“The data to be presented at ECCMID highlight the anticipated utility of our Potentiator Platform and we believe validate this novel approach to treat multidrug-resistant Gram-negative infections,” said
SPR741 is a novel investigational agent that is designed to expand the spectrum and increase the potency of a partner antibiotic when administered in combination. The Phase I trial of SPR741 being presented at ECCMID demonstrated the drug to be generally well tolerated in single doses of up to and including 800 mg and at doses up to and including 600 mg every 8 hours for 14 days. A Phase 1b drug-drug interaction trial of SPR741 is ongoing to assess the impact, if any, on the pharmacokinetics of SPR741 or the pharmacokinetics of the beta-lactam combination drug when the two are dosed together. We continue to expect to receive top-line data from the SPR741 Phase 1b drug-drug interaction trial during the second quarter of 2018.
The following posters further detail the data from the Phase 1 SPR741 trial:
- Safety of SPR741, a novel polymyxin potentiator, in healthy adults receiving single- and multiple-dose intravenous administrations
Poster Presentation – P2206; Presenter:
Paul Eckburg Tuesday, April 24, 2018, 12:30 p.m.– 1:30 p.m. CET
- Determination of the pharmacokinetics of single (SAD) and multiple ascending doses (MAD) of SPR741 in healthy volunteers
Poster Presentation – P2233; Presenter:
Luke Utley Tuesday, April 24, 2018, 12:30 p.m.– 1:30 p.m. CET
The SPR741 Phase 1 SAD/MAD clinical trial was a two-part, randomized, double-blind, placebo-controlled, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending intravenous doses of SPR741. The study enrolled 96 healthy adult volunteers in cohorts up to and including an 800 mg single dose and up to and including a 600 mg dose every 8 hours for 14 days. SPR741 was generally well tolerated in single doses of up to and including 800 mg and at doses up to and including 600 mg every 8 hours for 14 days. SPR741, administered up to 400 mg every 8 hours for up to 14 days, displayed linear and proportional pharmacokinetics and showed no evidence of accumulation or time dependent changes in plasma exposure as measured by AUC, Cmax or Ctrough. Renal clearance decreased slightly with dose after 14 days of repeat dosing.
The following posters characterize the activity and synergistic effects of SPR741 in combination with a partner antibiotic:
- Bactericidal activity of ceftazidime in combination with SPR741 against susceptible, extended-spectrum beta-lactamase producing, and multi-drug resistant Escherichia coli, Klebsiella pneumoniae, and Enterobacter species
Poster Presentation – P1674; Presenter:
Nicole Cotroneo Monday, April 23, 1:30 p.m.– 2:30 p.m. CET
- Bactericidal activity of piperacillin-tazobactam in combination with SPR741 against susceptible, extended-spectrum beta-lactamase producing, and multi-drug resistant Escherichia coli, Klebsiella pneumoniae, and Enterobacter species
Poster Presentation – P1675; Presenter:
Nicole Cotroneo Monday, April 23, 2018, 1:30 p.m.– 2:30 p.m. CET
The in vitro data suggest that the addition of 8 mg/L of SPR741 to ceftazidime or piperacillin-tazobactam may significantly enhance the antimicrobial potency and cidality of the agents against clinical isolates of Enterobacteriaceae.
- Antimicrobial activity of Ceftazidime and Piperacillin-Tazobactam tested in combination with a potentiator molecule (SPR741) against Enterobacteriaceae causing urinary-tract infections
Poster Presentation – P1671; Presenter:
Rodrigo E. Mendes Monday, April 23, 2018, 1:30 p.m.– 2:30 p.m. CET
An assessment of the in vitro activity of ceftazidime or piperacillin-tazobactam in combination with SPR741 against Gram-negative urinary tract infection, or UTI, pathogens, including Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, suggests that SPR741 has the ability to extend the potency of these standard-of-care agents.
- Evaluation of synergistic effects of a potentiator molecule (SPR741) when tested in combination with a series of beta-lactam agents against a challenge set of Gram-negative pathogens
Poster Presentation – P1672; Presenter:
Rodrigo E. Mendes Monday, April 23, 2018, 1:30 p.m.– 2:30 p.m. CET
The in vitro data suggest that SPR741 significantly potentiates the antimicrobial activity of ceftazidime, piperacillin-tazobactam, mecillinam and temocillin against a challenge set of pathogens that express a diverse array of beta-lactam antimicrobial resistance mechanisms, including plasmid AmpC (pAmpC), extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), metallo-β-lactamase (MBL), and OXA-48-like enzymes.
