Kymera Results Presentation Deck

IRAK4 Scaffolding Function is Critical in Myddosome Formation and Pathway Signaling IL-1R (or TLRs) IRAK4 Degradation but Not Inhibition is Required to block IL1R/TLR Pathway MyD88 Recruitment IRAK4 Recruitment/ MyD88 Limitation IRAK1 Recruitment IRAK4 scaffolding role functions to limit MYD88 oligomer size and trigger myddosome formation Source: Deliz-Aguirre, et al. J. Cell Biol., 2021 KYMERA ©2022 KYMERA THERAPEUTICS, INC. IRAK4 Degradation, but not Kinase Inhibition, can Block TLR- induced NF-KB Translocation B Cell CpG-B → IL-6 % IL6 (Control) %Phos-NF-kBp65/Control 150 100 50- 0 0.1 150 100 50 O IC50-18 NM 500 |PF-06550833 IRAK4 Degrader 1 10 Dose (nM) PF-06550833 IRAK4 Degrader 125 31.25 7.8125 1.953125 Dose (nM) 100 0.488281 1000 0.12207 150 100 50 0 -6 IRAK4 Degradation, but not Kinase Inhibition, can block IL1R+TLR activation LPS + IL-18 → IL-6 HA ▶ -4 HA 101 -2 Log[Compound] (nM) Compound IRAK4 Degrader Negative Control IRAK4 SMI (PF-06550833) 2 IL-6 IC50 (NM) 0.8 450 N/A PAGE 25

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