Exeliom Biosciences: a new generation of microbiota-derived biotherapies

While modern medicine has made giant strides with immunotherapy, there is still a significant hurdle to this success. Depending on the tumour, only 20% to 30% of cancer patients achieve a durable response to current treatments. To overcome this limitation, research is increasingly turning to intestinal microbiota, among other things. It is in precisely this niche that Exeliom Biosciences is positioned. Founded on major discoveries made almost twenty years ago within the ProbiHôte team, this deep tech start-up is now developing a drug candidate, EXL01.

From clinical correlation to a global discovery

The story began in 2006 with the launch of a collaboration between Philippe Langella, research director at INRAE, and Harry Sokol, a researcher at the French National Institute of Health and Medical Research (Inserm) and gastroenterologist at Hôpital Saint-Antoine (AP-HP), affiliated with Sorbonne University. By comparing the microbiota of people suffering from Crohn's disease, a chronic inflammatory condition of the digestive tract, they observed that a specific bacterium, Faecalibacterium prausnitzii (Fprau), was consistently absent in patients experiencing a relapse but present in those in remission. "That was the beginning of a long story that changed our lives. We were the first to identify a next-generation probiotic bacterium based on human clinical data," recalls Philippe Langella. In 2008, their findings, published in the journal PNAS, and now cited more than 4,000 times, established for the first time the immunomodulatory properties of this commensal bacterium.

For nearly a decade, the researchers worked to further their understanding of the mechanisms of action. Joined by Patrick Gervais, an expert in process engineering, and later by CEO Benjamin Hadida, they founded Exeliom Biosciences (formerly Nextbiotix) in 2016, bringing an entrepreneurial dimension to the project. "The idea was to develop an immunomodulator derived from a live bacterium with naturally beneficial health properties," explains Philippe Langella. The launch of the start-up was supported by INRAE transfert, a specialist in technology transfer. Since then, Exeliom Biosciences has raised close to 32 million euros through successive funding rounds, beginning with its first capital raising in July 2018, supplemented by support from Bpifrance (I-Lab, Deep tech, 2030 Recovery Plan) and the H2020 programme, a highly selective European grant.

EXL01: targeting innate immunity

Exeliom Biosciences' core technology is based on EXL01, a non-genetically modified strain of the intestinal bacterium Faecalibacterium prausnitzii (F. prausnitzii). It relies on a single-strain approach that meets the standards of the modern pharmaceutical industry. EXL01 has two distinct modes of action, depending on the targeted disease. One is immunomodulatory, which acts through the cellular reprogramming of the innate immune system in cancer settings, with the aim of activating it. This reprogramming occurs notably at the level of macrophage metabolism - immune cells capable of ingesting and destroying pathogens and cellular debris - leading to changes in their behaviour and function. By guiding innate immune cells towards a pro-inflammatory profile, EXL01 creates an immune microenvironment more conducive to attacking tumours. This mechanism makes it possible to enhance the immune response of patients treated with immunotherapy.

A lean biotech model for oncology

Exeliom Biosciences operates as a lean biotech model with seven employees. To manage its six clinical trials, the project relies on French and international academic collaborations. "This collaborative model is a decisive strategic lever in a post-COVID financial environment that has become more demanding for biotechnologies, and in particular for novel therapeutic modalities," comments Benjamin Hadida.

In oncology, EXL01 is being evaluated for four cancer types: gastric cancer, in partnership with Gercor - an organisation dedicated to improving oncology treatments - along with liver, lung and kidney cancers. The kidney cancer trial is being carried out in the United States with City of Hope Hospital (California) and aims to improve treatment efficacy in patients who do not respond to conventional immunotherapies.

At the same time, the start-up is running two clinical trials outside the field of oncology. The first focuses on infectious diseases in partnership with the Lyon University Hospital (CHU), the Hospices Civils de Lyon (HCL). The other targets Crohn's disease with the REMIND academic group, which specialises in translational research in inflammatory diseases of the digestive tract.

Industrial ambitions

The robustness of the Exeliom Biosciences project lies in its unprecedented industrial expertise. The challenge lies in cultivating this strict anaerobic bacterium - which dies on contact with oxygen - and encapsulating it while maintaining its stability. The start-up has established a manufacturing process capable of producing kilogramme-scale batches, guaranteeing product stability for three years when stored between 2 and 8°C. This makes it possible to deliver a precise dose in gastro-resistant capsule form and marks the achievement of an industrial proof-of-concept.

The next few years will see major clinical milestones, with initial Phase 2 results expected between 2026 and 2028. "Our ambition is to be in a position to move forward with a Phase 3 submission by 2029, for a first commercial launch around 2033," says Benjamin Hadida. The initial focus will be on gastric cancer in Europe, the United States and Japan. "Beyond Exeliom, if we succeed in demonstrating the efficacy of our clinical trials, the entire field of microbiota-related biotechnologies could well enjoy a second wave of growth," concludes the CEO.