Kymera Investor Presentation Deck
Kymera's MDM2 Degrader Investigational Drug, KT-253 is Superior to
MDM2/p53 Small Molecule Inhibitors
KT-253 is a potent MDM2 degrader
% MDM2 Remaining
Company
300
250-
200
150
100
80
60
40
20
0
0.00001
KT-253
p53 MSD, 2h
-DS-3032
2500-
2000
GED
1500-
1000
500-
Clinical stage
RS4-11 IC50
KT-253
DS-3032
Baseline
MDM2-HiBiT
0.0001
0.001
0.01
Compound
Concentration, μM
DC50=0.4nM
(nM) (AML Cell Killing)
MDM2-HiBiT, DC50 (nM) (Degradation)
KT-253, unlike SMI's such as DS-
3032, strongly stabilizes p53...
3000-
KT-253
Kymera
IND
enabling
0.3
0.4
0
¹0000¹0
0.0001
0.001
0.01
DMSO
Concentration, μM
DS-3032
Sankyo/Rain
Ph II /
combo AML
67
RG7388
Roche
Ph II / III
... which leads to superior
tumor cell killing (pM range)
RS4;11, 24h CTG
220
100
80-
60
40-
20
-20
10000'0
KT-253
DS-3032
0.0001
SAR405838
Sanofi
620
Paused
0.001
0.01
Concentration, μM
HDM201
Novartis
PhI/II
163
DMSO
AMG-232
Amgen/Kartos
Multiple Ph II;
combo AML
280
KT-253 is >200-fold more potent in tumor cell killing assays than SMI's due to its mechanism of action
Proteomics show selective degradation of KT-253
KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC.
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