Efficacy Study in Mouse Cardiac Hypertrophy TAC model

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

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)

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 (www.cardio-lab.com)