OSE Immunotherapeutics Presents Positive Preclinical Data on Combination of Anti-IL-7 Receptor Lusvertikimab in Chronic Colitis In Oral Presentation at 20th Congress of ECCO

OSE Immunotherapeutics Presents Positive Preclinical Data on Combination of Anti-IL-7 Receptor Lusvertikimab in Chronic Colitis
In Oral Presentation at 20^th Congress of ECCO

NANTES, France – February 20, 2025, 6:00pm CET - OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), today presented positive preclinical data on the combination of anti-IL-7 receptor (IL-7R) with anti-IL-12/23 monoclonal antibody (mAb) in chronic colitis at the 20^th Congress of ECCO (European Crohn’s and Colitis Organization), held from February 19-22, 2025, in Berlin (Germany).

The oral communication, entitled "Anti-IL-7 Receptor Plus Anti-IL12/23 Combination Induces Complete Histological Normalization in Chronic Colitis”, presented by Nicolas Poirier, reported that
IL-7 drives resistance to anti-IL-23 inhibition. The administration of anti-IL-7R in combination with an anti-IL-12/23 acts synergistically to achieve profound preclinical control of chronic colitis, characterized by complete histological healing.

Nicolas Poirier, CEO of OSE Immunotherapeutics, comments: "Our latest research shows that IL-7 prevents the inhibitory effect of IL-23 antagonists on the control of human Th17 T lymphocytes. Additionally, IL-7R overexpression in the colon of ulcerative colitis or Crohn’s disease patients correlates with high IL-23 expression. We demonstrated that combining anti-IL-7R with anti-IL-12/23 mAb is well tolerated and synergizes to control chronic colitis symptoms in a validated preclinical model. It also demonstrates complete histological normalization compared to monotherapies.

"Together with the positive efficacy seen in the Phase 2 Lusvertikimab monotherapy clinical results on endoscopic and histological remission in ulcerative colitis, to be presented in the Top-10 highlighted plenary session at ECCO, these latest preclinical data for the combination of the inhibition of upstream (IL-7) and downstream (IL-23) inflammatory mechanisms expand and strengthen the potential positioning of our first-in-class drug candidate in the Immuno-Inflammation (I&I) therapeutic landscape. I would like to warmly thank the OSE research, translational, computational biology and clinical teams for their coordinated efforts in achieving these significant milestones.”

More details on the presentation:

• Interleukin-7 (IL-7) drives not only the survival but also the differentiation of human T lymphocytes subsets, such as Th17 (IL-17-secreting pathogenic T lymphocytes). IL-23 is the primary driver of Th17 differentiation, and IL-23 antagonists (currently one of the standards of care in Inflammatory Bowel Diseases [IBD]) inhibit the generation of Th17 cells. However, in the presence of IL-7, IL-23 antagonists lose their inhibitory activity in vitro. Combining Lusvertikimab with an anti-IL-23 monoclonal antibody (eg. Guselkumab) restores the inhibition of human Th17 cells in the presence of both IL-7 and IL-23.
• High IL-7R tissue expression has previously been observed in the colon of IBD patients with resistance to anti-TNF or anti-integrin therapies¹. OSE Immunotherapeutics’ R&D team has shown that IL-7R is also overexpressed in the mucosa of patients with resistance to anti-IL-12/23 antagonist therapy, and that IL-7R expression correlates with high mucosal IL-23 expression.
• Using a well-validated preclinical chronic colitis model, OSE Immunotherapeutics’ R&D team reported that while the IL-12/23 antagonist mAb is efficient, it is not sufficient in monotherapy to achieve complete remission at both macroscopic and histological levels. In contrast, the combination of anti-IL-7R mAb and anti-IL-12/23 mAb has been shown to induce significant reduction of all colitis symptoms (e.g. macroscopic colon weight and length ratio) as well as complete microscopic histological remission and normalization, with no histological lesions, immune cell infiltrates, or epithelial cell hyperplasia. Additionally, a significant decrease in T-lymphocyte immuno-staining was observed in the colon, along with a significant increase in the Foxp3+ to Treg ratio, confirming the original mechanism of action of the IL-7R antagonist.
  
  

Upcoming oral and poster presentations at ECCO’25 congress:

ABOUT OSE IMMUNOTHERAPEUTICS

OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology (IO) and immuno-inflammation (I&I) that address the unmet patient needs of today and tomorrow. We partner with leading academic institutions and biopharmaceutical companies in our efforts to develop and bring to the market transformative medicines for people with serious diseases. OSE Immunotherapeutics is based between Nantes and Paris and is quoted on Euronext.

Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com. Follow us on X and LinkedIn

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1 Belarif L et al.IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease. Journal of Clinical Investigation 2019

Attachment

• EN_250220_ECCO Preclinical presentation