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The MAR Inhibitors
Leading applications of MAR Inhibitors include:
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Preventing Severe Pulmonary Infections - Ventilated patients, patients with cystic fibrosis (CF), those with severe
chronic bronchitis, and non-ambulatory patients in hospitals and nursing homes are at risk for severe pulmonary infections.
Ventilator-associated pneumonia (VAP) is particularly difficult to treat with antibiotics because of the high incidence of
difficult-to-treat bacteria such as P. aeruginosa, Acinetobacter and Burkholderia, and mortality following infection can
be as high as 50% even with aggressive antibiotic therapy. Pseudomonas and other causative bacteria contain a MAR homolog
without which the organism is unable to sustain infections in animal models of lung infection. Paratek is testing its
small molecule MAR inhibitors as prophylactics which may be administered to ventilated patients and any others at risk
of hospital-acquired and severe pneumonias to prevent the onset of these life-threatening infections.
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Prevention of Nosocomial and Recurrent Urinary Tract Infections (UTIs) - The frequency and impact of urinary tract
infections is extraordinary as up to 40% of all hospital-acquired infections originate from urinary catheters accounting
for more than 1.5 million UTIs each year in U.S. hospitals and long-term care facilities (such as nursing homes and
rehabilitation centers). UTIs are also a major source of morbidity among ambulatory patients with millions of American
men and women chronically suffering from recurrent UTIs such as cystitis and prostatitis. For affected patients, the
use of broad-spectrum antibiotics can be continued intermittently for years and even be chronic causing unpleasant side
effects and compromising the effectiveness of antibiotics due to resistance development. Paratek has demonstrated the
effectiveness of its MAR inhibitors in in vivo models of UTI and against prominent urogenic bacterial pathogens.
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Bioterror Applications - Paratek is investigating the use of MAR inhibitors to prevent bioterrorism-related bacterial
infections. A number of bacterial agents that could be used by terrorists are of concern to U.S. and other governmental
authorities. MAR and related proteins have been identified in most potential bioterror bacterial agents, including gram-negative
bacteria, such as diarrheagenic E. coli, Vibrio spp., Shigella spp., Salmonella spp., Y. pestis, and gram-positive bacteria such
as B. anthracis.
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Combination with Antibiotics - The main emphasis for the MAR program has been the prevention of infection.
However, as the infection process is dynamic, MAR inhibitors could be used alone or in conjunction with antibiotics
to more effectively treat moderate to severe infections. MAR inhibitors have shown promise in combinations with
antibiotics by improving activity of current antibiotics.
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