Development of a topical bacteriophage gel targeting for acne prone skin and results of a phase 1 cosmetic randomized clinical trial.

Background: Topical antibiotics are frequently used to treat acne vulgaris. Their prolonged use, often for longer durations than recommended, has led to antibiotic resistance in , a bacterium implicated in acne pathophysiology. Bacteriophage (phage), which specifically target by a different mechanism of action and do not harm potentially beneficial bacteria, may offer an alternative approach for improvement of the appearance of acne prone skin.

Objectives: To identify and characterize targeting phage, carry out a comprehensive preclinical safety evaluation of phages selected for further development and examine their safety, tolerability and ability to target facial when applied topically in a cosmetic clinical study including participants with mild-to-moderate acne.

Methods: Phages were isolated by conventional microbiological methods also used to examine their breadth of host range on different strains and specificity to this bacterial species. Safety assessment of three selected phages was carried out by complete genomic analysis to assure the absence of undesired sequences and by ex vivo models employed to evaluate the safety, irritability and potential systemic bioavailability of phage applied topically. A randomized, controlled clinical study assessed safety, tolerability and efficacy in targeting facial .

Results: Wide host range phages that also target antibiotic resistant were identified. Their genomes were shown to be free of undesired genes. The three-phage cocktail, BX001, was not irritant to human skin or ocular tissues in ex vivo models and did not permeate through human epidermis. In a cosmetic clinical study, topically applied BX001 was safe and well tolerated and reduced the facial burden of .

Conclusions: Combined in silico and ex vivo approaches successfully predicted the observed safety and efficacy of targeting phage when these were topically administered in a well-controlled cosmetic clinical study.