There has been a significant decrease in the number of novel IV antibiotics in development and approved over the past 40 years for the treatment of Gram-negative infections. The physiology of Gram-negative bacteria – specifically the make-up of the outer-membrane of these bacteria – is one of the primary roadblocks hindering scientific advancement and innovation.
While Gram-positive bacteria possess a single phospholipid cell membrane, Gram-negative bacteria have a phospholipid inner membrane (akin to the Gram-positive membrane), plus an outer membrane bilayer composed primarily of phospholipid at the inner surface and lipopolysaccharide (LPS) at the outer leaflet. It is this layer of highly polar, negatively charged LPS that excludes many excellent target-based inhibitors, including a trove of clinically useful Gram-positive antibiotics from entering Gram-negative bacteria to do their work.
Chemical Formula
Active peptide: C52H82ClN15O12
Acetate Salt: C52H82ClN15O12 nC2H4O2 3.2.4
Molecular weight of SPR206 active compound: 1144.77 Da
Molecular weight of SPR206 acetate salt (assumes n=5): 1445.03 Da 508.45
Spero Therapeutics is currently developing IV-administered SPR206, as an innovative potential option to treat MDR Gram-negative bacterial infections within the hospital.
SPR206 is an innovative, investigational IV direct-acting antibiotic that has shown antibiotic activity against MDR Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in preclinical studies.
SPR206 completed non-clinical, IND-enabling studies supporting its advancement as a potential clinical candidate designed to treat MDR and extensively drug-resistant (XDR) bacterial strains. Based on microbiological and in vivo testing, we believe that SPR206 has the potential to offer a broad-spectrum of activity, including against XDR bacterial strains.
Spero is planning a Phase 2 clinical trial of SPR206, a novel investigational intravenously (IV) administered next generation polymyxin antibiotic being developed to treat multi-drug resistant (MDR) Gram-negative bacterial infections. The planned trial is designed to enroll patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). It is supported by preclinical data as well as the results of multiple Phase 1 clinical trials. These Phase 1 trials have demonstrated SPR206’s lack of nephrotoxicity at predicted therapeutic dose levels and its ability to continuously achieve mean lung epithelial lining fluid exposures above its MIC (minimum inhibitory concentration) for targeted gram-negative pathogens, when administered three times daily at 100 mg. Spero expects to file an IND for the planned Phase 2 trial of SPR206 in the fourth quarter of 2023.
SPR206 is designed to interact with the LPS to disrupt the outer membrane and is designed to have antibiotic activity as a single agent against MDR and XDR bacterial strains, including carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae.
In our Phase 1 SAD/MAD clinical trial, all reported adverse events were mild to moderate and there were no reported severe or serious adverse events. No evidence of nephrotoxicity was observed.
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Patients can follow the progress of SPR720 as the candidate moves through clinical trials. ClinicalTrials.gov is a database of clinical studies conducted worldwide.
(Blog post authored by Ankit Mahadevia)
