Development

Lefamulin

Nabriva is a clinical-stage biopharmaceutical company engaged in the research and development of novel antibiotics to treat serious infections, with a focus on the pleuromutilin class of antibiotics. Nabriva is developing is 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.

Lefamulin is a semi-synthetic compound that inhibits the synthesis of bacterial protein, which is required for bacteria to grow. Lefamulin acts by binding to the peptidyl transferase center, or PTC, on the bacterial ribosome in such a way that it interferes with the interaction of protein production at two key sites known as the “A” site and the “P” site, resulting in the inhibition of bacterial proteins and the cessation of bacterial growth. Lefamulin’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes.

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 and was shown to be generally safe and well tolerated. LEAP 1 was a multi-center, randomized, controlled, double-blind, global study comparing lefamulin to moxifloxacin, a fluoroquinolone antibiotic with or without linezolid. The trial was designed to evaluate the efficacy and safety of lefamulin (IV/oral) compared to moxifloxacin (IV/oral) in adults with moderate to severe CABP.

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. LEAP 2 is a multi-center, randomized, controlled, double-blind, global study comparing oral lefamulin to moxifloxacin. The trial is designed to evaluate the efficacy and safety of oral lefamulin compared to oral moxifloxacin in subjects with moderate CABP. The company expects to complete enrollment in the fourth quarter of 2017, with initial data analysis to be completed in the spring of 2018.

We believe 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. Based on our research, we also believe that the availability of both intravenous (IV) and oral formulations of lefamulin, and an option to switch to oral treatment, could reduce the length of a patient’s hospital stay and the overall cost of care. Nabriva owns exclusive, worldwide rights to lefamulin.

Attributes that make lefamulin well suited for use as a first-line empiric monotherapy for the treatment of CABP include:

  • Novel mechanism of action
  • Targeted spectrum of activity covering key CABP pathogens, including against multi-drug resistant pathogens
  • Potential for slow development of bacterial resistance over time
  • Achievement of substantial drug concentrations in lung tissue and fluids
  • Convenient dosing regimen – potential for switching from IV to oral treatment
  • Demonstrated efficacy and favorable safety and tolerability profile

We intend to further pursue the development of lefamulin and are developing a formulation of lefamulin that is appropriate for pediatric use. We believe that lefamulin’s product profile also provides the opportunity to expand to additional indications beyond pneumonia, such as the treatment of acute bacterial skin and skin structure infections (ABSSSI), sexually transmitted infections (STIs), ventilator-associated bacterial pneumonia (VABP), hospital-acquired bacterial pneumonia (HABP), osteomyelitis and prosthetic joint infections.

BC-7013

BC-7013 is a semi-synthetic compound derived from pleuromutilin with the potential to be developed for the topical treatment of Gram-positive infections, including uncomplicated skin and skin structure infections (uSSIs). We have completed a Phase 1 clinical trial for BC-7013.

Research Program

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.