The microbiome – all the bacteria that reside in and on the human body – is a new, exciting, and fast-developing field at the crossroads of pharmaceuticals and nutrition, offering abundant opportunities for the development of new medicines. The multitude of biological processes and indications affected by the microbiome make the bacteria in the human microbiome critical to health. The composition of bacteria forming the microbiome, mainly gut bacteria, has been linked to various health conditions, including allergies, gastrointestinal disorders, obesity, and cancer. However, the microbiome’s diversity presents a challenge for identifying specific targets and developing new medicines to treat its imbalance.
Our platforms use cutting edge computational and synthetic biology to discover and validate proprietary bacterial targets and customize our natural and engineered phage compositions against these targets
Target Bacteria Discovery
TARGET BACTERIA DISCOVERY
Unique approaches (‘lenses’) to examine the complex microbiome to identify key harmful bacteria
We apply the following approaches on metagenomic and metatranscriptomicdata to pinpoint harmful bacteria linked to disease states
Strain Level Relative Abundance
Using this platform, we combine alignment of metagenomic data against the entire NCBI RefSeq database and DeNovo DNA assembly to accurately profile samples at strain-level resolution, pinpointing the reference assemblies that are closest to the actual organisms in the sample. For reads that match multiple assemblies, we use advanced algorithms for genome selection, to infer the single assembly from which the read was originated.
Bacterial Growth Dynamics
This pipeline allows growth dynamics profiling, also known as PTR (Peak to Trough), from a single metagenomic sample and is based on pioneering research from the Weizmann Institute of Science (Korem et al., Science, 2015, https://www.ncbi.nlm.nih.gov/pubmed/26229116). It calculates the momentary growth rates for each organism in the sample by measuring the ratio between genomic sequences derived from regions closer to the organism’s origin of replication and sequences derived from regions closer to its terminus. This information gives a unique approach for analyzing the microbiome by pinpointing the actively-dividing bacteria at a given time.
RNA Level Response To Stimuli
This platform characterizes the direct dynamic response and changes in gene expression of the microbiome to a given stimuli (e.g. a pharmaceutical drugs). The approach simultaneously measures the RNA expression of hundreds of microbiome species in a single experiment. The transcriptome of each microbiome bacteria is reconstructed to the single-base resolution using a combination of proprietary experimental protocols and computational tools, allowing accurate identification of the specific genes and pathways that drive the microbiome reaction to the given trigger. The platform was developed in the Weizmann Institute of Science at Prof. Sorek’s lab and resulted several publications in top-tier journals(e.g. Dar et al., Science, 2016, https://www.ncbi.nlm.nih.gov/
Develop customized phage therapies that seek and destroy harmful bacteria targets
The BiomX platform allows screening, identification, characterization, and engineering (if necessary) of phages specific to a given bacteria target.
This process results in a customized phage cocktail – a combination of several natural or engineered phage – that is validated in-vitro/in-vivo to be efficient at targeting the harmful bacteria and could advance to product development.
THE PHAGE DISCOVERY PROCESS IS COMPRISED OF:
Screening and Identification
We apply proprietary, high throughput, automated screening methodologies, use a wide array of clinical and environmental phage-containing samples, and screen against a range of bacterial hosts to dramatically increase discovery rates of natural phage.
Synthetic Phage Engineering
In cases where natural phage are not identiﬁed, we use multiple methods to synthesize phage that are reactive to the target bacteria. These include “reprogramming” of lysogenic (dormant) phage to a strictly lytic (active) mode, and the expansion of the phage host range to both achieve eradication of a wider array of bacterial strains and overcome bacterial resistance.
Candidate phage are characterized with respect to a large number of parameters in order to allow selection of an optimal phage cocktail. These include high throughput genomic approaches to rapidly characterize identified phage. The phage combinations are designed to allow broad coverage of target strains and prevent the appearance of resistant strains. Manufacturing considerations are also taken into account in selecting phage for inclusion in the therapeutic cocktail. Speciﬁc parameters for examination are: absence of toxic genes, potential hosts, host range from various geographic locations, stability, and production characteristics. Our platform applies a weighted multi-parameter scoring scheme to select optimal phage cocktails.
Proprietary assays and processes for pre-clinical and clinical development of our pipeline products.
BiomX is establishing the necessary capacities and assets both internally and through collaboration in order to rapidly drive our pipeline to clinical testing. These include building proprietary assays, processes, and analyses to support products during clinical testing while adhering to strict regulatory specifications.
Our first project to demonstrate pre-clinical development of customized phage therapies addresses acne and is comprised of naturally occurring phages capable of eradicating P. acnes, which is a main cause of acne. The phage therapy does not affect other bacteria beneficial to the skin and has demonstrated efficient eradication of a broad host range of P. acne bacteria lines, including antibiotic resistant lines. cGMP manufacture is underway and preclinical development has commenced.
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