Research & Development

Complementary Research & Development areas of expertise in immunology

Accelerating target identification, product validation and beyond

Delivering first-in-class therapies activating and regulating the immune system

Identification of new targets

OSE Immunotherapeutics’ integrated Research & Development engine focuses on developing innovative immunotherapies for immune regulation in the fields of Immuno-Oncology and Immuno-Inflammation. It is based on three areas of expertise in immunology:

Immuno-Oncology: focused on myeloid targets, Immuno-Inflammation, Preclinical platforms: Myeloid and BiCKI® platforms.

Building on unparalleled experience in clinical immunology initially applied to transplantion, OSE’s research benefits from a fully translational platform fully intertwined with academic centers with complementary expertise in immunotherapy (INSERM, Center for Research in Transplantation and Immunology, University Hospital of Nantes, etc.).

Leveraging these collaborations and in-house expertise on novel target discovery, OSE’s team identifies innovative agonists or antagonists of the immune response and generates viable therapeutics using the following technological platforms: optimized neo-epitopes, myeloid checkpoint inhibitors, monoclonal antibodies, and bispecific antibodies.

Complementarity

Complementary Research & Development areas of expertise in immunology

Continuity

From target identification to product validation and beyond

Quality

First-in-class therapies activating and regulating the immune system

Immuno-Oncology

Tumor cells are usually recognized and destroyed through a complex mechanism of immune surveillance involving different immune cells (antigen presenting cells, macrophages, lymphocytes, etc.) and helper proteins (interleukins, growth factors, etc).

Tumor cells can escape this surveillance mechanism by blocking activation of immune cells. For example, they can express specific antigens that are also expressed by healthy cells to avoid being recognized, or block immune cell activation checkpoints to neutralize the immune response.

OSE’s platform in immuno-oncology is focused on identification of specific targets to help the immune system recognize tumors and take appropriate action to kill them.

OSE Immunotherapeutics’ R&D team focuses on the key aspects of the immune response

Tedopi®

Tedopi® is a therapeutic vaccine program based on a combination of nine selected and optimized neo-epitopes from five tumor antigens plus one epitope giving universal helper T cell response targeting T cell activation. This is not a classic preventive vaccine, but a tumor-specific T cell-based immunotherapy. Tedopi® activates a cytotoxic T response able to destroy the cancer cells it recognizes and to restore an immune surveillance of these cells in HLA-A2 responder patients. Tedopi® is OSE’s most advanced product with a Phase 3 clinical trial that was conducted in non-small cell lunger cancer after failure with a PD-1/PD-L1 checkpoint inhibitor. A confirmatory Phase 3 study with a companion diagnostic strategy is under preparation to support the registration of Tedopi® as a potential new standard of care in second line for non-small cell lung cancer patients in secondary resistance to immune checkpoint inhibitors based on positive regulatory advice from FDA and EMA. Tedopi® is being evaluated in several additional Phase 2 trials.

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OSE-279

OSE-279 is an anti-PD1 antibody that blocks a T lymphocyte brake enabling activation of non-specific T cells in oncology. It is currently in Phase 1/2 clinical trial in advanced solid tumors and lymphomas. It is also the “backbone” component of a platform called BiCKI® for new original bispecific or bifunctional therapies.

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BI 765063

BI 765063 (OSE-172), a monoclonal antibody antagonist of SIRPα-mediated “Don’t Eat Me” signal, selectively blocks the SIRPα/CD47 interaction and thus increases the function of myeloid cells: phagocytosis of tumor cells by macrophages and presentation of tumor antigens by dendritic cells. BI 765063 is a selective inhibitor of SIRPα that lacks significant binding to a very similar receptor called SIRPɣ which ensures that T lymphocyte responses are retained to enable T cell-mediated tumor killing. BI 765063 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors as part of a license and collaboration agreement with Boehringer Ingelheim.

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Similar to cancer, autoimmune diseases are characterized by an abnormal immune reaction against normal cells

Ulcerative colitis, rheumatoid arthritis, Crohn’s disease, psoriasis and Sjögren’s syndrome are examples of the 80 different diseases that have been associated to autoimmune dysfunction.

Autoimmune dysfunction happens through a deregulation of the immune response or of immune cell maturation. As a result, immune cells target normal cells instead of disease cells, generating pathological situations that can profoundly affect the daily life of patients.

