We are only
just beginning to understand what is collectively known as the human
microbiome, what it is, what it does, and how it benefits human health. Researchers
are increasingly recognizing the essential role of the microbiome in human
development, contribution in metabolic functions, protection against pathogens
and how it educate the immune system. While there is still a great deal to learn,
especially about the underlying mechanisms driving these functions, we are
already developing interventions aimed at preventing and treating diseases by
manipulating and restoring the balance of the microbiome.
The startup Synlogic is powering the microbiome by developing a new class of medicines called ‘synthetic biotics’. Based on the work of Jim Collins and Timothy Lu, they combine the human microbiome and synthetic biology, to engineer probiotic bacteria that blend with the existing microbiome to restore functionality that has been lost in organs throughout the body. The engineered bacteria carry specialized assemblies of DNA, called genetic circuits, allowing the synthetic biotic to sense a patient’s internal environment and respond by turning engineered metabolic pathways on. Similarly, the metabolic pathway is turned off when there is no need for the synthetic biotic anymore.
Their innovative platform starts by understanding the metabolic dysregulation that causes disease in order to correct it. The startup then assemble and test prototype genetic circuits that can carry out the metabolic transformation. The optimized genetic circuit is inserted into the genome of the microbe, before the synthetic biotic is designed as oral medicines.
The startup recently raised a $40 million Series B round led by new investor Orbimed Healthcare Fund Management, together with existing investors Atlas Venture and New Enterprise Associates. They will use the money to get their first two programs into clinical testing. Both aim to treat rare metabolic diseases: phenylketonuria, which causes the amino acid phenylalanine to build up in the body, and urea cycle disorders, in which the body’s waste-disposal system malfunctions. Earlier this year, Synlogic also announced a collaboration with AbbVie to create synthetic biotics for the treatment of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis.
While there are a growing number of companies focusing on taking advantage of the microbiome to treat multiple diseases, Synlogic differentiate themselves by combining the microbiome with synthetic biology. Jim Collins initially thought to use the technology to develop diagnostics or treatments for infectious diseases like cholera, but backers steered the company toward rare genetic metabolic disorders. This shows the huge application and potential of the technology. On one hand, they can focus on rare diseases with few or no treatment options, but is also able to collaborate with pharmaceutical giants to target major diseases. The flexible nature of the technology could even make it a powerful tool in personalized medicine. However, this is a major problem for many startups. They do not have the resources to explore all the alternative applications, and are forced to make difficult strategic decisions with limited information that could make or break their future.