By Joseph Straus, Staff Writer
TEL AVIV, Israel – “The microbiome is still in its diapers,” says Nitsan Maharshak, somewhat tongue in cheek.

Though the challenges are many and microbiome science is still in its infancy, it is becoming increasingly clear that the microbiome plays a major role in the pathophysiological processes related to various diseases. Maharshak, an assistant professor at the Faculty of Medicine at Tel Aviv University and head of the Bacteriotherapy Clinic of the Department of Gastroenterology, points to the exponential growth in related publications over the last 15 years, many facilitated by tools derived from the
human genome project.
While fecal microbial transplant (FMT) is approved as a therapy only for recurrent, therapy resistant Clostridium difficile(C. diff) infections and is expected to be approved as first line therapy for this condition in the near future, various other initiatives based on microbiome science are in development in Israel.

These initiatives were on display during the 15th Israel Advanced Technologies Industry (IATI) – Biomed conference here in May.
Prof. Eran Segal of the Department of Computer Science and Applied Math and Prof. Eran Elinav of the Department of Immunology, both at the Weizmann Institute of Science in Rehovot are leading much of the microbiome related science in Israel today.
One company working in the space is Mbcure Ltd., a biopharmaceutical company that is part of the Futurx biotech incubator in Ness Ziona. Futurx is financed by a syndicate of J&J Innovation, Takeda Ventures, OrbiMed Israel Partners and the Israel Office of the Chief Scientist.
Mbcure is developing new therapeutics for diseases that result from microbiome dysbiosis, using bacteria-specific bacteriophage cocktails. Bacteriophages are viruses that destroy bacteria by invading them. They are effective in low doses, as they replicate within the bacteria. Their amplification
is self-limiting since it requires the presence of the target bacteria. For these reasons, and because phage cannot infect human cells, phage-based therapeutics are expected to be non-toxic.
Phage drugs can target and suppress specific diseaseassociated bacteria. Most importantly, it is anticipated that target bacteria will be unable to develop resistance to Mbcure’s advanced phage therapy. Phage technology is used in various settings, including the treatment of foods to prevent spoilage.
CEO Naomi Zak explained that phages are another tool with which to carry out directed modulation of the microbiome.
Mbcure is preparing for its first study in humans of a dermatological indication and is working towards an IND by the end of 3Q17 and proof of activity by mid-2018.
Looking ahead, Mbcure is also pursuing several oncological indications and is eying metabolic and autoimmune diseases, as well as infections with antibiotic resistant bacterial strains.
In addition to natural phage, the company is also creating designer phage equipped with robust lytic abilities through synthetic biology approaches. Mbcure’s technology is licensed from the Weizmann Institute as well and its team includes founders Rotem Sorek, a renowned phage expert and CrispR
researcher, and Elinav.
Ness Ziona based Mybiotics Pharma Ltd. is another microbiome therapeutics company, and is at the forefront of the newly emerging field of pharmabiotics. The company is manufacturing (instead of harvesting) fecal microbes and then deploying the live bacteria as a drug.
The team is developing a line of these products or “probiotics version 2.0”. The company’s MyCrobe is a platform to culture single bacteria and multi-bacterial communities on a specific medium, including bacteria that could not be successfully cultured previously. In a targeted treatment setting the bacteria
are administered to colonize and thrive in the colon. The bacteria compete with the resident pathological population and re-establishes a well-balanced, healthy microbiome.

Taking this concept much further, Mybiotics developed its Superdonor technology, a feces-free FMT product line cultured in-vitro as an alternative to donor FMT therapy.
CEO David (Didi) Dabush says complete microbiome replacement with an artificial product that closely resembles human feces and subsequent colonization and maintenance in vivo is a technological breakthrough.
“The ability, unlike with other probiotic products, to overcome the body’s natural resistance and to colonize the gut with an appropriate, essential manufactured bacterial population represents an important, novel therapeutic alternative for patients with a variety of medical indications,” said Dabush.
The first indication for Superdonor will be the treatment of C.
diffinfections with intent to cure. Subsequently, Mybiotics will focus on antibiotic side-effect reduction and post-antibiotic microbiome restoration and on the treatment of other microbiome related indications.
Mybiotics has completed three successful pre-clinical experiments with Mycrobe, which demonstrated effective bacterial delivery and colonization. First in human trials with Mycrobe in a post antibiotic treatment setting are scheduled to begin at the end of this year and different studies in C. diff
infections are planned for next year.
Another company working on the microbiome is Hy Laboratories Ltd. (Hylabs), founded in 1974 in Rehovot. The company provides a full range of microbiology and molecular biology products and services. In 2015 it launched Project Obediome, in collaboration with South Plainfield, N.J., based
Genewiz, a privately held global CRO specializing in genomics services.
The Obediome project is conducting a multi-center clinical trial in Israel, designed to detect and determine the relative presence of bacterial and archaeal species in the microbiome of obese and diabetic patients undergoing bariatric surgery using the 16S Metavx patent-pending assay and medical metadata.
A second company in this space is Rondinx Ltd., a technologydriven biotechnology company founded in 2015 and located in Tel Aviv. The company has licensed a family of algorithms from YEDA, the technology transfer office of the Weizmann Institute, with which it is building a platform for the discovery of microbiome related targets, drugs and companion diagnostics.
Using algorithms developed at Eran Segal’s lab and machine learning, the company’s proprietary, cloud-based Peak-toTrough (PTR) technology can harness raw meta-genomics to determine which bacterial strains in an individual’s microbiome are proliferating most actively. This can provide insights
into the pathogenesis of specific diseases. According CEO Guy Harmelin, the company is now seeking collaborations with major pharma to further develop and commercialize its computational pipeline.
Yet another company, Day Two Ltd., based in Moshav Adanim also licensed its technology from the Weizmann Institute, which built it based on a collaboration between Segal and Elinav. Day
Two has developed clinical applications of algorithms which can predict a person’s individual glycemic response to various foods and individualize optimized nutrition based on the person’s unique colonic flora.
Meanwhile, Segal and Elinav are now conducting a new study in pre-diabetics and Type II diabetics to determine whether diets can optimize the establishment of donor bacteria in the colon of recipients of FMT from lean, non-diabetic donors. /

Source: MedicalDeviceDaily

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