Alloreactivity (i.e. antigens from an individual of the same species but with a different genetic and tissue structure) remains a major obstacle to organ and tissue transplants since immunological rejections result in relatively rapid loss of the graft without immunosuppressive therapy. Alloreactive lymphocytes are at the heart of these rejections and develop high intensity immune responses that we try to block. OSE Immunotherapeutics develops monoclonal antibodies against innovative targets in order to regulate the response of myeloid cells (macrophages, neutrophils), T lymphocytes and antibodies with the common objective of restoring immune balance, restoring immune tolerance and / or triggering the resolution of inflammation.

OSE Immunotherapeutics is developing promising products focusing on different receptors

OSE-127/Lusvertikimab

The IL-7 receptor (also called the CD127 receptor) is a key element of autoimmune diseases. IL-7 is a cytokine that controls the proliferation, apoptosis and activation of CD4 and CD8 effector T-cells in humans. OSE-127 is an antagonist of the IL-7 receptor present on T-cells thus downregulating immune activity. Based on positive Phase 1 clinical results, a Phase 2 is being conducted in ulcerative colitis.

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FR104

The CD28-receptor is a key receptor in the T-cell signalling pathway which controls both T-cell activation and downregulation of regulatory T-cells. This receptor is believed to be at the heart of several autoimmune diseases. FR104, a monoclonal antibody fragment and CD28 antagonist, selectively tackles effector T lymphocytes while favouring Treg suppressive function, thus promoting the immune tolerance. FR104 is being evaluated in a Phase 1/2 clinical trial in renal transplant.

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Two proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapeutics

In parallel, OSE Immunotherapeutics expects to be able to generate further significant value from its two proprietary drug discovery platforms:

  • BiCKI® platform focused on immuno-oncology (IO) is a bispecific fusion protein platform relying on the proprietary anti-PD1 backbone (OSE-279) to increase anti-tumor efficacy. The most advanced BiCKI® candidate is targeting anti-PD1xIL-7.
  • Myeloid platform, which is focused on optimizing the therapeutic potential of myeloid cells in IO and immuno-inflammation (I&I). OSE-230 (ChemR23 agonist mAb) is the most advanced candidate generated by the platform, with the potential to resolve chronic inflammation by driving affected tissues to tissue integrity.

Preclinical programs from innovative research platforms

BiCKI®

BiCKI® is a novel bispecific antibody platform built using the key backbone component anti-PD-1 antibody (OSE-279), combined with innovative second targets to increase the anti-cancer immuno-oncology effects. The BiCKI® platform strives to inhibit key immune checkpoints (via anti-PD-1) while simultaneously delivering intratumoral cytokines with ability to modulate Treg function and/or increase exhausted T cell responses. The BiCKI® platform also has potential to modify the tumor microenvironment by delivering costimulatory signals to rewire anti-tumoral T cell activities or other modalities re-instating, for example, macrophage polarization and phagocytic functions. BiCKI® is designed to extend the spectrum of patients responding to anti-PD-1 immunotherapies. BiCKI® utilizes the second generation of PD-(L)1 inhibitors that have been implemented to increase antitumor efficacy in hard-to-treat cancers by addressing untapped immune evasion mechanisms.

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OSE-230

Persistent inflammation is a characteristic feature of all chronic inflammatory or autoimmune diseases and if not controlled or resolved, it can lead to further tissue damage and give rise to tissue fibrosis with eventual loss of organ function. Most anti-inflammatory agents act using a mechanism that blocks pro-inflammation pathways. In contrast, OSE Immunotherapeutics is developing OSE-230 as a first-in-class therapeutic agent with the potential to resolve chronic inflammation by driving affected tissues to complete the inflammation program and restore tissue integrity. OSE-230 is the first monoclonal antibody developed in the resolution of inflammation. This is an antibody agonist against ChemR23, also known as “chemerin chemokine-like receptor 1” (CMKLR1), a G-protein coupled receptor (GPCR) expressed on myeloid immune cells known to modulate inflammation.

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CLEC-1

OSE’s R&D teams and its academic partners have characterized a new myeloid checkpoint target, CLEC-1 (a C-type lectin receptor) and identified the first monoclonal antibody antagonists of CLEC-1 as an innovative new approach in cancer immunotherapy. CLEC-1 is a novel myeloid cell “Don’t Eat Me” signal (similar to the SIRPα-CD47 axis) and CLEC-1 antagonist antibodies developed by OSE Immunotherapeutics restore the phagocytosis function of macrophages and dendritic cells and demonstrates synergistic anti-cancer effects, in particular, when paired with chemotherapy. Preclinical research on CLEC-1 is conducted in collaboration with Dr. Elise Chiffoleau (Center for Research in Transplantation and Immunology, UMR – INSERM 1064, Nantes University Hospital).

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