Savara Inc. is a clinical-stage specialty pharmaceutical company focused on the development and commercialization of novel therapies for the treatment of serious or life-threatening rare respiratory diseases. Savara’s strategy involves expanding its pipeline of potentially best-in-class products through indication expansion, strategic development partnerships and product acquisitions, with the goal of becoming a leading company in its field. Savara’s management team has significant experience in orphan drug development and pulmonary medicine, in identifying unmet needs, developing and acquiring new product candidates, and effectively advancing them to approvals and commercialization.
Nontuberculous mycobacterial lung infections are a considerable therapeutic challenge due to the unique ability of these 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. For instance, GM-CSF knock out mice inoculated with Mycobacterium abscessus develop a chronic lung disease resembling human chronic infection, whereas wild type mice with intact GM-CSF production typically clear the bacteria quickly, and fail to develop chronic infection. In animal studies, GM-CSF has been shown to kill NTM with similar efficacy compared to commonly used NTM antibiotics, and the simultaneous use of GM-CSF with antibiotics can further improve the antibacterial effect of either GM-CSF or antibiotics given alone. In two thus far unpublished clinical case reports, inhaled GM-CSF was shown to eradicate or dramatically reduce the bacterial burden in patients with refractory M. abscessus lung infection, which suggests the promising animal data may be translatable to humans, and that the potential therapeutic role of GM-CSF in NTM lung infection warrants more intensive investigation. Among the various NTM species, M. abscessus is a particularly challenging clinical problem, being one of the most resistant organisms to antibiotics. Importantly, GM-CSF is not an antibiotic, but instead targets the human immune response, not the bacteria directly, thus avoiding the increasing problem of antibiotic resistance.
There are approximately 30,000 people living with cystic fibrosis in the U.S. Cystic fibrosis is a life-shortening genetic disease characterized by thick, sticky mucus in the lungs and chronic lung infections resulting in gradual loss of lung function. The most prevalent lung pathogen in cystic fibrosis patients is Pseudomonas aeruginosa, which is commonly treated using inhaled antibiotics. In recent years, methicillin-resistant Staphylococcus aureus (MRSA), a bacterium that is resistant to conventional antibiotics (1), has become increasingly common, with a prevalence of almost 30% of the U.S. cystic fibrosis patient population. Recent publications indicate that cystic fibrosis patients with chronic MRSA infection have more hospitalizations, faster decline in lung function, and reduced life expectancy. (2,3,4)  Gorwitz RJ et al. Journal of Infectious Diseases. 2008:197:1226-34.  Prevalence and impact on FEV1 decline of chronic methicillin-resistant Staphylococcus aureus (MRSA) coloniation in patients with Cystic Fibrosis: A single-center case control study of 165 patients. Vanderhelst E, De Meirleir L, Verbanck S. et al. s.l. : J Cystic Fibrosis, 2012, Vol. 11, pp. 2-7.  Persistent Methicillin-resistant Staphylococcus aureus and Rate of FEV1 Decline in Cystic Fibrosis. Dasenbrook EC, Merlo CA, Diener-West M, et. al. s.l. : Am J Respir Crit Care Med, 2008, Vol. 178, pp. 814-821.  Elliott C. Dasenbrook; William Checkley; Christian A. Merlo; Michael W. Konstan; Noah Lechtzin; Michael P. Boyle. Association Between Respiratory Tract Methicillin-Resistant Staphylococcus aureus and Survival in Cystic Fibrosis. JAMA, 2010; 303 (23): 2386-2392.