IN.PACT BTK Update

Thomas Zeller, MDUniversity Heart Center Freiburg – Bad KrozingenBad Krozingen, Germany

Faculty Disclosure

For the 12 months preceding this presentation, I disclose the following types of financial relationships:• Honoraria received from: Abbott Vascular, BIBA Medical, Biotronik, Boston Scientific Corp.,

Cook Medical, Efemoral, Gore & Associates, Medtronic, Philips-Spectranetics, Shockwave, Veryan

• Consulted for: Boston Scientific Corp., CSI, Gore & Associates, Medtronic, Veryan, Intact Vascular, Shockwave, Bayer, Vesper Medical

• Research, clinical trial, or drug study funds received from (institution): Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical, Gore & Associates, Medtronic, Philips, Terumo, TriReme, Shockwave, Med Alliance, Intact Vascular, B. Braun; CSI, Boston Scientific, University of Jena

• Common stock: QT Medical

Thomas Zeller, MD

Brand names are included in this presentation for participant clarification purposes only. No product promotion should be inferred.

IN.PACT DEEP TRIAL

IN.PACT BTK – Where we are comingfrom

IN.PACT DEEP Trial TimelineFully Enrolled with Follow-up Completed

Through 5 Years

First subject enrolled

Sep. 2009

Last subject enrolled Jul. 2012

Voluntary withdrawal of Amphirion DCBDec. 2013

1-year data presented at LINC Jan. 2014

1-year data Published in JACC Oct. 2014

Study Closure Aug. 2018

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

5-year data presents at AMP Aug. 2019

IN.PACT DEEP Trial Overview

• Prospective, Multicenter, Randomized• 358 Subjects enrolled from September 2009 to July

2012, across 13 Centers and 6 European Countries

1. Third-party safety monitoring, CEC, and external data monitoring services provided by Genae Associates, Antwerp, Belgium. (CEC endpoints adjudicated through2 years and site-reported years 3-5. All-cause death adjudicated to 5 years)

2. Angiographic and Wound Core lab: SynvaCor, Springfield, IL, US (Angiographic core lab through 1 year, wound core lab through 2 years)

Objective: Evaluate the safety and efficacy of the IN.PACT Amphirion DCB vs PTA for infrapopliteal revascularization in patients with CLI

• Independent Data Safety Monitoring Board (DSMB) and Clinical Events Committee (CEC)1

• Independent Angiographic and Wound Core Labs2

• Subjects followed through 5 yearsZeller T. et al. JACC 2014

Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: 5 Year Follow-up

1. CD-TLR defined as any TLR associated with deterioration of Rutherford category and/or an increase in the size of pre-existing wounds and/or occurrence of new wounds.

2. All- cause death Adjudicated by an independent CEC through 5 years

• Clinically-driven TLR (CD-TLR)1Efficacy

• Composite of freedom from CD-TLR, major amputation and all-cause death2

Safety

Zeller T. et al. JACC 2014Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial Key EligibilityKey Inclusions

• Rutherford Class 4-6• 18-85 yrs + life expectancy >1yr• Target vessel: Infrapopliteal (incl

Tibioperoneal Trunk) above the ankle1

• RVD 2-4 mm• Single or multiple lesions (≥70%)

of any length• At least one non occluded crural

vessel with documented run-off to the foot either direct or through collaterals

Key Exclusions• Planned major index limb

amputation• Inflow impaired or non re-

established• Failure to cross the target lesion

with a 0.014” guide wire• In-stent restenosis• Thrombus or aneurysm

Zeller T. et al. JACC 2014Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial Design

Randomized Controlled Trial

Full Clinical Cohort (n=358)Randomized 2:1

Clinical Outcomes through 5 Years

IN.PACT Amphirion

DCB(n = 239)

PTAControl

(n = 119)

Zeller T. et al. JACC 2014Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Baseline CharacteristicsBaseline Clinical Characteristics IN.PACT DCB

(N=239 Subjects)PTA

(N=119 Subjects) P-value

Age (years) 73.3 ± 8.2 71.7 ± 9.9 0.106Male 76.2% 70.6% 0.304Hypertension 89.5% 89.1% 1.000Diabetes mellitus 75.7% 68.9% 0.204History of smoking 51.9% 49.6% 0.737Previous amputation 23.4% 17.6% 0.222Previous target limb revascularization

32.2 % 21.8 % 0.047

Previous revascularization location: PA

10.9% 4.2% 0.045

Previous revascularization location: TPT 7.1% 0.8% 0.009

Rutherford category

0.5814 14.2% 17.6%5 84.1% 77.3%6 1.7% 4.2%

Zeller T. et al. JACC 2014Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Baseline CharacteristicsLesion Characteristics

IN.PACT DCB(N=239 Subjects)(N=351 Lesions)

PTA (N=119 Subjects)(N=181 Lesions)

P-value

Target Lesion Mean Length (cm ±SD) 10.2 ± 9.1 12.9 ± 9.5 0.002

Target Lesion RVD (mm) 2.462 ± 0.691 2.405 ± 0.555 0.304Impaired Inflow (≥50% core lab reported) 40.7% 28.8% 0.035

