Editor’s note: This is the first part in a series that will explore the current and potential developments of microbiome research, and how those developments interface with intellectual property protection. It should be noted that Shoreline Biome and Azitra, both mentioned in this article, are clients of Dilworth IP.

This is the first installment in a series on advancements in microbiome research and development. Our goal with this series is to inform readers about developments in this important and growing field and to highlight, where possible, Connecticut’s role in fostering this research. This first article will provide a brief overview of this technology area, featuring both prominent pharmaceutical companies and research labs. Future articles will discuss progress in commercializing this research, review new and relevant patents, and explore issues of law and policy in microbiome R&D.

Research into the microbiome seeks to characterize the microorganisms that live in and on different environments. Although these environments can be broadly terrestrial, extraterrestrial aquatic, and biological, we often use the term specifically to describe the bacteria living in and on different sites of the human body. The word “microbiome” refers either to the organisms themselves (also called “microbiota”) or their collective genomes. Within the human gut, the most bacteria-rich organ, these genes outnumber those in the human genome 100: 1, providing attractive candidates for pharmaceutical intervention. Inflammatory bowel disease (IBD), childhood-onset asthma, diabetes, obesity, cardiovascular disease, colorectal cancer, and antibiotic-associated diarrhea are some of the diseases that involve changes in the composition or loss of the function of the microbiome.

Microbiomics Companies

2015 is shaping up to be a banner year for microbiome-based drug development, or “microbiomics.” This year, Google Ventures President Bill Maris named microbiomics one of eight technologies with the potential to revolutionize life sciences, comparing its potential for impact to that of stem cells research, artificial intelligence, and gene editing. In late June, Seres Therapeutics became the first microbiomics company to go public, with a $134 million IPO. Table 1 provides more information about Seres and other leading companies in the microbiomics space.

Table 1. Microbiomics Companies
Company Name Location Highlights
ActoGeniX Belgium ActoBiotics™ platform for gastrointestinal, metabolic, immune diseases includes phase I candidate for treatment of IBD
AvidBiotics San Francisco Avidocin™ and Purocin™ engineered bacteriocins to target specific bacterial pathogens without disrupting the microbiota
Enterologics St. Paul Probiotics for FDA approval
Enterome BioScience (Paris) Paris Microbiome-based personalized medical tests and companion diagnostics
4D Pharma Research Limited (formerly GT Biologics) United Kingdom Thetanix and Rosburix live bacteria (“live biotherapeutic products”) for treatment of autoimmune diseases
Metabiomics Manassas, VA MultiTag™ DNA sequencing platform for non-invasive, early detection of colon polyps and colorectal cancer
Metabogen Sweden MetaboGen platform for identifying biomarkers of atherosclerosis and diabetes.
Microbiome Amsterdam Partnership with Belgium company Biocartis to develop diagnostic platform for bacterial sepsis
MicroBiome Therapeutics LLC (formerly NuMe Health) New Orelans Three candidate microbiome modulators for treatment of obesity and diabetes
Miomics New York Commensal bacteria for treatment of rheumatoid arthritis
Osel Mountain View, CA Pipeline features three candidates in Phase II trials for treatment of Clostridium difficile infection (CDI) and maintenance of women’s health
Ritter Pharmaceuticals Los Angeles Pipeline focuses on treatment for lactose intolerance and digestive health
Rebiotix (formerly MicroBex) Roseville, MN Treatment for recurrent CDI
Second Genome San Francisco Lead candidate is a small molecule designed to address microbiome-mediated inflammation and pain in IBD; collaboration Janssen Biotech for Ulcerative Colitis (UC) treatment
Seres Therapeutics Boston Lead candidate, an oral microbiome therapeutic for CDI, received   breakthrough therapy designation; EcobioticTMplatform for treatment of IBD
Symberix Durham, NC Microbiome modulators to alleviate cancer drug toxicity
Symbiota Boston Applications of the plant microbiome
Symbiotic Health New York Novel therapies for CDI
Symbiotix Biotherapies Boston Lead candidate involves first molecule to emerge from the human microbiome; features first-in-class oral immune-modulatory therapy
Vedanta Boston Microbiome modulators for treatment of autoimmune disease; collaboration with Janssen Biotech
ViThera Boston EnLact® strains engineered lactic acid and probiotic bacteria express beneficial proteins

Several local startups seek to enter this market. Mark Driscoll and Thomas Jarvie, formerly of 454 Life Sciences in Branford, have founded Shoreline Biome to develop diagnostics and therapeutics targeting the human microbiome. Azitra, the brainchild of Yale students in medicine and public health, is building a platform that combines microbiomics and synthetic biology for the treatment of skin disease.

