Technology Turns Off 'Master Switch' Underlying Bacterial Infection and May
Have Broad Use in Preventing Critical Bacterial Infections
BOSTON, Sept. 18 /PRNewswire/ -- Paratek Pharmaceuticals, Inc. announced today the most advanced preclinical results of the Company's Multiple Adaptation Response (MAR) inhibitor program. MAR proteins in bacteria serve as the "master switch" controlling virulence and antibiotic resistance. Paratek has shown that shutting down this switch disables bacterial virulence and prevents bacteria from causing infection. Paratek is developing MAR inhibitors that can prevent serious and life-threatening bacterial infections in high-risk patients.
The results were reported in a "late breaker" poster presentation titled, "A Novel Anti-Virulence Approach for Treatment of Pneumonia Caused by Pseudomonas aeruginosa," at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) taking place in Chicago. The findings demonstrated that small molecule agents which block the activity of ExsA (a MAR protein) in Pseudomonas aeruginosa significantly reduced bacterial virulence and were protective in an animal model from pneumonia. Lead authors on the research are Michael P. Draper, Ph.D., Director of Anti-Infective Drug Discovery at Paratek Pharmaceuticals, and Stuart B. Levy, M.D., Chief Scientific Officer and Co-Founder of Paratek.
In addition, Paratek announced a newly released publication showing efficacy of the Company's MAR inhibitors against E. coli in urinary tract infection in another animal model of serious bacterial infection. The article, titled, "Novel anti-infection agents: Small-molecule inhibitors of bacterial transcription factors," is appearing in the current August 2007 issue of Bioorganic & Medicinal Chemistry Letters.
Dr. Levy commented, "We are very pleased with the progress of the MAR program. We have shown proof of concept in E. coli, Yersinia and now Pseudomonas, a gram-negative bacterium with increasing multi-drug resistance which is a leading cause of hospital-acquired infections and death. We have also supported previous evidence that MAR inhibitors act as non-antibacterial compounds, which means they do not inhibit growth of bacteria and should therefore be less likely to foster resistance development. This new paradigm in infectious diseases will be very useful in preventing a broad range of critical bacterial infections."
Thomas J. Bigger, President and CEO of Paratek Pharmaceuticals, stated, "Paratek's MAR program has the potential to reshape the course of existing antibiotics and create a new standard in anti-infective therapy by directly preventing infection. The Company plans to achieve further proof of concept and enter into IND-enabling preclinical studies in 2009."
About the MAR Proteins
MAR proteins such as ExsA and its homologues in other bacteria constitute a novel "master switch" that controls the expression of multiple other proteins involved in serious infections including those caused by bacteria such as Escherichia coli, Yersinia, and Pseudomonas aeruginosa. When activated, the MAR system initiates a number of bacterial survival and defense mechanisms, including processes whereby bacteria establish infections and develop resistance to a broad range of antibiotics and other toxic substances. MAR inhibitors interfere with protein function, specifically eliminating the synthesis of proteins controlling virulence, and act as effective agents for preventing infection. MAR inhibitors are also non-antibacterial and therefore, not under the same selection pressure for multi-drug resistance as traditional antibiotics. Initial potential applications include preventing and treating severe pulmonary infections in ventilator-assisted patients, other nosocomial infections and recurrent urinary tract infections.
About Paratek Pharmaceuticals
Paratek Pharmaceuticals, Inc. is engaged in the discovery and commercialization of new therapeutics that treat serious and life-threatening diseases, with a particular focus on the growing worldwide problem of antibiotic resistance. Paratek is advancing novel compounds that can circumvent or block bacterial resistance involving technology initially developed by Paratek co-founder Dr. Stuart Levy's laboratory at Tufts University School of Medicine, and licensed by Paratek. Paratek's lead compound, PTK 0796, is a broad spectrum antibiotic derived from the tetracycline class with oral and IV formulations that is being developed for the treatment of the most common serious and hospital bacterial infections, including those caused by resistant strains such as MRSA (methicillin resistant Staphylococcus aureus). In addition to PTK 0796 and its MAR inhibitor program Paratek is also developing community-targeted broad-spectrum antibiotics and narrow-spectrum antibiotics to treat acne and C. difficile associated-diarrhea (CDAD).
Outside the antibacterial therapeutic area, Paratek has also established an effort to exploit its novel tetracycline derivatives and their unique mechanism of action in selected inflammatory and neurodegenerative conditions. Paratek has an active chemical synthesis effort to produce novel and diverse small molecules, with the goal of developing non-antibacterial compounds with improved activity in serious inflammatory and neurodegenerative diseases based upon a growing body of clinical research supporting this approach.
Paratek has active collaborations with Merck, MerckSerono, Warner-Chilcott and FSMA to develop orally available small molecule drugs for community bacterial infections, multiple sclerosis, acne & rosacea, and spinal muscular atrophy (SMA), respectively. Paratek is privately held and headquartered in Boston, Massachusetts, USA. For more information about Paratek and its research and development initiatives, visit Paratek's website at http://www.paratekpharm.com/.
|SOURCE Paratek Pharmaceuticals, Inc.|
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