Managing the microbiome

A roundup of a few recent news stories related to microbiome discoveries

Mel J. Yeates
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There have been many mentions of the microbiome rocketing around what seems like every corner of the pharma industry, recently. And here are a few more to add to the buzz: a research collaboration between Enterome and the Dana-Farber Cancer Institute for microbiome cancer immunotherapies, a collaboration between Servier and Harvard University intending to create therapeutics for type 2 diabetes and NAFLD, and Phase Genomics creating a microbiome discovery platform.
Microbiome-derived cancer immunotherapy alliance
PARIS & CAMBRIDGE, Mass.—Enterome SA has entered into a research and development collaboration with Dana-Farber Cancer Institute to evaluate and develop gut microbiome-derived antigens as potential cancer immunotherapies.
Enterome’s approach to cancer immunotherapy is based on the concept of molecular mimicry, whereby microbiome-derived bacterial antigens show molecular similarity with tumor-associated antigens (TAAs) and tumor-specific neoantigens (TSNAs). Based on this similarity, bacterial antigens (onco-mimics) mimic key tumor antigens that are highly expressed by tumors to trigger tumor-specific cytotoxic T cell immune responses.
Enterome has developed a discovery platform to identify such onco-mimics from the human gut microbiome, and has advanced EO2401 as its first clinical candidate. EO2401 comprises several microbiome-derived antigens that mimic antigens highly expressed by brain tumors, and is targeting first clinical trials in 2019 as a potential new immunotherapy for recurrent glioblastoma multiforme, for which no curative treatments exist.
The collaboration brings together Enterome’s ability to identify potential TAAs and TSNAs, as well as to generate bacterial onco-mimics for the selected TAAs and TSNAs with the complementary translational expertise from the research groups at Dana-Farber Cancer Institute led by Dr. David Reardon at the Center for Neuro-Oncology and Dr. Paul Kirschmeier at the Belfer Center for Applied Cancer Science. Reardon’s and Kirschmeier’s groups are focused on research programs and clinical trials to improve cure rates in patients with brain and spinal cancers, with a particular focus on immunotherapies.
“We are delighted to have signed this collaboration with one of the most esteemed cancer research institutions in the US,” said Pierre Belichard, CEO of Enterome. “Drs. Reardon and Kirschmeier are accomplished and renowned clinician-scientists in their respective fields, and their groups have pioneered novel approaches to cancer therapy, particularly in the brain. We believe that this collaboration will be highly productive in further validating our onco-mimic immunotherapy approach and enable us to develop our pipeline of new candidates for multiple cancer indications.”

Servier collaborates with Harvard against metabolic diseases
PARIS—Servier recently entered into a collaborative study with Harvard University researchers in order to explore a new avenue for the treatment of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Servier and the Harvard researchers have planned a three-year preclinical research project with the ultimate objective of developing therapeutics targeting the microbiota for the treatment of type 2 diabetes and NAFLD. The work will be conducted by a multidisciplinary team of researchers from both parties. The Harvard research team will be led by Emily P. Balskus, a professor of chemistry and chemical biology, and the Servier team will be led by Philippe Delerive, head of research for cardiovascular and metabolic diseases.
The alliance combines the expertise of Servier researchers in the field of metabolism and drug development with Balskus’ expertise in chemical discovery relating to the gut microbiome, with the hope of making important advances in understanding disease biology and using emerging technologies to develop new treatment options for diseases with high unmet medical need.
“Gut microbiota is an untapped resource for the identification of novel targets in the field of metabolic diseases. It opens up new perspectives for the development of increasingly precise and personalized innovative therapies. The close collaboration between our researchers and academic researchers from Harvard represents a major step in this direction, for the ultimate benefit of patients,” stated Servier’s executive vice president of research and development, Claude Bertrand.
This project is under the strategic alliance established between Servier and Harvard University in 2017. Under the terms of the alliance agreement, Servier will support multi-year research projects initiated by Harvard faculty and focused on the development of innovative treatments in the company’s therapeutic fields of expertise. Identifying new therapeutic targets in the type 2 diabetes field is one of Servier’s priorities, as well as research of specific therapeutic solutions to diabetes-linked complications such as diabetic nephropathy and NAFLD.

Microbiome discovery platform receives new funding
SEATTLE—In February, Phase Genomics announced a year-long grant awarded by the Bill & Melinda Gates Foundation to develop an improved computational method for extracting genomic information from complex microbiome samples. This new tool will help researchers identify, with an unprecedented level of detail, new species and strains of gut microbes, and understand how microbial strains are passed between mothers and infants.
“The impact of the microbiome on human health is broad-ranging, but the mechanism is poorly understood,” noted Dr. Justin Sonnenburg, an associate professor of microbiology and immunology at Stanford University and Phase Genomics collaborator. “By collaborating with Phase Genomics on the development of metagenomic proximity-ligation technology we hope to increase our understanding of the microbes that impact human health, with a focus on understudied samples from the developing world. Our goal is to produce a tool that will make the highest resolution microbiome analysis accessible to researchers around the globe.”
Phase Genomics plans to use its unique metagenomic proximity ligation technology to develop the new software and improve the resolution of microbiome studies relative to current methods. This news follows the recent release of two papers highlighting new discoveries about tracking antimicrobial resistance in the microbiome of wastewater and cow rumen. Using the proximity-ligation data analysis tool, ProxiMeta Hi-C, the research also led to the discovery of hundreds of previously unknown microorganism species.
“The technology we’re developing, we believe, will improve the quality and accuracy of microbiome analysis by nearly every relevant metric,” commented Dr. Ivan Liachko, CEO and co-founder of Phase Genomics. “We also anticipate that our platform will lower the cost of metagenome assembly and put this powerful culture-free technology within reach of healthcare and research leaders in developing countries.”

Mel J. Yeates

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