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Relative Quantification (% Vehicle, p53/ACTB) KT-253 Potently Degrades MDM2 leading to Pathway Impact and Antitumor Activity Superior to SMI in ALL and AML Models e 2000 1500- 1000 500 0 MDM2 Degradation Leads to Superior P53 Upregulation vs SMI %MDM2 Remaining (Norm. to Vehicle, ACTB) 18 24 250- 200- 150- 100- 50- MDM2 Protein Levels 1h post dosing p53 Protein Levels 6% 1 8 24 1 8 24 1 8 24 1 8 24 Time (Hours) 8% Relative Quantification (% Vehicle, GDF15/IPO8) 10000 8000 6000 4000 2000 0 KYMERA ©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 GDF15 Protein Levels p53 Activation 1 8 24 1 8 24 18 24 1 8 24 Time (Hours) 1 8 24 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 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 O 2500 2000 1500 0 1000- 500- 0 0 7 14 Days Post Treatment 21 7 14 Days Post Treatment 21 28 28 RS4;11 Vehicle KT-253 3 mg/kg IV, SD KT-253 1 mg/kg IV, SD DS-3032 30 mg/kg PO, 3 on/11 off DS-3032 100 mg/kg PO, 3 on/11 off MV4;11 Vehicle KT-253 3 mg/kg IV, SD KT-253 1 mg/kg IV, QWx3 -DS-3032 30 mg/kg PO, 3 on/11 off DS-3032 100 mg/kg PO, 3 on/11 off 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 36

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