Investor Presentaiton
Combination Effect of MAT2A Inhibitor and PRMT5MTA Inhibitor
Combined Inhibition Deepens Biological Response through Maximal Pathway Suppression
Gene Expression Analysis
Combination Deepens Observed
Monotherapy Activity
HCT 116 MTAP (-/-)
°
°
°
°
.
°
°
Alternative Splicing Analysis
Combination Increases Alternative Splicing Events
HCT 116 MTAP (-/-)
IDE397
PRMT5MTA-2
IDE397 + PRMT5MTA-2
Retained Intron Analysis
Combination shows Selective Response
by Retained Introns Analysis^
HCT 116 MTAP (-/-)
n=87
n=413
HALLMARK PATHWAYS
IDE397
°
°
°
°
°
°
num DE in
Leading Edge
°
°
°
• 25
°
°
о
о
75
°
°
NES
°
2
°
°
°
°
°
°
°
O o O o
°
.
°
°
°
°
°
о
°
OOOOOOOO • • OO●●●
°
PRMT5MTA
Combo
-1
0.5
0
Quantitative Assessment of IDE397 / PMRT5i
Effect on pre-mRNA Splicing
>2800 significant Splicing Events only in the
Combination Treatment Arm+
MTAP (-/-)
-Log10(Padj)
MTAP wt
-Log10(Padj)
25
25
15
75
25
0
75
75
n-1
Significance
in treatment
in treatment
⚫ not significant
Analysis by RNAseq; Color = Normalized Enrichment Score (NES);
Shape = Number of Differentially Expressed (DE) Genes in Leading Edge;
Black Circular Border = Statistically Signifcant (P.adj <0.05)
+ Identified as novel splice junctions or as not meeting significance criteria in monotherapy arms
Color = heatmap of Z-scored TMM-normalized counts per million
26
IDEAYA Data: AACR 2023 M. Fischer et. al.; PRMT5MTA = representative MTA-cooperative PRMT5 inhibitor, including designated as PRMT5MTA-2
0
-30
-20
-10
0
10
20
30
^ Retained Introns by DEXseq for Combination Treatment Arm
IDEAVA
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