Magazine Article | May 31, 2019

Companies To Watch: Synlogic

Source: Life Science Leader

By Wayne Koberstein, Executive Editor, Life Science Leader magazine
Follow Me On Twitter @WayneKoberstein

Living microorganisms engineered to serve as therapeutic agents for rare metabolic diseases


Aoife Brennan
Synlogic is an early-stage developer of “synthetic biotic” medicines — therapeutics consisting of beneficial microbes genetically engineered to treat rare metabolic diseases. It currently has four main products in development: lead product, coded SYNB1020, in Phase 1b/2a for treating hyperammonemia–hepatic encephalopathy and urea cycle disorders; SYNB1618, in Phase 1/2a for phenylketonuria (PKU); and SYNB1891, an immuno-oncology therapy for solid tumors, for which the company expects to file an IND application in 2H2019. One product in inflammatory bowel disease is partnered with AbbVie. Other products are in earlier development stages for various metabolic and oncology indications.


More and more companies I interview for this column are developing small molecule drugs rather than the products of biotechnology, yet we now routinely include them under the umbrella term of “biopharma.” The first bio medicines were mimics of natural proteins produced by rDNA-engineered micro-organisms grown in fermentation vats. Nowadays, companies like Synlogic have moved on to genetic engineering of microbes such as bacteria into active therapeutic agents on their own. Synlogic is one company coming full circle to the original meaning of bio, “made with life.”

Aoife (ee-fa) Brennan ascended to the CEO chair at the company just last year, after 18 months as the chief medical officer. For more than a decade, she had led drug development primarily for rare diseases, most notably at Biogen, heading rare disease innovation. As Synlogic’s CEO, she has focused on shifting the company from platform to product development with the candidates in its current pipeline.

The “synthetic biotic” medicines of Synlogic are simple in concept but purposefully complex in their mechanisms and effects. Rather than a molecule engaging a particular receptor to hit a pharmacological target, a synthetic biotic medicine consists of living bacteria genetically altered to operate on multiple metabolic pathways. “Our technology is based at the intersection of two different fields of science,” says Brennan. “On one side is synthetic biology, which is fundamentally grounded in biotechnology and innovations that increase our ability to read and print DNA. On the other side is the concept of the microbiome. We have bacteria on and around us that have a big impact on our health and disease. Our company is at the intersection of both of those areas of science — we can genetically modify beneficial bacteria to perform specific functions within the human body that can help compensate or treat diseases in ways that are not possible with a small molecule.”

Brennan says the shift to more focus on drug development began the “second era” of the company. “We need to maintain complete leadership in our technology and continue to build our platform, which is the core of the company. But we need to do that in the service of patients, because ultimately we’re on a journey to develop treatments for patients, using synthetic biology as a way to do that as opposed to recombinant biology as an end in itself.” Now Synlogic is entering its third era, not only having multiple development programs, but also programs covering multiple therapeutic areas.

“We are moving from a company where everyone’s essentially working on the same program to a company with program teams where one group of people is working on one program and other groups are working on other programs. We are having to talk about trade-offs, prioritization, and specialization to a place where not everyone can be in every discussion. We have to empower cross-functional teams to run programs and to check in when they need advice and feedback.” Ultimately, Synlogic appears to be headed toward a commercial model, marketing its own products in its niche, rare-disease markets. It is assembling the kind of team and resources needed for the long haul — and for us, a long watch.

Vital Statistics

Employees: 80
Headquarters: Cambridge, MA

$30.5M Series A
$40.2M Series B
$40.4M Series C

Reverse merger into MIRNA therapeutics in August 2017: $40.4M
Follow-on offering Jan. 2018: $54M
Registered direct offering April 2018: $29M (single investor Wellington)

Research Partnership Funding:
AbbVie collaboration to develop treatment for IBD; up-front payment of $2M, research milestones of $16.5M

Latest Updates:
March 2019 achievement of milestone in collaboration with AbbVie
January 2019: publication of first-inhuman clinical data and supporting preclinical data for SYNB1020