AP-PA02 is a therapeutic phage cocktail that targets the pathogen P. aeruginosa, to treat serious respiratory infections, with an emphasis on patients with cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (NCFB).
AP-PA02 is one example of the novel product candidates to emerge from Armata’s robust research and development capabilities. Phages that comprise AP-PA02 were selected with desired attributes for a product candidate targeting P. aeruginosa lung infections. AP-PA02 is comprised of a cocktail of natural P. aeruginosa phages originating from distinct families and subfamilies, targeting multiple receptor classes, functioning with compatibility and cooperativity, and further characterized by being highly potent and having a broad host range. Preclinical highlights of AP-PA02 include:
- Significantly reduced P. aeruginosa biofilm mass in vitro;
- Persistence of active phage particles in the lung;
- Limited systemic and off-target organ distribution;
- Decreased mortality in a murine model of acute P. aeruginosa lung infection;
- Components are stable in relevant biological fluids, such as sputum;
- Not antagonistic with standard of care antibiotics; and
- Active in the presence of other CF therapies.
AP-PA02 is developed as a sterile liquid formulation, suitable for delivery by inhalation. Clinical trial material of AP-PA02 is manufactured under cGMP at Armata’s production facility in Marina del Rey, California.
AP-PA02 is currently in clinical development. Armata has received FDA clearance for its Investigational New Drug (IND) application to initiate the “SWARM-P.a.” study – a Phase 1b/2a, double-blind, randomized, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial to evaluate the safety, tolerability and phage recovery profile of AP-PA02 administered by inhalation in subjects with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa infection. The SWARM-P.a. study is supported by the CFF, which in March 2020 granted us a Therapeutics Development Award of up to $5.0 million. With positive outcomes from this first study, SWARM-P.a., we plan to initiate follow-on studies that will investigate the efficacy of AP-PA02 in chronically-infected patients and potentially other CF patient populations. Our goal is to bring AP-PA02 to the CF community at large as a new FDA-approved novel therapy to treat airway P. aeruginosa infections and improve the long-term health of people with CF.
Screening P. aeruginosa isolates from people diagnosed with NCFB revealed that the AP-PA02 cocktail offers broad coverage and robust potency in this indication as well. Armata plans to advance AP-PA02 into a Phase 2 trial in NCFB in 2022.
Representing the different physiology of acute pneumonia lung infections as compared to chronic CF and NCFB respiratory infections, a novel cocktail is in development for the clinical indication of pneumonia. Armata has deployed its extensive clinical isolate collection and phage library to identify a candidate phage cocktail, AP-PA03, that is undergoing manufacturing with a regulatory filing expected in 2022 or 2023.
Target Market and Medical Need
P. aeruginosa is consistently recognized as among the most dangerous and difficult-to-treat pathogens associated with significant impacts on health, quality of life, and economic burden. Pseudomonas is particularly problematic for CF patients given that their compromised lung function leads to chronic infections. CF affects over 30,000 people in the U.S. (70,000 people worldwide) with approximately 1,000 new diagnoses per year. Outcomes for people with CF have improved significantly in recent years through early screening, the development and use of CFTR modulators, and other therapies. However, people with CF still suffer significant morbidity and mortality due to pulmonary infection with P. aeruginosa. Chronic P. aeruginosa infections occur in 55% of CF patients by age 25, and are strongly associated with worsening lung function, frequent pulmonary exacerbations, and increased mortality. In 2018, the median survival age was 47 years. Regular standard-of-care antibiotics treatments often fail to completely eradicate the pathogen, and the problem is further complicated by rising rates of antibiotic resistance due to a growing number of multidrug-resistant isolates emerging, particularly with long term use. Hence the need for more effective therapies, ideally with a different mechanism of action compared to traditional antibiotics, for the treatment of chronic P. aeruginosa infection. GlobalData projects that total antibiotic sales in the CF market will exceed $400 million in 2020.
In addition to CF lung infections, Armata has begun charting the appropriate clinical and regulatory paths for other respiratory infections with high unmet medical need, such as non-cystic fibrosis bronchiectasis (NCFB). NCFB is a chronic respiratory disease affecting more than 110,000 people in the U.S. and 200,000 people in Europe, characterized by recurrent respiratory infections that lead to a vicious cycle of impaired mucociliary clearance, chronic infection, bronchial inflammation, and progressive lung function loss. P. aeruginosa is the most prevalent pathogen responsible for these recurrent infections. It is found in approximately 30% of cases and is associated with enhanced disease progression, including poorer lung function and lower quality of life, more frequent exacerbations, increased hospitalizations, and higher mortality. NCFB patients frequently become chronically colonized with multidrug-resistant strains of P. aeruginosa because of the need for repeated courses of antibiotic treatment. There are currently no approved inhaled antibiotics for the treatment of NCFB patients with chronic P. aeruginosa respiratory infections.
Hospital-acquired pneumonia and ventilated-associated pneumonia is one of the most common causes of death among all hospital‐acquired infections, with approximately 300,000 hospitalization each year in the U.S. due to Pseudomonas. Infection with Pseudomonas results in mortality rates ranging as high as 35‐50%, drives considerable healthcare costs, and accounts for around 50% of all intensive care unit antibiotics.