At a Glance

Autoimmune PAP is a rare lung disease characterized by the build-up of surfactant in the alveoli, or air sacs, of the lungs. It is a specific disease belonging to a family of distinct rare lung diseases collectively known as PAP syndrome. Autoimmune PAP represents about 90% of all patients with PAP and is estimated to have a prevalence of approximately 2,500 patients in the U.S., with a similar or higher prevalence reported elsewhere in the world. The disease process underlying aPAP involves an autoimmune response against GM-CSF, a naturally occurring protein, suppressing the stimulating activity of GM-CSF on lung macrophages which function to clear excess surfactant from the alveoli. The disease has a meaningful impact on quality of life. Symptoms include breathlessness, significantly reduced exercise capacity, frequent fatigue and, in severe cases, infection, progressive respiratory failure or even pulmonary fibrosis requiring a lung transplant. Currently, there are no approved pharmacological treatment options for aPAP, with whole lung lavage (WLL) being the current standard of care. WLL is an invasive surgical procedure performed under anesthesia to physically remove surfactant from a patient’s lungs.

Savara believes Molgradex has the potential to replace the inactivated GM-CSF in aPAP patients, thereby, restoring the surfactant clearing activity of the alveolar macrophages.

Nontuberculous mycobacteria are naturally occurring organisms in the environment. NTM lung infection is a rare and serious lung disorder that occurs when an individual inhales the organism and develops a slowly progressive and destructive lung disease. NTM infections often become chronic and require long courses of multiple antibiotics and, despite the aggressive treatment regimens, treatment failure rates are high and recurrence of infection common. NTM lung infections are associated with increased rates of morbidity and mortality and are a considerable therapeutic challenge due to the unique ability of the bacteria to evade the normal killing mechanisms of alveolar macrophages (a type of immune cells responsible for killing bacteria in the lungs).

There is increasing scientific literature suggesting that GM-CSF plays an important role in enhancing the ability of macrophages to clear mycobacteria. Unlike antibiotics that target bacteria directly, Molgradex may boost the body’s natural defenses, essentially helping the immune system clear the infection.

NCFB is a chronic lung disease characterized by abnormal widening of the airways associated with thickened and scarred walls due to infection and inflammation. Patients with bronchiectasis typically experience a chronic and productive cough, lung infection, malaise and increased hospitalizations due to pulmonary exacerbations, all of which negatively impact quality of life. The underlying pathology in bronchiectasis is a mix of infection, reduced immune response and inflammatory damage of the lungs. Currently, there are no pharmaceutical therapies approved for NCFB.

Savara believes that Apulmiq may increase the time-to exacerbation as well as reduce the density of Pseudomonas aeruginosa, a bacteria that is associated with more severe disease and higher morbidity and mortality.

CF is a life-shortening genetic disease characterized by thick, sticky mucus in the lungs and frequent lung infections, which result in loss of lung function. As the disease progresses, the lungs of people living with CF are typically infected with bacteria that are difficult to eradicate. Physicians have been using nebulized antibiotics to treat these infections and have sought new options for treatment in the chronic care setting. Persistent infection by MRSA has become increasingly common in the U.S. and is associated with faster decline in lung function and reduced survival. Currently there are no approved inhaled therapies for MRSA infection in people living with CF.

Savara believes that delivering AeroVanc directly to the site of infection may improve clinical efficacy and reduce adverse effects due to lessor systemic drug exposure as compared to IV antibiotic treatment.