— Bactericidal results support continued development of Potentiator molecules for the treatment of multidrug resistant Gram-negative infections —
CAMBRIDGE, MA, USA I April 18, 2017 I Spero Therapeutics, LLC, a biopharmaceutical company founded to develop novel therapies for the treatment of bacterial infections, will present preclinical data supporting the use of SPR741 combination therapy for the treatment of multidrug resistant (MDR) Gram-negative infections at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) April 22-25, 2017 in Vienna, Austria.
“Our ongoing preclinical research helps broaden and deepen our understanding of the efficacy and safety of potential SPR741 combinations to enhance the utility of many classes of new or existing antibiotics against a range of bacterial infections of diverse origin,” said Dr. Troy Lister, Head of Chemistry at Spero Therapeutics. “Antibiotic resistance has been identified as one of the greatest public health threats worldwide so we are working diligently with our partners to establish the scientific foundation upon which we can build a successful clinical program to help accelerate our efforts to deliver new treatments to patients.”
Details of the presentations are as follows:
- In vivo Efficacy of Combinations of Novel Antimicrobial Peptide SPR741 and Rifampicin in Neutropenic Murine Thigh Infection Models of Gram-Negative Bacterial Infection (Oral Presentation – OS0563; Monday, April 24, 9:48 a.m. – 9:58 a.m. CET)
The combination of SPR741 with rifampicin was effective at reducing the thigh burden of mice infected with Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae, including carbapenem resistant strains, compared to those left untreated or treated with either drug alone. The combination of SPR741 with rifampicin led to containment or reductions in burden compared to pre-treatment levels; while higher doses of SPR741 combined with rifampicin, reduced burdens to below pre-treatment levels, indicating bactericidal activity.
- In vivo Efficacy of Combinations of Novel Antimicrobial Peptide SPR741 and Rifampicin in Neutropenic Murine Pneumonia Models of Gram-Negative Bacterial Infection (Poster Presentation – P1282; Monday, April 24, 12:30 p.m. CET – 1:30 p.m. CET)
The combination of SPR741 with rifampicin led to highly significant reductions in bacterial burden compared to pre-treatment levels in mice infected with K. pneumonia, and Acinetobacter baumannii bacteria, while treatment with SPR741 or rifampicin alone had little effect on lung burden. For both bacterial species the reductions in burden were to below pre-treatment levels, indicating bactericidal activity, and potential to drive efficacy in models of infectious pneumonia.
- Polymyxin B Nonapeptide is Nephrotoxic in Male Cynomolgus Monkeys Following 7-Days of Repeated Intravenous Dosing (Poster Presentation – P1282; Monday, April 24, 12:30 p.m. CET – 1:30 p.m. CET)
PMBN was administered to male cynomolgus monkeys as a 60-minute IV infusion three times a day for 7 days. Toxicokinetic samples were taken on study day 1 and 7. PMBN is nephrotoxic in a clinically relevant species for assessing polymyxin nephrotoxicity. The systemic exposure of PMBN associated with the nephrotoxicity is comparable to reported polymyxin B exposure in monkeys.
In December 2016, Spero began a Phase 1 double-blind, placebo-controlled, ascending dose, multi-cohort trial evaluating safety, tolerability and pharmacokinetics of SPR741 in healthy volunteers. Results are expected later this year.
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
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 classes of 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 extended spectrum beta lactamases (ESBLs), and Gram-positive bacteria. Spero Therapeutics also has a robust preclinical pipeline including SPR720, which is a preclinical oral therapeutic candidate for nontuberculous 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.
SOURCE: Spero Therapeutics
Post Views: 28
— Bactericidal results support continued development of Potentiator molecules for the treatment of multidrug resistant Gram-negative infections —
CAMBRIDGE, MA, USA I April 18, 2017 I Spero Therapeutics, LLC, a biopharmaceutical company founded to develop novel therapies for the treatment of bacterial infections, will present preclinical data supporting the use of SPR741 combination therapy for the treatment of multidrug resistant (MDR) Gram-negative infections at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) April 22-25, 2017 in Vienna, Austria.
“Our ongoing preclinical research helps broaden and deepen our understanding of the efficacy and safety of potential SPR741 combinations to enhance the utility of many classes of new or existing antibiotics against a range of bacterial infections of diverse origin,” said Dr. Troy Lister, Head of Chemistry at Spero Therapeutics. “Antibiotic resistance has been identified as one of the greatest public health threats worldwide so we are working diligently with our partners to establish the scientific foundation upon which we can build a successful clinical program to help accelerate our efforts to deliver new treatments to patients.”
Details of the presentations are as follows:
- In vivo Efficacy of Combinations of Novel Antimicrobial Peptide SPR741 and Rifampicin in Neutropenic Murine Thigh Infection Models of Gram-Negative Bacterial Infection (Oral Presentation – OS0563; Monday, April 24, 9:48 a.m. – 9:58 a.m. CET)
The combination of SPR741 with rifampicin was effective at reducing the thigh burden of mice infected with Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae, including carbapenem resistant strains, compared to those left untreated or treated with either drug alone. The combination of SPR741 with rifampicin led to containment or reductions in burden compared to pre-treatment levels; while higher doses of SPR741 combined with rifampicin, reduced burdens to below pre-treatment levels, indicating bactericidal activity.
- In vivo Efficacy of Combinations of Novel Antimicrobial Peptide SPR741 and Rifampicin in Neutropenic Murine Pneumonia Models of Gram-Negative Bacterial Infection (Poster Presentation – P1282; Monday, April 24, 12:30 p.m. CET – 1:30 p.m. CET)
The combination of SPR741 with rifampicin led to highly significant reductions in bacterial burden compared to pre-treatment levels in mice infected with K. pneumonia, and Acinetobacter baumannii bacteria, while treatment with SPR741 or rifampicin alone had little effect on lung burden. For both bacterial species the reductions in burden were to below pre-treatment levels, indicating bactericidal activity, and potential to drive efficacy in models of infectious pneumonia.
- Polymyxin B Nonapeptide is Nephrotoxic in Male Cynomolgus Monkeys Following 7-Days of Repeated Intravenous Dosing (Poster Presentation – P1282; Monday, April 24, 12:30 p.m. CET – 1:30 p.m. CET)
PMBN was administered to male cynomolgus monkeys as a 60-minute IV infusion three times a day for 7 days. Toxicokinetic samples were taken on study day 1 and 7. PMBN is nephrotoxic in a clinically relevant species for assessing polymyxin nephrotoxicity. The systemic exposure of PMBN associated with the nephrotoxicity is comparable to reported polymyxin B exposure in monkeys.
In December 2016, Spero began a Phase 1 double-blind, placebo-controlled, ascending dose, multi-cohort trial evaluating safety, tolerability and pharmacokinetics of SPR741 in healthy volunteers. Results are expected later this year.
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
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 classes of 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 extended spectrum beta lactamases (ESBLs), and Gram-positive bacteria. Spero Therapeutics also has a robust preclinical pipeline including SPR720, which is a preclinical oral therapeutic candidate for nontuberculous 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.
SOURCE: Spero Therapeutics
Post Views: 28
