LOS ANGELES — Armata Pharmaceuticals has announced the publication of new research examining the structural biology of a bacteriophage used in the development of therapies targeting difficult-to-treat bacterial infections.
The paper, published in the peer-reviewed Journal of Molecular Biology, focuses on Ar-KM, a phiKMV-like bacteriophage that targets Pseudomonas aeruginosa, the pathogen addressed by Armata’s AP-PA02 clinical program.
AP-PA02 is an inhaled bacteriophage product candidate that has completed Phase 2 clinical studies in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis who have chronic pulmonary P. aeruginosa infections.
Researchers used cryo-electron microscopy, proteomics and bioinformatics to examine three states of the phage particle from a single purified preparation. They also developed atomic models for 11 structural proteins at near-atomic resolution.
According to Armata, the research provides new insight into how Ar-KM keeps its genome packaged before infection and then releases and delivers the genetic material into bacterial cells. The study also identified an enzyme activity that helps the phage penetrate the bacterial cell envelope and characterized a previously unrecognized protein involved in genome delivery.
“Stability before infection and efficient genome delivery at the point of infection are fundamental characteristics of a viable phage therapeutic, and this work provides important new insight into how Ar-KM can achieve both,” said Deborah Birx, M.D., Chief Executive Officer of Armata and a co-author of the paper.
Birx said the company’s research collaboration is helping Armata better understand the structural biology and mechanisms underlying phage activity and could support development of its anti-infective pipeline.
The study marks the fourth publication from Armata’s collaboration with Gino Cingolani, Ph.D., Anderson Family Endowed Chair in Medical Education, Research & Patient Care and Professor in the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham.
Armata said it is also extending the research to cryo-electron microscopy reconstruction of its proprietary Staphylococcus aureus bacteriophages.
“This study builds on our productive collaboration with Armata and provides a detailed structural view of Pseudomonas phage Ar-KM,” Cingolani said.
He said the research showed how the bacteriophage remains stable before infection and undergoes coordinated structural changes that allow it to release its genome after encountering a bacterial host.
“These insights also help connect the fundamental biology of the phage with characteristics important to the development of effective phage therapies, including stability, infectivity and efficient genome delivery,” Cingolani said.
Armata is developing pathogen-specific bacteriophage therapeutics for antibiotic-resistant and difficult-to-treat bacterial infections.
