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The game changing drug in Crohn’s Disease : a unique standard of care for a healthy long-term remission

Periodic Reporting for period 1 - EXL01 (The game changing drug in Crohn’s Disease : a unique standard of care for a healthy long-term remission)

Reporting period: 2020-08-01 to 2021-11-30

Exeliom Biosciences is a biotechnology company with a dramatically new vision to improve healthcare for patients suffering from immune-mediated chronic diseases.

Founded in 2016 by Prof. Harry Sokol, Dr. Philippe Langella, Prof. Patrick Gervais and Benjamin Hadida, Exeliom Biosciences’ work aims at developing innovative treatments resolving inflammation, with unprecedented levels of safety, to treat diseases such as Crohn’s disease, ulcerative colitis, psoriaris, atopic dermatitis, and even some cancers.

These diseases are associated with vicious circles causing repeated disease-related crisis. That is what makes them chronic. Our goal is to break those vicious circles with treatments mimicking naturally occurring mechanisms that keep our body healthy. By doing so, we avoid the toxicity and adverse events of existing treatments, and we improve the quality of life of patients in the long run.

Our lead candidate, EXL01, uses the unique anti-inflammatory properties of a naturally occurring bacterium from the human gut microbiota to treat inflammatory bowel diseases. EXL01 aims at harnessing this key bacterium (Faecalibacterium prausnitzii) to modulate the body’s immune system to resolve inflammation in the long run, using mechanisms that result from millions of years of co-evolution between the microbiome and the human gut.

With EXL01, Exeliom Biosciences is about to reach a decisive milestone by becoming a clinical-stage biotechnology company. For the first time, EXL01, a Live Biotherapeutic drug candidate, will be administered to Crohn’s disease patients in a Phase 1/2a clinical trial in 2022.

But to reach this clinical milestone, we must first overcome the technical challenges of manufacturing this intestinal bacterium at large industrial scale in regulatory-compliant facilities. It has never been done before, and this would simply be a first worldwide. By doing so, our objective is to enrich our intellectual property and to develop new know-hows to make this ambitious project a reality. Having our own pilot manufacturing unit will help us protect these precious know-how by keeping them secret.
To make our EXL01 product, two steps are needed: first, produce the Drug Substance (ie. the bacterium in the form of lyophilized powder), and then, produce the Drug Product (ie. the Drug Substance mixed with excipients and encapsulated in a protective capsule specially designed to release the Drug Substance in the right area of the gut).

The bacterium contained in our lead candidate, EXL01, was deemed impossible to produce at large industrial scale at the start of this project, notably due to its extreme sensitivity to oxygen.

To make our ambition to administer EXL01 to Crohn’s Disease patients a reality, we had to go against that fact.

We decided to adopt a pragmatic approach that was twofold: firstly, find a process that would allow to produce a batch large enough to cover the needs of our first clinical trial, and, secondly, work in parallel on scale-up optimizations to make the project more industry-compatible in the long-run and, therefore, more competitive.

Following this approach, we achieved several things in parallel.

First, we successfully manufactured enough drug substance to produce a test batch of Drug Product (ie. Engineering Batch), setting up the process parameters for this crucial manufacturing step. This batch of Drug Substance was manufactured in regulatory-compliant facilities (ie.GMP) and is, therefore, fit for purpose to be used in our planned clinical study.

Second, we successfully set up our own pilot manufacturing unit to work on process optimizations and scale-up in industrially-compatible equipment. Third, we managed to produce for the first-time ever this bacterium in pilot scale industrial fermenters, and by doing so, to identify the key scale-up factors to ultimately optimize the process. This batch will then be used to manufacture the Drug Product batch that will serve in our clinical study in Q1 2022.

Last but not the least, additional scale-up and optimization works have already been initiated in our pilot manufacturing unit to create new intellectual property and consolidate our competitive position.
The exceptional therapeutic potential of microbiome-based approaches is still largely underused notably due to the complex manufacturing challenges involved with such drug candidates.

EXL01 is the perfect illustration of such issue.

By manufacturing EXL01 at large scale, in industrial conditions, and in compliance with health agencies’ requirements, we reached a turning-point not only for our lead program but also for an entire field of research worldwide.

Getting access to microbiome-based treatments will be a game-changer for the way patients suffering from chronic inflammatory diseases (starting with Crohn’s Disease) are treated. On top of that, having the possibility to internalize the manufacturing know-how that we developed with our partners within our pilot manufacturing unit, and ultimately to generate new intellectual property is critical to keep our competitive advantage.

In the longer run, the next step for us will be to set up our own large scale manufacturing unit and to obtain the regulatory authorizations to manufacture all the clinical baches for our future studies. It will be a way to keep European know-hows on European ground, but also to create new jobs within a new European industrial leader in the pharma industry.