Spero Therapeutics To Present Data on the Impact of Targeted MvfR-Regulon Inhibitors on Gram Negative Bacteria at Upcoming ICAAC Meeting

Spero Therapeutics To Present Data on the Impact of Targeted MvfR-Regulon Inhibitors on Gram Negative Bacteria at Upcoming ICAAC Meeting

August 19, 2014

— Data are being presented showing application in pre-clinical models of acute
lung infection and burn infection –

— Company successfully leverages unique pathway to combat resistant bacteria;
potential for whole new treatment approach —

CAMBRIDGE, Mass. – August 19, 2014 – Spero Therapeutics, LLC, a biopharmaceutical company founded to develop novel therapies for treatment of bacterial infections, today announced that data on the original compounds that serve as the foundational research for the company’s MvfR inhibitor program will be presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).  Spero will present data in symposium and poster sessions showing activity of MvfR inhibitors against Pseudomonas aeruginosa bacteria.  The conference will take place on September 5-9th at the Walter E. Washington Convention Center, Washington, DC.

Session # 144
Title: Alternative Treatment Approaches for Bacterial Infections.
Speaker:  Laurence G. Rahme, Massachusetts General Hospital/Harvard Medical School, Boston, Mass.
Session Type: Symposium
Topic:  Inhibition of Pseudomonas aeruginosa MvfR Reduces Acute Virulence and Chronic Infection Phenotypes
Date:  Monday, September 8, 2014
Presentation Time:  8:30 to 10:30 AM
Location:  Room 143 A

Summary:

  • Infections caused by Gram-negative bacterial pathogens are becoming increasingly difficult to treat due to resistance to current antibacterial drugs.  There is an urgent need to identify new antimicrobial drugs that will help circumvent the current antibiotic resistance crisis.
  • Bacterial pathogens often develop resistance to antibiotic drugs that target bacterial growth or viability. However strategies that specifically target virulence pathways non-essential for growth could limit selection for resistance.
  • This study examines the bacterial communication system MvfR (PqsR), which is known to control virulence of the opportunistic bacterial pathogen P. aeruginosa. Small molecule compounds were identified and optimized that effectively silenced the MvfR communication system, and as a result blocked P. aeruginosa virulence both in vitro and in vivo.
  • These new compounds are the first known to restrict the ability of bacteria to form antibiotic-tolerant cells and consequently proved to be very effective at preventing persistent infection in a mammalian infection model.
  • Conclusion: Because of their ability to simultaneously block acute and persistent infections, these new molecules may provide a strong basis for the development of next generation antimicrobials.

Session # 168
Title:  Advances against Gram-Negative Pathogens
Poster Title:  Identification of Anti-Virulence Compounds that Disrupt Quorum-Sensing
Regulated Acute and Persistent Pathogenicity
Presentation # F-1555
Authors:  M. Starkey #1, F. Lepine #2, D. Maura #1, A. Bandyopadhaya1, B. Lesic1, J. He1, T. Kitao1, V. Righi1, S. Milot2, A. A. Tzika1, L. G. Rahme1;
1Massachusetts Gen. Hosp., Harvard Med. Sch., Shriners Hosp., Boston, MA, 2INRS-Inst. Armand Frappier, Laval, QC, Canada
Date:  Monday, Sep 08, 2014
Presentation Time:  11:00 AM – 1:00 PM
Location: Exhibit Hall B

Summary:

  • Etiological agents of acute, persistent, or relapsing clinical infections – such as Pseudomonas aeruginosa – are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance.
  • Forty MvfR-regulon inhibitors, that specifically inhibit infection without affecting bacterial growth or viability to mitigate resistance selection, were identified using a whole-cell, high-throughput screen of ~300,000 compounds.  Subsequently the potency of the compounds was improved.
  • As a result, these inhibitors reduced P. aeruginosa virulence in vivo in both murine acute lung infection or burn infection models.
  • In addition, these compounds reduced antibiotic-tolerant persisters formation by inhibiting the pro-persistent QS molecule 2-AA, and consequently proved to be very effective at preventing persistent infection in mice.
  • Conclusion:  Molecules targeting the MvfR-regulated P. aeruginosa quorum sensing (QS) virulence pathway provide for the development of next-generation clinical therapeutics to treat deleterious bacterial-human infections refractory to existing therapies.

About Spero
Spero is a product-focused biopharmaceutical company developing a pipeline of novel treatments for bacterial infections and is located in Cambridge, Massachusetts.  Spero’s MvfR inhibitor program works differently from existing antibiotics by targeting a pathway involved in two critical bacterial processes: virulence and persistence.   Spero’s drug candidates may uniquely reduce the morbidity caused by severe infections and promote their clearance, including in bacterial strains highly resistant to even the most potent existing antibiotics.  For more information, please visit www.sperotherapeutics.com.

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CONTACT:

Spero Therapeutics:
Ankit Mahadevia, M.D.
Venture Partner at Atlas Venture

Maureen L. Suda (Media)
Suda Communications LLC
585-387-9248