24-Month Update on AVeVA:Study of the CoveraTM Vascular Covered Stent in the

Treatment of Venous Anastomotic Lesions in AV Grafts

BD-15248

Bart Dolmatch MD, FSIR

The Palo Alto Medical FoundationEl Camino Hospital Mountain View

January 30, 2020

• Bart Dolmatch MD, FSIR

• I have the following potential conflicts of interest:

– Consulting: Becton Dickinson Inc, Merit Medical Systems Inc, Medtronic Inc, Bluegrass Vascular Medical Inc, Black Swan Vascular Inc, Graftworx Inc

Disclosures

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CoveraTM Vascular Covered Stent

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Study Device: CoveraTM Vascular Covered Stent

Configurations and Encapsulations

• Flared & Straight Configurations• ePTFE encapsulated nitinol stent • Diameters: 6-10 mm • Lengths: 40, 60, 80, and 100 mm

(30 mm straight only)

Flared

Straight

Thumbwheel Delivery System:• Sheath compatibility: 8-9 F• Working length: 80 & 120 cm • 0.035” over-the-wire system with

atraumatic tip

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AVeVA: ObjectiveTo assess the CoveraTM Vascular Covered Stent for the

treatment of stenotic lesions at the graft-vein anastomosis of hemodialysis patients dialyzing with an

AV graft.

• Design: Prospective, Multicenter, Non-Randomized, Single-Arm

– 110 patients

– 14 Study Sites in the United States

• Follow-up:

– 24-month data presented today

AVeVA Study Criteria

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Key Inclusion Criteria Key Exclusion Criteria

• Synthetic upper extremity AV access graft implanted for 30 days

• At least one successful dialysis session

• Stenosis ≥ 50% (by visual estimate) at the graft-vein anastomosis with clinical graft dysfunction

• Target lesion(s) ≤ 9 cm in length

• Reference vessel diameter: 5.0 -9.0mm

• Placement in an existing stent or stent graft, or across the elbow joint or in the central veins

Select Patient Demographics & Risk Factors

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All-Treated Covered Stent Group

Number of Patients (ITT), N 110

Mean Age, years + SD 64.3 + 14.0

Male/Female, %/% 45.5/54.5

Mean BMI, kg/m2 + SD 28.7 + 6.6

Mean Time on Dialysis, months + SD 19.7 + 20.0

Clinical Indicators of Access Dysfunction, % (n)*

Pulsatility 57.3 (63)

Decreased Access Blood Flow 23.6 (26)

Elevated Venous Pressure 23.6 (26)

Prolonged Bleeding 20.9 (23)

Diminished or Abnormal Thrill 18.2 (20)

Risk Factor, % (n)

Hypertension 98.2 (108)

Smoker (Current & Former) 8.2%/30.9%

Diabetes (Type 2) 61.8 (68)

Dyslipidemia 56.4 (62)

* Some patients had multiple clinical indicators of access dysfunction

Circuit/Lesion Characteristics & Procedural Details

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Covered Stent Group

Lesion Type (Restenotic), % (n) 71.8 (79)

Outflow Vein, % (n)

Axillary 49.1 (54)

Basilic 40.0 (44)

Brachial 9.1 (10)

Mean Lesion Length, mm + SD 24.1 + 15.3

Mean Baseline Target Lesion Stenosis, % + SD 71.5 + 14.8

Thrombosis at Baseline, % (n) 25.5 (28)

Outflow Vein Diameter, mm + SD 8.5 + 2.0

Graft Diameter, mm + SD 6.8 + 0.7

Procedure

Flared/Straight Stent Graft Configuration, %/% 83.6/16.4

Final Residual Stenosis (post covered stent & post-dilation), % + SD 0.9 + 2.8

Peri-procedural Complications, % (n) 7.3 (8)

Acute Technical Success1/Procedural Success2, %/% 100/100

1Successful deployment to the intended location2Anatomic success (residual stenosis < 30%) and resolution of the pre-procedure clinical indicators of stenosis

