TYRX use. .pptx

Ppi

1. SIGNIFICANT REDUCTION of cied * infections 1 TYRX ™ absorbable antibacterial envelope *Cardiac Implantable Electronic Device. 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med . 2019;380(20):1895-1905.

2. 2 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 The Challenge & The Impact The Solution — TYRX Absorbable Antibacterial Envelope * TYRX WRAP-IT Study Results The largest randomized, controlled, global CIED trial The Economic Value TYRX™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. *The TYRX Envelope is intended to hold a CIED in order to provide a stable environment.

3. 3 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 The Challenge & The Impact The Solution — TYRX Absorbable Antibacterial Envelope * TYRX WRAP-IT Study Results The largest randomized, controlled, global CIED trial The Economic Value TYRX™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. *The TYRX Envelope is intended to hold a CIED in order to provide a stable environment.

4. > 3x mortality risk at 1 year 7 22–56% of patients are considered to be at an increased risk for CIED infection 4,5 4 The Challenge and the Impact CIED INFECTIONS 1–4% of CIED patients have been shown to develop infection 2,3 $56K–83K range of average hospital cost to treat an infection *5-8 $6K–31K range of average margin loss to treat an infection *7 $2K average patient out-of-pocket costs *7 9–18 DAYS average days in hospital *6,7 An estimated 1.5 million patients worldwide receive a cardiac implantable electronic device (CIED) every year. 1 Infections are a serious CIED procedure-related complication, associated with significant morbidity, mortality, and cost. TYRX WRAP-IT Study Overview | December 2020 Mond HG, et al. Pacing Clin Electrophysiol . 2011;34:1013-1027. Tarakji KG, et al. Arrhythm Electrophysiol Rev . 2016;5:65-71. Tarakji KG, et al. N Engl J Med . 2019;380:1895-1905. Mittal S, et al. Heart Rhythm . 2014;11:595-601. Eby E,  et al. EP Europace . 2018;20:i106. Sohail MR, et al. Arch Intern Med . 2011;171:1821-1828. Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280. Lopatto , et al. Antibacterial Envelope is Associated with Medical Cost Savings in Patients at High Risk for Cardiovascular Implantable Electronic Device Infection. Poster presented at ACC 2017 Scientific Sessions. Data on file with Medtronic plc. *Based on analyses from U.S. patients.

5. 5 mortality risk at 1 year IS > 3x for patients with a major cied infection 1 1 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:3008280. Mortality Rate (%) Hazard ratio through 12 months: 3.41 (95% Cl: 1.81–6.41); P-value: < 0.001) Hazard ratio through all follow-up: 2.30 (95% Cl: 1.29–4.07); P-value: 0.004) 3 6 9 12 15 18 21 24 27 30 33 36 67 6836 59 6680 54 6546 52 6361 46 6142 39 4963 30 4373 26 3528 19 2808 10 1613 6 1157 1 411 1 253 Infection No infection Number at Risk Months from Index Procedure Patients with major infections within first 12 months Patients with no major infection within first 12 months 16% 5% 11% 19% 25% 18% 40% 30% 20% 10% 0% TYRX WRAP-IT Study Overview | December 2020 * Analysis included only patients with successful CIED procedures. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Title Impact of CIED Infection: A Clinical and Economic Analysis of the WRAP-IT Study Objective To evaluate the clinical and economic impact of CIED infection from prospectively collected, longitudinal data. Study Design Pre-specified analysis of WRAP-IT Study patients with major CIED infections N = 6,903 patients * at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters

6. 6 TYRX WRAP-IT Study Overview | December 2020 Reducing CIED infection AND READMISSION As defined by the CDC, effective July 17, 2020, people of any age with the following conditions are at increased risk of severe illness from COVID-19 1 : 1 Wortham JM, et al. Characteristics of Persons Who Died with COCID-19 — United States, February 12-May 18, 2020. Centers for Disease Control and Prevention MMWR. 2020;69(28):923-929. Available at: https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6928-H.pdf. Accessed September 29, 2020. During a pandemic, reducing CIED infections and readmissions is important so patients have fewer medical needs, thereby reducing risk of exposure for themselves and their clinicians. Frequently Seen Cancer Chronic kidney disease COPD Obesity (BMI ≥ 30) Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies Type 2 diabetes mellitus Infrequently Seen Immunocompromised state (weakened immune system) from solid organ transplant Sickle cell disease Now more important than ever

