Development, production and clinical use of therapeutic phages to treat infections due to antibiotic resistant bacteria

The PHAG-ONE project, funded under the Future Investment Program and supported by the Hospices Civils de Lyon (HCL), is an innovative and ambitious project which aims to structure the first French public platform for phage therapy. PHAG-ONE began on September 8, 2021 with a kick-off meeting attended by the 10 partners and representatives of the main project authorities (HCL, University Lyon 1, CIRI, INSERM, CNRS).

The first work carried out made it possible to develop the tools necessary for the isolation of bacteriophages, then their genetic characterization (NGS, GWAS analysis) and the determination of their spectrum of activity in connection with the CNR collections of staphylococci (WP1 -F. Laurent, HCL-Lyon) and the Antibiotic Resistance CNR (WP1-L. Dortet, Paris-Saclay University). Thus, 17 anti-Staphylococcus aureus phages, 11 anti-Staphylococcus epidermidis phages and 19 anti-Escherichia coli phages were isolated and genetically characterized. Preliminary results show that these phages are effective on a large panel of prevalent and multi-resistant clones of the target species. Furthermore, a method of directed evolution has been developed in order to specifically broaden the spectrum of activity of a phage. This approach has been used successfully for anti-S phages. aureus (WP1-F. Laurent, CIRI-HCL) and is being validated for anti-E. coli (WP1-R. Froissart, CNRS Montpellier).

These promising results made it possible to initiate the development of pharmaceutical processes for the production (WP2-M. Medina, CIRI-Lyon), purification and quality control of the first anti-S therapeutic phages. aureus (WP3-F. Pirot, FRIPharm-Lyon). This work, implemented within the FRIPharm pharmaceutical platform, is part of a quality approach faithful to compliance with the requirements of the drug regulatory authorities (ANSM, EMA).

The final validation of the rabbit tissue-cage model for performing efficacy tests is in progress (WP4-F. Valours, CIRI-Lyon).

The protocol for a clinical cohort study, named PHA-SA-CO (PHAGE-SAFETY-COHORT-STUDY), has been finalized and submitted to the CPP (WP6-T Ferry, HCL-Lyon). The study will likely begin by summer 2022.

For his part, C. Brives (WP7, CED-Bordeaux) initiated the epistemological and socio-anthropological work of the project by exploring the Lyon context, as well as an inventory of phage therapy practices in France.

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR therefore declines all responsibility for its content.