Primary Endpoint Analyses

Safety (30 Days): Freedom from a Primary Safety Event

Primary Safety Endpoint(Proportional Analysis)

ITT Group(N= 110)

[90% CI]p-value

Freedom from a Primary Safety Event, (n/N) 96.4% (106/110)[91.9, 98.7]

p=0.002

Efficacy (6 Months): Target Lesion Primary Patency (TLPP)

✓ Greater than the PG of 88% (p-value = 0.002)

Primary Efficacy Endpoint(Proportional Analysis)

Group [90% CI]p-value

Target Lesion Primary Patency, (n/N) 70.3% (71/101)[61.9, 77.7]P<0.0001

✓ Greater than the PG of 40% (p-value <0.0001)

24-Month AVeVA Results:Freedom from Loss of TLPP

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Rates are estimated using the Kaplan-Meier method, and the 95% confidence intervals are estimated using Greenwood’s formula

COVERATM VASCULAR COVERED Stent

71.1%(180 Days)

CoveraTM Covered Stent

54.2%(365 Days)

36.9%(730 Days)

Time Point #of Subjects Left #of Subjects Censored

#of Subjects with TLPP

Failure TLPP Rate [95% CI]*180 Days 70 9 30 71.1% [61.3%, 78.8%]

365 Days 45 19 45 54.2% [43.7%, 63.6%]

730 Days 14 37 58 36.9% [26.6%, 47.1%]

AVeVA Clinical Study 24 months

Secondary Observations through 24 Months• Acute Technical & Procedural Success: 100%• TLPP: 36.9% at (24 months)• Secondary Circuit Patency: 73.6% (24 months)

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AVeVA Summary

This first-in-man study of the CoveraTM vascular

covered stent compared outcomes to

predicted goals from prior similar studies.

Results met or exceeded

predicted safety and efficacy

goals at 6 months.

At 24 months, target lesion patency was 37%

and assisted circuit patency 74%.

12-Month Update AVeNEW Clinical Study:Upper Extremity Venous Outflow Stenosis in AVF

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AVeNEW Clinical Study ObjectiveTo compare CoveraTM Vascular Covered Stent to PTA for treating

stenotic lesions in upper extremity AV fistulae (AVF’s)

• Prospective, Multicenter, Randomized

– 280 patients

– 1:1 randomization of PTA vs PTA/CoveraTM

– 24 International Sites

• Follow-up

– Primary safety end-point at 30 days

– Primary efficacy end-point at 6-month

– 12-month data presented today

– Ongoing through 3 years

COVERA is a trademark of C.R. Bard, a wholly-owned subsidiary of Becton, Dickenson and Company.

AVeNEW Study Criteria

Key Inclusion Criteria Key Exclusion Criteria

• Upper extremity AV fistula

• > 1 successful dialysis session

• Angiographic stenosis ≥ 50%

• Clinical or hemodynamic fistula dysfunction in the venous outflow circuit

• Target lesion(s): ≤ 9 cm in length

• Vessel diameter: 5.0 - 9.0mm

• Lesion across elbow, in cannulation zone, within a stent, or in a thoracic central vein

Patient Demographics

Covered Stent Group PTA Group p-value

Number of Patients (ITT), N 142 138

Mean Age, years + SD 63 + 13.2 62 + 11.5 0.70

Male/Female, %/% 62.7/37.3 60.9/39.1 0.76

Race, % (n) 0.08

Caucasian 70.4 (100) 66.7 (92)

African American 25.4 (36) 26.1 (36)

Mean BMI, kg/m2 + SD 30.8 + 6.3 28.9 + 5.8 0.01

Risk Factor, % (n) 0.54

Hypertension 97.9 (139) 96.4 (133)

Smoker (Current & Former) 43/7 (62) 44.9 (62)

Diabetes (Type 2) 71.1 (101) 68.1 (94)

Congestive Heart Failure, % (n) 24.6 (35) 29.0 (40) 0.41

Coronary Artery Disease, % (n) 32.4 (46) 37.7 (52) 0.35

Peripheral Artery Disease, % (n) 16.9 (24) 21.0 (29) 0.38

Circuit/Lesion Characteristics & Procedural Details

Covered Stent Group PTA Group

Outflow Vein, % (n)