7. 7 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 The Challenge & The Impact The Solution — TYRX Absorbable Antibacterial Envelope * TYRX WRAP-IT Study Results The largest randomized, controlled, global CIED trial The Economic Value TYRX™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. *The TYRX Envelope is intended to hold a CIED in order to provide a stable environment.

8. 8 TYRX WRAP-IT Study Overview | December 2020 TYRX™ Envelope DEMONSTRATED CIED STABILIZATION, REDUCED INFECTION 1-9 1 Tarakji KG, et al. N Engl J Med . 2019;380:1895-1905. 2 Huntingdon Life Sciences Study TR-2011-054. 3 Osoro M, et al. Pacing Clin Electrophysiol . 2018;41:136-142. 4 Bloom HL, et al. Pacing Clin Electrophysiol . 2011;34:133-142. 5 Mittal S, et al. Heart Rhythm . 2014;11:595-601. 6 Kolek MJ, et al. J Cardiovasc Electrophysiol . 2015;26:1111-1116. Now available with up to 12 months shelf life. Locally delivered minocycline and rifampin 10 Multifilament knitted mesh fully absorbs in approximately 9 weeks 10, 11 Polymer-controlled antibiotic elution, sustained for 7 days 10 Minimum Inhibitory Concentration 7 Shariff N, et al. J Cardiovasc Electrophysiol . 2015;26:783-789. 8 Henrikson CA, et al. JACC Clin Electrophysiol . 2017;3:1158-1167. 9 Kolek MJ, et al. Pacing Clin Electrophysiol . 2013;36:354-361. 10 Huntingdon Life Sciences Study TR-2013-001. 11 Sinclair Labs Study D13599.

9. 9 TYRX WRAP-IT Study Overview | December 2020 Demonstrated CIED stabilization 1,2 TYRX ™ ENVELOPE Implantable devices such as CIEDs and Implantable Neurostimulators (INSs) elicit a host response which triggers formation of a fibrous capsule around the device. This response is typically observed approximately 30 days after implantation. 1 In vivo models demonstrate that the porous mesh of the TYRX Envelope enables dense fibrous connective tissue ingrowth immediately after implant which firmly anchors the device in 7–14 days. 2   The TYRX Envelope is present for ~9 weeks (63 days), long after tissue ingrowth has taken place to anchor the device and stabilize the implant. 2,3 The TYRX absorbable material has a significant advantage over non-absorbable materials due to the absence of any permanent implant material, which could become a nidus for bacterial infection in the long term. 4,5 *Huntingdon Life Sciences Study TR-2011-054 (Photos from in vivo animal implants).  † Photo courtesy of Francois Philippon , M.D. Laval University Hospital, Quebec City, Canada 1 Klinge U, et al. Biomaterials . 1999;20:613-623.  2 Ferrando JM, et al. World J Surg . 2001;25:840-847.  3 Huntingdon Life Sciences Study TR-2011-054.   4 Huntingdon Life Sciences Study TR-2013-001. 5 Sinclair Labs Study D13599. TYRX Envelope Explant at 1 day * Fibrous Connective Tissue Response TYRX Envelope Explant at 7 days * Immediate Tissue Ingrowth Anchors Device TYRX Envelope Absorbed at 5 weeks † TYRX Absorbed After Pocket Formation

10. 10 TYRX WRAP-IT Study Overview | December 2020 Polymer controlled elution TYRX ™ ENVELOPE Proprietary combination of polymer with antibiotic agents minocycline and rifampin Tyrosine-based polymer controls the drug release Minimum inhibitory concentration (MIC) is reached within 2 hours, and maintained for a minimum of 7 days 1 1 Huntingdon Life Sciences Study TR-2013-001. TYRX Envelope

