information: Presentation of results at a congress
Announcement: publication of results in Nature Communications
Company: OSE Immunotherapeutics (France)
Product: OSE-127 (Effi-7)
- monoclonal antibody. OSE-127, previously known as Effi-7, is a monoclonal immunodulatory antibody targeting the CD127 receptor, the alpha chain of the interleukin-7 receptor (IL-7R) that blocks both the IL-7 and the internalization of the receptor. It therefore induces a powerful antagonist effect for better long-term control of the pathogenic T lymphocytes. The strategy of blocking the IL-7 is different from conventional methods, as well as the latest anti-inflammatory drugs used in clinic, and has demonstrated efficacy in restoring the impaired immune balance in autoimmune diseases of the bowel in several clinical models.
- OSE-127 is being developed as part of the consortium EFFIMab, led by OSE Immunotherapeutics. The project is co-financed by Bpifrance in the amount of € 9.1 million (for a total amount of €20 million).
- OSE Immunotherapeutics has signed a license option agreement with Servier in December 2016 for the development and commercialization of OSE-127.
Disease: inflammatory bowel diseases including Crohn's disease and ulcerative colitis
area: Autoimmune diseases - Inflammatory diseases - Digestive diseases
- • On October 29, 2018, OSE Immunotherapeutics announced publication in Nature Communications of its monoclonal antibody (OSE-127) targeting IL-7 Receptor (IL-7R) with full antagonist properties. This compound controls antigen-specific memory T cells mimicking pathogenic situations and chronic inflammation.
- As IL-7 is the fuel driving chronic autoimmune and inflammatory diseases, this interleukin regulates mainly
T cell proliferation and survival. Mature T cells express high levels of the IL-7 Receptor (IL-7R) except regulatory T cells expressing low level of IL-7 receptor. In the article, the authors develop an original mechanism of action as in vivo the anti-IL-7 receptor mAb targeting IL-7R demonstrates full antagonist properties related to its particular structure blocking 2 sites of IL-7R (“Sites 1 and 2b”). Two other mAbs, also against IL-7R but targeting only Site 1 of IL-7R, were tested in parallel and presented paradoxical agonist and antagonist properties limiting their efficacy.
- In addition, the transcriptome (gene expression measured by RNA-SEQ) of human peripheral blood mononuclear cells (PBMCs representing lymphocyte types and monocytes) was analysed after incubation with the two types of IL-7R antagonists (Site 1 restricted mAbs or “Sites 1 and 2b” mAb/OSE-127). The results on human blood cells showed significant differences, as Site 1 restricted antibodies induced
significant translational modifications of human PBMCs compatible with T cell activation and inflammatory
responses, while” Sites 1 and 2b” mAb/OSE-127 did not induce such activation.
- OSE-127 is targeting selectively pathogenic effector cells while preserving quiescent T cells and natural T cell regulators. These significant features are very important for clinical applications in autoimmune diseases and chronic inflammation. OSE-127 is now expected to enter phase 1 clinical phase and we are focused on this next coming step”.
(IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation. Lyssia Belarif et al)
- • On May 7, 2018, OSE Immunotherapeutics presented new preclinical data that further support the potential of OSE-127 for the treatment of inflammatory bowel diseases, at the annual congress of the American Association of Immunologists (4-8 May 2018, Austin, Texas). The results from colon biopsies of patients with ulcerative colitis confirm that OSE-127 antibody, IL-7R? antagonist, significantly decreases the inflammation as measured by a reduced gamma interferon secretion level. In parallel, an increase of the score of regulatory T lymphoctyes (transcriptomic signature), the cells that help fighting inflammation, was demonstrated after treatment with OSE-127 antibody. By specifically targeting IL-7R (predictive for non-response to inflammatory bowel
- disease treatments) and by enhancing in parallel regulatory T lymphocytes in the mucosa, OSE-127 offers an original clinical profile to be developed in invalidating chronic bowel diseases.
- • On December 19, 2017, OSE Immunotherapeutics announced that the company has presented new data on OSE-127 (Effi-7) at the 11th European Workshop on Immune Mediated Inflammatory Diseases. The oral presentation, entitled "Interleukin-7 receptor pathway controls human T cell homing to the gut and predicts response to anti-TNF? in patients with inflammatory bowel disease" further supports the potential of OSE-127 (Effi-7) for the treatment of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. The presentation reported results from a transcriptomic analysis of colon biopsies in more than 500
patients and 100 controls in a large database available for specialized bioinformaticians. This analysis showed that both interleukin-7 receptor (IL-7R, target of OSE-127) and IL-7R signaling signature transcripts are strongly overexpressed in colon biopsies from patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, in therapeutic failure following treatment with corticosteroids, immunosuppressors or anti-TNF? treatment. Moreover, the level of IL-7R overexpression in colon biopsies from these patients was significantly correlated and predictive of non-response to anti-TNF? treatment.
- OSE Immunotherapeutics is now looking forward to initiating clinical phase for OSE-127 in 2018.
- • On June 15, 2017, OSE Immunotherapeutics presented new data for OSE-127 (Effi-7), an antagonist of the interleukin-7 receptor (IL-7R), at the 2017 Federation of Clinical Immunology Societies held in Chicago from June 14 to 17. The communication entitled “IL-7 pathway controls human T cell homing to the gut and culminates in inflammatory bowel disease mucosa” shows efficacy results for OSE-127 in various preclinical acute or chronic colitis models and ex vivo human biopsies. In preclinical humanized models reconstituted with human T lymphocytes, OSE-127 significantly blocked pathological homing of human T lymphocytes to the inflamed colon thereby preventing destruction of gut mucosa by the T lymphocytes.
- In a separate translational study conducted in human in collaboration with Professor Thomas McDonald (Blizard Institute, Barts and the London School of Medicine), OSE-127 significantly reduced production of gamma interferon expressed by proinflammatory mucosal T lymphocytes ex vivo in colon biopsies from patients with inflammatory bowel disease. Increased expression of IL-7R, IL-7 and genes involved in the IL-7R signalling pathway was observed in the
patients’ inflammatory colon biopsies and correlates with a lack of response to current immunosuppressive treatments.
- The expression of the product’s target (IL-7R) in human tissues in case of therapeutic escape represents a major clinical interest for OSE-127, with potential identification of responder patients.
- • On June 27, 2016, OSE Immunotherapeutics announced the presentation of preclinical efficacy results for Effi-7, an antagonist of the interleukin 7 (IL-7) receptor in regulation immunotherapy, at the annual international congress of immunology, « Federation of Clinical Immunology Societies, » held in Boston from June 21 to June 25, 2016. The preclinical results presented (1) showed efficacy of Effi-7, an antagonist of the IL-7 receptor, in
ulcerative colitis (UC) models, an autoimmune inflammatory bowel disease of the colon. Efficacy was observed in parallel with an innovative mechanism of action of Effi-7 in the prevention of the infiltration of human T lymphocytes, responsible for the inflammatory damage to the colon mucosa.