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

Project Information

EXL01

Grant agreement ID: 960623

DOI

10.3030/960623

Project closed

EC signature date 28 July 2020

Start date 1 August 2020

End date 31 March 2023

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

€ 3 573 612,50

EU contribution

€ 2 501 528,75

Coordinated by

EXELIOM BIOSCIENCES
France

Periodic Reporting for period 2 - EXL01 (The game changing drug in Crohn’s Disease : a unique standard of care for a healthy long-term remission)

Reporting period: 2021-12-01 to 2023-03-31

Summary of the context and overall objectives of the project

Exeliom Biosciences is a biotechnology company with a dramatically new vision to improve healthcare for patients suffering from immune-mediated diseases by acting on the gut microbiota-host interactions. 70% of our immune-system is located in our gut.

Founded in 2016 by Prof. Harry Sokol, Dr. Philippe Langella, Prof. Patrick Gervais and Benjamin Hadida, Exeliom Biosciences’ work aims at developing innovative immuno-modulatory treatments, with unique safety profiles, to treat a variety of diseases such as inflammatory bowel diseases, psoriaris, infections, and cancers.

Our lead candidate, EXL01, uses the unique anti-inflammatory properties of a naturally occurring bacterium (Faecalibacterium prausnitzii) from the human gut microbiota to trigger beneficial therapeutic effects.

Inflammatory bowel disease (IBD) results in various degrees of abdominal pain, diarrhea, and intestinal bleeding. IBD is a chronic (ongoing and life long) condition affecting more than 5.5 million people in the US, Japan and EU5 in which symptoms vary from person to person and range from mild to severe and have a significant impact on Quality of Life (QOL). Symptoms change over time, with periods of few or no symptoms (remission) alternating with periods of active symptoms.

With our lead program in Crohn's disease, EXL01 aims at modulating the immune system to resolve inflammation, and thus, at maintaining patients in remission longer. By administering a selected strain of Faecalibacterium prausnitzii, we leverage natural mechanisms that result from millions of years of co-evolution between this key dominant bacterial species and the human gut.

Thanks to the H2020 accelerator grant support, Exeliom Biosciences has been able to reach the clinics with its lead candidate EXL01 in Crohn's disease; a decisive milestone turning Exeliom Biosciences into a clinical-stage company. For the first time, EXL01, a Live Biotherapeutic drug candidate, is administered to Crohn’s disease patients in a clinical trial.

To reach this clinical milestone, we had first to overcome the technical challenges of manufacturing this intestinal extremely oxygen-sensitive bacterium at large industrial scale in regulatory-compliant conditions. It had never been done before. We successfully developed secret manufacturing know-how to produce the first large scale clinical batch of F. prausnitzii worldwide. By doing so, we have therefore significantly enriched our intellectual property. Thanks to the H2020 accelerator grant support, we have also been able to set up our own pilot manufacturing unit; allowing us to develop and protect our know-hows.

With our first clinical results expected in the coming months and years, we are now well positionned to become a global leading player in the field of microbiome-based medicines.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

SCALE-UP & MANUFACTURING A CLINICAL BATCH OF EXL01

The bacterial strain EXL01 is extremely sensitive to oxygen and was deemed impossible to manufacture in industrial large-scale conditions when we initiated our project.

We successfully developed a large-scale manufacturing process for the Drug Substance using industrial fermenters. We produced the first (worldwide) large-scale clinical batch of EXL01's drug susbtance in Good-Manufacturing-Practices conditions. We produced the first clinical bacth of EXL01's drug product in Good-Manufacturing-Practices conditions while maintaining strict anaerobic conditions. We pursued the development and optimizations of our industrial drug substance manufacturing process, while developing a unique manufacturing control strategy, in our newly set-up Pilot Unit Laboratory (including pilot scale fermenters)

This work allowed us to:
1- Initiate our first clinical trial to evaulate EXL01
2- Develop new secret manufacturing & control know-hows
3- Develop unique in-house expertise used to generate critical control data and optimization data for our regulatory dossier
4- Position Exeliom Biosciences as a global leader in the field of microbiome-based medicines by being the first worldwide to produce a large-scale batch of F. prausnitzii and by initiating the first clinical trial with a Live Biotherapeutic Product in Crohn's disease patients

CLINICAL TRIAL

Live Biotherapeutic Products form a novel regulatory category. It, therefore, requires multiple interactions with competent authorities to receive a clinial trial authorization.
Crohn's disease is a very competitive field when it comes to operating clinical trials. Therefore, a great deal of preparatory activities were required. The level of complexity was even brought higher by the fact that our study was a maintenance trial, when the vast majority of trials in Crohn's disease are induction trials. It means that clinical sites were less used to the type of design that we wanted to pursue.

Having this in mind:
1- We conducted Scientific Advice meetings with several national agencies in Europe. These meetings allowed us to better understand what would be required to obtain a clinical trial authorization in Europe.
2- We selected a clinical contract research organization with a good track record in inflammatory bowel diseases
3- We worked in parallel on the preparatory work for the submission of our clinical trial authorization request, and on the preparatory work for the clinical activities (selection of the site, finalization of the clinical quality documents, selection of the clinical research assistant, finalization of the protocol, etc.)
4- We activated the first clinical sites and we started to monitor the study

This work allowed us:
1- To obtain the first clinical trial authorization in Europe of a single-strain live biotherapeutic product (first worldwide with a single-strain F. prausnitzii-based product)
2- To recruit the first patient in our clinical study: https://clinicaltrials.gov/ct2/show/NCT05542355

The results from the first part of the clinical trial are expected in end of 2023, and the results from the second part are expected in end of 2025.

We have activaly made our successes known from the public through communications during industry events or via our social media.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The exceptional therapeutic potential of microbiome-based approaches is still largely underused notably due to the complex manufacturing & regulatory challenges involved with such drug candidates.

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 keep our manufacturing know-how in-house, 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.

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