IL18RAP

OSE’s Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Image Credit: Gorodenkoff / Shutterstock. The French company OSE Immunotherapeutics has provided an update for its clinical pipeline, with plans to start a confirmatory Phase III study for its cancer vaccineTedopi in the US in Q2 2024. The company has received positive recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on the positive data from the Phase III trial (NCT02654587) evaluating Tedopi as a second or third-line therapy in patients with advanced non-small cell lung cancer patients following treatment failure with immune checkpoint inhibitors (ICI). Additionally, OSE is seeking approval from the FDA to validate the companion diagnostic test for Tedopi, developed by Genome Diagnostics. Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Apart from the Phase III trial, OSE is also conducting three Phase II trials evaluating Tedopi as a combination therapy in solid tumours such as pancreatic, ovarian and lung cancers. The results from the Phase II trial of Tedopi in combination with chemotherapy in pancreatic cancer patients are expected this year. Data from the Phase II trials (NCT04713514 and NCT03806309) for Tedopi in combination with MSD’s Keytruda (pembrolizumab) and Bristol Myers Squibb ’s Opdivo (nivolumab), respectively, is expected in 2025. OSE’s ulcerative colitis therapy lusvertikimab (OSE-127) is being investigated in a Phase II placebo-controlled trial (NCT04882007). The recruitment for the trial is expected to be completed in Q1 of this year, with initial results expected by mid-2024, as per a 19 January press release. The interleukin (IL)-7 receptor antagonist is also being evaluated in preclinical studies as a treatment for acute lymphoblastic leukaemia (ALL). In July 2023, OSE received a positive opinion on Orphan Drug Designation for lusvertikimab for the treatment of ALL by the EMA. OSE-279 is a programmed cell death 1 (PD-1) inhibiting monoclonal antibody. It is being evaluated as a treatment for solid tumours or lymphomas in a dose-finding and expansion Phase I trial (NCT05751798). OSE is also developing two monoclonal antibodies against signal regulatory protein α (SIRPα), BI 765063/ OSE-172 and BI 770371, in collaboration with Boehringer Ingelheim. BI 765063 is being evaluated as a combination therapy with different cancer therapies such as Boehringer’s ezabenlimab, BI 836880, chemotherapy and Eli Lilly’s Erbitux (cetuximab) in a Phase I trial (NCT05249426). BI 770371 is being evaluated as a monotherapy and in combination with a PD1 inhibitor, BI 754091, in an international Phase I dose escalation and expansion trial (NCT05327946) in patients with solid tumours. OSE is advancing the anti-CD28 selective monoclonal antibody FR104/VEL-101 in partnership with Denmark-based Veloxis Pharmaceuticals. It is researched as a treatment to help prevent organ rejection in people who have had a kidney transplant. In February 2022, the therapy received a fast track designation by the FDA for prophylaxis against transplant rejection. Veloxis is planning Phase II trials for the subcutaneous therapy.

Designed to deliver coordinated blockade of PD-1/PD-L1 pathway with targeted, enhanced IL-18 signaling to critical antitumor effector cells T cells co-expressing PD-1 and IL-18 receptors are highly enriched in the tumor microenvironment (TME) versus peripheral blood, providing rationale for tumor-selective targeting with BPT567 Marked expansion of CD8+ T-cells and reduction of regulatory T-cells, with mediation of tumor regression via CD8+ T-cell dependent mechanism(s) SAN DIEGO and BASEL, Switzerland, April 17, 2023 (GLOBE NEWSWIRE) -- Bright Peak Therapeutics, a biotechnology company developing multifunctional precision immunotherapies for cancer and autoimmune disease, today announced the presentation of new data characterizing the highly targeted biological and therapeutic effects of BPT567 that contribute to its potent single agent anti-tumor activity at the American Association for Cancer Research (AACR) Annual Meeting being held on April 14-19, 2023, in Orlando, FL. Bright Peak has leveraged its world-class protein engineering capabilities to functionally optimize the master cytokine IL-18, creating an IL-18 binding protein-resistant molecule with enhanced affinity for the IL-18 receptor, and integrate it with PD-1 checkpoint blockade to create a first-in-class PD1-IL18 immunocytokine, BPT567. "BPT567 is designed to coordinately engage antigen-experienced Teff cells that are known to co-express both PD-1 and the IL-18 