OSE Immunotherapeutics is a clinical-stage biotechnology company focused on developing therapies that control the immune system. We have extensive expertise in organ transplantation and are applying our knowledge of macrophages and T lymphocytes to develop and optimize novel approaches, including neoepitopes, myeloid checkpoint inhibitors, and agonist/antagonist monoclonal antibodies (mAbs).
We use next-generation sequencing, transcriptomics, artificial intelligence, and other technologies to interrogate the mechanism of resistance to checkpoint inhibitors in cancer patients. Our research group functions as an R&D engine to identify new candidates with high potential for therapeutic success.
Building on our foundation in clinical immunology applied to transplants, OSE benefits from a fully translational platform historically intertwined with academic centers with expertise in immunotherapy. Leveraging these collaborations, OSE’s team has acquired unique expertise focused on novel target discovery to generate innovative agonists or antagonists of the immune response
Immune checkpoint inhibitors are considered a new standard of care against a wide range of cancers. However, these therapies are ineffective in a significant percentage of patients, and some initial responders eventually develop resistance to these therapies with relapsed disease. Sustained tumor antigen stimulation may result in a state of functional impairment, referred to as exhaustion of tumor T lymphocytes. Disarming T regulatory (Treg) cells is also important, as Treg cells contribute to dampening antitumor response. OSE has several candidates in development that are designed to address the problem of checkpoint inhibitor resistance by targeting various aspects of the tumor microenvironment (TME).
Our most advanced product is Tedopi®, a patented combination of 10 optimized neoepitopes selected from five tumor-associated antigens expressed in various cancers. In HLA-A2+ (a key receptor for the cytotoxic T immune response) responder patients, Tedopi activates a cytotoxic T cell response, leading to the destruction of cancer cells and restoration of immune surveillance. Phase I and II trials demonstrated the ability of Tedopi to restore the immune surveillance of cancer cells in HLA-A2+ responder patients while inducing early T cell memory response. In a separate phase II trial, patients suffering from non-small-cell lung cancer (NSCLC) with poor prognoses treated with Tedopi showed a better survival rate and a positive correlation between epitope response and survival. The drug has received orphan status in the U.S. for HLA-A2+ patients in NSCLC and personalized medicine status in HLA-A2 positive patients in Europe. Tedopi is currently in a phase III study in NSCLC after immune checkpoint inhibitor failure — and in a phase II trial in combination with checkpoint inhibitor Opdivo® in pancreatic cancer (a trial sponsored by the GERCOR cooperative group in oncology).
OSE’s R&D team has also focused on the SIRPa/CD47 pathway, which controls the activation of macrophages and dendritic cells. OSE-172 is an SIRPa antagonist and first-in-class myeloid checkpoint inhibitor that selectively inhibits the SIRPa receptor expressed on myeloid protumor suppressive cells, thus restoring the activity of tumor-associated macrophages (TAMs) and dendritic cells. Preclinical studies demonstrated the ability of this candidate to inhibit protumorigenic cells while activating antitumorigenic ones. The early results with OSE-172 attracted the interest of Boehringer Ingelheim, which signed a global license and collaboration agreement in April 2018 to develop this candidate, now known as BI 765063. BI 765063 is currently being evaluated in a phase I clinical trial in patients with advanced solid tumors. A phase I clinical trial is ongoing to evaluate BI 765063 as a single agent and in combination with BI’s monoclonal antibody PD-1 antagonist BI 754091, a lymphocyte T checkpoint inhibitor in patients with advanced solid tumors.
Another important OSE candidate, OSE-703, is a humanized monoclonal antibody directed against the extracellular domain of the alpha-chain of the receptor for interleukin-7 (CD127) and is cytotoxic for human cells expressing CD127. OSE-703 is currently being developed in partnership with the Memorial Sloan Kettering Cancer Center in New York to define its efficacy profile and potential development strategy. It has the potential to improve the efficacy of chimeric antigen receptor (CAR) T cell therapies.
BiCKI® is a novel bispecific fusion protein based on an engineered anti-PD-1 bifunctional antibody (OSE-279) platform designed to fight primary and secondary resistance mechanisms developed by cancers to evade checkpoint inhibitor therapies. 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. It can also modify the tumor microenvironment by delivering costimulatory signals to rewire anti-tumoral T cell activities or other modalities reinstating, among others, macrophage polarization and phagocytic functions.
IL-7 is the first cytokine selected to be paired with the anti-PD-1 in the bispecific antibody. OSE’s bifunctional anti-PD1/IL-7 favors the T cell effector over regulatory immune balance by stimulating effector T cell functions while disarming regulatory T cells.
Tackling autoimmune disease is a natural extension of our work in the field of immuno-oncology, allowing us to derisk the business by pursuing drug targets relevant to multiple therapeutic areas.
Our first product, FR104, is a monoclonal antibody fragment and CD28 receptor antagonist. The CD28 receptor controls both T cell activation and Treg downregulation and is believed to be involved in multiple autoimmune diseases including RA, while CTLA-4 is a CD28 homologue expressed on activated T cells. FR104 is designed to inhibit CD28 co-stimulation while sparing the CTLA-4 co-inhibitory signal, resulting in downregulation of effector T cells and promotion of Treg activity. In a 2016 phase I clinical study, this candidate exhibited good clinical safety and immunosuppressive activity. A phase II study with FR104 in an auto-immune indication is currently being planned. We are pursuing clinical development of FR104 and evaluating the best options for continuing the sustainable development of the product, including worldwide partnering opportunities.
The cytokine IL-7 has also been shown to control the proliferation, apoptosis and activation of effector T-cells in humans, which play a role in autoimmune diseases. OSE-127, a humanized mAb, is an antagonist of the IL-7 receptor present on T cells (CD127) and thus downregulates immune activity. OSE-127 is under an option license agreement signed with Servier in December 2016 to be developed up to the completion of a phase II clinical trial planned in Sjögren’s syndrome, the second most common autoimmune disease. In parallel, OSE is developing OSE-127 in ulcerative colitis.
We have witnessed a major shift in cancer treatment with the arrival of immuno-oncology drugs targeting PD-1 and PD-(L)1. The next phase will involve the development of treatments to overcome checkpoint inhibitor resistance and the failure of these drugs in many patients. It is our hope that macrophage and bispecific products developed by OSE will become an important part of the solution to this pressing problem.
We are exploring additional antibodies that target myeloid cell and macrophage receptors, as well as several new approaches focused on modulating the tumor microenvironment.
Alexis Peyroles has more than 20 years of international management and financial control experience, having served in multiple related positions. Since 2013, Alexis Peyroles has been involved in OSE Pharma, both as CFO and in charge of Business Development. From May 2016 to April 2018, he served as COO of OSE Immunotherapeutics, in charge of Finance, Business Development and Operations. Alexis Peyroles graduated from EDHEC Business School and holds an Executive MBA from Imperial College in London.