Results from the Rheos Pivotal Trial Baroreflex Activation Therapy Sustainably Lowers Blood Pressure in Patients with Resistant Hypertension John Bisognano, Domenic Sica, Mitra Nadim, Luis Sanchez, George Bakris, On Behalf of the Rheos Pivotal Trial Investigators

Baroreflex Activation Therapy (BAT) The CVRx Rheos® System Programming System Baroreflex Activation Leads Implantable Pulse Generator

Autonomic Nervous System Baroreflex Activation Therapy (BAT) Continuously Modulates the Autonomic Nervous System Carotid Baroreceptor Stimulation Brain Autonomic Nervous System Inhibited Sympathetic Activity Enhanced Parasympathetic Activity Heart Vessels Kidneys ↓ HR ↑ Vasodilation ↓ Stiffness ↑ Diuresis ↓ Renin secretion 2

Rheos Hypertension Pivotal Trial Design Prospective randomized double-blind trial 322 patients at 49 sites 55 roll-in patients / 265 randomized (2:1) Co-primary endpoints Short Term Acute Response Long Term Sustained Response Short Term Procedural AEs Short Term Hypertension Therapy AEs Long Term Device AEs Implant Randomization 6-Month Blinded Evaluation Period 6-Month Blinded Evaluation Period Long-Term Follow-Up N = 181 Group A – Device ON Group A – Device ON N = 84 Group B – Device OFF Group B – Device ON -1 3 6 9 12 (months) 3 3

Key Inclusion Criteria SBP ≥ 160 mmHg DBP ≥ 80 mmHg 24 hour ABPM ≥ 135 mmHg At least one month of maximally tolerated therapy with at least three appropriate antihypertensive medications, including a diuretic

Pivotal Trial Baseline Characteristics Group A (N = 181) Group B (N = 84) Gender 64% Male 55% Male Race 73% Caucasian 78% Caucasian Age (mean years ± sd) 54 ± 11 53 ± 10 BMI (mean kg/m2 ± sd) 33 ± 5 32 ± 6 Antihypertensive Meds (mean # ± sd) 5.2 ± 2 Systolic BP (mean mmHg ± sd) 179 ± 22 176 Diastolic BP (mean mmHg ± sd) 103 ± 16 ± 13 Heart Rate (mean bpm ± sd) 74 ± 14 75

Pivotal Trial Baseline Medications Group A (N = 181) Group B (N = 84) Diuretic 96% 92% Beta Blocker 86% 83% Calcium Channel Blocker 65% 71% ACE Inhibitor 57% 54% ARB 47% 43% Alpha Blocker 12% 18% Sympatholytic 44% Minoxidil 14% 15% 6

1st Endpoint – Short Term Acute Response 20% super-superiority – Responder rate device ON vs. device OFF N = 84 65% 20% A - B 45% TRIAL ASSUMPTIONS N = 181 54% 8% N = 181 N = 84 46% TRIAL RESULTS 70 60 50 40 % of Patients with ≥ 10mmHg SBP Reduction at 6 Months 30 Goal Diff (A-B) >20% 20 10 Month-6 ON Month-6 OFF Month-6 ON - OFF 7

2nd Endpoint – Long-term Sustained Response Percent of Sustained Responders at 12 Months 100 90 88% 80 p-value < 0.001 % of Sustained Responders at 12 months 70 OPC: 65% 60 N = 97 Month-12 ON 8

3rd Endpoint – Short Term Procedure Adverse Events 30-Day Event Free rate 90 Types of Adverse Events 4.4% permanent nerve injury (numbness, dysphagia, dysphonia) 4.8% transient nerve injury 4.4% general surgical complications (86% resolved) 2.6% respiratory complaints (100% resolved) 76% of all adverse events fully resolved OPC: 82% 80 75% 70 % of Patients Event Free at 30 days 60 50 N = 270 30-day Groups A+B 9

4th Endpoint – Short Term HTN Therapy Adverse Events 6-Month Event Free Rate 100 91.7 87.6 90 80 15% + C.I. 72.6 Goal Diff (A-B) < 15% % of Patients Event Free at 6 Months 70 60 p-value < 0.001 N = 170 N= 85 Month-6 OFF Month-6 ON 40% Reduction of Hypertensive Crises, 23% Reduction of Events 10

5th Endpoint – Long Term Device Adverse Events 12-Month Event Free Rate 100 p-value < 0.001 90 88% Types of Adverse Events 2% hypertension-related strokes All other events < 2% 76% of all adverse events fully resolved 80 % of Patients Event Free at 12 Months OPC: 72% 70 60 N = 265 12 Months Groups A+B 11