receptor. These T-cells have been reported to be highly cytotoxic and enriched in the tumor microenvironment, and as a PD1-IL18 immunocytokine, BPT567 is uniquely targeted to these cells,” said Jon Wigginton, M.D., President of Research and Development of Bright Peak Therapeutics. "Upon further characterization of the biological activity of BPT567 in preclinical tumor models, we found that it was indeed able to more selectively target the potent pro-inflammatory effects of IL-18 to the tumor with limited activation of immune cells in the periphery. It is anticipated that this could ultimately contribute to an improved risk-benefit pro BPT567 in the clinical setting." Details regarding the upcoming AACR abstract presentations are as follows: April 17, 2023, 9:00 AM – 1:30 PM (EST) Poster 1850: A First-in-Class PD1-IL18 Immunocytokine (BPT567) Targets PD-1+ IL18R+ CD8+ T Effector Cells Enriched in the Tumor Microenvironment and Exhibits Potent Antitumor Efficacy With Excellent Tolerability Abstract Highlights: Bright Peak's unique protein engineering and chemical conjugation platform enables the generation of immunocytokines (ICs) via rapid and site-specific conjugation of optimized cytokines to the Fc domain of existing human antibodies. IL-18 is a master proinflammatory and antitumor cytokine that integrates and stimulates both innate and adaptive immunity and activates antigen-experienced T cells marked by IL-18 receptor (IL-18R) expression, making it an ideal payload to generate an oncology IC. BPT567 is a multifunctional, PD-1 targeted IL-18 based IC consisting of an optimized IL-18 payload with enhanced affinity for IL-18R and significant resistance to the neutralizing factor IL-18 binding protein (IL-18BP), then conjugated to a clinical stage anti-human PD-1 antibody (lipustobart). BPT567 is designed to deliver coordinated PD-1/PD-L1 blockade and IL-18 signaling to the same cell (cis-signaling), with targeting and activation of PD-1+ IL-18R+ (“double-positive") CD8+ T cells that have been reported to be highly cytotoxic and enriched in the tumor microenvironment (TME). BPT567 demonstrated significantly greater stimulation of IL-18 induced IFNγ release on PD-1high versus PD-1low immune cells in vitro, consistent with cis-signaling-mediated enhancement of potency. In pharmacodynamic (PD) studies performed on MC38 tumor-bearing transgenic mice expressing human PD-1, significant expression of both PD-1 and IL-18R was detected in T cells within the tumor, whereas immune cell populations in the blood expressed low levels of either PD-1 or IL-18R but not both. Detailed characterization revealed that enrichment of simultaneous PD-1 and IL-18R expression occurred principally within CD8 and CD4 memory T cells within the tumor. Accordingly, after BPT567 administration, marked expansion of CD8+ effector memory cells was observed within the tumor with minimal expansion in the blood, while the proportion of regulatory T cells (Tregs) was significantly suppressed in the tumor and unchanged in the blood. Concurrent with these changes in the composition of tumor-infiltrating lymphocytes, BPT567 induced significant release of proinflammatory cytokines within the tumor, including IFNγ, TNF, and GM-CSF, with a far lower extent of cytokine release in the periphery. In preclinical tumor models, administration of BPT567 mediated synergistic antitumor activity that was superior to anti-PD-1 alone, a control non-targeted HER2 IL-18 IC, or the combination of anti-PD-1 and non-targeted IL-18 IC. All mice that were cured of their initial tumors rejected rechallenge with MC38 implantation, confirming the development of long-term immunologic memory induced by BPT567. The abstract will be made available for viewing on Bright Peak’s website upon presentation at the AACR 2023 Annual Meeting ( ). About Bright Peak Therapeutics Bright Peak Therapeutics is a biotechnology company advancing a portfolio of multifunctional immunotherapies for the treatment of patients with cancer and autoimmune disease. We accomplish this by leveraging our world class protein engineering capabilities and our unique cell-free technology platform to chemically synthesize and conjugate novel protein therapeutics that reflect state-of-the-art insights into cytokine and immune checkpoint biology. Our pipeline stretches from discovery to IND-enabling and encompasses antibody-cytokine conjugates and other novel formats. Bright Peak is based in Basel, Switzerland and Del Mar, CA and is funded by a syndicate of leading healthcare investors. Contact: info@brightpeaktx.com