Nabriva Presents Data on Lefamulin at the 2015 ID Week in San Diego

Nabriva is developing its lead product candidate, lefamulin, to be the first systemically available pleuromutilin for human use and expects to begin enrolling patients in the first of two Phase 3 clinical studies of lefamulin for the treatment of community acquired bacterial pneumonia (CABP) in the fourth quarter of 2015. Lefamulin possesses potent in vitro activity against the most common pathogens associated with CABP, specifically S. pneumoniae, H. influenzae, S. aureus, M. pneumoniae, M. catarrhalis, L. pneumophila, and C. pneumoniae, including multi-drug resistant strains.

Dr. Colin Broom, Chief Executive Officer of Nabriva, commented: "We believe that the lack of a single product that can confidently target the common pathogens causing CABP, including atypical pathogens and multi-drug resistant bacteria, superimposed upon the  problem of  growing bacterial resistance represent an increasingly important global public health threat. The development of new antibiotics with a novel mechanism of action against these pathogens is therefore critically important.  Lefamulin is currently in late-stage development for both intravenous and oral administration, and we believe that its novel mechanism of action, spectrum of activity and favorable tolerability profile differentiate lefamulin from currently available antibiotics and make lefamulin well suited for use as a first-line empiric monotherapy for the treatment of CABP.  We look forward to enrolling patients into our first Phase 3 clinical study later this quarter."

The poster abstract is as follows:
Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment (TA) Analyses Supporting Lefamulin Dose Selection for the Treatment of Patients with Community-Acquired Bacterial Pneumonia (CABP)
Sujata M. Bhavnani, PharmD, MS, Paul G. Ambrose, PharmD, FIDSA, Wolfgang W. Wicha, M.S., Zrinka Ivezic-Schoenfeld, Ph.D., William T. Prince, Ph.D., MB, BChir, FFPM and Christopher M. Rubino, Pharm.D.
Background: Lefamulin is a semi-synthetic intravenous (IV) and oral pleuromutilin antibiotic entering Phase 3 late-stage clinical development for CABP. Lefamulin is active against pathogens commonly associated with CABP, including multi-drug resistant (MDR) S. pneumoniae (SP), M. pneumoniae, and S. aureus (SA). Using in vitro, non-clinical PK-PD, and clinical pharmacokinetic (PK) data, PK-PD TA analyses were performed to provide support for the selection of a lefamulin dosing regimen for the treatment of patients with CABP.

Methods: Data utilized included a population PK (PPK) model describing the disposition of lefamulin developed using Phase 1 and 2 data, non-clinical PK-PD targets based on neutropenic murine-lung infection models and MIC data from isolates collected from North America (NA) and the European Union (EU) for lefamulin against SP and SA (SENTRY Program). The PPK model used was a 3-compartment model with first-order elimination with saturable protein binding. Lefamulin concentrations in epithelial lining fluid (ELF) were modeled using first-order rate constants into and out of the ELF compartment. Using the PK parameter estimates, ELF and free-drug plasma concentration-time profiles were generated for 2000 simulated patients following lefamulin 150 mg IV q12h; Day 1 AUC0-24 values were calculated. Non-clinical ELF and free-plasma AUC:MIC ratio targets (median and second highest) associated with a 1-log10 CFU reduction from baseline for SP and SA were evaluated. Percent probabilities of PK-PD TA by MIC value and over MIC distributions for SP and SA were determined.
Results: Percent probabilities of PK-PD TA by MIC are shown for SP and SA for ELF targets in the Figure. Percent probabilities of attaining median ELF AUC:MIC ratio targets were 97.0% at the MIC99 of 0.5 mg/L for SP and 99.4% at the MIC99 of 0.25 mg/L for SA. For the second highest targets, >=97.0% PK-PD TA was achieved at MIC90 values for each pathogen. Overall percent probabilities of attaining AUC:MIC ratio targets for SP and SA based on NA and EU MIC data were >=96.6%. Results based on plasma targets were similar for SP and SA.
Conclusion: Results of these PK-PD TA analyses for SP and SA provide support for the selection of lefamulin 150 mg IV q12h for the treatment of patients with CABP.

About Nabriva Therapeutics AG
Nabriva Therapeutics is a clinical stage biopharmaceutical company engaged in the research and development of novel anti-infective agents to treat serious bacterial infections, with a focus on the pleuromutilin class of antibiotics. Nabriva's medicinal chemistry expertise has enabled targeted discovery of novel pleuromutilins, including both intravenous and oral formulations of its lead product candidate, lefamulin. Nabriva is developing lefamulin to be the first systemically available pleuromutilin antibiotic for human use.  Lefamulin is being developed for the treatment of moderate to severe community acquired bacterial pneumonia (CABP). Future studies are planned to evaluate lefamulin for additional anti-infective indications.

About Lefamulin
Nabriva's lead pleuromutilin product candidate, lefamulin, is being developed to be the first systemically available pleuromutilin for human use and is the first new class of antibiotic to reach late stage clinical development for CABP in over a decade. The company expects to begin enrolling patients into the first of its two planned lefamulin Phase 3 CABP clinical studies in the fourth quarter of 2015. Nabriva believes lefamulin is well positioned for use as a first-line empiric monotherapy for the treatment of moderate to severe CABP due to its novel mechanism of action, targeted spectrum of activity, achievement of substantial drug concentration in lung tissue and fluid, oral and IV formulations and favorable tolerability profile. Nabriva also intends to further pursue the development of lefamulin for additional indications, including the treatment of acute bacterial skin and skin structure infections, and is developing a formulation of lefamulin appropriate for pediatric use.  
Nabriva owns exclusive, worldwide rights to lefamulin, which is protected by composition of matter patents issued in the United States, Europe and Japan.

Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for Nabriva, including statements about the development of Nabriva's product candidates, such as plans for the design, initiation and conduct of Phase 3 clinical trials of lefamulin for CABP, the clinical utility of lefamulin for CABP and Nabriva's plans to bring lefamulin to market, the development of lefamulin for additional indications, the development of additional formulations of lefamulin, plans to pursue research and development of other product candidates and other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "likely," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials in different disease indications will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates, the sufficiency of cash resources and need for additional financing and such other important factors as are set forth under the caption "Risk Factors" in Nabriva's final prospectus dated September 17, 2015 for its U.S. initial public offering as filed with the United States Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Nabriva's views as of the date of this release. Nabriva anticipates that subsequent events and developments will cause its views to change. However, while Nabriva 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 Nabriva's views as of any date subsequent to the date of this release.