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William E. Cohn, MDDirector, Center for Technology Innovation

Texas Heart Institute, St. Luke’s Episcopal HospitalProfessor of Surgery

Baylor College of MedicineProfessor of Bioengineering, University of Houston

TEXAS HEART INSTITUTE

at St. Luke’s Episcopal Hospital

TEXAS HEART INSTITUTE

at St. Luke’s Episcopal Hospital

ASDIN Orlando, Feb 2015

Endovascular AVFistula Creation

with magnetic catheters

In the interest of maintaining academic integrity,I would like to disclose the following conflicts…

“I am a founder and board member of TVAMedical, an early stage medical devicecompany that has developed thetechnology described in this presentation,and in which I have a financial interest.”

This presentation describes devices andprocedures that are not approved bythe FDA for clinical use in the United

States

Hemodialysis Market

1 USRDS 2012 Annual Report (2010 data)2 Gilbertson DT, et al. Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc

Nephrol. 2005 Dec;16(12):3736-413 Meichelboeck, W 7th International Congress of Vascular Access Society, Istanbul, May 2011

Key Growth drivers:• Diabetes• Hypertension• Cardiovascular disease

CMS spends $47 billion per year on end-stage renal disease

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3-4 hours of hemodialysis 4 times/weekcan maintain the anuric patient…

…but every patient needs a reliable wayto be connected to the dialysis machine

Dual lumen central venous catheters areeasy to use and provide great access…

Dual lumen central venous catheters areeasy to use and provide great access…

…but catheter infections and sepsisremain serious limitations

Prosthetic AV graftsunder the skin arerelatively easy to

construct…

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…but they are easilyinfected and often

develop thrombosis,requiring multiplere-interventions

There is overwhelming consensus that thebest option is a native arterio-venous fistula

There is overwhelming consensus that thebest option is a native arterio-venous fistula 1 Rates reported are per patient per year. Mortality at 3 years

2 Perl J., et al. Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival. JASN June 1,2011 vol. 22 no. 6 1113-1121

3 Woo K., et al. Influence of Vascular Access Type on Sex and Ethnicity-Related Mortality in Hemodialysis-Dependent Patients. PermJ 2012 Spring;16(2):4-9

AV fistulas are clinically andeconomically superior

34%

40%

73%-84%

SurgicalAV Fistula

AV Graft

CentralVenousCatheter

Mortality Infection rate Reoperation rate Annual Cost

0.180.52

0.390.61

1.45 2.82

Infection SepsisSeries

0.47

1.10

0.86

Series

$64K

$79K

$90K

Challenges with Surgical AV Fistulas

Primary failure rate2-4 30-60%

Mean maturation time1 4-9 months

Average time to usable AVF3* 5-12months

Average interventions for successfulAVF1 2-3

Occlusions (thrombosis)5,6 17-25%

* Mean time to useable AV fistula defined as time from referral for vascular access to dialysis1 Kimball, et al. Efficiency of the kidney disease outcomes quality initiative guidelines for preemptive vascular access in an academic setting. Journal of Vascular Surgery. Vol 54, No 3. 20112 Peterson W., et al. Disparities in Fistula Maturation Persist Despite Preoperative Vascular Mapping. Clin J Am Soc Nephrol. 2008 March; 3(2):437-4413 Lee, T. et al. Tunneled Catheters in Hemodialysis Patients: Reasons and Subsequent Outcomes. American Journal of Kidney Diseases, Vol 46, No 3 (September), 2005: pp. 501-5084 Biuckians A, Scott EC, Meier GH, et al. The natural history of autologous fistulas as first-time dialysis access in the KDOQI era. J Vasc Surg 2008; 47:415–4215 Dember LM, Beck GJ, Allon M, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008; 299:2164–21716 Stolic R. Most Important Chronic Complications of Arteriovenous Fistulas for Hemodialysis. Med Princ Pract. 2012

AV Fistulas are operator dependent, have a high failure rate,require frequent interventions to maintain functionality, andoften take months before they are useable for hemodialysis

17

Diagnosis and management of acute traumatic arteriovenous fistulaKamal Nagpal, MS MRCS,1 Kamran Ahmed,MRCS,1 and RJ Cuschieri, FRCS2,Int J Angiol. 2008 Winter; 17(4): 214–216.

Penetrating trauma occasionally results in AV fistula formation

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Endovascular Catheter-based AVF

Advantages

• Percutaneous, non-surgical

• No implant left behind

• No incision so reduced woundinfections and complications

• Facilitates AV fistula placementby interventional andendovascular specialties inoutpatient setting

• Potential to improve AVFsuccess rates:

– No vessel trauma

– No surgical anastomosis

Investigational device. This product is not approved for marketing by FDA and is not available for commercial sale.

