Connecting Innovation to Purpose

9 Is the 2nd generation Seagen linker the cause? Similar dose limiting toxicities seen across divergent ADCs that share same constellation of 'linker + payload' Val-Cit linker + vedotin (MMAE] payload ADC drug PadcevⓇ Enfortumab vedotin Adcetris®Ⓡ Brentuximab vedotin TivdakⓇ Tisotumab vedotin Polivy Ⓡ Polatuzumab vedotin AidixiⓇ Disitamab vedotin TAA Nectin-4 CD30 TF CD79B HER2 Average DAR 3.8 4 4 3.5 4 Skin Rash Peripheral Neuropathy E 0% 10% 20% 30% 40% 50% 60% 0% 10% 20% 30% 40% 50% 60% 70% All grades Padcev® Val-Cit linker + payload = mc-VC-PABC = Maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyl alcohol p-nitrophenyl carbonate Source(s): 1. Fu et al., Science. 2023 doi: 10.1016/j.isci.2023.107778. Padcev® Prescribing information, Adcetris® Prescribing Information, Tivdak® Pescribing Information, Polivy Ⓡ Prescribing Information. Shi et al., 2022 https://doi.org/10.1080/10717544.2022.2069883 Aidix® https://www.adcreview.com/drugmap/disitamab-vedotin

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