Nabriva is developing its lead product candidate, lefamulin, to be the first pleuromutilin antibiotic available for systemic administration in humans. We are developing both intravenous (IV) and oral formulations of lefamulin for the treatment of community-acquired bacterial pneumonia (CABP) and intend to develop lefamulin for additional indications other than pneumonia.
Nabriva’s lead pleuromutilin product candidate, lefamulin, is being studied for the treatment of moderate to severe CABP. We have completed the LEAP 1 Phase 3 trial evaluating the safety and efficacy of intravenous (IV) to oral lefamulin in patients with community-acquired bacterial pneumonia (CABP).
In LEAP 1, our first clinical trial in patients with CABP, Lefamulin met all primary FDA and EMA endpoints of non-inferiority compared to moxifloxacin, with or without adjunctive linezolid, and was shown to be generally safe and well tolerated. We are currently enrolling patients in the LEAP 2 Phase 3 trial evaluating the efficacy and safety of oral lefamulin compared to oral moxifloxacin in subjects with moderate CABP.
We believe that lefamulin is well suited for use as a first-line empiric monotherapy for the treatment of CABP because of its novel mechanism of action; spectrum of activity, including against multi-drug resistant pathogens; achievement of substantial drug concentrations in lung tissue and fluids; availability as both an intravenous (IV) and oral formulation; and favorable safety and tolerability profile.
We have also completed a Phase 2 clinical trial for acute bacterial skin and skin structure infections (ABSSSI), in which IV lefamulin achieved a high cure rate against multi-drug resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In addition, in preclinical studies, lefamulin showed potent antibacterial activity against a variety of Gram-positive bacteria, Gram-negative bacteria and atypical bacteria, including multi-drug resistant strains.
The preclinical studies and clinical trials we have conducted to date suggest that lefamulin’s novel mechanism of action is responsible for the lack of cross resistance observed with other antibiotic classes and may result in slow development of bacterial resistance to lefamulin over time. As a result of the favorable safety and tolerability profile we have observed in our clinical trials to date, we believe lefamulin will present fewer potential complications relative to the use of current therapies.
Through our research and development efforts, we have identified a topical pleuromutilin product candidate, BC-7013, for which we have completed a Phase 1 clinical trial. We believe that this pleuromutilin compound is well suited for the topical treatment of a variety of Gram-positive infections, including uncomplicated skin and skin structure infections (uSSSIs).
Our pleuromutilin research program is based on our large and diverse proprietary compound library. We believe that our expertise in the areas of medicinal chemistry, pharmacology and toxicology have enabled targeted discovery of novel pleuromutilins through modification of side chains and core positions in the mutilin moiety. These modifications have resulted in alterations in microbial activity, ADME and toxicity of the semi-synthetic molecules.
We are actively pursuing an in-house discovery program to sustain our pipeline with future product candidates. The aim of this program is the development of novel pleuromutilins with enhanced affinity for the bacterial ribosome directed at increasing the antimicrobial potency and broadening the spectrum of activity to include rare strains with known mechanisms of resistance to the pleuromutilin class (e.g. cfr or Vga mutants). We believe next generation pleuromutlins have the potential to exhibit improved antibacterial activity and a pharmacokinetic profile that may make them well suited for the treatment of respiratory tract infections, acute/complicated bacterial skin infections, sexually transmitted infections and biothreat organisms.
Nabriva was incorporated as a spin-off from Sandoz GmbH Antibiotics Research Institute (ABRI) in Vienna, Austria and commenced operations in February 2006. The new organization included small molecule assets, including pleuromutilin structure activity relationships (SAR) knowledge and was focused on synthesis of pleuromutilins for systemic human use. Following identification of our lead compound lefamulin and based on the clinical results of lefamulin for Acute Skin and Skin Structure Infections (ABSSSI), we believed that targeted in vitro spectrum of activity for the common pathogens causing Community Acquired Bacterial Pneumonia (CABP), would allow us to develop lefamulin as the first pleuromutilin IV and oral antibiotic for human systemic administration for CABP.
In 2014, we opened our US office in King of Prussia, Pennsylvania and completed an IPO on the NASDAQ under the ticker NBRV in September 2015. We initiated two global, registrational Phase 3 clinical trials of lefamulin for the treatment of moderate to severe CABP.In June 2017, we redomiciled our corporate headquarters to Dublin,Ireland.
We reported positive top-line efficacy and favorable tolerability data from the LEAP 1 Phase 3 trial in September of 2017. Additionally, based on current projections, we continue to expect to complete patient enrollment for LEAP 2 in the fourth quarter of 2017 and anticipate receiving top-line data for LEAP 2 in the spring of 2018. If the results of these trials are favorable, including achievement of the primary efficacy endpoints of the trials, we expect to submit applications for marketing approval for lefamulin for the treatment of CABP in the United States in the second half of 2018.
As of July 15, 2017 Nabriva employed 66 employees at its headquarters in Dublin, Ireland and at its locations in Vienna, Austria and King of Prussia, Pennsylvania, United States.