11. 11 TYRX WRAP-IT Study Overview | December 2020 Unique combination of minocycline and rifampin TYRX ™ ENVELOPE This unique combination of minocycline and rifampin p rotects a gainst the 2 b acteria that a ccount for > 70% of a ll CIED infections 1-7 50 45 40 35 30 25 20 15 10 5 C oa g ( - ) staph S aureus G r a m ( - ) rods Ot h e r F u n g i Poly- m ic r o b i al Cu l t u r e (-) % of CIED Infections 1 1 Wisplinghoff H, et al. Clin Infect Dis . 2004;39:309-317. 2 Klug D, et al. Circulation . 2007;116:1349-1355. 3 Da Costa A, et al. Circulation . 1998;97:1791-1795. 4 De Oliveira JC, et al. Circ Arrhythm Electrophysiol . 2009;2:29-34. 5 NNIS System Report. Am J Infect Control . 2004;32:470-485. 6 Lekkerkerker JC, et al. Heart . 2009;95:715-720. 7 Chua JD, et al. Ann Intern Med . 2000;133:604-608. 43 26 8 8 9 3 TYRX Envelope TYRX Envelope

12. 12 TYRX WRAP-IT Study Overview | December 2020 Localized delivery of Synergistic, broad-spectrum antibiotics TYRX ™ Envelope TYRX reaches a minimum inhibitory concentration (MIC) within 2 hours of implant, maintained for a minimum of 7 days 2 Uses <5% of recommended oral daily dosage, non-systemic 1,2 Medium size envelope: 8.0 mg rifampin, 5.1 mg minocycline Large size envelope: 11.9 mg rifampin, 7.6 mg minocycline MINOCYCLINE activity against CIED infection pathogens 1 RIFAMPIN activity against CIED infection pathogens 1 GRAM (+) BACTERIA GRAM (-) BACTERIA GRAM (+) BACTERIA GRAM (-) BACTERIA S aureus S pneumoniae E coli M catarrhalis S aureus (including MRSA) S epidermidis C jeikeium S pneumoniae H influenzae M catarrhalis MECHANISM OF ACTION Bacteriostatic; inhibits protein synthesis MECHANISM OF ACTION Bacteriocidal; inhibits DNA - dependent RNA polymerase activity 1 Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy . 39th ed . 2012: Antimicrobial Therapy Inc.; Hyde Park, VT . 2 Huntingdon Life Sciences Study TR-2013-001. GRAM (+) BACTERIA GRAM (-) BACTERIA MECHANISM OF ACTION Bacteriostatic; inhibits protein synthesis GRAM (+) BACTERIA GRAM (-) BACTERIA MECHANISM OF ACTION Bacteriocidal; inhibits DNA - dependent RNA polymerase activity

13. 13 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 The Challenge & The Impact The Solution — TYRX Absorbable Antibacterial Envelope * TYRX WRAP-IT Study Results The largest randomized, controlled, global CIED trial The Economic Value TYRX™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. *The TYRX Envelope is intended to hold a CIED in order to provide a stable environment.

14. 14 TYRX WRAP-IT Study Overview | December 2020 The largest randomized, controlled, global CIED trial 1 TYRX ™ WRAP-IT STUDY 181 centers 25 countries 776 implanters 6,983 patients at an increased risk for pocket infection * * Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. U.S. AND CANADA : 5,143 LATIN AMERICA : 5 EUROPE AND MIDDLE EAST : 1,696 ASIA PACIFIC : 139 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

15. 15 TYRX WRAP-IT Study Overview | December 2020 STUDY AIM 1 TYRX ™ WRAP-IT Study To evaluate the safety and effectiveness of the TYRX Envelope in reducing CIED infections in addition to standard infection prevention strategies TYRX ™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