Cephalic 73.9 (105) 68.8 (95)

Basilic 24.6 (35) 30.4 (42)

Lesion Location, % (n)

Cephalic Arch 54.9 (78) 50.7 (70)

Cephalic Vein Outflow 17.6 (25) 17.4 (24)

Basilic Vein Swing Point & Outflow 20.4 (29) 23.9 (33)

Mean Lesion Length, mm + SD 28.8 + 17.4 29.7 + 17.0

Flared/Straight Stent Graft Configuration, %/%

46.1/53.9 na

Final Mean Residual Stenosis, % + SD 2.2 + 5.8 15.0 + 18.0

Dialysis Resumed at 30 Days, % (n) 96.5 (137) 97.8 (135)

Acute Technical Success1 100% na

Acute Procedural Success2 98.6% 98.4%

1Successful deployment to the intended location2Anatomic success (residual stenosis < 30%) and resolution of the pre-procedure clinical indicators of stenosis

Primary Endpoints

Freedom from a Primary Safety Event (30 days)*

Covered Stent Group PTA Group Difference [90% CI] p-value1

95.0%(133/140)

96.4%(132/137)

-1.4%[-7.3%, 4.6%]

0.002

Target Lesion Primary Patency (TLPP) at 6 months^Covered Stent Group

[95% CI]PTA Group

[95% CI]Hazard Ratio

[95% CI]p-value2

78.7%[70.8%, 84.7%]

47.9%[38.7%, 56.6%]

0.322[0.213, 0.519]

<0.001

1 Farrington Manning non-inferiority test2 One-sided p-value calculated using the log-rank test

Safety with COVERA was non-inferior to PTA

TLPP with COVERA was superior to PTA^ Kaplan-Meier Analysis

*Binary/proportional Analysis

Freedom from Loss of TLPP: 6 and 12 monthsSu

rviv

al P

rob

abili

ty

57.5%(48.4 , 65.6%)

21.2%(14.2% , 29.2%)

Time to Event (Days)

78.7%(70.8% , 84.7%)

47.9%(38.7% , 56.6%)

p < 0.001

Covered Stent

PTA Alone

180 Days

365 Days

Rates are estimated using the Kaplan-Meier method, and the 95% confidence intervals are estimated using Greenwood’s formula

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The CoveraTM Vascular Covered Stent was

superior to the PTA control with respect to TLPP

at 6 & 12 months

12-Month Outcomes

Follow-up at 12 Months: 83.9% (235/280 patients)

OutcomesCovered Stent

GroupPTA Group Difference

Target Lesion Primary Patency (TLPP)(proportional analysis), (n/N)

55.6% 20.2% 35.5%

Target Lesion IPF (IPF-T) 1, days + SD259.8 + 115.4

160.6+ 87.3

99.1 + 13.4

1 IPF-T: Index of Patency – Target Lesion; the time from the initial study procedure to study completion or access abandonment divided by the number of reinterventions at the target lesion to maintain vascular access.

12-month Exploratory Subgroup Analysis of TLPP by Lesion Characteristic

Sub

gro

up

s

Sample Size HR [95% CI]

Favors COVERATM

VASCULAR COVERED STENTFavors PTA

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Freedom from Loss of ACPP (through 12 months)

Rates are estimated using the Kaplan-Meier method, and the 95% confidence intervals are estimated using Greenwood’s formula

Surv

ival

Pro

bab

ility

28.9%(21.2, 36.9%)

17.7%(11.3%, 25.4%)

Time to Event (Days)

50.7%(42.0%, 58.8%)

43.8%(34.7%, 52.5%)

p = 0.02Covered Stent

PTA Alone

One-sided p-value calculated using the log-rank test

180 Days

365 Days

AVeNEW Summary

AVeNEW Trial follow-up is ongoing through 3 years

This study prospectively compared outcomes

using a covered stent versus PTA to treat AV

fistula stenosis.

