Kymera Investor Day Presentation Deck
DNA
Damage
MDM2 Degradation, Not Inhibition, Efficiently Restores p53
p53
Stressors
Hypoxia
#
Inhibitor
I
MDM2
T
Degrader
p53
Oncogenes
ub
ub
ub
p53
MDM2
Tumor Suppression
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Other
p53 Degradation
p53 Targets
Feedback
Loop
Cell Cycle
Arrest
(p21, Ptprv)
Apoptosis
(Noxa, Bax,
Puma)
Clinical Validation
• MDM2 small molecule inhibitors of
MDM2/p53 interaction show activity in the
clinic..
...but they induce MDM2 feedback loop
resulting in limited impact on pathway
Degrader Advantage
• MDM2 degraders, by removing the protein,
can overcome the p53-dependent feedback
loop that upregulates MDM2
●
MDM2 degrader can induce an acute
apoptotic response in tumor cells, increasing
efficacy and therapeutic index vs a small
molecule inhibitor
KYMERA R&D DAY - December 16th, 2021
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