- In vitro activity of ceftazidime alone and in combination with SPR741 against anaerobic bacteria
Poster Presentation – P1673; Presenter:
Aileen Rubio Monday, April 23, 2018, 1:30 p.m.– 2:30 p.m. CET
An assessment of the MIC90 values suggest that SPR741 or ceftazidime alone, or in combination is unlikely to significant impact the viability of common anaerobic bacteria, and thus, unlikely to cause significant perturbations to the gut microbiota.
The following poster characterizes the mechanism of action of SPR741:
- Characterization of SPR741, a potentiating polymyxin B analog, using atomic force microscopy and chemical-genomics profiling
Oral Presentation – O0249; Presenter:
Aileen Rubio Saturday, April 21, 2018, 5:06 p.m.– 5:16 p.m. CET
The outer membrane of Gram-negative bacteria acts as a formidable permeability barrier for some antibiotics. Studies to assess the impact on the outer membrane and potential mechanism of action of SPR741 suggest that it acts as an outer membrane disruptor and its potential molecular target may be distinct from the structurally similar compound polymyxin B nonapeptide.
Complete abstracts for the presentations listed above can be accessed through the ECCMID website.
About the Spero Potentiator Platform
Our Potentiator Platform molecules are designed to treat Gram-negative bacterial infections through the molecules’ interactions with the bacteria’s outer cell membrane as a monotherapy or by co-administering our Potentiator Platform molecules with existing antibiotics, thereby making the existing antibiotics more effective by clearing a path for them to enter and kill the bacteria. We have two Potentiator Platform product candidates – SPR741, our combination IV-administered agent that has demonstrated in vitro the ability to expand the spectrum and increase the potency of a co-administered antibiotic; and SPR206, our direct acting IV-administered agent that has demonstrated in vitro activity alone. Both have demonstrated potency against Gram-negative bacteria, including organisms identified by the Centers for Disease Control and Prevention, or the CDC, and the World Health Organization, or the WHO, as urgent and serious threats to human health. SPR741 has demonstrated an ability to potentiate over two dozen existing antibiotics by expanding their activity against Gram-negative pathogens. SPR206 is designed to also have antibiotic activity as a single agent against MDR and extremely drug resistant, or XDR, bacterial strains, including variants isolated in Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae.
The work on these compounds was partially supported by non-dilutive funding from the
Spero Therapeutics is a multi-asset, clinical-stage biopharmaceutical company focused on identifying, developing and commercializing novel treatments for multidrug-resistant (MDR) bacterial infections.
Spero is advancing SPR994, a carbapenem-class antibiotic, which is designed to be the first broad-spectrum oral antibiotic for use in adults to treat MDR Gram-negative infections.
Spero is also advancing its Potentiator Platform, which it believes will enable the development of drugs that will expand the spectrum and potency of existing antibiotics, including formerly inactive antibiotics, against Gram-negative bacteria. The product candidates are two IV-administered agents, SPR741 and SPR206, designed to treat MDR Gram-negative infections in the hospital setting.
Spero is also advancing SPR720, its novel oral therapy product candidate designed for the treatment of pulmonary non-tuberculous mycobacterial (NTM) infection, an orphan infectious disease.
Forward Looking Statements
This press release may contain forward-looking statements. These statements include, but are not limited to, statements about the initiation, timing, progress and results of the Company’s preclinical studies and clinical trials and the Company’s research and development programs, including statements regarding management’s assessment of the results of such preclinical studies and clinical trials, the timing of clinical data, the Company’s cash forecast and anticipated expenses and the sufficiency of the Company’s cash resources. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “aim,” “anticipate,” “could,” “intent,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether the Company’s product candidates will advance through the preclinical development and clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether the Company’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the “Risk Factors” section of the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on April 2, 2018, and risks described in other filings the Company may make with the Securities and Exchange Commission in the future. The forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release.
Spero Investor Contact:
Director, Investor Relations
Source: Spero Therapeutics, Inc.