– 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 profile for 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 (www.brightpeaktx.com).
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