16. 16 TYRX WRAP-IT Study Overview | December 2020 Study Design & Patient Selection 1 TYRX ™ WRAP-IT Study Study Design Prospective, randomized, controlled, multicenter, global trial Randomized 1:1 to TYRX Envelope vs Control (no TYRX) Independent Clinical Events Committee Electrophysiologists & Infectious Disease specialists Independent Data Monitoring Committee Independent validation of results The Cleveland Clinic Coordinating Center for Clinical Research Patient Selection Included patient at increased risk of pocket infection due to Any CIED generator replacement, system upgrade, or revision* Initial CRT-D implantation* Excluded patients at highest risk of systemic infection due to Hemodialysis or peritoneal dialysis Immunosuppressive agents (chronic oral or ≥ 20 mg of prednisone) Recent (< 12 months) or existing infection TYRX ™ Envelope *Medtronic CIEDs Only.

17. 17 TYRX WRAP-IT Study Overview | December 2020 CIED Infections DefinITIONS 1 TYRX ™ WRAP-IT STUDY The TYRX WRAP-IT Study defined CIED infections as: Superficial cellulitis with wound dehiscence, erosion, or purulent drainage, or Deep incisional or generator pocket infection Persistent bacteremia, or Endocarditis Major CIED infections are defined as those resulting in one or more of the following: CIED system removal Any invasive procedure (e.g., pocket opened) without system removal Extended antibiotic therapy if the subject is not a candidate for system removal Death TYRX ™ Envelope Note : All other CIED infections including superficial incisional SSIs that meet the CDC criteria, independent of the time from surgery, were defined as minor CIED infections unless they met the major CIED infection criteria. 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

18. 18 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 TYRX ™ WRAP-IT STUDY 61 % reduction of pocket infections 1 40 % reduction of major CIED infections, * meeting the primary objective 1 SAFETY ENDPOINT MET No increased risk of complications with use of TYRX through 12 months 1 *Primary endpoint included CIED infections requiring system extraction or revision, long-term antibiotic therapy with infection recurrence, or death within 12 months of the CIED procedure. TYRX ™ Envelope Conclusion Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. 1 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. THE NEW ENGLAND JOURNAL OF MEDICINE

19. 19 TYRX WRAP-IT Study Overview | December 2020 40% reduction of major infections * with TYRX ™ Envelope 1 TYRX ™ WRAP-IT STUDY Title Antibacterial Envelope to Prevent Infections of Cardiac Implantable Devices Objective To evaluate the safety and effectiveness of the TYRX Envelope in reducing the risk of CIED (Cardiac Implantable Electronic Device) infection. Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,983 patients at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters *Primary endpoint included CIED infections requiring system extraction or revision, long-term antibiotic therapy with infection recurrence, or death within 12 months of the CIED procedure. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Major CIED Infection Rate (%) 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

20. 20 TYRX WRAP-IT Study Overview | December 2020 61% reduction of pocket infections with TYRX ™ Envelope 1 TYRX ™ WRAP-IT STUDY *Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Major CIED Pocket Infection Rate (%) 75% of initial major CIED infections were pocket infections.  Title Antibacterial Envelope to Prevent Infections of Cardiac Implantable Devices Objective To evaluate the safety and effectiveness of the TYRX Envelope in reducing the risk of CIED (Cardiac Implantable Electronic Device) infection. Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,983 patients at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

21. 21 TYRX WRAP-IT Study Overview | December 2020 Use of Tyrx ™ envelope did not increase complication risk *1 TYRX ™ WRAP-IT STUDY * Procedure and system-related complications through 12 months. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Complication Rate (%) Prespecified secondary analysis for non-inferiority, as treated When excluding the primary endpoint major infections, the 12-month Kaplan-Meier complication event rates were 5.7% Envelope vs. 5.9% Control. Title Antibacterial Envelope to Prevent Infections of Cardiac Implantable Devices Objective To evaluate the safety and effectiveness of the TYRX Envelope in reducing the risk of CIED (Cardiac Implantable Electronic Device) infection. Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,983 patients at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

