LEO Foundation expands support for phage therapy with a new translational grant against flesh-eating disease

The LEO Foundation has awarded a new translational research grant to an international consortium led by Thomas Sicheritz-Pontén at the University of Copenhagen and Martha Clokie at the Becky Mayer Centre for Phage Research, University of Leicester. The project aims to accelerate the development of bacteriophage therapy against invasive Group A Streptococcus (GAS), the bacterium responsible for necrotizing soft tissue infections (NSTIs), commonly known as "flesh-eating disease".

Thomas Sicheritz-Ponten - Linkedin

With this latest award, the LEO Foundation has now committed a total of 12 million DKK (approximately €1.6 million) across three complementary research projects, each funded at around 4 million DKK. Rather than supporting isolated studies, the Foundation is investing in a long-term research strategy that spans the entire innovation pipeline, from fundamental phage discovery to preclinical therapeutic development.

The programme began with a large-scale effort to identify bacteriophages capable of infecting clinically relevant GAS strains. Until recently, very few lytic phages active against these highly virulent pathogens had been described. Over several years, the research team isolated 19 bacteriophages targeting clinically important GAS isolates while generating a collection of 63 newly sequenced GAS genomes. These genomic resources not only expanded knowledge of GAS diversity but also enabled the development of BAPS, a genome-guided computational pipeline designed to recover complete lytic bacteriophages directly from bacterial genome assemblies. This approach substantially accelerates phage discovery by reducing the need for conventional environmental screening.

During the development of these genomic and machine-learning tools, the researchers also uncovered an unexpected biological phenomenon. Approximately 15% of the sequenced bacteriophages appeared to encode two adjacent endolysins acting cooperatively, a feature the team describes as "Twin Endolysins". Endolysins are peptidoglycan-degrading enzymes produced by bacteriophages to lyse bacterial cells at the end of their replication cycle. Understanding why certain phages maintain two complementary lytic enzymes could reveal new antimicrobial strategies capable of selectively eliminating pathogens while preserving the surrounding microbiota. This second project therefore focuses on the molecular biology and evolutionary significance of these dual enzyme systems.

The newly announced grant represents the translational phase of the programme. Having established both a diverse phage collection and robust experimental models, the consortium will now concentrate on transforming these discoveries into clinically relevant therapeutic candidates. Over the next three years, researchers will develop bacteriophage cocktails designed to remain effective despite bacterial resistance, optimise local phage delivery using hydrogel-based formulations capable of penetrating necrotic tissues, and evaluate bacterial clearance in advanced human living-skin models that closely reproduce the pathology of necrotizing soft tissue infections.

This translational strategy addresses one of the major obstacles facing phage therapy for invasive streptococcal disease. Necrotizing soft tissue infections progress rapidly, causing extensive tissue destruction and poor vascularisation that severely limits antibiotic penetration. Local administration of phages embedded within biomaterial-based delivery systems could potentially achieve high concentrations directly within infected tissues while maintaining prolonged therapeutic activity. Human skin models further provide an intermediate platform between laboratory experiments and animal studies, allowing researchers to evaluate efficacy under physiologically relevant conditions before progressing toward clinical development.

The project also illustrates the increasing importance of interdisciplinary collaboration in modern phage therapy research. Alongside the University of Copenhagen and the Becky Mayer Centre for Phage Research, the consortium includes Rigshospitalet, Hvidovre Hospital and Bispebjerg Hospital, bringing together expertise in clinical microbiology, bacterial genomics, computational biology, phage biology, bioengineering and infectious disease medicine.

Although clinical application remains several years away, this programme represents one of the most comprehensive research efforts currently underway against invasive GAS infections. By combining systematic phage discovery, comparative genomics, machine learning, enzymology and translational biomedical engineering within a single coordinated framework, the consortium is establishing a complete pipeline that extends from basic biological discovery to preclinical validation. Continued support from the LEO Foundation provides the stability required to pursue long-term therapeutic development while addressing one of the most devastating bacterial infections encountered in modern medicine.

Sources :

1. University of Copenhagen. Innovative phage therapy project to combat "flesh-eating disease". 2023.

2. LEO Foundation. 14 pioneering and illuminating projects round off an exciting year of skin research grants. 2024.

3. Thomas Sicheritz-Pontén and collaborators. Announcement of the new LEO Foundation translational grant for bacteriophage therapy against Group A Streptococcus necrotizing soft tissue infections. LinkedIn, July 2026.