Complementary Research & Development platforms in immunology
From target identification to product validation and beyond
Delivering first-in-class therapies activating and regulating the immune system
OSE Immunotherapeutics’ Research & Development is focused on developing innovative immunotherapies for immune activation and regulation in the fields of immuno-oncology and autoimmune diseases. It is based on three research platforms from its areas of expertise in immunology:
- T-cell-based vaccination
- Immuno-Oncology (focus on myeloid targets)
- Auto-Immunity & Inflammation.
Building on 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: optimized neoepitopes, myeloid checkpoint inhibitors, monoclonal antibodies.
We have already delivered multiple first-in-class products that activate or regulate the immune system. The novelty 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 T cell based vaccination
OSE Immunotherapeutics leverages its expertise in the selection and optimization of small proteins called peptides (epitopes or neo-epitopes) to deliver a rationally designed combination of multiple peptides with beneficial therapeutic potential.
The Company uses the knowledge and expertise gained from its Memopi® epitope (neo-epitope) optimization vaccine technology to induce a T lymphocyte memory immune response in the respiratory tract and in the lung.
Two products based on T cell vaccine technology
OSE’s most advanced program, Tedopi® is an antitumor neo-epitope combination being evaluated in advanced lung cancer: this selection of epitopes is intended to deliver a therapeutic vaccine. This is not a classic preventive vaccine, but a 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® demonstrated strong clinical benefit in Step-1 of a Phase 3 study in HLA-A2 positive patients with non-small cell lung cancer (NSCLC) after PD-1/PD-L1 immune checkpoint inhibitor failure. The primary endpoint was met in the predefined Step-1 analysis of this Phase 3 trial with a 12-month survival rate in Tedopi® treated patients.
Tedopi® is also being investigated in other Phase 2 trials:
- Pancreatic cancer, under the sponsorship of the GERCOR, a cooperative group in oncology,
- Ovarian cancer, under the sponsorship of ARCAGY-GINECO, another cooperative group in oncology,
- NSCLC, in combination with checkpoint inhibitor Opdivo®(nivolumab), under the sponsorship of the Italian Foundation FoRT.
CoVepiT is a prophylactic vaccine against COVID-19 based on optimized peptides selected to induce a lasting sentinel T lymphocyte immune response against SARS-CoV-2 in barrier tissues such as the respiratory tract and the lung.
The results from both preclinical and human ex vivo studies build a strong basis for supporting the development of CoVepiT as a novel and differentiated COVID-19 vaccine designed against multiple SARS-CoV-2 targets with vaccinal technology known to induce memory T lymphocytes.
In April 2021, a Phase 1 clinical trial started to evaluate the safety, reactogenicity and immunogenicity of CoVepiT in healthy adult volunteers.
In July, after receiving a preliminary update regarding a limited number of Grade 1 and one Grade 2 adverse events, in particular, persistent nodules around injection points, out of an abundance of caution and in agreement with the independent Safety Monitoring Committee (SMC), the Company has decided to voluntarily and temporarily pause dosing in its ongoing clinical study and assess the evolution of these nodules before determining the best way forward for this product and its target population.
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 on the key aspects of the immune response and delivers monoclonal antibodies targeting myeloid cell receptors and macrophages
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 also a selective inhibitor of SIRPα that by virtue of this specificity and lack of binding and blocking of a very similar receptor called SIRPɣ, ensures that response of T lymphocytes is 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.
OSE’s R&D teams 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 step in cancer immunotherapy.
CLEC-1 is a novel “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.
The R&D on CLEC-1 is conducted in collaboration with Dr. Elise Chiffoleau (Center for Research in Transplantation and Immunology, UMR – INSERM 1064, Nantes University Hospital).
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 Autoimmunity & Inflammation
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 IL-7 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. 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.
Based on positive Phase 1 clinical results, a Phase 2 is being conducted in ulcerative colitis (OSE sponsor) and an independent Phase 2a is planned in Sjögren’s syndrome (Servier sponsor). OSE-127 is being developped in partnership with Servier.
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 being evaluated in a Phase 1/2 clinical trial in renal transplant and is Phase 2-ready to be evaluated in a niche indication in auto-immune diseases.
OSE-230, 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.
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 an agonist antibody 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.