CAMBRIDGE, Mass.—Synlogic, a privately held biopharmaceutical company, has announced a multiyear global R&D collaboration with AbbVie, reportedly representing the first industry collaboration using a combined microbiome/synthetic biology approach for drug development. The result could have major implications for hundreds of thousands of people suffering from inflammatory bowel disease (IBD) and could have “enormous” commercial potential, according to the companies.
The collaboration is focused on developing novel medicines for the treatment of IBD using Synlogic’s proprietary approach for a new class of synthetic biotic medicines that power the microbiome. A key objective is to combine AbbVie’s expertise in metabolic and inflammatory diseases with Synlogic’s platform to generate and advance to the clinic a novel, oral probiotic therapeutic candidate.
According to Synlogic CEO Jose-Carlos Gutiérrez-Ramos, Synlogic has “reimagined the potential of probiotics,” natural bacteria that have grown in popularity for general health, “by transforming them into therapeutics designed to have measurable and predictable benefits for treating serious diseases. They are engineered to sense and respond to stimuli.”
The synthetic biotics created by Synlogic are probiotic bacteria that are therapeutically engineered with genetic switches to perform specific metabolic functions. Synthetic biotics operate from the microbiome and perform specific metabolic transformations to correct disease-causing metabolic dysregulation throughout the body. This approach enables the shifting of a corrected and enhanced metabolic function from a disease organ to a stable, non-colonizing fraction of the microbiome.
Synlogic became interested in working with AbbVie, a leader in the treatment of IBD, including diseases such as Crohn’s disease and colitis, because the company “had the expertise and clinical know-how to help us explore the potential of our technology,” Gutiérrez-Ramos explained. Based in North Chicago, Ill., AbbVie—a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories—develops and markets advanced therapies that address complex and serious diseases. Gutiérrez-Ramos described the partnership with AbbVie as “a part of our overall strategy for enabling the broad potential of our synthetic biotics platform by forging partnerships with pharmaceutical and biotechnology leaders to pursue major disease indications affecting millions of patients, while simultaneously accelerating Synlogic’s internal pipeline in rare orphan diseases toward the clinic.”
Under the terms of the collaboration, Synlogic will discover, characterize and optimize synthetic biotics-based drug candidates targeting IBD, with special emphasis on Crohn’s disease and ulcerative colitis. The two companies expect to produce an IND and two potential backups in a three-year period. Synlogic and AbbVie will evaluate synthetic biotics candidates that modulate certain effectors involved in the IBD pathway and advance them through preclinical development, with AbbVie being responsible for regulatory filings, clinical development and worldwide marketing of any resulting products.
A drug based on synthetic biotics would be taken orally every day, travel through the highly perfused, 25-foot gastrointestinal system and be activated when there was a flareup, Gutiérrez-Ramos said. It would be engineered to produce beneficial metabolites or destroy toxic metabolites. The drug might produce a substance to increase mucosal healing, break down inflammatory molecules from the disease or produce anti-inflammatory molecules to treat it.
The synthetic biotics approach has the flexibility to combine as many as four mechanisms of action in one bacterium and to build high potencies, Gutiérrez-Ramos added. While patients would be on the drug all the time, it would only be activated when the bacterium senses that there is a flareup and only treat the GI tract when needed. It would sense the inflammation and activate the appropriate mechanism to treat it.
“Synlogic’s innovative approach to targeting the microbiome offers a new way to address inflammatory bowel disease,” said Jim Sullivan, vice president of pharmaceutical discovery for AbbVie. “AbbVie is committed to collaborating with scientific leaders with new technologies and therapeutic advances that complement AbbVie’s internal expertise and share our commitment to advancing the standard of care for patients.”
Gutiérrez-Ramos concluded, “Inborn errors of metabolism in the liver, pancreas, muscles and other organs cause people to accumulate something that is bad or to not have enough of something to be healthy, and we hope to treat these systemic diseases. Synthetic biotics combine the safety of probiotics with the pharmacological capability of conventional drugs, and we’re excited that these could be a whole new class of safe and effective medicines that change patients’ lives.”