EXL-01: A Comprehensive Analysis of a First-in-Class NOD2-Targeting Live Biotherapeutic for Immunomodulation in Oncology and Inflammatory Disease

Executive Summary

EXL-01 is a first-in-class, clinical-stage investigational medicine being developed by Exeliom Biosciences. It is classified as a Live Biotherapeutic Product (LBP), consisting of a single, unmodified strain of the commensal gut bacterium Faecalibacterium prausnitzii. Formulated for oral administration in a gastro-resistant capsule, EXL-01 is designed for targeted release in the small intestine to exert a localized immunomodulatory effect. Its mechanism of action is centered on the hyperactivation of the Nucleotide-binding Oligomerization Domain-containing protein 2 (NOD2) pathway in myeloid cells, which drives a context-dependent metabolic reprogramming of monocytes and macrophages. In inflammatory conditions such as Crohn's disease, this reprogramming leads to a potent anti-inflammatory response characterized by the production of Interleukin-10 ($IL-10$). In the immuno-oncology setting, the same mechanism is leveraged to enhance the efficacy of immune checkpoint inhibitors (ICIs) by improving antigen presentation and boosting anti-tumor T-cell activation.

The clinical development program for EXL-01 is extensive and strategically diversified across three therapeutic areas: immuno-inflammation, infectious disease, and immuno-oncology. In Crohn's disease, following a terminated Phase 1 trial (MAINTAIN) that nonetheless demonstrated an excellent safety profile, the program has pivoted to a Phase 2 study (MAINTAIN-POP) focused on preventing post-operative recurrence. For infectious diseases, a Phase 1/2 trial (LIVEDIFF) is evaluating EXL-01's potential to prevent the recurrence of Clostridioides difficile infection in high-risk patients.