Kymera Investor Day Presentation Deck
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KT-474 is Superior to IRAK4 Small Molecule Inhibitor (SMI) Across
Multiple Preclinical
Immune-inflammatory In Vivo Models
In vivo IRAK4
Degradation
in Whole Blood
Naive
rmlL-33 Intradermal
Challenge Model
Vehicle
Degrader 15 mg/kg
*
Degrader 50 mg/kg
Degrader 150 mg/kg
****
SMI 30 mg/kg
Dexamethasone mg/kg
% of Vehicle Control
150
100
50
0
IL-5 in
Ear
Tissues
Naive
Vehicle
Degrader 15 mg/kg
Degrader 50 mg/kg
SMI 30 mg/kg
Degrader 150 mg/kg
Dexamethasone mg/kg
% of Vehicle Control
KYMERA ©2021 KYMERA THERAPEUTICS, INC.
150
100
50
rhlL-36aßy Intradermal
Challenge Model
In vivo IRAK4
Degradation
in Whole Blood
Naive
Vehicle
Der 15 mg/kg
50 mg/kg
Degrader 150 mg/kg
l 30 mg/kg
Dexamethasone mg/kg
100
80
40
20
0
Naive
Degrader
Ear
Thickness
15e
Degrader 50 mg/kg
40 €
g/kg
Dexamethasone mg/kg
120
KYMERA R&D DAY - December 16th, 2021
100
80
60
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Th17-mediated Multiple
Sclerosis Model
In vivo IRAK4
Degradation
in Whole Blood
Naive
Vehicle
Degrader 150 mg/kg
SMI 30 mg/kg
FTY720 3 mg/kg
EAE Clinical Scores
4
3-
1
0-
5
MOG-EAR¹
+ Vehicle
+ Degrader 150 mg/kg
SMI 30 mg/kg
+FTY720 3 mg/kg
10
Treatment
Vehicle
Degrader 150 mg/kg
SMI 30 mg/kg
FTY720 3 mg/kg
15 20 25 30
Day
Mean Max Score +/- SD p value
3.40 +/-0.54
2.69 +/- 0.52
3.07 +/-0.42
2.70 +/- 1.28
IRAK4 knockdown of ≥85% in whole blood achieved anti-inflammatory effect comparable to potent corticosteroids or approved standard of care drugs
in these models as well as in models of TLR4 (MSU-Gout) or TLR7/8 (Imiquimod-Psoriasis) activation that was superior to IRAK4 small molecule inhibitor
1. Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis (MOG-EAR) Model
0.0018
0.0822
0.0271
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