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Spero Therapeutics Presents New Data on Lead Potentiator Candidate SPR741 at ASM Microbe 2017

Presentations include new toxicology and mechanism of action data validating the Potentiator approach for Gram-negative infections


News provided by

Spero Therapeutics

May 30, 2017, 08:30 ET

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CAMBRIDGE, Mass., May 30, 2017 /PRNewswire-USNewswire/ -- Spero Therapeutics, LLC, a biopharmaceutical company founded to develop multiple novel therapies for the treatment of bacterial infections, today announced the presentation of 21 posters, including new data supporting the ongoing clinical development program of the Company's lead Potentiator candidate, SPR741, and the Company's third drug candidate, SPR720, which Spero is currently testing in tuberculosis and non-tuberculous mycobacteria (NTM) lung disease. The data will be presented at the American Society of Microbiology (ASM) Microbe 2017 Conference, taking place June 1-5 in New Orleans.

"We are committed to expanding our portfolio to meet the high unmet need that exists with Gram-negative bacteria and orphan infectious disease," said Ankit Mahadevia, M.D., Chief Executive Officer of Spero. "The data presented at ASM Microbe will continue to validate the broad utility of SPR741 and further validate its safety profile. In addition, we are excited to continue the development of SPR720 for NTM given the high unmet need and lack of available approved options."

Posters that expand the understanding of the safety profile of SPR741 include the following:    

  • A GLP 14-Day Repeat Dose Toxicology Study of SPR741 in Sprague-Dawley Rats
    Poster 250, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D
  • A GLP 14-Day Repeat Dose Toxicology Study of SPR741 in Monkeys
    Poster 251, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D
  • SPR741 GLP Safety Pharmacology Studies Across Cardiac, Pulmonary and Central Nervous Systems
    Poster 252, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D
  • SPR741 is Non-Genotoxic in the ICH Battery of GLP Ames, Chromosomal Aberration, and In Vivo Micronucleus Studies
    Poster 253, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D

Several posters provide further evidence of the disruptive effects of SPR741 on the outer membrane of Gram-negative bacteria, validating the broad impact of SPR741 on expanding the Gram-negative spectrum of both generic and new chemical entity drugs. These posters include:

  • Electron Microscopy Reveals Activity of SPR741 at the Cell Envelope of Escherichia coli
    Poster 165, Friday, June 2, 12:45 p.m. CDT, Exhibit Hall D
  • Polymyxin Derivative SPR741 Disrupts Gram-Negative Outer Membrane Architecture Without Substantial Impacts on the Cytoplasmic Membrane
    Poster 248, Saturday, June 3, 12:15 p.m. CDT, Exhibit Hall D
  • Mechanistic Insight Into the Antibiotic Potentiating Activity of SPR741 Using Electron Microscopy
    Poster 222, Sunday June 4, 12:15 p.m. CDT, Exhibit Hall D

Further details of the pharmacokinetic data used to plan the Phase 1 study of SPR741 include the following posters:   

  • Pharmacokinetics of SPR741 in Rats and Non-Human Primates after a One Hour Intravenous Infusion
    Poster 247, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D
  • In-Vitro ADME Properties of SPR741 Support Progression Into Clinical Development 
    Poster 254, Saturday June 3, 12:15 p.m. CDT, Exhibit Hall D

Posters on the utility of SPR720 in treating nontuberculosis mycobacteria (NTM) and Mycobacterium tuberculosis (TB) include the following:

  • Activity of a Novel Gyrase Inhibitor In Vitro and in an Acute SCID Mouse Model of Infection Caused by Mycobacterium abscessus
    Poster 42, Sunday June 4, 12:15 p.m. CDT, Exhibit Hall D
  • Efficacy of SPR720 and SPR750 Gyrase Inhibitors in a Mouse Mycobacterium tuberculosis Infection Model
    Poster 43, Sunday June 4, 12:15 p.m. CDT, Exhibit Hall D

About The Spero Potentiator Platform
Spero's Potentiator Platform comprises novel compounds designed to specifically and potently interact with the lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria. LPS acts as the persistent barrier to entry for many antimicrobial agents, including most Gram-positive antibiotics, and disruption of this barrier by SPR741 allows access to otherwise impermeable compounds.

About SPR741
SPR741 is Spero's lead Potentiator candidate. Preclinical studies of SPR741 in combination with Gram-positive antibiotics have shown success in reducing the bacterial burden of infections caused by several common drug-resistant pathogens, including Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae. Spero communicated the preclinical broad-spectrum efficacy, safety and pharmacokinetics of SPR741 in 14 posters and an oral presentation at ASM Microbe 2016. SPR741 is currently in Phase 1 clinical trials. Spero in-licensed the rights to SPR741 from Northern Antibiotics, Espoo, Finland.

About Spero's Novel Gyrase Inhibitors
Spero is currently investigating the potential of SPR720 in tuberculosis (TB) as well as non-tuberculous mycobacteria (NTM) lung disease, a rare and often chronic fatal infection for which there are no approved treatments. These compounds also possess good in vitro antibacterial activity against a variety of pathogens including Gram-positive bacteria. Spero in-licensed the rights to SPR720 from Vertex Pharmaceuticals and SPR750 from Biota Pharmaceuticals in 2016.

About Spero
Spero Therapeutics is a global multi-asset clinical-stage biopharmaceutical company headquartered in Cambridge, Massachusetts dedicated to developing a novel and highly differentiated pipeline of antibacterials focused on unmet needs of patients with drug resistant bacterial infections. Spero Therapeutics is advancing two lead programs in parallel, SPR741 and SPR994. SPR741, also called Potentiator, is a platform approach to combination therapy to treat serious and life-threatening multidrug resistant Gram-negative infections, such as Enterobacteriaceae and Acinetobacter baumannii, including carbapenem resistant strains. SPR741 increases the spectrum and potency of more than two dozen Gram-positive antibiotics to include activity against multidrug resistant Gram-negative infections when used in combination. SPR994 is a novel oral agent that has demonstrated potent in vitro activity against a wide variety of Gram-negative bacteria, including those harboring extended spectrum beta lactamases (ESBLs), and also Gram-positive bacteria. Spero Therapeutics also has a robust preclinical pipeline including SPR720, which is a preclinical oral candidate for mycobacterial infections including non-tuberculous mycobacteria (NTM) lung disease, a rare and often chronic fatal infection. In addition, Spero Therapeutics has a variety of other discovery stage antimicrobials focused on drug resistant infections.

For more information, please visit https://sperotherapeutics.com   

SOURCE Spero Therapeutics

Related Links

https://sperotherapeutics.com/

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