faecalibacterium prausnitzii EXL01-strain (EXL01) / Exeliom Biosciences - LARVOL DELTA

FAECALIBACTERIUM PRAUSNITZII - EXL01 IN CROHN'S DISEASE: FROM PRECLINICAL DISCOVERY TO FIRST-IN-HUMAN CLINICAL TRIAL IN PATIENTS WITH MILD TO MODERATE CROHN'S DISEASE (UEGW 2025) - "EXL01, administered during and after CS tapering, was safe and well tolerated for up to 24 weeks in patients with CD. Though limited by small sample size, the study supports the biological activity of EXL01, notably through its impact on ileal gene expression. A phase 2 randomized controlled trial is ongoing to further assess efficacy."

First-in-human • P1 data • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

FAECALIBACTERIUM PRAUSNITZII EXL01 EXHIBITS A SPECIFIC PEPTIDOGLYCAN THAT IS INVOLVED IN ITS ANTI-INFLAMMATORY EFFECT IN A NOD2-DEPENDENT WAY (UEGW 2025) - P1 | "Our study showed that Faecalibacterium and its PG activate NOD2, and therefore the production of IL-10, in a different way than other Gram-positive bacteria. These results provide new insight into the molecular pathways underlying the immunomodulatory effects of F. prausnitzii, and highlight NOD engagement as a key immunological feature. Identification of PG as a molecule responsible for the therapeutic effects paves the way for the next generation of Faecalibacterium-based drugs, whether whole-cell or component-driven, in inflammatory diseases such as CD."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Inflammation • Inflammatory Bowel Disease • CD14 • GLI2 • IL10 • TNFA

BIG: First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group | Trial completion date: Dec 2029 ➔ Apr 2029 | Trial primary completion date: Apr 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • PD-L1

Immunotherapy (Nivolumab and Ipilimumab) With and Without a Live Biotherapeutic Product (EXL01) for the Treatment of Metastatic Renal Cell Cancer (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

MOTHER: Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=34 | Recruiting | Sponsor: Center Eugene Marquis | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

BIG: First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group | Trial completion date: Mar 2029 ➔ Dec 2029 | Trial primary completion date: Mar 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • PD-L1

MAINTAIN-POP: Target Engagement of EXL01 in the Prevention of Post-operative Recurrence of Crohn's Disease (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Madeleine Bezault

New P2 trial • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

MOTHER: Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=34 | Recruiting | Sponsor: Center Eugene Marquis | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor

Faecalibacterium prausnitzii induces an anti-inflammatory response and a metabolic reprogramming in human monocytes (ECCO-IBD 2025) - P1 | "These results provide new insight into the mechanisms underlying the anti-inflammatory effects of F. prausnitzii and are crucial for a better understanding of its potential use in the treatment of IBD. The well-characterised F. prausnitzii EXL01 is already in clinical development in Crohn's disease (NCT05542355), and the results of the first phase 1/2A study involving 8 patients will be available in early 2025."

Crohn's disease • Inflammation • Inflammatory Bowel Disease • CD14 • IL10

EXLIBRIS: EXL01 in Combination With Nivolumab for Advanced NSCLC Refractory to Immunotherapy. (clinicaltrials.gov) - P1/2 | N=21 | Recruiting | Sponsor: University Hospital, Lille | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Exeliom Biosciences | Active, not recruiting ➔ Terminated; Due to low recruitment

Trial termination • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

MOTHER: Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Center Eugene Marquis

Immuno-oncology • New P2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

BIG: First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2024 ➔ Jul 2024

Combination therapy • Enrollment open • Metastases • Trial initiation date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors. (PubMed, Oncoimmunology) - "F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future."

Checkpoint inhibition • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Exeliom Biosciences | Recruiting ➔ Active, not recruiting | N=67 ➔ 8 | Trial completion date: Oct 2025 ➔ Oct 2024 | Trial primary completion date: Oct 2025 ➔ Oct 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

EXLIBRIS: EXL01 in Combination With Nivolumab for Advanced NSCLC Refractory to Immunotherapy. (clinicaltrials.gov) - P1/2 | N=21 | Not yet recruiting | Sponsor: University Hospital, Lille

Combination therapy • Metastases • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

LIVEDIFF: Evaluation of EXL01, a New Live Biotherapeutic Product to Prevent Recurrence of Clostridioides Difficile Infection in High-risk Patients (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Hospices Civils de Lyon | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease

LIVEDIFF: Evaluation of EXL01, a New Live Biotherapeutic Product to Prevent Recurrence of Clostridioides Difficile Infection in High-risk Patients (clinicaltrials.gov) - P1/2 | N=56 | Not yet recruiting | Sponsor: Hospices Civils de Lyon

New P1/2 trial • Infectious Disease

BIG: First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group

Combination therapy • Metastases • New P2 trial • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=67 | Recruiting | Sponsor: Exeliom Biosciences

Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=67 | Recruiting | Sponsor: Exeliom Biosciences | Initiation date: Sep 2022 ➔ Mar 2023

Trial initiation date • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • CRP

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=67 | Recruiting | Sponsor: Exeliom Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • CRP

MAINTAIN: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (clinicaltrials.gov) - P1 | N=67 | Not yet recruiting | Sponsor: Exeliom Biosciences

New P1 trial • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • CRP