At 12 months, target lesion and circuit

patency were superior for the

covered stent group.

COVERA™ Vascular Covered Stent

US Indication For Use: The COVERA™ Vascular Covered Stent is indicated for use in hemodialysis patients for the treatment of stenoses in the venous outflow of an arterio-venous (AV) fistula and at the venous anastomosis of an ePTFE or other synthetic AV graft.

Contraindications: There are no known contraindications for the COVERA™ Vascular Covered Stent.

Warnings: This device should be used only by physicians who are familiar with the complications, side effects, and hazards commonly associated with dialysis access shunt revisions and endovascular procedures.· DO NOT use in patients with known hypersensitivity to nickel-titanium or tantalum. · Placing a covered stent across a vessel side branch may impede blood flow and hinder or prevent future procedures. · DO NOT place a flared covered stent with the flared end in a straight vessel segment since this may lead to flow turbulences. · Covered stent placement beyond the ostium of the cephalic vein into the axillary/subclavian vein may hinder or prevent future access.

Precautions: Prior to covered stent implantation refer to the sizing table and read the Instructions for Use. · The covered stent (implant) cannot be repositioned after total or partial deployment. · Once partially or fully deployed, the covered stent cannot be retracted or remounted onto the delivery system. · During covered stent release DO NOT hold the 30 cm long distal catheter assembly segment as it must be free to move and slide into the white stability sheath. · The effect of placing the device across an aneurysm or a pseudo-aneurysm has not been evaluated. · The effect of using the device in central veins has not been evaluated. · The effect of placing the device across a previously placed bare metal stent has not been evaluated. · The effect of placing the device across the antecubital fossa has not been evaluated. · The effect of using the device in pediatrics has not been evaluated. · The effects of direct cannulation of the covered stent have not been evaluated. Notify the patient that the covered stent should not be directly cannulated for hemodialysis and that applying pressure to the implant area should be avoided. · The device has not been tested for use in an overlapped condition with a bare metal stent or covered stent. · Higher deployment force may be encountered with longer length covered stents. · The device has not been tested for tracking and deployment around an AV loop graft.

Potential Complications and Adverse Events: Complications and Adverse Events associated with the use of the COVERA™ Vascular Covered Stent may include the usual complications associated with endovascular stent and covered stent placement and dialysis shunt revisions.

Please consult product labels and package inserts for indications, contraindications, hazards, warnings, cautions, and information for use.

COVERA™ Vascular Covered Stent

EU Indication For Use: The Covera™ Vascular Covered Stent is indicated for the treatment of stenoses in the upper extremity venous outflow of patients dialyzing with an arterio-venous (AV) access graft or fistula.

Contraindications: There are no known contraindications for the COVERA™ Vascular Covered Stent.

Warnings: This device should be used only by physicians who are familiar with the complications, side effects, and hazards commonly associated with dialysis access shunt revisions and endovascular procedures. • DO NOT expose the covered stent to temperatures higher than 680 °F (360 °C). ePTFE decomposes at elevated temperatures, producing highly toxic decomposition byproducts. • DO NOT use the device if packaging / pouch is damaged. • The Covera™ Vascular Covered Stent device is supplied STERILE and is intended for SINGLE USE ONLY. DO NOT RESTERILIZE AND/OR REUSE the device. Reuse, resterilization, reprocessing and/or repackaging may create a risk to the patient or user, may lead to infection or compromise the structural integrity and/or essential material and design characteristics of the device, which may lead to device failure, and/or lead to injury, illness, or death of the patient. Reusing this medical device bears the risk of cross-patient contamination as medical devices – particularly those with long and small lumina, joints, and/or crevices between components – are difficult or impossible to clean once body fluids or tissues with potential pyrogenic or microbial contamination have had contact with the medical device for an indeterminable period of time. The residue of biological material can promote the contamination of the device with pyrogens or microorganisms which may lead to infectious complications or death. • DO NOT use in patients with uncorrectable coagulation disorders. DO NOT use in patients with bacteremia or septicaemia and/or evidence of fistula or graft infection. • DO NOT use in patients that cannot be adequately pre-medicated. • DO NOT use in patients who have a known allergy or sensitivity to contrast media. • DO NOT use in patients with known hypersensitivity to nickel-titanium or tantalum. • DO NOT use in patients whose AV access grafts have been implanted less than 30 days or in an immature fistula. • DO NOT use the device in patients where full expansion of an appropriately sized PTA balloon catheter could not be achieved during pre-dilation with an angioplasty balloon. • Placing a covered stent across a vessel side branch may impede blood flow and hinder or prevent future procedures. • Covered stent placement beyond the ostium of the cephalic vein into the axillary/subclavian vein may hinder or prevent future access. • DO NOT place a flared covered stent with the flared end in a straight vessel segment since this may lead to flow turbulences. • The device has not been tested for tracking and deployment around an AV loop graft.

