Phage Therapy: The Rising Precision Treatment Against Drug-Resistant Infections

Building an Alliance with Phage Therapy

Phages, the Third Therapeutic Approach

In 1915, bacteriologist Frederick Twort first discovered a "viral factor" that could lyse bacteria, marking the beginning of phage research. Two years later, d’Herelle observed similar phenomena in Shigella bacteria and named the "viral factor" as "bacteriophage." In 1919, at the Paris Children’s Hospital, four dysentery patients ingested a phage suspension prepared by d’Herelle. Under the expectant gaze of the crowd, the patients’ symptoms rapidly improved within a short period, marking the first intentional clinical application of phage therapy.

Phages are like delicate rockets, precisely landing on the surface of target bacteria, then injecting genetic material, using all bacterial resources to copy themselves countless times. Finally, the bacteria burst like fireworks, releasing more phage rockets to search for the next landing point.

The precise targeting and killing of pathogenic bacteria by phages once excited the academic community. However, with the emergence of broad-spectrum, highly effective, and easy-to-produce penicillin, phage therapy lost its spotlight in the anti-infection treatment field. For decades, antibiotics reigned supreme, but "superbugs" artificially selected by antibiotic use have gradually defeated them. Multi-drug resistant bacteria have become a global public crisis. More and more infected patients face a dead-end with no available drugs. Humanity once again turns its attention to a third bactericidal approach beyond physical and chemical methods: phage therapy.

The Second Evolution of Phage Therapy

Limited by early 20th-century technology, phage therapy long remained confined to laboratories and sporadic case treatments—low cultivation efficiency, difficult screening, unclear host matching, and challenging industrial production. But the valuable experience accumulated by predecessors, combined with today's advanced technology and the worsening problem of drug resistance, has inspired a new wave of biotech innovators. They have chosen diseases such as liver abscesses and chronic wound infections as breakthroughs, launching an assault on severe infections threatening human health. Phage therapy is on the rise.

Nterica Bio, founded in 2021 by Professor Bernd Schnabl from the University of California San Diego School of Medicine, is dedicated to translating research results in gut microbiota and liver diseases. According to Mabwell Biotech’s 2024 annual report, Mabwell Therapeutics, Mabwell Biotech’s wholly-owned U.S. subsidiary, increased its investment in Nterica Bio this February to support phage therapy development, cumulatively investing 4 million USD and increasing its stake to 39.22%. The company’s oral phage therapy NTR-101 received FDA clearance in January 2025 to begin Phase I clinical trials (NCT06750588).

NTR-101 is a phage "cocktail" therapy composed of three natural phages that selectively target and eliminate cytolysin-positive Enterococcus faecalis. Studies have shown that cytolysin-positive Enterococcus faecalis plays a key role in liver damage in patients with acute alcoholic hepatitis (AH), a life-threatening inflammatory liver disease with no effective targeted treatments and high patient mortality risk. NTR-101 selectively reduces gut pathogenic bacteria load and is expected to fill the therapeutic gap for AH.

Preclinical data indicate that NTR-101 significantly reduces cytolysin levels in the liver and effectively prevents ethanol-induced liver damage in a humanized mouse model colonized with AH patient gut microbiota, strongly supporting the potential of NTR-101 to treat AH.

Israeli phage therapy company BiomX, founded in 2017, announced positive results this March from its Phase II clinical study of phage therapy "BX211" for treating Staphylococcus aureus-associated diabetic foot osteomyelitis (DFO). Topline data showed that from week 7, the treatment group separated from the placebo group, with a difference greater than 40% at week 10. By week 13, statistically significant improvements were seen in ulcer depth and reduced ulcer area expansion, demonstrating BX211’s strong therapeutic potential in complex, refractory infectious DFO and potentially helping reduce amputation risks.

Researchers are also using new phage therapies to overcome resistance bottlenecks: cystic fibrosis (CF) patients face life-threatening repeated lung infections by multidrug-resistant Pseudomonas aeruginosa, with limited effective antibiotics. A Yale University team designed personalized phage nebulization compassionate use treatments for nine adult CF patients who previously failed standard antibiotic therapy. After treatment, median sputum Pseudomonas levels significantly decreased, and lung function improved. This study was published in April in Nature Medicine (doi.org/10.1038/s41591-025-03678-8), anchoring a new coordinate for treating respiratory drug-resistant infections.

Outlook

Nterica Bio’s oral NTR-101 targets gut microbiota; BiomX’s BX211 clears ulcer wounds; Yale’s team uses nebulized inhalation targeting lung infections… the possibilities of phage therapy have vast untapped potential.

Currently, few phage therapies worldwide have entered clinical stages, and traditional pharmaceutical companies rarely invest heavily in phage therapy. Regulatory frameworks lag behind; the U.S. FDA only approved phage therapy clinical trials in 2016, and no formal clinical trials have been approved in China.

Mabwell Biotech’s cross-border investment in Nterica Bio is a bold exploration, and the successful FDA clinical clearance for NTR-101 also proves the promising future of phage therapy, while supplementing its own biotech portfolio’s critical pieces. This move may open a path for technologies precisely matching clinical needs and introduce unique approaches, providing new ideas for domestic phage therapy development and application.

With breakthroughs in synthetic biology, gene editing, and artificial intelligence, we can endow phage therapy with more connotations—expanding host range, drug delivery capability, on-site individualized precision therapy, and solving infectious disease crises… The intricate relationship between microbes and human disease is being unveiled by scientists. Will microbiome comprehensive therapies become a supermarket rivaling oncology and autoimmune fields? What role will phages play? Let’s wait and see.