The Vessix Global Clinical Program REDUCE-HTN: REINFORCE Michael Weber, MD

Michael Weber, MD Disclosures Consulting: Boston scientific, Medtronics, Ablative Solutions, ReCor, Novartis Research: Medtronics, Boston Scientific, ReCor, Ablative Solutions, Novartis, Boehringer Ingelheim

Boston Scientific Renal Denervation REDUCE-HTN Clinical Series Multicenter, Non-randomized, feasibility CE Mark and TGA Approval N = 128 Multicenter, Non-randomized, post market surveillance N = 100 Multicenter, randomized N = TBD Multicenter, Non-randomized, single cohort REDUCE-HTN FIM REDUCE-HTN PMS TReatment of rEsistant hypertension using a raDiofrequency percUtaneous transluminal angioplasty CathetEr REDUCE-HTN: REINFORCE REDUCE-HTN Global Pivotal REDUCE-HTN Regional Approvals

REDUCE-HTN FIM+PMS Vessix™ Renal Denervation System Balloon-based technology 4 - 7 mm diameters Helical pattern of bipolar RF electrodes All electrodes are activated simultaneously 30 second treatment time Temperature-control algorithm for energy delivery at 68°C One button operation 7F compatible (Vessix Reduce™ Catheter) * Vessix System is an investigational device and not available for sale in the US. CE Mark received 2012.

REDUCE-HTN FIM+PMS Reduction in Office Blood Pressure The REDUCE-HTN FIM + PMS results showed significant and sustained blood pressure reductions through 24 months P<.0001 for each timepoint vs baseline. Error bars represent 95% confidence bounds. Sievert , H. TCT 2015. * Vessix System is an investigational device and not available for sale in the US.

Safety Profile Through 24 Months Serious Adverse Events Procedure related serious adverse events (within 6M of procedure) Event Number of events Number of patients Onset Hematoma 1 0 days Vomiting Bilateral flank pain 1 day Femoral artery thrombus Pseudoaneurysm at access site 3 days Access site infection 2 6 and 31 days Renal artery stenosis requiring treatment 6 months Occurrence > 6 months post-procedure 4 patients had hypertensive emergencies unrelated to medication or non-compliance Adjudicated as possibly related to the device because renal artery stenosis could not be ruled out due to lack of recent renal artery imaging Sievert , H. TCT 2015. * Vessix System is an investigational device and not available for sale in the US.

REDUCE-HTN: REINFORCE Study Principal Investigators: US IDE Study REDUCE-HTN: REINFORCE Study  Renal Denervation Using the Vessix Reduce™ Catheter and Vessix™ Generator for the Treatment of HyperTensioN: REINFORCE Principal Investigators: Martin B. Leon, MD Michael Weber, MD * Vessix System is an investigational device and not available for sale in the US.

US IDE Study The REDUCE-HTN:REINFORCE study: Intends to demonstrate the effects of renal denervation in the absence of potentially confounding antihypertensive medications Includes an antihypertensive medication wash-out phase Similar to pharmaceutical study designs looking at early efficacy (Phase II studies)

REDUCE-HTN: REINFORCE Study Overview Prescreen N=100 at up to 20 US sites Informed Consent Washout Period (4 weeks) Final Eligibility Assessment OSBP ≥150 and ≤180 mmHg ASBP ≥135 and ≤170 mmHg Vessix RDN Masked Procedure N=100 2:1 Randomization (RDN:Control) Primary Follow-up Period – No Meds (unless rescue) Visits: 2, 4 and 8 weeks Primary Efficacy Assessment (ASBP) – 8 weeks Procedural Safety Assessments – 4 weeks Secondary Follow–up Period – Med Additions per Protocol Visits: 12, 16, 20 and 24 weeks Secondary Efficacy Assessment (ASBP) – 24 weeks Safety Assessment – 24 weeks Long-term Follow–up through 3 years

REDUCE-HTN: REINFORCE Study Overview Phase II Pilot study (n=100) with sham control (2:1 randomization) in early stage HTN ABPM at baseline, 4, 8, 24 and 52 weeks Primary (powered) efficacy assessment at 8 weeks Drug washout prior to randomization in all patients Minimizes confounding due to medication changes Rescue therapy allowed by protocol, but will become a study endpoint Treatment Assignment: Test = renal denervation Control = renal angiogram only (no active therapy) Medication burden in test and control arms assessed during secondary follow-up period Safety assessment at 6M

