Valo SPAC Presentation Deck
OPL-0301: Preclinical and Phase I data suggests differentiated biology
A biased S1P, agonist designed to avoid the side effects of other
S1P, modulators will unlock therapeutic benefit for post-MI left
ventricular dysfunction and acute kidney injury patients
We believe Opal has the potential to enable
accelerated development of a biased S1P, agonist for
CV development. Intent to enter Phase 2 in 4Q214
THERAPEUTIC
HYPOTHESIS
Absolute change Heart Rate (bpm)
Phase I safety data
20- Absolute change from baseline heart rate
15- on day 14
10-
-5-
-10-
-15-
-20-
-25
A
TOh30
T1h
Placebo
OPL-0301 2.5 mg
OPL-0301 15 mg
T6h30
Theoretical Time
OPL-0301 0.5 mg
OPL-0301 5 mg
T12h
11
T24h
OPL-03011 mg
OPL-0301 10 mg
Unlike other S1P,s, Phase I data suggests that at doses
<= 5 mg, OPL-0301 evokes little or no effects on heart
rate (no symptomatic bradycardia or tachyphylaxis)
Phase I efficacy data
Effect of 28 day once-daily treatment of OPL-0301 (1
and 5mg), or placebo on % flow-mediated dilation
(FMD)
%FMD
(change from baseline)
%FMD
(change from baseline)
1.5
0.5
0.0
Post-hoc analysis¹
D14
All FMD data¹
12 15 15
D21
D14
D21
D28
D28
OPAL
VALIDATION
Placebo (n=6)
OPL-0301 1mg (n=15)
D35
D35
D42
D42
average
D14-28
12 15 15
average
D14-28
OPL-0301 5mg (n=15)
Sildenafil 50mg (n=6)
average
D14-42
average
D14-42
Evidence for dose and time-dependent endothelial
effects of OPL-0301, at least as good as sildenafil²
(FMD is correlated with cardiovascular events³)
Therapeutic hypothesis
Lower plasma S1P in patients admitted for MI
compared to controls. Further reduction over
subsequent 5 days
Sphingosine-1-phosphate
[pmol/ml]
Creatininemia
600
(1/10url)
500
400
300
200
100
-...
00000 p=0.0001
0
Control Infarction 5d later
400
300
p=0.002
200
100
p=0.0001
0
Significant renal function preservation in rat
acute kidney injury model
500
sham
250
p<0.0001
200
0
150
100-
50
Infarction 5d later
ischemia/reperfusion
[1] Exclusion criteria in post-hoc analysis was to exclude FMD for all subsequent time-points following an increase in hsCRP of >2.5 mg/L compared to baseline. FMD expressed as change from baseline. Bars are mean +/-
Valo SEM. Number of FMD data points shown within each bar chart; [2] Study and analysis conducted by third party. [3] Matsuzawa, Yasushi, et al. "Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and
Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis." J Am Heart Assoc. (Nov13, 2015), PMID: 26567372. [4] Reflects management's 2021 goals
p<0.05
-89% -96%
1
3
0.3
OPL-0301 mg/kg orally
p < 0.001
2Q21
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