Precautions: Prior to covered stent implantation refer to the sizing table (Table 1) and read the Instructions for Use. • The delivery system is not intended for any use other than covered stent deployment. • The covered stent (implant) cannot be repositioned after total or partial deployment. • Once partially or fully deployed, the covered stent cannot be retracted or remounted onto the delivery system. • If unusual resistance is met during covered stent system introduction, the system should be removed and another covered stent system should be used. • DO NOT introduce or manipulate the delivery system without an appropriately sized guidewire and without fluoroscopic guidance. • DO NOT use a kinked delivery system. • During covered stent release DO NOT hold the 30 cm long distal catheter assembly segment as it must be free to move and slide into the white stability sheath. • Careful attention by the operator is warranted to mitigate the potential for distal migration of the covered stent during deployment. • The covered stent cannot be post dilated beyond its labelled diameter. The flared distal end does not require post dilation. • The safety and effectiveness of the device when placed across an aneurysm or a pseudo-aneurysm has not been evaluated. • The safety and effectiveness of the device when used in central veins has not been evaluated. • The safety and effectiveness of the device when placed across a previously placed bare metal stent has not been evaluated. • The safety and effectiveness of the device when placed across the antecubital fossa has not been evaluated. • The safety and effectiveness of the device when used in pediatrics has not been evaluated. • The effects of direct cannulation of the covered stent have not been evaluated. Notify the patient that the covered stent should not be directly cannulated for hemodialysis and that applying pressure to the implant area should be avoided. • The device has not been tested for use in an overlapped condition with a bare metal stent or covered stent. • Higher deployment force maybe encountered with longer length covered stents.

Potential Complications and Adverse Events: Complications and Adverse Events associated with the use of the Covera™ Vascular Covered Stent may include the usual complications associated with endovascular stent and covered stent placement and dialysis shunt revisions.

Please consult product labels and package inserts for indications, contraindications, hazards, warnings, cautions, and information for use.

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Disclaimers

• The speaker’s presentation today is on behalf of BD Peripheral Intervention. The physician has been compensated by BDPI for the time and effort to present this information.

• Any discussion regarding BD products during the presentation today is limited to information that is consistent with BD labeling for those products.

• Please consult product labels and inserts relevant to your geography for indications, contraindications, hazards, warnings, cautions, and instructions for use.

• The opinions and clinical experiences presented herein are for informational and educational purposes only. The results presented may not be predictive for all patients.

• Results may vary depending on a variety of experimental and clinical parameters. Individual results may vary depending on a variety of patient specific attributes.

• The views and opinions and treatments describe in this presentation represent those of the presenting physician. Please consult product labeling for appropriate use.

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Thank you

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Company. Illustrations by Mike Austin. All Rights Reserved. Bard Peripheral Vascular, Inc. |

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BD-15228

24-Month Update on AVeVA:Study of the CoveraTM Vascular Covered Stent in the

Treatment of Venous Anastomotic Lesions in AV Grafts

BD-15248

Bart Dolmatch MD, FSIR

The Palo Alto Medical FoundationEl Camino Hospital Mountain View

January 30, 2020