Phase 1b/2a clinical trial assessing safety, tolerability, and efficacy of BX004 in CF subjects with chronic PsA pulmonary infection. Part 1 Results included: Study drug was well-tolerated; No premature discontinuations from study drug or study; No adverse events related to study drug; No adverse events of special interest (acute pulmonary exacerbations or pulmonary worsening after study drug administration); Microbiologic Efficacy - Mean P. aeruginosa CFU reduction at Day 15 vs Baseline: 1.42 log 10 (BX004 A) vs 0.28 log 10 (placebo).
Phase 1b/2a clinical trial assessing safety, tolerability, and efficacy of BX004 in CF subjects with chronic PsA pulmonary infection, showed that all subjects in Part 1 had high levels of Screening PsA , with all PsA morphotypes susceptible to BX004 phage cocktail. Study drug was well tolerated with notable microbiologic efficacy in BX004 A treated subjects
Primary sclerosing cholangitis (PSC) is marked by progressive biliary inflammation and fibrosis. We discovered abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, independent of intestinal complications. Carriers of these pathogens experience high disease activity and poor clinical outcomes. In mice, PSC-derived Kp colonization amplifies hepatic Th17 cell responses, worsening liver injury through bacterial translocation. Our lytic phage cocktail effectively targets PSC-derived Kp, reducing its levels without disrupting the microbiota. Oral and intravenous phage administration successfully suppresses Kp, mitigating liver inflammation and disease severity in mice prone to hepatobiliary injury. These results hold promise for Kp targeting in PSC.
Human gut commensals are increasingly suggested to impact non-communicable diseases, such as IBD, yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut.
Next-Generation Sequencing is widely used as a tool for identifying and quantifying microorganisms pooled together in either natural or designed samples. However, a prominent obstacle is achieving correct quantification when the pooled microbes are genetically related. In such cases, the outcome mostly depends on the method used for assigning reads to the individual targets. To address this challenge, we have developed Exodus—a reference-based Python algorithm for quantification of genomes, including those that are highly similar, when they are sequenced together in a single mix.
BX001, a formulated phage cocktail, was designed to target a wide host range of C. acnes and was demonstrated to be safe for topical use by comprehensive preclinical in silico and ex vivo approaches. BX001 safety and tolerability was confirmed in a double-blind, randomized, vehicle-controlled cosmetic trial in which it was administered to subjects with mild to moderate acne vulgaris.
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