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 Targets
CE
p53 Degradation
Feedback
Loop
Cell Cycle
Arrest
(p21, Ptprv)
Apoptosis
(Noxa, Bax,
Puma)
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