Omadacycline Concentrations Exceed Tigecycline Lev

VIENNA, Austria, April 25, 2017 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc. (Nasdaq: PRTK ) today presented new data from a Phase 1 study confirming that its once-daily oral and IV, broad spectrum investigational antibiotic omadacycline effectively penetrates lung tissue and epithelial lining fluid and has a broad antimicrobial activity against those bacteria most commonly associated with community-acquired bacterial pneumonia (CABP). Data from a second Phase 1 study evaluating the safety of omadacycline compared to tigecycline reported no serious adverse events following IV treatment with either compound and reported that omadacycline was associated with a lower incidence of gastrointestinal adverse events compared to tigecycline. The new findings were presented at the annual meeting of the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2017) in Vienna, Austria.

“Intravenous dosing of omadacycline at 100 mg produced steady-state concentrations in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) that were three-fold higher than tigecycline in healthy subjects.  Our observed lung concentrations along with the minimum inhibitory concentration values for respiratory pathogens support the recent results of omadacycline being as effective as moxifloxacin in the treatment of patients with community-acquired bacterial pneumonia,” said Keith Rodvold, Pharm.D., professor in the College of Pharmacy, Co-Director of the Section of Infectious Diseases Pharmacotherapy at University of Illinois at Chicago. 

“Throughout our clinical development program, we have worked to generate a thorough understanding of all aspects of omadacycline and share that information with the scientific and clinical community,” said Evan Loh, M.D., President, Chief Operating Officer and Chief Medical Officer, Paratek. “These data add to the growing body of evidence to support omadacycline as an effective agent in the treatment of serious acquired bacterial infections, particularly where resistance is of concern to prescribing physicians.”

Phase 1 Bronchoalveolar Lavage Study The Phase 1 PK/PD study compared serial plasma concentrations of omadacycline and tigecycline in healthy adults. Subjects receiving omadacycline (n=41) received 100 mg IV every 12 hours for 2 doses then 100 mg IV once-daily; subjects in the tigecycline arm (n=17) received a 100 mg IV loading dose followed by 50 mg IV every 12 hours. To assess the concentration of both omadacycline and tigecycline in epithelial lining fluid (ELF) and alveolar macrophages (AM), bronchoalveolar lavage (BAL) was performed on all subjects. 

The AUC _0-24 /MIC ₉₀ ratios for omadacycline were greater than tigecycline across all measurements. Specific results showed omadacycline plasma ratios to be 3.2-fold higher (97.8 vs. 30.8) for S. pneumoniae and MSSA and 1.5-fold higher (46.9 vs. 30.8) for MRSA. The AUC _0-24 /MIC ₉₀ ratios in the ELF were 2.7-fold higher for omadacycline (143.6 vs. 52.7) for S. pneumoniae and MSSA and 1.3-fold higher (68.9 vs. 52. 7) for MRSA. AM ratios for L. pneumophila were 126-fold higher for omadacycline.

Phase 1 Safety and Tolerability Study In an open-label safety study presented yesterday, 63 healthy adults were randomized to omadacycline (n=42) or tigecycline (n=21). Dosing was similar to the PK/PD study and treatment duration was four days with a follow up assessment conducted 7 to 14 days after the final dose. Treatment emergent adverse events were mild-to-moderate in both groups and included headache, nosebleed (epistaxis), nausea, decreased appetite and vomiting. Fewer individuals in the omadacycline group reported gastrointestinal adverse event. There were two discontinuations in the tigecycline group due to nausea that were considered related to study drug.  No omadacycline subjects discontinued study treatment due to adverse events.

About Paratek Pharmaceuticals, Inc. Paratek Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative therapies based upon its expertise in novel tetracycline chemistry. Paratek's lead product candidate, omadacycline, is the first in a new class of tetracyclines known as aminomethylcyclines, with broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria. Omadacycline is a new, once-daily oral and intravenous broad spectrum antibiotic being developed for use as empiric monotherapy for patients suffering from serious community-acquired bacterial infections, such as acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, urinary tract infections, and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern to prescribing physicians. Omadacycline has been granted Qualified Infectious Disease Product designation and Fast Track status by the U.S. Food and Drug Administration for the target indications.

In June 2016, Paratek announced positive efficacy data in a Phase 3 registration study in acute bacterial skin and skin structure infections (ABSSSI) demonstrating the efficacy, general safety and tolerability of intravenous (IV) to once-daily oral omadacycline compared to linezolid. In April 2017, Paratek announced positive efficacy data in a Phase 3 registration study in community-acquired bacterial pneumonia (CABP) demonstrating the efficacy, general safety and tolerability of IV to once-daily oral omadacycline compared to moxifloxacin. A Phase 3 registration study in ABSSSI comparing once-daily oral-only dosing of omadacycline to twice-daily oral-only dosing of linezolid was initiated in August 2016. Top-line data from this study are expected as early as the end of June. The Company plans to submit its new drug application (NDA) in the U.S. as early as the first quarter of 2018 with an EMA submission later in 2018.

In addition to its Phase 3 program for omadacycline, a Phase 1B study in uncomplicated urinary tract infections (UTI) was initiated in May 2016 and positive top-line PK proof-of-principle data was reported in November 2016. The Company plans to begin enrolling patients in a proof-of-concept Phase 2 study of omadacycline in acute pyelonephritis, the most common subset of complicated urinary tract infections, as early as December 2017.

In October 2016, Paratek announced a research agreement with the U.S. Department of Defense to explore the utility of omadacycline against pathogenic agents causing infectious diseases of public health and biodefense importance including plague and anthrax.

Paratek's second Phase 3 product candidate, sarecycline, is a well-tolerated, once-daily oral, narrow spectrum tetracycline-derived antibiotic with potent anti-inflammatory properties for the potential treatment of acne and rosacea in the community setting. Allergan owns the U.S. rights for the development and commercialization of sarecycline. Paratek retains all ex-U.S. rights. Allergan and Paratek reported positive results from two identical Phase 3 registration studies of sarecycline for the treatment of moderate to severe acne vulgaris in March 2017. Allergan has publicly announced plans to submit an NDA in the U.S. in the second half of 2017. 

Forward Looking Statements This press release contains forward-looking statements including statements related to our overall strategy, product candidates, clinical studies, prospects and expected results, including statements about the timing of advancing omadacycline and otherwise preparing for clinical studies, the timing of enrollment in our clinical studies and of our reporting of the results of such studies, the potential for omadacycline to serve as an empiric monotherapy treatment option for patients suffering from ABSSSI, CABP, UTI, and other bacterial infections when resistance is of concern, the prospect of omadacycline providing broad-spectrum activity, and our ability to obtain regulatory approval of omadacycline. All statements, other than statements of historical facts, included in this press release are forward-looking statements, and are identified by words such as "advancing," "believe," "expect," "well positioned," "look forward," "anticipated," "continued," and other words and terms of similar meaning. These forward-looking statements are based upon our current expectations and involve substantial risks and uncertainties. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in our forward-looking statements and you should not place undue reliance on these forward-looking statements. Our actual results and the timing of events could differ materially from those included in such forward-looking statements as a result of these risks and uncertainties. These and other risk factors are discussed under "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2016, and our other filings with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to update or revise any forward-looking statements contained herein.

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