Our knowledge around these therapies is growing fast and the industry has learned from earlier setbacks. The PhagoBurn trial, one of the first modern randomised controlled studies of phage therapy in burn wounds, failed to meet its endpoints. Investigators later discovered that phage stability had degraded in storage, reducing active titres and underpowering the study⁶. This experience underscored the importance of robust formulation, quality control processes, and dosing strategies. Since then, trial design has improved considerably, with adaptive protocols, real-time phage-bacteria matching, and combination therapies being explored. Modern trials now reflect these learnings and are better poised to show efficacy.

Today, companies are testing phage cocktails against bacterial infections, in women’s health, in infections happening during stem cell transplants in oncology or in patients with Crohn’s disease (Figure 2 right panel). BiomX is working on BX004, a phage therapy cocktail targeting Pseudomonas aeruginosa – a main contributor to morbidity in patients with Cystic Fibrosis. The treatment has already shown clinically meaningful improvement in a phase Ib/2a trial. More recently, BiomX reported positive Phase 2 results for another asset, BX211, in diabetic foot osteomyelitis—a notoriously difficult-to-treat condition. Patients receiving BX211 exhibited significantly better wound healing outcomes and reduced infection progression, with no major safety concerns⁷.

Armata Pharmaceuticals reported encouraging topline results from its phase 2 Tailwind study evaluating AP-PA02, an inhaled phage therapy targeting chronic Pseudomonas infections in non-cystic fibrosis bronchiectasis. While each study cohort alone didn’t show significant differences, a combined post-hoc analysis revealed a meaningful reduction in bacterial load in patients receiving phage therapy, with approximately one-third achieving which researchers described as a 100-fold reduction in bacterial counts. The treatment was well tolerated, with only mild, self-limiting adverse events reported⁸.

Innovators are moving beyond selecting phages from nature, instead genetically engineering them. Leading this effort is Locus Biosciences, which is developing LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage therapy aimed at Escherichia coli, the cause of urinary tract infections (UTIs)⁹. Supported by $85 million in funding from BARDA (Biomedical Advanced Research and Development Authority), including $24 million designated for clinical development, Locus is moving forward with Phase II trials, expecting crucial data by 2027–2028¹⁰. Large pharmaceutical companies are also acknowledging the potential of phage therapies. Notably, in 2019 Johnson & Johnson has partnered with Locus Biosciences in a collaboration potentially valued at up to $818 million to develop CRISPR-enhanced phage products targeting respiratory pathogens. In the field of microbiome modulation, Eligo Bioscience is using phage-derived particles to deliver CRISPR-Cas systems for precise base editing bacteria in the gut and has successfully raised $30 million in its series B financing led by Sanofi Ventures in December 2023¹¹. This entirely new approach could enable the development of treatments that deactivate specific genes associated with diseases in bacteria, while preserving the overall composition of the microbiome¹².

From compassionate use towards frameworks

Regulators are beginning to recognise the unique challenges of approving “living medicines.” Unlike small-molecule drugs, phage compositions can vary over time to address evolving bacterial resistance. While this adaptability is a scientific advantage, it presents challenges for clinical development and regulatory approval—particularly in ensuring consistency of manufacturing, quality control, and therapeutic effect across batches. Regulators and developers are actively exploring models such as pre-qualified phage libraries or adaptive phage platforms to manage this complexity¹³. The Centre for Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego not only coordinates trial access but has also facilitated dozens of compassionate use cases offering phage therapy to patients with life-threatening, drug-resistant infections without alternatives¹⁴. The FDA continues to support compassionate use phage therapy via eINDs (expanded access Investigational New Drug applications) and has signalled openness to novel approval pathways¹⁵.

Belgium has taken a leading role with its magistral phage framework. Since 2018, it has allowed hospital pharmacies to produce custom phage preparations for individual patients upon physician request, bypassing centralised marketing authorisation while adhering to quality standards¹⁶. Such a model could serve as a template for other nations, bringing immediate benefits and complementing future commercial products.

The way forward

As these advancements continue, crucial clinical results are expected in the coming years. The incorporation of phage therapy into clinical practice could transform the treatment of resistant infections and provide new strategies for microbiome modulation but several challenges will need to be addressed.

