Investor Presentaiton
IDE161: Potential First-in-Class Phase 1 PARG Inhibitor
IDE161 Profile: Potent, Selective with Favorable Properties
IDE161 is a potent, selective small
molecule PARGI for tumors with HRD
Demonstrated cellular activity and
efficacy in biomarker defined settings
Positive physical property profile
Favorable preclinical tolerability
IDE161 induces Selective DDR → Synthetic Lethal in HRD
MSD Assay ECL counts
IDE161-induced DNA Damage Response
500000
P-ATM
p-KAP1 P-RPA
400000-
300000-
200000-
100000
25000
12500
6h
48h
72h
% Inhibition
100
8 8 8
40-
20-
0-
80-
Biochemical IC50
60-
PARGI IC 50
~0.002 UM
=
-8
-7
-6
-5
-4
-3
log [PARGI MM]
31
IDEAYA Data: AACR 2023 D. Munoz et al.
750000
600000
450000-
300000
150000
50000
MSD PAR Assay
ECL counts
25000-
IDE161-induced Cellular
PAR Accumulation
T T T T T T T
0.00 0.16 0.31 0.63 1.25 2.50 5.00 10.00
IDE 161 conc (uM)
Normalized Z-score IDE161
low dose vs DMSO
S
0
0
0.0411
0.1234
0.37
0
0.0411
0.1234
0.37
0
0.0411
0.1234
0.37
IDE161 conc (uM)
IDE161 is Synthetic Lethal with BER Gene Disruption
Ovarian HRD Model
TYMS
RFC1
PARG
XRCC1
-10
EXO1
POLB
LIG1
-10
-5
0
5
Normalized Z-score IDE161 high dose vs DMSO
PARG poly (ADP-ribose) glycohyrdolase; PAR = poly (ADP-ribose); DDR = DNA Damage Response; HRD = Homologous Recombination Deficiency; BER = Base Excision Repair
RFC1
LIG1
POLB
EXO1
TYMS
PARG
XRCC1
Gene Network generated
from whole genome CRISPR
screens anchored with
IDE161 using significant
synthetic lethality hits across
4 models
IDEA A
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