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    DRUG:

    Opal

    i
    Other names: Opal, PD-1xCD137L fusion protein
    Company:
    Cullinan Therap
    Drug class:
    PD1 inhibitor, CD137 agonist
    Related drugs:
    2years
    Opal is a conditional 4-1BB agonistic fusion protein comprising trimerized 4-1BB ligand and a high affinity variant of the extracellular domain of PD-1 (AACR 2022)
    4-1BB agonizing monoclonal antibodies have thus far failed to progress beyond early clinical development, either due to hepatic toxicities caused by FcγR-crosslinking (urelumab) or due to low clinical activity (utomilumab). When tumor-bearing mice were treated IP with Opal at 1 mg/kg, 7/10 mice exhibited durable cures without significant body weight loss. Taken together, the preclinical data suggests that Opal may exhibit single-agent activity in solid tumors by conditionally activating effector cells in the tumor microenvironment via 4-1BB agonism while concurrently blocking the PD1/PDL1/PDL2 axis.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • PD-L2 (Programmed Cell Death 1 Ligand 2)
    |
    PD-L1 expression
    |
    Opal • utomilumab (PF-05082566) • urelumab (BMS-663513)