Endpoint Summary Description Timeframe N p-value Short Term Acute Efficacy 6 months 265 0.97 Long Term Sustained Efficacy 12 months 97 <0.001 Short Term Procedure Adverse Events 30 days 1.00 Short Term BAT Adverse Events Long Term Device Adverse Events 7.7% 0% 20% 87.6 65% 100% 74.8 82% 100% 2.4% -15% 0% 87.2 72% 100% 12 12 12 12

Pre-Specified Ancillary Efficacy Analysis % of Patients at SBP ≤ 140mmHg 60 53% p = 0.005 51% N = 171 N = 81 45 42% N = 172 SBP ≤ 140 mmHg % of Patients 30 24% N = 80 15 Month-6 ON Group A Month-6 OFF Group B Month-12 ON Group A Month-12 ON Group B 13

Pre-specified Echo Sub-Study Long Term Regression in Left Ventricular Hypertrophy 120 117 p-value < 0.01 115 110 LV Mass Index (kg/m2) 105 Left Ventricular Mass Index Red = severely abnormal Lt green = mild to moderately abnormal Dk green = reference range 102 100 95 N = 60 N = 60 90 Baseline 12 Months 14 14

Percent Patients at SBP Goal Additional Observations – Post-Hoc Efficacy Analysis Results at 12 Months and Beyond 81% of patients were responders (SBP ≥ 10 mmHg relative to pre- implant) The average SBP drop at 12 months among responders was 44 mmHg 63% of responders reached blood pressure goal Therapeutic efficacy continued to improve over time: 40 60% 35 54% 43% 30 26 45% SBP Reduction (mmHg) Percent Patients at SBP Goal 20 30% 10 15% Month-6 ON Month-12 ON Month-6 ON Month-12 ON

These data justify further development of BAT Conclusions 3 primary endpoints achieved: long term efficacy, long term device safety, and short term therapy safety 2 primary endpoints not achieved: short term efficacy and procedure adverse events Weight of overall evidence suggests long term efficacy of BAT to reduce blood pressure in resistant hypertension These data justify further development of BAT 16

Moving Forward: Miniaturization to Reduce Procedure Invasiveness 1st Generation CSL New Generation CSL

Investigators and Participating Centers US Mark Passman; University of Alabama, AL Mason Weiss; Apex Cardiology Consultants, CA Fred Weaver; University of Southern California, CA Preston Flanigan; VISOC, CA Fadi Matar; Florida Cardiovascular Institute, FL Harischandra Karunaratne; Florida Hospital Cardiovascular Institute, FL Peter Wassmer; Heart & Vascular Institute, FL Jeffrey Travis; Southeast Regional Research Group, GA Michael Park; Iowa Heart Center, IA George Bakris; University of Chicago, IL Sibu Saha; University of Kentucky, KY Mitchell Weaver; Henry Ford Health System, MI Marcus Rothstein; Washington University, MO Paul van Bemmelen; Temple University, PA Gregory Roberts; Baptist Hospital of East Tennessee, TN Eric Peden; The Methodist Hospital System, TX Paul Kramer; Liberty Hospital, TX Stephen Motew; Novant Clinical research Inst, NC Vasilios Papademetriou; Veteran’s Affairs Medical Center, DC Branislav Schifferdecker; Oklahoma Cardiovascular Research, OK Gregory Trachiotis; GW Medical Faculty Associates, DC James Fogartie; Rex HealthCare, NC Deepak Gangahar; Nebraska Heart Institute, NE Massimo Napolitano; Hackensack University Medical Center, NJ Daichi Shimbo; Columbia University Medical Center, NY John Bisognano; University of Rochester, NY Anthony Comerota; Jobst Vascular Center, OH Eugene Chung; The Lindner Clinical Trial Center, OH Jean Starr; Ohio State University Medical Center, OH Satish Muluk; Allegheny General hospital, PA Paul Casale; Lancaster General Hospital, PA William Todd Bohannon; Scott & White Memorial hosp, TX William Edwards; St Thomas Research Institute, TN James Hermiller; St Vincent Medical group, IN Pat Kelly; Sanford research, SD Michael Koren; jacksonville Center Clinical research, FL Todd Reil; U of Minnesota, MN Europe Peter De Leeuw; University of Maastricht, Netherlands Hermann Haller; University of Hannover, Germany