Eligo raises $20M to take bacteria-killing CRISPR drug into clinic

Eligo CSO David Bikard and CEO Xavier Duportet

Khosla Ventures and Seventure Partners have driven Eligo Bioscience to a $20 million (€17 million) series A. The round equips Eligo to move its lead CRISPR-enabled, bacteria-killing candidate toward the clinic in a rare disease indication.

Eligo raised the money on the strength of in vivo proof-of-concept data suggesting its lead drug can selectively kill bacteria in the gut. The candidate achieves such selective killing through the use of CRISPR/Cas9 targeted at specific genetic sequences, such as those that code for a toxin or make bacteria resistant to antibiotics.  

“If the sequence is present, then the Cas is going to cut … and the bacteria will not repair its DNA and so it will lead to the death of the bacteria,” Eligo CEO Xavier Duportet, Ph.D., said.

The potential for CRISPR/Cas9 to enable targeted attacks on bacteria—sniper shots compared to antibiotic WMDs—has raised hopes the gene editing technology can address the antibiotic crisis. It has also attracted the attention of biotechs including Locus Bioscience and multiple academic groups.

Eligo’s platform could enable it to go after troublesome, drug-resistant bacteria such as MRSA. But, following a well-worn path, the biotech plans to validate its approach in a currently undisclosed rare disease caused by a pathogenic gut bacteria before branching out to tackle bigger indications. 

The relatively low cost of developing drugs in rare diseases means Eligo expects the series A to see it beyond its anticipated entry into the clinic early in 2020 and through to the generation of phase 2 data in the rare disease. 

In theory, Eligo’s platform can treat any disease for which a causal relationship with a bacteria exists. The upshot is the opportunity Eligo’s platform can address could mushroom if the boom in microbiome research uncovers more and more causal relationships. And Eligo’s work to deliver its gene-snipping payloads has put it at the foothills of opportunities beyond CRISPR/Cas9. 

Eligo shares a cofounder with Intellia Therapeutics—Luciano Marraffini, Ph.D.—but since pulling in seed funding in 2015 it has pivoted away from being a pure-play CRISPR company. That evolution is a result of Eligo’s research into how to efficiently deliver CRISPR/Cas9 to bacteria and achieve good expression, which, with the latter gene clocking in at about 4.1­ kb and the gut microbiome being a complex environment, posed a considerable challenge.

Paris-based Eligo tried to overcome the challenge by stripping back bacteriophages. 

“We found a way to remove the genome of phages and replace it with synthetic DNA circuits that contain the protein we want to express,” Duportet said “It's not phage anymore at all. We take the best of the phage for us, which is just the shell, the protein capsid. [This] enables us to target and have our payload delivered only in bacterial cells in a very efficient way and in a transient way.”

Eligo developed the technology to deliver CRISPR/Cas9. But having found a way to deliver large, complex circuits of synthetic DNA, Eligo will use the platform to carry a range of genetic payloads. These payloads could enable bacteria in the body to produce therapeutic proteins and, in doing so, modulate host-microbiome interactions. 

Eligo will use a slice of the series A to start up a few non-CRISPR programs. In parallel, Eligo is also building out its team. Having operated with a six-person team until recently, Eligo has scaled up to a headcount of 15 and plans to top 20 by early next year.