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Spero Therapeutics Unveils Data on Lead Potentiator Candidate for the Treatment of Multidrug Resistant Gram-Negative Infections at ASM Microbe 2016

Monday, June 20, 2016 Drug News J E 4
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-- SPR741 data highlighted in Early New Antimicrobial Agents oral session and 15 poster presentations --

CAMBRIDGE, Mass., June 20, 2016 /PRNewswire-USNewswire/ -- Spero Therapeutics, LLC, a biopharmaceutical company founded to develop novel therapies for the treatment of bacterial infections, today revealed efficacy, safety, potency, mechanism of action, and dosing data related to SPR741, the Company's lead Potentiator candidate. The data were presented at the first annual ASM Microbe 2016 conference in Boston.

Novel approaches to the treatment of multidrug resistant (MDR) Gram-negative bacterial infections are urgently required. Current treatment options are limited to drugs that are only modestly effective or are highly toxic at effective doses. Through their Potentiator program, Spero is seeking to improve the potency and enhance the utility of many classes of new or existing antibiotics by combining them with one of their Potentiator candidates.

In multiple studies presented at ASM, researchers assessed the impact of different combinations of SPR741 and various antibiotics on mouse, rat and primate models of MDR Gram-negative bacterial infections. Based on the results of these and other studies, Spero expects to file an Investigational New Drug (IND) application for SPR741 with the U.S. Food and Drug Administration (FDA) by the end of 2016 with clinical testing to begin shortly after. 

"We are excited to present this important collection of data on our Potentiator program to the microbiology community at ASM Microbe," said Ankit Mahadevia, M.D., Chief Executive Officer of Spero. "Our highly experienced and skilled researchers and partners have worked diligently to establish the scientific rigor necessary for us to confidently move the Potentiator program forward toward the clinic, in the hopes of helping to address the growing global crisis of antibiotic resistance."

  • Efficacy of SPR741 in Combination with Rifampicin and Clarithromycin Four posters (#496, #497, #498, #561) demonstrate that the combinations of SPR741 with rifampicin and clarithromycin were effective at reducing the bacterial burdens in mice infected with E. coli, K. pneumonia, and A. baumannii bacteria, while treatment with SPR741, rifampicin, or clarithromycin alone did not achieve bacteriostatic effects against any bacteria tested.   
  • Safety/Toxicity Profile of SPR741 SPR741 is a derivative of the compound Polymyxin B, which is known to exhibit kidney toxicity. In poster #523, researchers demonstrate that in non-human primates (cynomolgus monkeys) SPR741 was not associated with kidney toxicity at any dose level tested following seven days of repeated, three-times daily, one hour infusions, compared to the active control, Polymyxin B, which demonstrated the anticipated toxicity. In rats, SPR741 was associated with a low degree of kidney toxicity at the highest dose tested (30 mg/kg/day).  
  • SPR741 Increases the Potency of Multiple Antibiotics Five posters (#490, #492, #500, #501, #502) demonstrate that adding SPR741 to a range of antibiotics, including azithromycin, aztreonam, clarithromycin, fusidic acid, meropenem, mupirocin, rifampicin, telithromycin, and retapamulin effectively reduced the doses of those antibiotics required to inhibit bacterial growth of multiple types of MDR bacteria, including E. coli, K. pneumoniae, E. cloacae, and A. baumannii.  
  • SPR741 Mechanism of Action Confirmed Poster #493 confirms, through the use of fluorescent stains, that SPR741 disrupts the cell membrane structure of Gram-negative bacteria (E. coli) and increases the permeability of the outer membrane, which allows antibiotics (azithromycin and bocillin) to enter the cell. Without the introduction of SPR741, the E. coli cell is typically impenetrable to those two antibiotics.
  • Human Dose Range of SPR741 Identified Poster #494 demonstrates, through well-established pharmacokinetic modeling, that the anticipated efficacious adult human dose of SPR741 would be consistent with reasonable CMC requirements and dose-linear pharmockinetics.

About The Spero Potentiator Program Spero's Potentiator Program disrupts the cell membrane of Gram-negative bacteria to permit access of antimicrobial agents previously only active against Gram-positive pathogens. Molecules are designed to disrupt the cell wall of Gram-negative bacteria, permitting Gram-positive antimicrobial agents access through periplasm and cytoplasmic membrane.

About SPR741SPR741, Spero's lead Potentiator candidate, is a derivative of the compound Polymyxin B, which interacts with phospholipids to disrupt the cell membrane structure. Unlike the parent molecule, Polymyxin B, which is an antibiotic itself, the potentiator molecule is not designed to cause bacterial cell death on its own. 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 E. coli, Acinetobacter baumannii, and K. pneumoniae. Spero intends to submit an Investigational New Drug (IND) application for its first SPR741 combination in 2016.

About SperoSpero is a biopharmaceutical company developing a pipeline of novel treatments for bacterial infections and is located in Cambridge, Massachusetts. The company's pipeline of anti-infective agents is one of the most unique in the industry. Spero's Potentiator technology is pioneering an entirely new therapeutic platform; this approach has yielded multiple molecules that enhance the spectrum utility and potency of many classes of existing drugs to include possible utility against Gram-negative pathogens. Spero's DHFR program is exploring the expansion of a novel antifolate's antibacterial spectrum to treat trimethoprim resistance isolates including resistant Gram-negative pathogens. The investors in Spero include Atlas Ventures, SR One, MRL Ventures, Lundbeckfond Ventures, The Kraft Group, Osage Partners and The Partners Innovation Fund. For more information, please visit www.sperotherapeutics.com.

 

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/spero-therapeutics-unveils-data-on-lead-potentiator-candidate-for-the-treatment-of-multidrug-resistant-gram-negative-infections-at-asm-microbe-2016-300286686.html

SOURCE Spero Therapeutics

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