SPR206: Direct Acting IV Potentiator

SPR206: Novel Intravenous Product Candidate for Treating MDR Gram-Negative Infections in the Hospital

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.

Unfortunately, a distinct incongruence between chemical properties required for Gram-negative penetration (both membranes), and that imposed by many of the known (and novel) bacterial targets, means that simple (or complex) medicinal chemistry tactics have not been able to provide a solution. We believe that SPR206 as an IV-administered next generation polymyxin product candidate developed from our potentiator platform may effectively lead to LPS disruption.

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.  In January 2020, we announced data from a Phase 1 clinical trial designed as a double-blind, placebo-controlled, ascending dose, multi-cohort study in healthy subjects.  Phase 1 clinical data suggested that SPR206 at doses that are likely to be within a therapeutic range for target MDR Gram-negative bacterial infections supports the further development of SPR206. In conjunction with our alliance partners, we plan to conduct a Phase 1 bronchoalveolar lavage (BAL) clinical trial assessing the penetration of SPR206 into the pulmonary compartment in the first half of 2021, as well as initiate a renal impairment study with SPR206.

  • SPR206 has demonstrated potency as a direct-acting agent in preclinical studies.

    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.


  • SPR206 safety findings in a Phase 1 clinical trial support ongoing development.

    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.


  • Preclinical potency against XDR gram-negative pathogens.

    We have seen in preclinical studies that SPR206 has the potential to offer a broad-spectrum of activity.



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