Research & Development

Research & Development

Our Research & Development

From target identification to product validation and beyond
Delivering first-in-class immunotherapies of activation and regulation

OSE Immunotherapeutics’ R&D is focused on developing innovative immunotherapies for immune activation and regulation in the fields of immuno-oncology and autoimmune diseases.

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

Leveraging these collaborations, OSE’s team has acquired unique expertise and knowledge focused on novel target discovery to generate innovative agonists or antagonists of the immune response, combined with several scientific and technological platforms: neoepitopes, myeloid checkpoint inhibitors, monoclonal antibodies.

We have already delivered multiple first-in-class products that activate or regulate the immune system. The originality and potential of these products have been recognized through a wide network of international collaborations with top international pharma, clinical and academic partners, notably in Europe and in the US.

Our Research & Development in 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…), proteins and mediators (interleukins, growth factors…).

Tumor cells can escape this surveillance mechanism by blocking immune cells’ activation. They can, for example, express specific antigens that are also expressed by normal cells thus avoiding being recognized, or block immune cell activation checkpoints neutralizing the immune response.

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

T-cell activation with Tedopi®, a patented combination of 10 optimized neo-epitopes selected from 5 tumor-associated antigens expressed in various cancers.

Tedopi® activates a cytotoxic T-cell response able to destroy cancer cells they recognize and restores the immune surveillance of cancer cells in HLA-A2 positive responder patients.

Tedopi® is the company’s most advanced clinical program, evaluated in a Phase 3 clinical trial in non-small cell lung cancer (NSCLC) after previous failure of immune checkpoint inhibitor treatment. The product has shown positive Step-1 Phase 3 results of its Phase 3 with a significant increase to overall survival and good safety profile. Tedopi® is also being evaluated in Phase 2 in monotherapy and in combination with checkpoint inhibitor Opdivo®  in pancreatic cancer.

Immune activation of the tumor microenvironment (TME) with BI 765063 (OSE-172), the company’s first-in-class myeloid checkpoint inhibitor targeting the SIRPα receptor expressed on myeloid pro-tumor suppressive cells.

BI 765063 blocks SIRPα (signal regulatory protein alpha), a receptor strongly expressed by myeloid and macrophage suppressor cells, on the strategic SIRPα / CD47 pathway. It restores effector functions of these suppressor cells, an activity which promotes immunosurveillance.

BI 765063 may also be combined with other immunotherapies, in particular with checkpoint inhibitors acting on T-lymphocytes, e.g. checkpoint inhibitors targeting the PD-1/PD-L1 axis or products triggering a stimulation of the immune system.

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.

OSE Immunotherapeutics is also exploring additional new cytotoxic antibodies that target myeloid cell and macrophage receptors.

BiCKI® is a novel bispecific fusion protein platform built on the key backbone component anti-PD-1 (OSE-279) and targeting innovative targets.

The BiCKI® platform strives to inhibit key immune checkpoints while simultaneously delivering intratumoral cytokines with Treg modulating function and/or increasing exhausted T cell responses. The BiCKI® platform can also modify the tumor microenvironment by delivering costimulatory signals to rewire anti-tumoral T cell activities or other modalities re-instating, among others, macrophage polarization and phagocytic functions.

Based on an engineered anti-PD-1 bifunctional antibody platform technology, BiCKI® is designed to extend the spectrum of patients responding to immunotherapies. BiCKI® represents the second generation of PD-(L)1 inhibitors that have been used to increase antitumor efficacy in hard to treat cancers by addressing untapped immune evasion mechanisms.

Our Research & Development in Autoimmune Diseases

Mirroring cancer, autoimmune diseases are characterized by an abnormal immune reaction against normal cells.

Rheumatoid arthritis, Crohn’s disease, psoriasis and Sjögren 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.

OSE Immunotherapeutics is developing promising products focusing on different receptors

The CD28-receptor that controls both T-cell activation and regulatory T-cell downregulation. This receptor is believed to be at the heart of several autoimmune diseases including rheumatoid arthritis. FR104, a CD28-antagonist, demonstrated during its Phase 1 clinical trial both good clinical safety and immunosuppressive activity.

FR104 is in Phase 2 status in auto-immune diseases or in transplantation .

The IL-7 receptor is another 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. With OSE-127, OSE’s R&D team is developing an antagonist of the IL-7 receptor present on T-cells, the CD127 receptor, thus downregulating immune activity.

OSE-127 is being developed in ulcerative colitis under a license option agreement with Servier.