22. 22 TYRX WRAP-IT Study Overview | December 2020 Reduction in Major CIED Infections is Consistent Across Sub-groups 1 TYRX ™ WRAP-IT STUDY The subgroup analysis was conducted to test for interaction among various baseline variables for the primary end point through 12 months. 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

23. Control 1.5% 23 Significant Reduction in Pocket Infections with TYRX ™ envelope through follow-up 1 TYRX WRAP-IT STUDY 1 Mittal S, et al. The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial: Long-term follow-up. Heart Rhythm . July 2020;17(7):1115-1122. Data are from the per-protocol cohort. Patients were followed for an average of 20.7 ± 8.5 months. < 6 months average time to pocket infection. 82% of initial major CIED infections were pocket infections in the control group. Title The WRAP-IT Study: Long-term Follow-up Objective To evaluate the safety and efficacy of the TYRX Envelope through all follow-up (36 months). Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,800 patients * at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters * Per protocol analysis included only patients who received their randomized treatment. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Envelope 0.6% Hazard ratio through all follow-up: 0.41 (95% Cl: 0.23–0.72) P-value 0.002 TYRX WRAP-IT Study Overview | December 2020 5% 4% 3% 2% 1% 0% 3 6 9 12 15 18 21 24 27 30 33 36 3,429 3,371 3,336 3,283 3,257 3,220 3,158 3,134 3,033 3,034 2,454 2,449 2,180 2,143 1,760 1,730 1,403 1,375 810 786 567 579 193 212 127 122 Control Envelope Number at Risk Months from Index Procedure Major CIED Pocket Infection Rate (%)

24. 24 Significant effect against pocket infections due to staph with tyrx ™ envelope 1 TYRX WRAP-IT STUDY 1 Sohail MR, et al. JACC Clin Electrophysiol . 2020. In press. DOI: 10.1016/j.jacep.2020.07.021 . Title Reduced CIED Infections with an Antibacterial Envelope: Microbiologic Analysis of the WRAP-IT Study Objective To characterize the long-term effects of the envelope on the clinical presentation and microbiology of major infections. Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,800 patients * at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters * Per protocol analysis included only patients who received their randomized treatment. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Data represent positive cultures of major CIED pocket infections in 24 control and 6 envelope patients, and classification of events are not mutually exclusive. Of the major CIED pocket infections 3 control and 0 envelope patients were not assayed, and 15 control and 11 envelope patients had negative cultures. Frequency by Patient Frequency by Pathogen Staphylococcus S. aureus S. ludgdunensis S. epidermidis CoNS Gram Positive P. Acnes Corynebacterium species Gram Negative E. coli P. aeruginosa K. pneumonia Pseudomonas species Serratia species E. cloacae Fungi C. albicans Control Envelope Control Envelope Control Envelope Control Envelope Hazard ratio for Staph infections: 0.24 (95% Cl: 0.08–0.71) P-value: 0.01 8 1 7 3 1 2 1 1 2 1 1 1 1 1 1 1 1 1 TYRX WRAP-IT Study Overview | December 2020

25. 25 Tyrx™ envelope recommended to reduce cied infection 1 Ehra international consensus document 1 Blomström -Lundqvist C, Traykov V, Erba PA, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace . 2020;22(4):515-549. European Heart Rhythm Society published an international consensus document on how to prevent, diagnose and treat CIED infections TYRX Envelope recommended for: WRAP-IT study population Patients with other high-risk factors Recommendation provided with a ‘ Green Heart ’ (i.e. should do this), based upon randomized, controlled trial data from the WRAP-IT study The EHRA Consensus Document is endorsed by the following: European Heart Rhythm Association (EHRA) Heart Rhythm Society (HRS) Asia Pacific Heart Rhythm Society (APHRS) Latin American Heart Rhythm Society (LAHRS) International Society for Cardiovascular Infectious Diseases (ISCVID) European Society of Clinical Microbiology and Infectious Diseases (ESCMID) European Association for Cardio-Thoracic Surgery (EACTS) TYRX WRAP-IT Study Overview | December 2020

