1. Efficacy Study in Mouse Cardiac Hypertrophy TAC model
Performed by CL Laboratory, LLC
From August 2017 to October 2017

2. Performed by CL Laboratory, LLC (www.cardio-lab.com)
Experimental Protocol
TAC
Echo
Echo
Echo
3 weeks
3 weeks
D1/D2/SA through osmotic mini-pump
Euthanized
Heart weight
Body weight
Histology (trichrome stain)
D1: Test Article 1
D2: Test Article 2
SA: Saline
Performed by CL Laboratory, LLC (

3. Performed by CL Laboratory, LLC (www.cardio-lab.com)
The Effect of D1 and D2 on Cardiac Hypertrophy
SHAM
TAC
TAC+D1
TAC+D2
10X
10X
10X
10X
Performed by CL Laboratory, LLC (

4. D2 Inhibited Cardiac Remodeling in Mouse TAC Model
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC * #
SHAM
TAC
TAC+D1
TAC+D2
Performed by CL Laboratory, LLC (

5. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Decreased Cardiac Hypertrophy in TAC Mice
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC * #
SHAM
TAC
TAC+D1
TAC+D2
Performed by CL Laboratory, LLC (

6. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Decreased Left Ventricular Contractility in TAC Mice
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC * * # #
SHAM
TAC
TAC+D1
TAC+D2 *
Performed by CL Laboratory, LLC (

7. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Increased LV Fractional Shortening and Ejection Fraction in TAC Mice
*: p < 0.01, TAC+D2 vs. TAC
#: p < 0.05, TAC+D1 vs. TAC
*: p < 0.01, TAC+D2 vs. TAC
#: p < 0.05, TAC+D1 vs. TAC * * * * # #
SHAM
TAC
TAC+D1
TAC+D2
Performed by CL Laboratory, LLC (

8. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Inhibited Left Ventricular Dilation After TAC
*: p < 0.01, TAC+D2 vs. TAC
#: p < 0.01, TAC+D2 vs. TAC # *
SHAM
TAC
TAC+D1
TAC+D2
LVESD: Left Ventricular End-Systolic Diameter
Performed by CL Laboratory, LLC (

9. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Inhibited Left Ventricular Hypertrophy After TAC
*: p < 0.01, TAC+D2 vs. TAC
#: p < 0.01, TAC+D2 vs. TAC
*: p < 0.01, TAC+D2 vs. TAC * # *
SHAM
TAC
TAC+D1
TAC+D2
IVSd: Interventricular Septal Thickness at Diastole
Performed by CL Laboratory, LLC (

10. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Delayed Diastolic Dysfunction After TAC
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC # * *
SHAM
TAC
TAC+D1
TAC+D2
Performed by CL Laboratory, LLC (

11. Performed by CL Laboratory, LLC (www.cardio-lab.com)
D2 Inhibited Cardiac Fibrosis in TAC Mice
*: p < 0.01, TAC vs. SHAM
#: p < 0.05, TAC+D2 vs. TAC * #
SHAM
TAC
TAC+D1
TAC+D2
Performed by CL Laboratory, LLC (

12. Performed by CL Laboratory, LLC (www.cardio-lab.com)
Summary
Test article D2 inhibited cardiac remodeling and preserved cardiac function in mice after TAC.
Test article D1 delayed cardiac dysfunction in TAC mice
Performed by CL Laboratory, LLC (