Microbiome Research: Connecticut and Beyond

Connecticut boasts several outstanding leaders in microbiome research. George Weinstock, a Professor and Director for Microbial Genomics at The Jackson Laboratory for Genomic Medicine (JGM) in Farmington led the Human Microbiome Project, a five-year, $115 million initiative to characterize the microbiome and its contribution to disease. Recent hire Julia Oh is bringing her innovative work on the skin microbiome to the JGM as an Assistant Professor. Her arrival adds to a growing community of microbiome scientists in the state, including Andrew Goodman, an Associate Professor of microbial pathogenesis at Yale University whose work was recently honored by the Burroughs Wellcome Trust. Yale is also home to metagenomics pioneer Jo Handelsman (currently on leave as Associate Director for Science at the White House Office of Science and Technology Policy), immunobiologists Richard Flavell and Ruslan Medzhitov, and physician-scientist Martin Kriegel. At University of Connecticut (UConn), Joerg Graf and Xiaomei Cong are collaborating to investigate whether early life stress exposure, microbiome disruption, and psychological dysfunction are linked in preterm infants.

The studies of CT-based scientists complement the work of other outstanding researchers in this field. These include Jeffrey Gordon at Washington University in St. Louis (WashU), Martin Blaser at New York University (NYU), Wendy Garrett at Harvard University, Michael Fischbach at University of California San Francisco (UCSF), Lora Hooper at University of Texas Southwestern Medical Center (UT Southwestern), Sarkis Mazmanian at California Institute of Technology (Caltech), Justin Sonnenburg at Stanford University, Peter Turnbaugh at UCSF, and many others. Several of these scientists also hold key patents in microbiomics and some have also started or advise microbiome-based pharmaceutical companies. Table 2 reviews these key researchers and their contributions.

Table 2. Microbiome Researchers in Connecticut and Beyond
Scientist Current Institution Research Focus Company Affiliations (from Table 1)
George Weinstock JGM microbial genomics
Julia Oh JGM skin microbiome
Andrew Goodman Yale human microbiome, functional genomics, and microbial ecology Seres Therapeutics (Advisory Board Member)
Jo Handelsman Yale metagenomics and microbial communities
Richard Flavell Yale innate and adaptive immunity Symbiotix Biotherapies (Advisory Board Member)
Martin Kriegel Yale microbiota in immune-mediated diseases
Dennis Kapser Harvard School of Public Health interactions of the microbiota with the mucosal and systemic immune systems Symbiotix Biotherapies (Co-Founder)
Ruslan Medzhitov Yale analysis of innate immune system and host-pathogen interactions Vedanta (Co-Founder, Chair of the Scientific Advisory Board)
Joerg Graf UConn beneficial microbes, the evolution of microbe-host associations and the spread of antibiotic resistance
Xiaomei Cong UConn regulation of early life stress by the brain-gut-microbiota axis and maternal-child health
Jeffrey Gordon WashU gastrointestinal development and the effect of gut microbial communities on host health
Martin Blaser NYU bacteria of the mucosal epithelium Avidbiotics (Advisory Board Member); Second Genome (Advisory Board Member)
Wendy Garrett Harvard School of Public Health host-microbiota interactions in health and disease
Michael Fischbach UCSF natural products in microbe-host and microbe-microbe interactions Symbiota (Advisory Board Member)
Kenya Honda Keio University (Japan) immunological attributes of the microbiota Vedanta (Co-Founder & Scientific Advisory Board Member)
Lora Hooper UT Southwestern effect resident intestinal bacteria on host biology
Sarkis Mazmanian Caltech host-microbe symbiosis, inflammatory and autoimmune diseases, and the brain-gut-microbiota axis Symbiotix Biotherapies (Co-Founder)
Justin Sonnenburg Stanford microbiota-accessible carbohydrate consumption by gut bacteria Second Genome (Advisory Board Member)
Peter Turnbaugh UCSF impact of the human gut microbiome on pharmacology and nutrition Seres Therapeutics (Advisory Board Member)

Closing

The microbiome represents a new frontier in health and disease. A number of microbiome-based therapies are now in the early stages of development. This recent flurry of commercialization would not be possible without basic research from labs both in CT and around the world. These trends will surely continue as R&D in this field progresses. Stay tuned for the next installment of this series, which will review the patent landscape in microbiome research, with a focus on applications and grants issued this year.

 

–   Jessica Miles and Anthony D. Sabatelli, PhD, JD