1. CC-1 Integrated Summary of V-HeFT and A-HeFT Trials Milton Packer, MD University of Texas Southwestern Medical Center at Dallas

2. CC-2 Characteristics of Major Trials With Isosorbide Dinitrate and Hydralazine in Heart Failure V-HeFT I (1980-1985)V-HeFT II (1986-1990)A-HeFT (2001-2004) SponsorVeterans Affairs NitroMed Number of patients6428041050 SexMale Male and female RaceAll races Blacks Drugs studiedPlacebo ISDN/HYD Prazosin Enalapril ISDN/HYD Placebo ISDN/HYD Target doses of ISDN/HYD ISDN 40 mg QID HYD 75 mg QID ISDN 40 mg QID HYD 75 mg QID ISDN 40 mg TID HYD 75 mg TID ISDN/HYDAs individual products As individual products As fixed-dose combination tablet (BiDil ® ) Severity of HFMild-to-severe Moderate-to-severe Background therapy for HF Digoxin Diuretics Digoxin Diuretics Digoxin Diuretics ACE inhibitors/ARBs Beta-blockers Aldosterone antagonists DV Final NDA20-727_Brief_Document.pdf T 1

3. CC-3 BiDil ® Effects in Black Patients With Heart Failure  Mortality  Hospitalization for heart failure  Quality of life DV NitroMed BB pp 11, 12

4. CC-4 Primary Endpoint—Composite Score † P = 0.016 DV A-HeFT CSR T 24 † Composite score range, –6 to +2. –0.16 –0.47 Mean ± SEM

5. CC-5 Components of Primary Endpoint DeathFirst HF hospitalizationChange in QoL at 6 mo A-HeFT T 26 pg 109, 116, 120; A-HeFT PTT 16.1 BiDil ® Placebo n = 32n = 54n = 85n = 130 Percent

6. CC-6 BiDil ® Effects in Black Patients With Heart Failure  Mortality  Hospitalization for heart failure  Quality of life DV NitroMed BB pp 11, 12

7. CC-7 BiDil 518463407360314253 Placebo532466401340285233 Effect on Mortality A-HeFT BiDil ® Placebo HR = 0.57 (0.37, 0.89) P = 0.012 Patients at risk, n 85 90 95 100 0 200300400500 Survival, % Time since baseline visit, days DV NitroMed BB F 16

8. CC-8 Effect on Mortality in Black Patients V-HeFT I Patients, n ISDN/HYD49433628168 Placebo79614429143 30 40 50 60 70 80 90 100 0365730109514601825 Survival, % Time since randomization date, days DV NitroMed BB F3 HR = 0.53 (0.29, 0.98) P = 0.04

9. CC-9 60 70 80 90 100 0 200300400500 Effect on CHF Hospitalization A-HeFT DV NitroMed BB T22, F18 Placebo BiDil ® HR = 0.61 (0.46, 0.80) P < 0.001 BiDil 5184303573052531976 Placebo53240732926420316012 Patients at risk Without hospitalization, % Time since baseline visit date, days

10. CC-10 Effect on CHF Hospitalization in Black Patients V-HeFT I and V-HeFT II 75 80 85 90 95 100 0365730 Without HF hospitalization, % 75 80 85 90 95 100 0365730 V-HeFT IV-HeFT II Time since randomization date, days Placebo ISDN/HYD Enalapril ISDN/HYD DV NitroMed BB F6, F13

11. CC-11 † Minnesota Living With HF questionnaire. Lower QoL score indicates better QoL. Mean ± SEM. MLHF Questionnaire Change in QoL From Baseline † DV A-HeFT CSR PTT 16.1 Improvement P = 0.014 Month P = 0.129P = 0.053P = 0.011P = 0.039P = 0.024P = 0.003 423441369371198184n =307305269250226218512528

12. CC-12 Quality of Life in Black Patients V-HEFT II P = 0.043 DV V-HeFT II PTT 35

13. CC-13 Overview  Concordance of data within and across trials support proposed indication: “BiDil ® is indicated for the treatment of heart failure as an adjunct to standard therapy in black patients to improve survival, prolong time to hospitalization for heart failure, and improve quality of life.”