Phage Product Candidate for Pseudomonas aeruginosa Respiratory Infections
AP-PA02 is a therapeutic phage cocktail that targets the pathogen P. aeruginosa, to treat serious respiratory infections, with an initial emphasis on cystic fibrosis (CF) patients.
Human exposure through treatment of single patients under the expanded access program with our first-generation phage product candidate, AP-PA01, indicate that it is generally well-tolerated. AP-PA01 was featured in the peer-reviewed journal Infection following the successful treatment of a CF patient who had developed a multidrug-resistant P. aeruginosa infection (Press Release). Another success with AP-PA01 used to treat a 77-year-old patient with ventilated-associated pneumonia and empyema was described in the American Journal of Respiratory and Critical Care Medicine. AP-PA01 has advanced through a pre-IND meeting with the U.S. FDA, and feedback from this meeting has been insightful for the regulatory path required for phage therapeutics in general, and specifically for a phage product candidate intended for respiratory infection.
Armata has leveraged its experiences with AP-PA01 to derive a development plan for our second-generation phage product candidate for P. aeruginosa, known as AP-PA02. AP-PA02 is one example of the novel candidates to emerge from our robust R&D capabilities, and offers significantly improved therapeutic attributes compared to AP-PA01. AP-PA02 is comprised of a cocktail of complementary P. aeruginosa phages that offer improved host range, increased potency, and aid in preventing the development of resistance. AP-PA02 demonstrates broad coverage against relevant clinical isolates.
AP-PA02 clinical trial material is manufactured at Armata’s production facility in Marina del Rey, CA, using cGMP, to support the required regulatory filing(s) for clinical entry in the U.S. and Europe. Armata anticipates initiating a Phase 1b/2a, multi-center, double-blind, randomized, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability, and preliminary efficacy of inhaled AP-PA02 in subjects with CF and chronic pulmonary P. aeruginosa infection, in 2020.
Armata received a $5 million Therapeutics Development Award through the Cystic Fibrosis Foundation. This nondilutive funding will partially support the Phase 1b/2 clinical study.
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 hospitalized pneumonia. Hospital-acquired pneumonia (HAP) and ventilated-associated pneumonia (VAP) is one of the most common causes of death among all hospital‐acquired infections, with mortality rates ranging as high as 35‐50% driving considerable healthcare costs, and accounting for around 50% of all intensive care unit antibiotics.