• Intellectual property: Developers should be aware that naturally occurring phages cannot typically be patented. Instead, IP protection often centres on innovations such as proprietary phage selection platforms, synthetic modifications, and optimized manufacturing processes. Genetically engineered phages or novel phage combinations may also be patentable, providing more robust commercial protection.
• Regulatory: Phage therapies are not the typical drugs and exact composition might vary depending on the infection. Hence, regulators should adopt a process more similar to that of vaccines that mirrors that for e.g., annually updated influenza vaccine or support a ‘phage-as-a-service’ model more akin to advanced medicinal products (ATMPs). Hospital-prepared formulations like those in Belgium could serve as an intermediary pathway.
• Clinical: Many phage therapies are developed using a personalised approach, where a specific cocktail is selected based on the patient’s bacterial isolate. However, standardised phage products and fixed cocktails are also in clinical development. Phages are often administered in combination with antibiotics, which can make it challenging to isolate their individual therapeutic effects in trials. Adaptive clinical trial designs — including interim modifications and stratified patient arms — may help accommodate the complexity of personalised and combination therapies.
• Commercial: Innovators will face and overcome similar challenges as seen for antibiotics. Phage therapies will not replace antibiotics but will be a treatment reserved as last line therapy. This will require high upfront investments to develop the infrastructure needed to provide diagnostics to identify disease-causing bacteria and to select tailored phage cocktails to fight the infection. Public-private partnerships, innovative pricing models like subscription models where a hospital pays a fixed rate for access to customised phage treatments as needed, along with subsidies to incentivise investment, can help ensure the commercial viability of the phage approach and pave the way for broader adoption and impact.

Phage therapy is not a panacea, nor is it a replacement for antibiotics. But it offers a much-needed, complementary tool in our antimicrobial arsenal. With targeted action, adaptability, and growing commercial support, the good virus might just be what modern medicine needs.

¹https://www.iqvia.com/locations/emea/blogs/2024/11/navigating-antimicrobial-resistance
²Abedon, S. T., García, P., Mullany, P., & Aminov, R. (2017). Phage therapy: Past, present and future. Frontiers in Microbiology, 8, 981. ³https://doi.org/10.3389/fmicb.2017.00981
⁴https://www.economist.com/science-and-technology/2023/05/03/western-firms-are-becoming-interested-in-a-soviet-medicine
⁵Clinicaltrials.gov
⁶Stacey, H.J.; De Soir, S.; Jones, J.D. The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials. Antibiotics 2022, 11, 1340. https://doi.org/10.3390/antibiotics11101340
7https://ir.biomx.com/news-events/press-releases/detail/130/biomx-announces-positive-topline-results-from-phase-2-trial
8https://investor.armatapharma.com/2024-12-19-Armata-Pharmaceuticals-Announces-Encouraging-Results-from-the-Phase-2-Tailwind-Study-of-Inhaled-AP-PA02-in-Non-Cystic-Fibrosis-Bronchiectasis-Subjects-with-Chronic-Pulmonary-Pseudomonas-aeruginosa-Infection
9https://www.locus-bio.com/locus-biosciences-announces-first-patient-treated-in-the-eliminate-registrational-phase-2-3-trial-of-lbp-ec01-for-urinary-tract-infections/
¹⁰https://www.ncbiotech.org/news/locus-biosciences-receives-239-million-barda-crispr-engineered-therapy-trial
¹¹https://eligo.bio/series-b/
¹²https://crisprmedicinenews.com/news/breaking-eligo-bioscience-reports-first-ever-in-vivo-microbiome-base-editing/
¹³Pirnay et al., 2015; FDA CBER Workshop, 2022; de la Fuente-Nunez et al., 2019
¹⁴https://idgph.ucsd.edu/research/center-innovative-phage-applications-and-therapeutics/index.html
¹⁵McCallin, S.; Sacher, J.C.; Zheng, J.; Chan, B.K. Current State of Compassionate Phage Therapy. Viruses 2019, 11, 343. https://doi.org/10.3390/v11040343
¹⁶Pirnay JP, Verbeken G, Ceyssens PJ, et al. The magistral phage. Viruses 2018; 10:64.