ZW270 / Zymeworks 
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  • ||||||||||  ZW270 / Zymeworks
    ZW270, a conditionally masked IL-12 cytokine fusion protein displaying potent anti-tumor activity absent systemic toxicity (Section 23; Poster Board #13) -  Mar 14, 2023 - Abstract #AACR2023AACR_5098;    
    In this model the predicted ratio of IL-12-receptor occupancy by active IL-12Fc in the tumor vs. blood was 18x greater for masked att IL-12Fc than for wt IL-12Fc, whereas the ratio was under 10x greater for masked wt IL-12Fc vs. wt IL-12Fc.In summary, the affinity attenuated, masked IL-12Fc lead ZW270 has potent and superior anti-tumor activity to wt IL-12Fc and masked wt IL-12Fc, and is well tolerated in NHPs to >30 mg/kg. Our data suggests that the combined strategy of masked, protease activated IL-12Fc and attenuated IL-12 potency has the potential to widen the therapeutic index and to have superior activity to masked, protease cleavable wt IL-12 and unmasked wt IL-12 fusions.