Gene editing in the microbiome could provide acne solution

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acne

Eligo Bioscience is a gene-editing company focused on addressing diseases driven by the expression of bacterial genes from the microbiome, and in its crosshairs, initially, is moderate to severe acne vulgaris, an inflammatory disease that affects about 3% of the global population. This week, we talk to Xavier Duportet, CEO of Eligo Bioscience, as the company looks to head to the clinic with its CRISPR treatment to treat moderate to severe acne vulgaris.

Eligo recently received $30 million Series B funding round, led by Sanofi Ventures. Other investors include Bpifrance (through its InnoBio 2 fund), and existing backers Khosla Ventures and Seventure Partners (with Health For Life Capital). 

The funding is earmarked for accelerating the development of Eligo’s flagship program, EB005. The investment will fuel pre-IND and IND activities to achieve early human data readouts in a phase 1b/2a clinical trial. Additionally, it will facilitate Eligo’s expansion into other chronic diseases, including oncology.

By focusing on the in-vivo delivery of genetic cargoes to the microbiome, Eligo’s technology goes beyond traditional gene therapy and gene editing, expanding the range of addressable genetic targets. Through precise genetic modification within the human microbiome, the company hopes the approach will radically alter the course of numerous chronic and life-threatening diseases that are either triggered or driven by the expression of bacterial genes.

About Eligo

Duportet said Eligo was founded based on an invention at Rockefeller University and MIT when he was doing a PhD. He noted that the applications of CRISPR were mostly focused on how to use CRISPR in eukaryotic cells. 

“We found out that you deliver CRISPR in bacteria and target the nuclease to create double strain break in the chromosome of the bacteria. Since prokaryotic cells do not have the same machinery to repair double-strand breaks, it actually kills the bacteria. 

“And so when we saw that, this is when we had basically the idea that this new mechanism of action could be used in the real world as a potential highly-precise antimicrobial mechanism of action. And so this is basically how Eligo was started, to translate this invention into a biotech to create drugs to solve real unmet needs and address diseases that were caused by specific bacteria in the microbiome.”

Revolutionizing genetic medicine: targeting microbiome with synthetic DNA payloads

Duportet said most current genetic medicines focus on correcting or adding genes into eukaryotic cells. 

“We are one of the only companies in the world developing genetic medicines to edit the genetic makeup of the microbiome,” he stated.

“We basically turn microbiome populations into local drug factories.”

Xavier Duportet, CEO, Eligo Bioscience

He added that to deliver genetic cargo to the microbiome bacteria, bacteriophages are used, essentially as a shell.

“We remove all its natural genetic components, and instead, we package in the shell of the virus a completely synthetic DNA payload. So once we have this viral particle that contains our synthetic DNA payload, we use it to deliver the payload in specific bacterial populations of the microbiome. “And the payload itself is modular in terms of what we can encode in the payload. We started by encoding in this payload the CRISPR-Cas system, so the nuclease and the guide RNAs, now we have also demonstrated that we can package base editors that we use to not kill bacteria in the microbiome, but instead edit their genome. 

“So, whether it is to modify one base pair in a protein to inactivate the catalytic site of an enzyme, or to increase or lower the production of a molecule from this bacteria in the body.” 

Duportet said mutating bacteria can be useful for applications where the bacteria associated in driving a disease cannot be eradicated from the microbiome. 

He explained that the third type of payload will enable the local expression of a molecule in the microbiome. 

“We basically turn microbiome populations into local drug factories. And so this really enables us to produce, whether it is nanobodies or small molecules, very locally where the bacterial population we’re targeting is residing, whether it’s on the skin, whether close to epithelial cells in the guts, in tumors.”

The microbiome beyond gut health

There are trillions of bacteria living in different parts of the body, including the gut to the skin. Duportet admitted that most of the research has been done on the gut microbiome and gut health. However, this is changing.  

Eligo is focused on the skin microbiome, and Duportet said it is now possible to understand the relationship between the expression of specific genes from this microbiome and disease. 

“And this is really where we believe the platform technology we have can have a real impact. We have found out that there are some specific genes that are responsible for the driver of lesions in acne and moderate to severe acne vulgaris. Now we’re starting to go at the genetic level and understand one gene or multiple genes, the relationship between one gene or multiple bacterial genes and disease. And I think this precision will really help us design drugs that will actually work to address microbiome-associated diseases.”

Game-changing CRISPR treatment: Eligo’s hope for clearing acne with EB005

EB005 is a first-in-class modality topical CRISPR treatment to treat moderate to severe acne vulgaris.

The skin microbiome contains the bacterium Cutibacterium acnes, which Duportet said represents 80% of the bacteria on the skin in terms of abundance. 

“What we’re developing at Eligo is a highly precise CRISPR drug that will be delivered into this bacterial species on the skin. And we’re programming the nuclease to specifically target regions in the bacterial genome that are unique to the subpopulation that is pro-inflammatory. And therefore, the whole goal of the treatment is to destroy these, very specifically, this subpopulation, while leaving the health-associated population of bacteria completely intact.

“When you kill just the inflammatory subpopulation, you free the niche for the healthy population to take over and fill this niche. I think this will be a game changer in the field because it’s going to be safe and efficient and likely durable. And this is what patients are looking for.”

Duportet said the CRISPR treatment for acne will be a locally-applied gel. He hopes the upcoming trial in the U.S. will yield results by 2025.

And more good news for patients – the cost.

“When you hear about CRISPR drugs, you think millions of dollars in pricing, typically,” Duportet said. 

“The beauty is that we are producing our modality by classical bacterial fermentation. And so the price of the drugs is also going to be lower.”

To learn more

Here are some links to more articles on the subject of treating acne, and CRISPR/ gene editing of the microbiome.

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