Nuvectis Pharma Investor Presentation Deck
NXP800 Mechanism of Action
NXP800 is a GCN2 kinase activator
Non-acylated
tRNA
GCN2
GCN2
Stalled ribosome
NXP800
GCN2
activation
NXP800 activates the GCN2 kinase
NuvectisPharma, Inc.
elF2a
phosphorylation
P
elF2a
↓
ATF4 translation
ATF4
Dimerization
partner
ATF4
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Cap-dependent
translation
Chronic activation:
Induction of cell death
Stress-
induced genes
C
Inhibition of cap-dependent translation and
chronic activation of the integrated stress
response (ISR) ➜ Cancer cell death
❖ ARID1a-mutated tumors display an increased
dependence on translation
Cell proliferation (% of vehicle control)
150
100-
50-
ICH
10
NXP800
NXP800 + A92 (GCN2 inhibitor)
100
NXP800 (NM)
1000
10000
Target validation
The GCN2 inhibitor A92 antagonizes the
antiproliferative effect of NXP800 in ARID1a- mutated
SKOV3 cells (approx. 50-fold change in Gl50)
Powers et al., AACR 2023
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