Change in SBP (mmHg) OmapatrilatEnalapril HCTZ (n = 2476) Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized Patients) Other Diuretics (n = 690) Amlodipine (n = 695) Other CCB (n = 735) ARB (n = 274) Beta Blockers (n = 890) OCTAVE (CV )

OCTAVE Group 3: Effectiveness of Omapatrilat in Patients Treated with HCTZ and Amlodipine at Randomization at Week 24 SBPDBP BP Change (mmHg) Omapatrilat (n = 65) Enalapril (n = 70) OCTAVE (CV )

Enalapril Comparison in Severe Hypertension (CV ) B71 Period A Single-Blind Placebo Lead-In Period C Long-Term Open-Label Period B Double-Blind Randomized SeDBP mmHg 40 B1B15 A B8B29 Level ILevel IILevel III Adjunct Omapatrilat Enalapril B1 B71C1 Forced titration to 40, elective to 80 Forced titration to 20, elective to 40

CV Primary Efficacy Results Mean Changed from Baseline in Trough SeDBP, and SeSBP and SePP at Week 10

Most Common Adverse Events * * Excluding Angioedema OCTAVE (CV )

OVERTURE Trial OVERTURE Trial –Included all hospitalizations attributable to heart failure as adjudicated by Endpoint Committee which required IV treatment and had a duration  24 hours SOLVD Treatment Trial SOLVD Treatment Trial –Included all hospitalizations attributable to heart failure by the investigator regardless of treatment or duration Definition of Hospitalization for Heart Failure OVERTURE (CV )

4 Wk Period B 10 mg 40 mg 80 mg Omapatrilat 3 Wk (max) Period A Placebo ETT ETT ETT ETT R wk 2 wk 4 Placebo Single blind Double blind Day 28 Day 29 wk 1 BMS data on file +CAD +Exertional angina Study Design (CV )

BMS data on file Primary Efficacy Results: Change in Peak Exercise Parameters vs Baseline ETT OmapatrilatPlacebo Time to Onset of Angina Maximal Exercise Duration Time to ST Depression p  Increased Time (sec) CV

Diabetic Patients (CV ) Type II diabetics with microalbuminuria ( mg/gram creatinine) or overt nephropathy (  300 mg/gram creatinine) 2 week placebo lead-in 20 mg 2.5 mg Randomization 12 week Double-blind 40 mg80 mg 5 mg10 mg wk 4wk 8 Elective titration DBP mmHg or SeSBP mmHg omapatrilat amlodipine

Adjusted GM% Change from Baseline OmapatrilatAmlodipine Study Week Summary of Primary Efficacy Results CV Adjusted Geometric Mean % Change from Baseline for Albumin Excretion Rate

omapatrilat Wk 52 (Echo) Baseline Echo LVH Hypertension DBP mmHg and / or SBP mmHg Force Titration Open-label adjuncts added to Level III Wk 8Wk 16Wk 24 (Echo) 20 mg40 mg80 mg + HCTZ80 mg +HCTZ/AML Losartan Comparison in LVH (CV ) 50 mg100 mg + HCTZ100 mg +HCTZ/AML losartan

Summary of Primary Efficacy Results CV Mean Changes from Baseline in Echocardiographic Measures at Week 24

BP Changes From Baseline Per Study Week Adjunctive therapy % Omapatrilat Losartan Week DBP SBP Change in BP (mmHg) CV Omapatrilat Losartan

CHOIRS Background (Conduit Hemodynamics of Omapatrilat International Research Study) Elevated pulse pressure, an indirect measure of increased vascular stiffness, associated with: Elevated pulse pressure, an indirect measure of increased vascular stiffness, associated with: –Myocardial infarction, stroke –Development and progression of heart failure –Increased mortality Current epidemic of uncontrolled systolic hypertension due to a lack of treatments that reduce arterial stiffness Current epidemic of uncontrolled systolic hypertension due to a lack of treatments that reduce arterial stiffness Natriuretic peptides have a favorable effect on large arteries in basic studies although their effects in humans have not been elevated Natriuretic peptides have a favorable effect on large arteries in basic studies although their effects in humans have not been elevated

CHOIRS: Study Design Randomize: Force-titration Wks 0, 2, 4 Omapatrilat 10 / 40 / 80 mg daily (n = 104) Enalapril 10 / 20 / 40 mg daily (n = 109) 8 Wks at maximal dose Trough (24 Hr) Hemodynamic Study (n = 80) Trough (24 Hr) Hemodynamic Study (n = 87) Withdrawn (n = 22) Withdrawn (n = 24) Baseline hemodynamic study (n = 213) SBP  160 mmHg