Human deep venous anatomy

Paired magnetic catheterswith electrosurgical cutting capabilities

Venous catheter

Arterial catheter

RF electrode

Paired magnetic catheterswith electrosurgical cutting capabilities

Paired magnetic catheterswith electrosurgical cutting capabilities

Strong rare-earth NdFeBo magnets

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Venous catheter introduced and advanced to site chosen for AVF Arterial catheter introduced and advanced to same location

Catheters rotated to allow magnetic alignment Venous electrode deployed and energized for 1.2 seconds with RF

Arterial injection shows widely patent AVF without extravasation 24 hours post-procedure

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1 month post procedure 3 months post procedure

3 months post procedure 3 months post procedure

1 year post procedure 1 year post procedure

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1 year post procedure 2 years post procedure

2 years post procedure Multiple Cannulation Options

40

Forearmcephalic +upper armcephalic

Forearmcephalic +basilic

Forearm cephalic + median cubital / basilic

FLEX StudyStudy Design and Baseline Characteristics

Total

(N=33)

Average Age, yrs (SD) 51.0 (11.4)

Male (%) 20/33 (61%)

Average BMI (SD) 24.3 (3.8)

BMI > 25 (%) 10/33 (30%)

Diabetes (%) 19/33 (58%)

PVD (%) 2/33 (6.1%)

Primary endpoints:

• Technical success

• Fistula patency and veinmaturation at 8-12 weeks withangiography and ultrasound

• Adverse events

Secondary endpoint:

• Creation of usablehemodialysis access (at least75% of dialysis sessions for atleast 4 weeks duration)

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FLEX Study Summary

Clinical Results

• Demonstrated clinicalsuccess

• 97% technical fistulasuccess (32/33)

• 96% patency at 6 months+

• Avg. procedure time 49min

• 27 patients initiateddialysis or dialysis ready

• 25 patients > 1 monthdialysis

• Avg. 58 days to AVFmaturation

• 1 serious device-relatedadverse event; mitigatedwith procedure change*

N=26 N=28N=33

.+ 1 patient developed venous hypertension at 37 days from a central vein stenosis. Patient receivedballoon angioplasty. EndoAVF occluded

at 106 days.*1 patient developed pseudoaneurysm during procedure due to arm motion from neuromuscular stimulation. Pseudoaneurysm was resolved

with thrombin injection. A procedure modification to limit arm motion mitigated this risk in subsequent cases.

Data reported per-protocol, not intent to treat

N=26

97% 96% 96% 96%

60%

65%

70%

75%

80%

85%

90%

95%

100%

Technicalfistula success

@ 24 hrs

AVF patency @6 months

Dialysisinitiation or

ready

Dialysis withendoAVF > 1

month

SuccessfulAVFs

Thrombosis17-25%AVF Failures

30-60%

OtherFailures

Successfulendo AVFs

96%

Endo-AVF compares favorably with Surgical AVF

Catheter-basedendoAVF

Surgical AVF

Data for surgical AVF is based on the 60% AVF failure rate at 4 months reported in the DAC study.endoAVF data is based on 6 month data (n=26)

Endo AVFs are usable > 4 months faster

179

58

0

20

40

60

80

100

120

140

160

180

200

Time to AVF Maturation

sAVF

endoAVF

68% reduction in time to auseable fistula

PRIMARY OBJECTIVE

To characterize the safety of the FLEX system (6 months) in up to 70 patients with CKD

who require a hemodialysis vascular access

STUDY DESIGN

Multi-center, prospective, single-arm study. Canada, Australia, and New Zealand

PRIMARY ENDPOINT

Percentage of patients who experience one or more serious device-related adverse events

during the first 6 months following AVF creation

ADDITIONAL DATA COLLECTED

Fistula efficacy: The percentage of AV fistulas that can provide prescribed hemodialysisaimed to achieve a spKt/V of > 1.2 or Urea Reduction Ratio (URR) of > 65% using 2needle cannulation for ≥ 67% of the dialysis sessions over 4 consecutive week period within 6 months of fistula creation

Primary patency

Interventions

Ultrasound flow rates

Novel Endovascular Access Trial

PRIMARY OBJECTIVE

To characterize the safety of the FLEX system (6 months) in up to 70 patients with CKD

who require a hemodialysis vascular access

STUDY DESIGN

Multi-center, prospective, single-arm study. Canada, Australia, and New Zealand

PRIMARY ENDPOINT

Percentage of patients who experience one or more serious device-related adverse events

during the first 6 months following AVF creation

ADDITIONAL DATA COLLECTED

Fistula efficacy: The percentage of AV fistulas that can provide prescribed hemodialysisaimed to achieve a spKt/V of > 1.2 or Urea Reduction Ratio (URR) of > 65% using 2needle cannulation for ≥ 67% of the dialysis sessions over 4 consecutive week period within 6 months of fistula creation

Primary patency

Interventions

Ultrasound flow rates

Novel Endovascular Access Trial 1st NEAT study patient @ 6 months

48

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“NEAT” patient with Dr. Lok and Dr. Rajan

Conclusions• Percutaneous catheter-based creation of AV fistulas is a new

technique that has the potential to change the way dialysisaccess is created

• The technique is safe, reproducible, and prescriptive

• By putting this technique in the hands of interventional andendovascular specialist, earlier and more frequent creation of AVFmay decrease dependence on central venous catheters.

• Early clinical data suggests that in-situ catheter-based AVFs maybe superior to surgical AVF with respect to patency, need for re-intervention, and time to usability.

• Additional study is needed.

• Initiating North American/Australian/New Zealand study.Charmaine Lok M.D. principle investigator; Dheeraj Rajan M.D.Co-PI