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BPT567 is a first-in-class, multifunctional bifunctional immunoconjugate designed for cancer immunotherapy. It consists of an optimized interleukin-18 (IL-18) payload with enhanced affinity for the IL-18 receptor and significant resistance to the neutralizing factor IL-18 binding protein, conjugated to a clinical-stage anti-human PD-1 antibody (lipustobart). The drug delivers coordinated blockade of the PD-1/PD-L1 immune checkpoint pathway together with targeted, potent IL-18 signaling specifically to T cells within the tumor microenvironment. This dual mechanism preferentially activates antigen-experienced CD8+ T cells co-expressing PD-1 and IL-18 receptors in tumors, leading to marked expansion of effector memory CD8+ T cells and reduction of regulatory T cells in tumors. Preclinical studies have shown that BPT567 mediates synergistic anti-tumor activity superior to either PD-1 blockade or untargeted IL-18 alone, including efficacy in both checkpoint inhibitor-sensitive and -resistant tumor models. BPT567 is currently being evaluated in a Phase 1/2a clinical trial for patients with locally advanced/unresectable or metastatic solid tumors.
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