Ocuphire Pharma Investor Presentation Deck
VEGF
In-vitro Validation of Mechanism of Action
APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection
APX3330 reduces VEGF protein
expression in preclinical stroke
model
Control
VEGF
% Positive area (+SE)
2.6
1.3
0.0
Ocuphire
0.1mm
VEGF
T1DM-MCAO
APX3330
*p<0.05
n=7/group
*
+APX3330
APX3330 reduces pro-inflammatory
cytokines in LPS stimulated macrophages
TNF-α
14000
12000
10000
8000
μg/mL 6000
4000
2000
0
APX3330
LPS (1 µg/mL)
14000
12000
10000
8000
6000
4000
2000
0
APX3330
LPS (1 µg/mL)
0 ug/mL
0 ug/mL
0 ug/mL
+
6.3 ug/mL 12.5 ug/mL 25 ug/mL
IL-6
h
0 ug/mL 6.3 ug/mL 12.5 ug/mL
+
+
+
25 ug/mL
+
Increasing APX3330 dose
% increase in APE1 repair activity
APX3330 increases DNA oxidative
repair and neuronal protection
120
115
110
105
100
95
N=4
0
*1
12.5
25
APX3330 (μM)
*
50
APX3330 enhances Ref-1
endonuclease activity in dorsal
root ganglion neurons
Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018
Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315
Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA
repair function of APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017).
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