Wound Depth (mm) 0.8 ± 1.3 1.8 ± 3.8 0.040

Procedural Characteristics

Pre-dilatation 90.5% 36.0% <.001

Inflation Time (sec ± SD) 166.0 ± 138.4 137.7 ± 111.3 0.010Max Inflation Pressure (atm ±

SD) 9.5 ± 2.4 10.3 ± 4.6 0.010

Post Procedural Dissections 12.3% 19.2% 0.046Zeller T. et al. JACC 2014

Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Effectiveness Outcomes

Kaplan-Meier through 60 months

IN.PACT DCB(N=239

Subjects)

Standard PTA(N=119

Subjects)

P-value

CD-TLR1 29.1% (50) 24.0% (22) 0.406Any TLR2 31.4% (55) 21.6% (22) 0.236

1. Defined as any TLR associated with deterioration of Rutherford category and/or an increase in the size of pre-existing wounds and/or occurrence of new wounds

2. Any repeat percutaneous intervention or bypass surgery performed on the target limb

Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Safety Outcomes

Kaplan-Meier through 60 months

IN.PACT DCB(N=239

Subjects)

Standard PTA(N=119

Subjects)

P-value

Primary Safety Endpoint Composite through 60-Months1

59.8% (128) 57.5% (61) 0.309

All-cause Death 39.4% (74) 44.9% (45) 0.727Major Target Limb Amputation2 15.4% (30) 10.6% (9) 0.108

CD-TLR2 29.1% (50) 24.0% (22) 0.406

1. Defined as composite of all-cause death, major amputation and CD-TLR2. Defined as Surgical removal of tissue in the ipsilateral limb of the target segment with resection point above the

trans metatarsal bones.3. Defined as any TLR associated with deterioration of Rutherford category and/or an increase in the size of pre-

existing wounds and/or occurrence of new wounds. Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Safety Outcomes

Kaplan-Meier Freedom from All-Cause Death through 5 Years

No statistically significant difference in mortality at any time point

Zeller T. et al. JACC CI 2020

IN.PACT DEEP Trial: Multivariable Analysis

Predictors of All-Cause Death through 5 Years P-valueAge (yrs) <.001Rutherford Category (>4 vs. <=4) 0.002Previous Peripheral Revascularization (Y vs. N) 0.026

After Forcing Dose into the Model: Paclitaxel is Still Not a PredictorPTX Dose(Lower vs. 0) 0.214PTX Dose(Upper vs. 0) 0.428PTX Dose(Mid vs. 0) 0.713

Zeller T. et al. JACC CI 2020

Conclusion• The IN.PACT DEEP Trial is the only 5-year data

available for the use of a DCB below the knee• When comparing DCB to PTA, there was no

significant difference in TLR, amputation or all-cause mortality rates through 5 years in this challenging CLI population

• Predictors of mortality included age, Rutherford >4 and previous revascularization but not paclitaxel dose

• Further studies with next generation devices are needed to provide evidence and identify best treatment options for this complex disease

IN.PACT BTK STUDYOverview

• Prospective, multicenter, randomized (1:1) feasibility study• Independent Duplex Ultrasound Core Lab1, Angiographic Core Lab2, Data

Safety Monitoring Board and Clinical Events Committee (CEC)3

• 50 CLI patients with CTOs enrolled in 9 sites across 5 European Countries and followed through 36 months4

• No formal hypothesis test is specified for this feasibility study. Descriptive statistics will be reported.

Purpose: To assess the safety and effectiveness of the IN.PACT 014 paclitaxel-coated DCB versus conventional PTA for the treatment of patients with chronic total occlusions (CTOs) in the infrapopliteal arteries

*Sponsored by Medtronic plc1. Vascore DUS Core Laboratory, Boston, MA, US 2. Beth Israel Deaconess Medical Center, Boston, MA, US3. Data Safety Monitoring Board and Clinical Events Committee services provided by Syntactx, Belgium4. Sponsor intends to extend follow-up through 60 months

17Footer Here IN.PACT BTK STUDYKEY ELIGIBILITY CRITERIA

Inclusion Exclusion• Rutherford Class 4 and 5• Infrapopliteal arteries above the

ankle • Single or multiple total occlusions (total length ≥ 40 mm) • Infection grade 0-2 and ischemia grade 2-3 according to WIfI• RVD 2-4 mm • Evidence of adequate distal run-off through the foot

• Planned target limb amputation• Inflow impaired or non re-established• Prior stents(s) or bypass surgery in the target vessel• Previous DCB within 6 months prior to procedure• Infection grade 3 and ischemia grade 0-1 according to WIfI• Documented active osteomyelitis, excluding the phalanges

§ Late Lumen Loss (LLL) 9 months after the index procedure

Effectiveness Endpoint

§ Composite of 30-day freedom from device-and procedure-related mortality and 9-month freedom from major target limb amputation and freedom from clinically-driven TLR

Safety Endpoint

IN.PACT BTK STUDYENDPOINTS

IN.PACT BTK STUDYCURRENT Study STATUS

Study Device – IN.PACT 014 BTK drug-coated balloon

Enrollment and 9-month follow-up complete