in vivo activity against both E. coli and K. pneumoniae."

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

Investigation of the Odilorhabdin Biosynthetic Gene Cluster Using NRPS Engineering. (PubMed, Angew Chem Int Ed Engl) - "This class exhibits broad-spectrum antibiotic activity and inspired the development of the synthetic derivative NOSO-502, which holds potential as a new clinical drug by breaking antibiotic resistance...For this, modules of the odilorhabdin NRPS fused to other synthetases were co-expressed with candidate hydroxylases encoded in the BGC allowing the characterization of the biosynthesis of three unusual amino acids and leading to the identification of a prodrug-activation mechanism by deacylation. Our work demonstrates the application of NRPS engineering as a blueprint to mechanistically elucidate large or toxic NRPS and provides the basis to generate novel odilorhabdin analogues with improved properties in the future."

Journal

Pharmacodynamic index driver of NOSO-502: conclusions from in vivo and in vitro studies (ECCMID 2024) - No abstract available

PK/PD data • Preclinical

In vitro activity of NOSO502, a novel action antimicrobial, against clinical strains of Enterobacterales, including multidrug-resistant strains (ECCMID 2023) - No abstract available

Preclinical

Effect of media type and composition on NOSO502 MIC values and test reproducibility (ECCMID 2023) - No abstract available

Exploring Cluster-Dependent Antibacterial Activities and Resistance Pathways of NOSO-502 and Colistin against Enterobacter cloacae Complex Species. (PubMed, Antimicrob Agents Chemother) - "In E. cloacae ATCC 13047, CST-hetero-resistance is conferred via modification of the lipid A by addition of 4-amino-4-deoxy-l-arabinose controlled by PhoPQ. We identified that the response regulator ECL_01761 is also involved in this resistance pathway by regulating the expression of the ECL_01760 membrane transporter."

Journal • Infectious Disease • Pneumonia

Antibacterial interactions of NOSO-502 studied by checkerboard method using combinations with amikacin, ciprofloxacin, colistin, meropenem and tigecycline against Enterobacterales (ECCMID 2022) - No abstract available

In vitro bactericidal activity of NOSO 502: a novel action odilorhabdin antibiotic (ECCMID 2022) - No abstract available

Preclinical

[VIRTUAL] Pharmacokinetics and pharmacodynamics of the odilorhabdin NOSO-502 in a thigh infection model in neutropenic mice (ECCMID 2021) - No abstract available

PK/PD data • Preclinical • Infectious Disease

Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance in Klebsiella pneumoniae. (PubMed, Antimicrob Agents Chemother) - "Upregulation of the kexD gene expression was observed for all CrrB mutants. Finally, plasmid expression of kexD in a K. pneumoniae strain missing the locus crrABC and kexD significantly increased resistance to NOSO-502."

Journal • Infectious Disease • Pneumonia

From Worms to Drug Candidate: The Story of Odilorhabdins, a New Class of Antimicrobial Agents. (PubMed, Front Microbiol) - "NOSO-502, the first ODL preclinical candidate was selected. This compound is currently under preclinical development for the treatment of multidrug-resistant Gram-negative infections in hospitalized patients."

Journal • Review

In Vivo Pharmacodynamic Characterization of a Novel Antibiotic Odilorhabdins, NOSO-502 against Escherichia coli and Klebsiella pneumoniae in a Murine Thigh Infection Model. (PubMed, Antimicrob Agents Chemother) - "The mean fAUC/MIC magnitude associated with net stasis endpoint for E. coli was 10.4. NOSO-502 represents a promising novel, first-in-class odilorhabdin antibiotic with in vivo potency against Enterobacteriaceae."

Journal • PK/PD data • Preclinical

In vitro and In vivo characterization of NOSO-502, a novel inhibitor of bacterial translation. (PubMed, Antimicrob Agents Chemother) - "There was no cytotoxicity against HepG2, HK-2, or HRPT cells, no inhibition of hERG-CHO or Nav 1.5 -HEK current, and no increase of micronuclei at 512 μM. NOSO-502, a compound with a new mechanism of action, is active against Enterobacteriaceae, including all classes of CRE, has a low potential for resistance development, shows efficacy in several mouse models, and has a favorable in vitro safety profile."

Journal • Preclinical