Enalapril Omapatrilat Central and Peripheral Pulse Pressure * =  † =  0.05 Mitchell, et al., Circulation 2002; 105:2955 * Central Pulse Pressure (80  20 mmHg) † Brachial Pulse Pressure (78.6  16.6 mmHg) †

Omapatrilat Target Population Patients with: A high risk of major cardiovascular events* A high risk of major cardiovascular events* –Cardiovascular disease (e.g., MI, CHF) –Target organ damage (e.g., LVH, proteinuria) –3 or more cardiovascular risk factors –Diabetes or renal disease and and Hypertension that is difficult to control with existing medications Hypertension that is difficult to control with existing medications *Based on WHO-ISH guidelines Use with special caution in black patients and current smokers

Subgroups at Increased CV Risk: Change in Systolic BP at Week 24 Adjusted SBP Change at Week 24 (mmHg) Omapatrilat Enalapril Difference (oma / ena) Severe Hypertension (n = 7197) Group 1 (n = 983) Diabetes Mellitus (n = 3275) Atherosclerotic Disease* (n = 2283) ISH (n = 1332) Renal Disease (n = 582) Heart Failure (n = 233) *Includes chronic stable angina, unstable angina, myocardial infarction, and stroke / TIA OCTAVE (CV )

Target Population – Baseline Demographics (Diabetes, Renal Disease, Athero Disease, HF) Omapatrilat (n = 2849) Enalapril (n = 2840) Age (Mean)62 Age, n (%)  65 years years  75 years 1654 (58%) 793 (28%) 402 (14%) 1652 (59%) 802 (28%) 385 (14%) Gender, n (%) Male Female 1602 (56%) 1247 (44%) 1566 (55%) 1273 (45%) White Black 2490 (87%) 314 (11%) Race, n (%) 2488 (88%) 309 (11%) OCTAVE (CV )

OCTAVE: Efficacy in Target Population at Week 24 (Diabetes, Renal Disease, Athero Disease, HF) Change in Systolic BP Use of New Adjunctive Therapy -3.6** SBP Change (mmHg) ** p  vs enalapril ** % of Patients Omapatrilat Enalapril

Target Population – Severity of Angioedema Events, Week 24 (Diabetes, Renal Disease, Athero Disease, HF) OCTAVE (CV ) Number (%) of Patients Omapatrilat (n = 2842) Enalapril (n = 2807) Severity I. No Treatment Administered or Antihistamines Only II. Treated with Catecholamines or Steroids III. Hospitalized but no Mechanical Airway Protection IIIa. No Airway Compromise IIIb. With Airway Compromise IV. Mechanical Airway Protection or Death from Airway Compromise Total 28 (0.99%)14 (0.50%) 15 (0.53%)2 (0.07%) 1 (0.04%) (0%) 45 (1.58%)17 (0.61%)

CV ASBP Change (mmHg) ACE-I Monotherapy (n = 171) ACE-I Combination (n = 75) Change in 24-Hour Average Ambulatory Systolic BP in Patients Uncontrolled with ACE-Inhibitor Regimens at Baseline Omapatrilat 80 mgLisinopril 40 mg -7.6** -11.5** Week 4 Maintenance * *p  vs. lisinopril

Patients uncontrolled with a regimen not including an ACE-I Omapatrilat provides consistent benefit in BP reduction over enalapril in each of these difficult to control populations. Difficult to Control Patients Untreated patients with severe hypertension Patients uncontrolled with a regimen including an ACE-I Difficult to Control Patients

BP Control in Uncontrolled Patients at Sites with Highest Adjunct Use (64.0% - 100%) at Week 24 OCTAVE (CV ) Change in SBP (mmHg) BP Control n / N (%) Omapatrilat (n = 967) Enalapril (n = 966) 544 / 907 (60.0%) 466 / 903 (51.6%) Difference

Omapatrilat Educational Program MD Education Initial MD-Patient Consultation Patient Brochure Rx Given Mandatory Counseling Service Retail Pharmacist Education Retail Pharmacist Validation of Counseling and Delivery of Patient Education Medication Dispensed in Unit-of-Use Packaging Message with PPI Follow-up MD Patient Consultation Rx Given Counseling Pharmacist Education