- Full Antagonist Mechanism of Action Demonstrated In Vivo
- Long-term Control of Specific Memory T Cell Mediated Autoimmunity and Chronic Inflammation
NANTES, France, Oct. 29, 2018 (GLOBE NEWSWIRE) — OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnémo: OSE) today 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 (monoclonal antibody OSE-127) 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 analyzed 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.
Alexis Peyroles, CEO of OSE Immunotherapeutics, said, “We warmly congratulate all the first-class OSE team and the network of experts involved for this major achievement. OSE-127, being developed in partnership with Servier (1), is 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 Belarif1,2,‡, Caroline Mary1,2,‡, Lola Jacquemont1, Hoa Le Mai1, Richard Danger1, Jeremy Hervouet1, David Minault1, Virginie Thepenier1,2, Véronique Nerrière-Daguin1, Elisabeth Nguyen1, Sabrina Pengam1,2, Eric Largy3, Arnaud Delobel3, Bernard Martinet1, Stéphanie Le Bas-Bernardet1,4, Sophie Brouard1,4, Jean-Paul Soulillou1, Nicolas Degauque1,4, Gilles Blancho1,4†, Bernard Vanhove1,2,†, Nicolas Poirier1,2,†.
1 Centre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, Nantes, France. 2 OSE Immunotherapeutics, Nantes, France.3 Quality Assistance, Thuin, Belgium. 4 ARNA laboratory, Université de Bordeaux, INSERM U1212, CNRS UMR5320, IECB, Bordeaux, France. 5 Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
([1]) Servier is an independent international pharmaceutical company governed by a foundation with Headquarters based in France.
ABOUT OSE Immunotherapeutics
OSE Immunotherapeutics is a biotechnology company focused on the development of innovative immunotherapies for immune activation and regulation in the fields of immuno-oncology and autoimmune diseases. Neoepitopes innovation (Tedopi®) is today in Phase 3 in advanced lung cancers (NSCLC) after checkpoint inhibitors failure (anti PD-1 and anti PD-L1). A global license and collaboration agreement was signed in April 2018 with Boehringer Ingelheim to develop checkpoint inhibitor OSE-172 (anti-SIRPa monoclonal antibody), for the treatment of advanced solid tumors. An option to license was exercised in July 2016 by Janssen Biotech to continue clinical development of FR104 (an anti CD28 mAb) in auto-immune diseases after positive phase 1 results. A 2-step license option was signed in 2016 with Servier Laboratories to develop OSE-127 (monoclonal antibody targeting the CD127 receptor, the alpha chain of the interleukin-7 receptor) to develop the product up to the completion of a phase 2 clinical trial planned in autoimmune bowel disease and Sjogren’s syndrome. The company has several scientific and technological platforms: neoepitopes, agonist or antagonist monoclonal antibodies, ideally positioned to fight cancer and autoimmune diseases. Its first-in-class clinical portfolio offers a diversified risk profile.
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