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KT-253 Potently Degrades MDM2 leading to Pathway Impact and Antitumor Activity Superior to SMI in ALL and AML Models Relative Quantification (% Vehicle, p53/ACTB) ● 2500 2000 1500- 1000 500 0 MDM2 Degradation Leads to Superior P53 Upregulation vs SMI KYMERA %MDM2 Remaining (Norm. to Vehicle, ACTB) 250 1 8 24 200 150 100 50 0 MDM2 Protein Levels 1h post dosing 6% p53 Protein Levels 8% 1 8 24 1 8 24 1 8 24 1 8 24 Time (Hours) Relative Quantification (% Vehicle, GDF15/IPO8) 10000 8000 6000 GDF15 Protein Levels p53 Activation 4000 2000 ©2023 KYMERA THERAPEUTICS, INC. Vehicle KT-253 3 mg/kg SD KT-253 1 mg/kg SD DS-3032 30 mg/kg QDx3 DS-3032 100 mg/kg QDx3 0 Targeted proteomic analysis of RS4;11 tumors demonstrates robust degradation of MDM2 one hour post dosing and associated pathway activation biomarkers including p53 and GDF15 I 1824 1 824 1 8 24 1 8 24 1 824 1 824 Time (Hours) MDM2 Degradation Leads to Superior Antitumor Responses in AML and ALL Preclinical Models Tumor Volume (mm³) Mean ± SEM Tumor volume (mm³) Mean ± SEM 2500 2000 1500 1000 500 0 2500 2000 1500 1000 500 0 O 14 7 Days Post Treatment 21 7 14 Days Post Treatment 21 28 28 RS4;11 Vehicle DS-3032 30 mg/kg PO, 3 on/11 off DS-3032 100 mg/kg PO, 3 on/11 off → KT-253 1 mg/kg IV, SD →KT-253 3 mg/kg IV, SD MV4;11 Sustained tumor regressions in RS4;11 (ALL) and MV4;11 (AML) CDX models after a single 3 mg/kg KT-253 dose No efficacy observed with clinically relevant dosing regimen of SM (DS- 3032) PAGE 34

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