Kymera Investor Presentation Deck

KT-253: Potent MDM2 Degrader and Best-in-Class p53 Stabilizer • KT-253 is a novel, highly potent and selective heterobifunctional MDM2 degrader • MDM2 is the E3 ligase that modulates p53, the largest tumor suppressor • Cancer genetics: p53 is NOT mutated in almost 50% of tumors • MDM2 overexpression and amplification can inactivate p53 • Large opportunity in wide variety of cancers Benefits of MDM2 Degradation • KT-253, unlike small molecule inhibitors, overcomes the feedback loop which up-regulates MDM2 production and in doing so more effectively stabilizes the tumor suppressor p53 • Broad franchise opportunities available for this mechanism (over 50% of tumors are p53 WT); focused on indications with specific sensitivity to degrader mechanism, through a biomarker strategy Clinical Activity Based on Preclinical Data: Strong antitumor activity in a wide variety of heme and solid tumors with an emerging signature (undisclosed) KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. MDM2 CRISPR Sensitivity Score 0.6 Dependency of p53WT cells on MDM2 0.4 0.2 O -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 DNA Damage p53 p53MUT p53WT Hypoxia Stressors MDM2 Graph generated with data obtained from DepMap.org p53 Cell Line Oncogenes p53 ub ub MDM2 Tumor Suppression Other p53 Degradation p53 Targets Feedback Loop Cell Cycle Arrest (p21, Ptprv) Apoptosis (Noxa, Bax, Puma) PAGE 32

View entire presentation