Synthetic Phage for Pseudomonas aeruginosa Respiratory Infections
Armata’s P. aeruginosa phage program is advancing through the synthetic phage drug discovery and development process. Multiple phages have been identified with desirable engineering attributes, and some lead engineered phage candidates have advanced to manufacturing. Clinical and regulatory planning has begun, charting the appropriate paths for respiratory infections with high unmet medical need, including hospital-acquired pneumonia (HAP) and ventilated-associated pneumonia (VAP), as well as cystic fibrosis (CF) lung infections.
HAP/VAP is the most common cause 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.
There are approximately 70,000 CF patients worldwide, of which up to 85% develop chronic P. aeruginosa infection by age 18-25. Median survival age is 40 years. Regular standard of care antibiotics, such as inhaled tobramycin, fail to completely eradicate the pathogen, with a growing number of multidrug-resistant isolates emerging, particularly with long term use.
In addition to our Pseudomonas synthetic phage program, Armata’s development of a synthetic phage targeting S. aureus would increase the number of treatable patients with, and market for the treatment of, respiratory infections including hospitalized pneumonia (HAP/VAP) and CF.
Partnered Synthetic Phage Program
Proprietary synthetic phage candidates designed to target an undisclosed infectious disease agent are being developed in collaboration with Merck.
In addition to our more advanced pipeline programs, Armata has phage discovery efforts underway to target other major pathogens of infectious disease (including ESKAPE pathogens) and preventable disease of the microbiome.
Phage Targeting ESKAPE Pathogens
Microbiologists at Armata are actively hunting for natural phages that target ESKAPE pathogens, and to evaluate the suitability of these phages for synthetic engineering. Klebsiella pneumoniae phage, for example, are a potentially important addition to treatment options for serious lung infections. A recent outbreak of VAP caused by a new emerging hypervirulent Klebsiella pneumoniae strain led to the death of five patients in the intensive care unit of a hospital in China (Lancet Infect. Dis.; Volume 18:1, Jan 2018).
The developing science of the microbiome highlights the potential to impact a broad array of human disease, from oral healthcare to systemic diseases, such as autoimmunity, and immuno-oncology. The complexity of the developing science demands a broad front effort in clarifying microbial-host interactions, designing intervention strategies, and crafting a viable clinical path. Armata’s strategy is to seek partners that share a long-term commitment to develop meaningful microbiome therapies utilizing natural and/or synthetic bacteriophages.
Streptococcus mutans is recognized as the major causative agent of dental caries (tooth decay). Due to the infective mode of action of phages, they have the potential to eliminate S. mutans from the pathological niche, enabling the oral microbiome to be reengineered to a healthy state. Phase 2 clinical trials (under U.S. IND) with C16G2, the lead antimicrobial peptide derived from our STAMP Platform, demonstrated a selective reduction of S. mutans in the oral cavity. Given Armata’s extensive experience with S. mutans, and the clinical expertise and infrastructure at our disposal, we believe a synthetic S. mutans phage engineered to express C16G2 could offer a valuable treatment and prevention option for millions of children, adolescents and adults worldwide.
The field of bacteriophages for oral pathogens is underdeveloped. Armata has active efforts to identify oral pathogen phages and has executed collaborative agreements related to specific S. mutans phages. We are interested in additional collaborations with scientific leaders who are pioneering phage hunting for oral pathogens.