Kymera Investor Day Presentation Deck
Kymera's MDM-2 Degrader Development Candidate, 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
KT-253
+ DS-3032
Baseline
100000
0.0001
MDM2-HiBiT
0.001
0.01
Compound
0.1
Concentration, μM
DC50=0.4nM
Clinical stage
RS4-11 IC50 (nM) (AML Cell Killing)
MDM2-HiBiT, DC50 (nM) (Degradation)
10
KT-253, unlike SMI's such as DS-
3032, strongly stabilizes p53...
p53 MSD, 2h
3000
100
80-
60
40-
CO
20
DMSO
-20
2500
2000
1500-
1000
500-
0-
0.00001
KT-253
Kymera
IND
enabling
0.3
0.4
KT-253
DS-3032
0.0001
0.001
0.01
Concentration, μM
DS-3032
Sankyo/Rain
Ph II /
combo AML
67
10
RG7388
Roche
Ph II / III
220
... which leads to superior
tumor cell killing (pM range)
KYMERA R&D DAY - December 16th, 2021
TO000'0
KT-253
DS-3032
620
SAR405838
Sanofi
Paused
0.0001
RS4;11, 24h CTG
0.001
0.01
0.1
Concentration, μM
HDM201
Novartis
PhI/II
163
DMSO
10
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 to its mechanism of action
Proteomics show selective degradation of KT-253
KYMERA ©2021 KYMERA THERAPEUTICS, INC.
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