Kymera Investor Day Presentation Deck

IRAKIMiDs are Potent Degraders of IRAK4 and IMID Substrates Targeting Redundant Pro-survival Pathways in MYD88MT DLBCL Single-agent therapies that target activated NFkB signaling in DLBCL show limited activity in preclinical or clinical settings • Redundant NFKB pathway activation and downregulation of Type 1 IFN is common in MYD88MT lymphoma, supporting need to seek combination therapies Targeting simultaneous degradation of IRAK4 and IMID substrates Ikaros and Aiolos shows synergistic activity in MYD88MT models, supporting this targeted combination IMiD Degrader CRBN IMiD (E3 Ligase) Binder IMID Substrates Degradation KYMERA IRAKIMID Degrader IMID CRBN (E3 Ligase) Binder IMID Substrates AND IRAK4 Degradation ©2021 KYMERA THERAPEUTICS, INC. IRAK4 Binder TLRs JNK AP1 Pathway P IL-1R MYD88MYD88 IRAK4 IRAK4 IRAK1 IRAK1 TRAF6 TRAF6 P IKKy IKKBIKKa KYMERA R&D DAY - December 16th, 2021 NFkB Pathway PROLIFERATION & SURVIVAL B Cell Receptor BTK CARD11 MALT1 BCL10 * A20 * IRF4 Autoantigens * CD79A/B Ikaros Aiolos ➡IRF7 IFN IFNAR1/2 IFN Pathway IFITS Pathway activating alterations in DLBCL Adapted from Yang et al. (2012) Cancer Cell 21, 6, pp723-737 PAGE 50

View entire presentation