Barriers to Randomization (after consent) Initial study sites were interventionalist-based and did not have direct access to hypertension patients, needed referrals or community advertising – Recently, experienced hypertension investigator sites have been added to the trial Average 24-hour ASBP must be >135 mmHg and <170 mmHg after screening – several patients lost through this criterion OSBP must be ≥150 mmHg and ≤180 mmHg based on an average of 3 blood pressure measurements after screening – another source of patient loss Eligible patients have declined randomization (often due to uncertain support of referring physicians) Unsuitable renal artery anatomy

Conclusion REDUCE-HTN: REINFORCE is a trial designed to isolate and measure the effects of renal denervation The Company has committed to completing enrollment for this trial in 2017 and will reach the study’s primary endpoint soon afterwards NOTE: The Vessix Catheter for renal denervation is not approved for use in the United States. Boston Scientific makes no claims in the United States regarding this product.

IMPORTANT INFORMATION: These materials are intended to describe common clinical considerations and procedural steps for the on-label use of referenced technologies as well as current standards of care for certain conditions. Of course, patients and their medical circumstances vary, so the clinical considerations and procedural steps described may not be appropriate for every patient or case. As always, decisions surrounding patient care depend on the physician’s professional judgment in light of all available information for the case at hand. BSC does not promote or encourage the use of its devices outside their approved labeling. The presenter’s experience with BSC products may not be interpreted or relied upon to support clinical claims about BSC devices or product comparison claims regarding BSC and competitive devices. The experiences of other users may vary. Results from case studies are not predictive of results in other cases. Results in other cases may vary.

REINFORCE Study Details REDUCE-HTN: REINFORCE Randomization 2:1 (Test:Control) Test: Renal Denervation Control: Masked Procedure (renal angiogram) Key Inclusion Criteria ≥18 and ≤75 OSBP ≥150 mmHg and ≤180 mmHg based on an average of 3 office-based blood pressure measurements Avg 24-hour ASBP ≥135 mmHg and ≤170 mmHg For each kidney, a main renal artery, with or without accessory renal arteries, with diameter ≥3.0 mm and ≤7.0 mm and length ≥20.0 mm Primary Efficacy Assessment Mean reduction in average 24-hour ambulatory systolic blood pressure (ASBP) at 8 weeks post randomization Safety Assessments Safety Assessments analyzed at all follow-up time points: All-cause death Renal failure Hospitalization for hypertensive crisis Hospitalization due to severe hypotension/syncope Additional Safety assessments completed at 4 weeks and 6 months All Safety Assessments will be adjudicated by an independent Clinical Events Committee

Future of Renal Denervation Managing Variability Solutions Stable baseline (careful drug wash-in phase) Ambulatory BP (fully automated and documented) OBP Readings Optimized catheter effects Consistent operator technique Catheter and Technique Phase II: Placebo controlled with no meds RCT (Stage I-II) Phase III: Placebo controlled with standardized meds RCT (Uncontrolled HTN) Drug changes & Compliance * Vessix System is an investigational device and not available for sale in the US.

Boston Scientific Renal Denervation REDUCE-HTN Clinical Series Multicenter, Non-randomized, feasibility CE Mark and TGA Approval N = 128 Multicenter, Non-randomized, post market surveillance N = 100 Multicenter, randomized N = TBD Multicenter, Non-randomized, single cohort REDUCE-HTN FIM REDUCE-HTN PMS TReatment of rEsistant hypertension using a raDiofrequency percUtaneous transluminal angioplasty CathetEr REDUCE-HTN: REINFORCE REDUCE-HTN Global Pivotal REDUCE-HTN Regional Approvals

Boston Scientific Renal Denervation RELIEVE Clinical Series Renal Denervation - Chronic Kidney Disease Prospective, single-center RCT, 1:1 - 20pts Status – Enrolling IMPROVE-HF Prospective, randomized, 1:1 – 70pts Status - Enrolling REDUCE-CAD – HTN with CHF, AF, or Diabetes Prospective, observation study – 100 pts Kidney Disease RELIEVE Clinical Series European Investigator Sponsored Research Collaboration for expanded disease states Heart Failure HTN with Comorbidities