Kymera Investor Presentation Deck

DNA Damage MDM2 Degradation, Not Inhibition, Efficiently Restores p53 • MDM2 SMI's show activity, but can induce feedback loop, limiting impact on pathway p53 KYMERA Stressors Hypoxia # Inhibitor 1 MDM2 T Degrader p53 Oncogenes p53 ub ub ub MDM2 Da Tumor Suppression p53 Targets Ⓒ2023 KYMERA THERAPEUTICS, INC. Other p53 Degradation Feedback Loop Cell Cycle Arrest (p21, Ptprv) Apoptosis (Noxa, Bax, Puma) MDM2 degraders remove the protein, can overcome the p53-dependent feedback loop that upregulates MDM2 • By inducing an acute apoptotic response in tumor cells, degraders can increase efficacy and therapeutic index vs a small molecule inhibitor MDM2 levels are kept at undetectable levels with MDM2 degrader KT-253, leading to p53 stabilization KT-253, IC90 Oh DMSO 2h 24h 4h 24h DMSO Oh DMSO 2h MDM2 levels are increased by the small molecule inhibitor (feedback loop), impairing p53 stabilization DS-3032, IC90 4h 24h MDM2 ACTB 24h DMSO MDM2 ACTB PAGE 52

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