Our 3-Tier Platform
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 3-TIER MICROBIOME MODULATION PLATFORM
Our end-to-end platform enables identification of target bacteria that drive microbiome dysbiosis, precision microbiome modulation through eradication or addition of specific bacteria, and high-end drug development.
Target Bacteria Discovery
TARGET BACTERIA DISCOVERY
A proprietary platform that enables real-time discovery of target bacteria through mining the extremely complex human microbiome.
Our innovative, proprietary platform for target discovery enables the identification of specific bacteria and molecules that drive or alleviate microbiome disorders. The approach enables accurate intervention in major diseases through the development of microbiome modulating drugs.
The human microbiome is extremely complex, comprised of 100 trillion bacteria from over 1,000 species, and over 3 million non-redundant genes. Our discovery process has the unique capability to rapidly measure the “real time” dynamic response of the whole microbiome to a given molecule or stimulus (e.g. a drug or clinical condition).
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 a proprietary computational platform, allowing accurate identification of the specific genes and pathways that drive the microbiome reaction to the given trigger.
The platform was developed in Prof. Rotem Sorek’s lab and resulted in over 10 publications in top-tier journals (e.g. PNAS 2009, Nature Methods 2010, Science 2016, Nature Microbiology 2016).
TARGET DISCOVERY PLATFORM: ADVANTAGES
• Real time – Direct measurement of the microbiome dynamic response – identifies key driver bacteria + microbiome MOA
• Flexibility – Applied at different time points (In response to stimuli)
• Efficiency – Screens millions of genes within days
• Proprietary – IP protected + unique know-how
Address disease by adding or eradicating bacteria or phage cocktails
that are native or engineered
Eradicating bacteria with phages: The BiomX platform allows screening, identification, characterization, and engineering (if necessary) of phages specific to a given bacteria target. phages are natural predators of bacteria. They evolve to bind and kill specific bacteria and are ubiquitous in nature. phages can therefore target specific harmful bacteria in the microbiome without affecting beneficial bacteria, while also providing the means to overcome growing resistance to antibiotics.
The platform has been developed with the expertise of our scientific collaborators from the Weizmann Institute of Science and MIT. It allows efficient development of phage therapeutics derived from both natural and synthetically engineered phage. Two of our phage discovery and development programs (acne and IBD) apply natural phage and one applies synthetic engineering to GI tract associated cancers.
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.
Adding beneficial bacteria: Our target bacteria discovery approach points to beneficial bacteria that offer therapeutic benefits. Methods are employed to develop these beneficial bacteria for the introduction into the commensal microbiome.
Optimal bacteria or bacterial cocktails that express the beneficial pathways are selected based on their ability for culturing in large scale, stability of expression of the desired pathways and reproducibility of characteristics following culture. Consideration are given to dose and method of administration to secure availability at site of action.
MICROBIOME MODULATION ADVANTAGES
• Flexible – Both natural and engineered solutions for adding and eradicating bacteria
• High-throughput – Diverse environmental samples with high-throughput capacity to drive phage identification
• Optimized – Multiple phage characterization schemes to optimize phage cocktail – host range, resistance, mutations, similarity, etc.
• Proprietary – IP protected + unique knowhow
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.