Nuvectis Pharma Investor Presentation Deck
NXP800 Mechanism of Action
NXP800 is a GCN2 kinase activator
NXP800 activates GCN2 >> GCN2 activates the Integrated Stress Response
(ISR) >> ISR activation causes a translational switch which includes
downregulation of HSF1-regulated genes
Non-
acylated
tRNA
Stalled
ribosome
Recognition by
GCN2
NXP800
GCN2
GCN2
GCN2
activation
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NuvectisPharma, Inc.
-
elF2a
phosphorylation
elF2a
Selective
ATF4
translation
ATF4
Dimerization
Cap-dependent
translation
partner ATF4
Translational switch -
including HSF1 regulated
proteins
Chronic activation:
Autophagic and apoptotic
cell death (CHOP and other
validated PD markers)
Stress-induced genes
ATF4 was induced in vivo in SKOV3 xenografts;
ATF4 Validated as biomarker for preclinical activity
X5 G150 (GI50 = 8.5nM)
Vehicle
Clarke et al, ENA 2022
ATF4
Vinculin
ATF4 induction observed in patient samples in the phase 1a
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