ZW270 / Zymeworks - LARVOL DELTA

Design of a Next Generation Tumor Targeted Masked IL-12Fc for Enhanced Tolerability and Localized Anti-Tumor Activity (SITC 2025) - "In syngeneic and transgenic models, with varying tumor antigen densities, targeted mZW270 activated a local tumor immune response, leading to strong anti-tumor activity, lowering the minimum effective dose without decreasing the tolerability. Initial characterization of a targeted ZW270 indicated translatability of these observations to a human therapeutic.Conclusions Overall, our combined strategies of masking, potency attenuation and tumor targeting can be incorporated to widen the therapeutic index of an IL-12 based therapeutic."

Oncology • IL12A

ZW270, a conditionally masked IL-12 cytokine fusion protein displaying potent anti-tumor activity absent systemic toxicity (AACR 2023) - "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."

Oncology • CD8 • IL12A

Zymeworks Showcases Preclinical Assets, Including New Therapeutic Platform, ProTECT, and Zanidatamab Mechanisms of Action at AACR Annual Meeting (Businesswire) - “Zymeworks…announced five presentations at the American Association for Cancer Research (AACR) Annual Meeting. The presentations highlight preclinical data that reveal new insights into the unique mechanisms of action of lead clinical candidate, zanidatamab, introduce Zymeworks’ fourth therapeutic platform, ProTECT™, and describe two new preclinical assets focused on the cytokine, IL-12, and the immune-oncology target, 4-1BB…Super-resolution imaging studies of zanidatamab: providing insights into its bispecific mode of action…ProTECT™, a novel antibody platform for integrating tumor-specific immune modulation and enhancing the therapeutic window of targeted multispecific biologics…IL-12 and 4-1BB Presentations; Increasing the therapeutic index of IL-12 by engineering for tumor-specific protease activation.”

Preclinical • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor