Antibiotic resistance is a public health problem worldwide. According to WHO, by 2050, over 10 million people will die every year. Microbiomics is a fast evolving field which could play an important role in fighting these resistant bacteria. And CRISPR is literally seen as the biggest Biotech discovery of this century. So, here’s a crazy thought… what would happen if you were to mix Antibiotics, Microbiome and CRISPR together?
Xavier Duportet is a young entrepreneur, co-founder and CEO of Paris-based Eligo Bioscience, trying to use CRIPSR and all its potential to cure microbiome diseases. Today, the one-year old company proudly announced that it raised €2M from French VC Seventure Partners, which recently opened the first fund dedicated to microbiomics.
I had the pleasure of meeting Xavier several times before, and every time I felt impressed with him. He is a brilliant scientist who did his PhD at MIT. Today, he organizes the Hello Tomorrow Challenge and is always very enthusiastic. I called him this time to know more about his new venture, its potential and also the milestones left to achieve.
So, Eligo Bioscience wants to redefine antibiotics. Instead of killing every bacteria, you want to use « Eligobiotics » to selectively kill pathogenic bacteria inside the microbiome. How does it work?
We are using phage capsids in which we encapsulate the CRISPR mechanism, to deliver it selectively to bacteria. The CRISPR system will search out and cut gene sequences unique to pathogenic, resistant or virulent bacteria within the microbiome. Since bacteria can not repair all double strand breaks, we have shown that this mechanism can lead to the rapid and efficient death of the targeted bacteria. Because we only use the capside of the phage, the replication mechanisms of phages are no longer active, allowing us to control the spreading of our “eligobiotics”.
The ultimate goal is to reduce the number of pathogenic microorganisms without hurting the « good » bacteria. This increases the natural pressure and helps repopulate the microbiome balance.
Did you use CRISPR because its trendy or for another good reason?
CRISPR is a really powerful technology. We could have used other technologies such as meganucleases, but CRISPR is much more versatile to kill resistant bacteria. Thanks to this new technology, we can easily target several spots in the bacteria’s genomes that present pathogenic mutations.
Should there be any pathogenic mutations in the gene we target, we can easily aim at several spots in the genome to be sure to kill the bacteria.
You did your PhD at the MIT and at the French Research Institute INRIA. Did you develop the technology there?
It is quite a nice story when I look back it today. We discussed about this project with David Bikard,who was a post-doc at Rockefeller University at that time, where he worked with Luciano Marraffini. Once he got preliminary results on gram-positive bacteria, I started to talk with them and Timothy Lu, Associate Professor at MIT. He then told me that he just developped the same technology and had the same results but on gram-negative bacteria. We therefore decided to join forces and we are now all cofounders of Eligo. David Bikard is now the CSO of Eligo, and recently opened his own lab at Institut Pasteur.
MIT and Rockefeller are two leading research institutes in the Biotech field and this is a great asset for Eligo. Furthermore, we are currently hosted by Institut Pasteur in Paris, an amazing place for biotech!
The CRISPR patent landscape is a bit touchy right now. Research institutes, such as the BROAD Institute, are fighting to own the rights on the technology. Where do you stand in all this?
It is indeed complicated right now. We have 2 published patents and others coming, but I can’t tell you more about it right now… All I can say is that we are building a strong portfolio!
Let’s move on to the therapeutics side of things. Which diseases are you going after?
We first started with Inflammatory Bowel Disease, a group of inflammatory conditions of the colon and small intestine. It is still an important disease leading to over 50,000 deaths every year and is still very hard to cure.
The second disease we are going after is Acne. Many teenagers around the world are suffering from this skin disease, and could be caused by a bacterial infection.
Microbiomics is still a young science and all the mechanism of action are not discovered yet. What challenges are you facing?
The knowledge concerning microbiome diseases is still weak. We need the science to prove the involvement of bacteria in the disease before making any assumptions or start any procedure. This limits the number of possible diseases available to treat to date, but we are confident for the future, since new evidence highlighting the link between specific strains and a disease is published every day.
Our second challenge is to prove that our technology works. Right now, we were able to demonstrate efficient and targeted decolonization, but only by testing on mice skin and on wax moth (Galleria mellonella). We now need to prove it works in the gut of an animal before heading to human trials.
Even if the microbiome field is young, it is exploding right now, as the recent $134M IPO of Seres Health illustrates. Who are you competing with?
Several companies are acting in the field of microbiome, but none are using our technology and approach. This opens up a boulevard to become a leading company in the field, and we want to seize this opportunity.
You announced you raised €2M today as a seed-stage round from Seventure Partners. What is this money intended for?
Two priorities: first, we will advance our clinical developments in pre-clinical and then clinical trials. Once that’s done, we will build a library of engineered phage capsids to target a wide variety of bacterial species.
Antibiotics, Microbiome, CRISPR, three trendy words. What is your vision on them?
We want to be the experts, able to kill any bacteria in a precise way! We want to become microbiome snipers!