Synthetic Biology Meets The Microbiome: Synlogic

Posted October 7th, 2014 in Atlas Venture, Portfolio news

Today Synlogic announced that the Bill & Melinda Gates Foundation joined the Series A financing to help power up its platform around developing therapeutic microbes (here).  Combining compelling elements of two exciting fields – engineering organisms with synthetic biology and harnessing the power of the gut microbiome to shape health – Synlogic’s approach has broad potential across a range of diseases.

Synlogic has been a great example of our seed-led model: uncover potentially transformational science, identify and build relationships with great scientific founders, seed invest around exploring the field to address if it warrants scaling into a company and what applications to pursue, and recruit great talent along the way.  With this announcement, we’ve now entered the launch and “build” phase of the story.

As background, we have known and interacted with the scientific founders of Synlogic for years: Jim Collins at Boston University (here), and Tim Lu, now at MIT but formerly Jim’s post-doc (here).  In fact, Jim and I were first introduced at the November 2007 Nature Biotech SciCafe, when he gave a talk on network biology.  We also connected shortly thereafter on the subject of engineered phage for the detection and eradication of pathogenic bugs (here), technology around which he and Tim helped found an industrial diagnostics startup called Sample6 (here).  Over the past decade, both Jim and Tim have established themselves at the forefront of synthetic biology and genome engineering – truly world-class co-founders.  Beyond their synthetic biology leadership, Jim’s antibiotic expertise has also been particularly helpful in our work at Spero Therapeutics and their work on novel antibiotic mechanisms.

The other half the story comes from the microbiome field.  Like many other early stage investors, a few years ago we began looking into the possible therapeutic applications derived from insights into the human gut microbiome.  There’s a litany of published papers on the role of gut microbe colonization in all sorts of diseases: autoimmune, cardiometabolic, CNS, etc…  And although there are a number of very interesting companies in the space (Second Genome, Seres, Vedanta, Symbiotix, many others), we either never had a chance to invest in them (several of the deals listed), or for a variety of reasons never got any host microbiome concepts through our deal process.  A big factor was that we couldn’t get comfortable with either end of the “microbiome” deal spectrum: the generic fecal transplant approach (e.g., the “poop in the pill” concept with processed human stool, here) on one side, or the more reductionist “this is the one key factor secreted by XYZ bug that will treat ABC disease” on the other.  Some of the more nuanced stories in between those poles are much more interesting. But as of today we haven’t made a “pure” microbiome bet, though I’m sure some of these companies will be very successful.

It was the convergence of manipulating the host microbiome with Collins’ and Liu’s ideas of engineering microbes that got us really excited: create therapeutic bugs (in a pill) that move through the gut, detect their local environment, turn on specific gene cassettes in the presence of the right signals, and turn them off in their absence – the ultimate in delivering a therapeutic to the right place at the right time.  The technology involves genetic toggle switches, shutoff switches, and gene circuit integration to engineer the precise functionality desired. Although early and risky, the work has already established compelling in vivo proof of concept, and engineered bugs have prior clinical and regulatory precedent.  The range of possible diseases is large: obviously the addressable conditions have to engage the gut in some fashion – but as the broader host microbiome literature has been telling us, the gut is a major integrator and communicator of lots of signals.

With great science comes great talent.  In early 2014, Synlogic was led by my Partner Peter Barrett, our Venture Partner Ankit Mahadevia (a Synlogic co-founder), and Atlas EIR Dean Falb – largely to secure the patent estates, identify the right lead indications for the platform, and confirm the excitement around the science.  More recently, we recruited two key hires for the leadership team: Alison Silva, who has extensive engineered bug experience from Cequent, as our Chief Operating Officer; and Paul Miller, formerly of AstraZeneca, is an expert in microbial genetics.

Like any big-biology platform company, this story begins with great science, great team, and solid foundational IP – the next key ingredient is capital.  And likely lots of it over time; to support this, we were pleased to have Ed Mathers of NEA join us in the $29M Series A back in July (announced here, here), and are looking forward to working with he and his partners.

But a story like this will require more than just equity capital: a platform this expansive has enormous opportunities to leverage partnerships to help expand its footprint, broaden its capabilities, and establish a large portfolio of therapeutics opportunities.  The company is already engaged in multiple advanced partnering conversations; at the risk of getting out over my skis, we expect the company to have multiple deals completed over the next 18 months.

One new partner was announced today, as the Bill & Melinda Gates Foundation has joined the Synlogic team – to help us explore the use of this platform for treating severe diarrheal diseases in the developing world in particular – which is both further validation of the potential of this new platform, and the additional of an experienced partner.

We’re excited about Synlogic’s launch out of stealthy-seed mode over the past few months – and its great to be working with superbly talented Synlogic team members like Jim and Tim, Alison and Paul, and Ankit and Dean.  The gut microbiome should be very scared with this team coming after them.

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