IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update
8
IDEAYA Data
IDE397 Pharmacodynamic Biomarker Data
Mechanism of Action and Key Pharmacodynamic Markers
MAT2A Inhibition is Synthetic Lethal with MTAP Loss
IDE397 Selectively Inhibits SDMA and pre-mRNA Splicing
Tumor-specific
MTAP deletion
IDE397
MAT2A
Hit 2
(15% of cancer)
220
120
100
80
60
50
MTA
Hit 1
SAM
40
30
Partial
antagonist
PRMT5
Required
Cofactor
20
Methylation of
splicing factors
(SDMA)
Pre-mRNA Splicing
(Essential)
DMSO
IDE397 (μM)
IDE397 (μM)
0.24
0.74
2.2
6.7
DMSO
0.24
0.74
HCT116
HCT116
2.2
MTAP-deleted
Multivariate Analysis of
Transcript Splicing
HCT116 5Day-MAT2Ai-
MTAP-/- 5Day-PRMT5i-
SDMA
HCT116
5Day-MAT2Ai-
5Day-PRMT5i-
Vinculin
0
Drug-induced splicing changes
1000
2000
3000
Skipped Exon (SE)
Retained Intron (RI)
MXE-Event
A5SS
A3SS
gsk
IDEAVA
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