About Savara Pharmaceuticals:
Savara Inc. (NASDAQ: SVRA) is an orphan lung disease company. Savara’s pipeline comprises a number of late stage therapeutics each targeting difficult to treat lung diseases.
For people not familiar with Savara, can you provide a brief overview and focus?
Neville: Savara was founded in 2008 and based in Austin, Texas. Our pipeline consists of the following products:
- Molgradex, an inhaled granulocyte-macrophage colony-stimulating factor, or GM-CSF, in Phase 3 development for autoimmune pulmonary alveolar proteinosis, or PAP. This is an autoimmune disease that causes a difficult to treat excess of surfactant in the lung.
- Molgradex in Phase 2a development for nontuberculous mycobacterial (NTM) lung infection. This is a very difficult to treat intra-cellular lung infection.
- AeroVanc, a Phase 3 stage inhaled vancomycin for treatment of MRSA infection in cystic fibrosis (CF). This is a drug-resistant infection in people living with the genetic disease of CF.
Our focus is getting these important medications to the market, but also expanding our pipeline through indication expansion, strategic development partnerships and product acquisitions, with the goal of becoming a leading company in our field.
You recently announced the initiation of the OPTIMA Phase 2 clinical trial for a new indication of your lead product candidate, Molgradex, for a rare disease known as nontuberculous mycobacterial (NTM) lung infection. Please explain what NTM lung infection is?
Neville: NTM lung infection is a rare and serious lung disorder associated with increased rates of sickness and death. NTM infection is caused by bacteria in the environment that you breathe in through your nose and mouth. If not adequately treated, the infection may become chronic and cause damage to the lungs. People with a history of lung conditions, like bronchiectasis, chronic obstructive pulmonary disease (COPD), CF or asthma are more likely to develop an infection. NTM is sometimes misdiagnosed or not diagnosed at all.
How common is NTM?
Neville: There are between 50,000 and 80,000 cases of NTM in the U.S., and this is increasing by approximately 8% every year. There are a number of species of NTM with the most common species being Mycobacterium avium complex, or MAC, and the more problematic Mycobacterium abscessus complex, or M. abscessus.
Why is NTM so difficult to treat and what are current treatment options?
Neville: These infections are a considerable therapeutic challenge. NTM lung infection is characterized by a macrophage dysfunction that allows the bacteria to survive and multiply inside this type of immune cells that are normally supposed to kill the bacteria. This makes the bacteria less susceptible to normal antibiotic treatment. Current treatment options include very long, multi-drug antibiotic regimens with significant patient burden, toxicity and frequent failure of achieving eradication.
Neville: Molgradex is an inhaled formulation of recombinant human GM-CSF. GM-CSF is not an antibiotic. Rather than targeting bacteria directly, GM-CSF stimulates the innate immune system in the lungs. The attraction of this approach is that we expect it can be used both with or without antibiotics and that the mechanism will not be affected by antibiotic resistance by the bacteria.
What do study results indicate so far?
Neville: 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 may further improve the antibacterial effect.
Two clinical case reports exploring the use of aerosolized GM-CSF for the treatment of M. abscessus were recently published in the European Respiratory Journal by clinicians at the Mayo Clinic College of Medicine. In these two cases with patients living with CF, inhaled GM-CSF either eradicated or dramatically reduced M. abscessus infection, improved clinical outcome, and was well tolerated.
Molgradex is delivered as an inhaled therapy. What makes this a desirable way to deliver drugs for this disease?
Neville: As with all our products, inhalation allows for targeted delivery of high concentrations of medications directly to the intended site of activity, which increases efficacy, with minimal systemic absorption and toxicity or side effects elsewhere in the body.
Can you explain the OPTIMA Phase 2 trial for Molgradex in NTM and when you’ll know results?
Neville: The OPTIMA study will be conducted at six investigative sites, four in Australia and two in the UK. The study will enroll patients affected by either MAC or M. abscessus and will include patients who are refractory to standard NTM antibiotics but still continue using them, as well as patients who have stopped antibiotic treatments because of intolerance or lack of efficacy. We believe Molgradex for use in treating NTM lung infection will be eligible for Orphan Status as well as Qualified Infectious Disease Product Status, and if the results of the OPTIMA study meet our expectations, the product may also qualify for Breakthrough Therapy Designation. We expect to complete enrollment in Q3 2018 and report top line results in H1 2019. As OPTIMA is an open label study, depending on enrollment and other factors, there is a possibility of interim results in 2018.
What’s in the store for Savara in 2018?
Neville: I am incredibly excited about the progress our team continues to make and in our ability to execute and consistently meet or even exceed our guidance. With two late-stage clinical studies ongoing, IMPALA and AVAIL, our focus in 2018 will be on the continued advancement of our core programs while actively exploring further expansion of our pipeline. Some key upcoming clinical milestones to look forward to in 2018 include the completion of the enrollment in our Phase 3 IMPALA study of Molgradex in PAP, expected in the third quarter of 2018 and the completion of patient enrollment in our Phase 2a OPTIMA study of Molgradex in NTM lung infection in the third quarter of 2018.
While our current focus is the treatment of PAP, MRSA lung infection in cystic fibrosis, and NTM, we are very much forward looking. We believe we are just beginning to explore the full potential of Molgradex, and we are hopeful that it could represent a paradigm shift in the treatment of lung infection via the stimulation of the innate immune system in the lung. We remain passionate about the potential of our treatments to have a positive impact on the lives of patients and we look forward to continued growth and value creation.