26. 26 TYRX WRAP-IT Study Overview | December 2020 SIGNIFICANT REDUCTION OF CIED INFECTIONS 1 The Challenge & The Impact The Solution — TYRX Absorbable Antibacterial Envelope * TYRX WRAP-IT Study Results The largest randomized, controlled, global CIED trial The Economic Value TYRX™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905. *The TYRX Envelope is intended to hold a CIED in order to provide a stable environment.

27. 27 CIED Infection is costly to the hospital reimbursement may not cover the FULL cost of infection-related care Hospital Cost Margin Loss $56K–83K range of average hospital cost to treat an infection *1-4 $6K–31K range of average margin loss to treat an infection *1 TYRX WRAP-IT Study Overview | December 2020 Sohail MR, et al. Arch Intern Med . 2011;171:1821-1828 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280. Eby EL,  et al. J Med Econ. 2020 Apr 22;1-8. doi : 10.1080/13696998.2020.1751649. Lopatto , et al. Antibacterial Envelope is Associated with Medical Cost Savings in Patients at High Risk for Cardiovascular Implantable Electronic Device Infection. Poster presented at ACC 2017 Scientific Sessions. *Patients treated for CIED infections in United States hospitals. $56k $83k ($6k) ($31k)

28. 28 TYRX WRAP-IT Study Overview | December 2020 TYrX envelope is a cost-effective therapy to reduce CIeD infection FOR THE WRAP-IT STUDY POPULATION 1 TYRX ™ Envelope Cost-effectiveness Analysis — tool to indicate which interventions provide the highest ”value for money.” 1 1 World Health Organization. Cost effectiveness and strategic planning (WHO-CHOICE). Available at: https:// www.who.int /choice/description/importance/ en /. Accessed May 1, 2020. 2 Wilkoff BL, et al. Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial. Circ Arrhythm Electrophysiol . 2020;13(10):e008503. doi:10.1161/CIRCEP.120.008503. 3 Anderson JL, et al. Circulation . 2014;129:2329-2345. TYRX WRAP-IT Study Cost-effectiveness Analysis 2 Based on costs and patient outcomes in the United States healthcare system Aligns with ACC/AHA practice guideline on cost/value methodology 3 Cost-effectiveness ratio well below the willingness to pay threshold of $150,000 per quality-adjusted life-year

29. 29 TYRX WRAP-IT Study Overview | December 2020 International consensus document recommends tyrx ™ envelope INCREASED RISK 2 (Randomized, Controlled Trial Data) > 1.0% major CIED infection rate through 12 months 40% reduction of major CIED infection and 61% reduction of pocket infection with TYRX HIGHEST RISK (Real-world Data) 1-4% major CIED infection rate through 12 months 3 70-100% reduction of major CIED infection with TYRX †4-9 † Studies included the non-absorbable antibacterial envelope. CIED Infection Risk CRT-D Increased * Increased * Highest ICD Low Increased * Pacemaker/ CRT-P Low Increased * Initial Procedure Replacement Revision Upgrade Dialysis Immunosuppressive Agents Recent Infection 3   Tarakji KG, et al. Arrhythm Electrophysiol Rev . 2016;5:65-71. 4 Bloom HL, et al. Pacing Clin Electrophysiol . 2011;34:133-142. 5 Mittal S, et al. Heart Rhythm . 2014;11:595-601. 6 Kolek MJ, et al. J Cardiovasc Electrophysiol . 2015;26:1111-1116. 7 Shariff N, et al. J Cardiovasc Electrophysiol . 2015;26:783-789. 8 Henrikson CA, et al. JACC Clin Electrophysiol . 2017;3:1158-1167. 9 Kolek MJ, et al. Pacing Clin Electrophysiol . 2013;36:354-361. * Included in the WRAP-IT Study patient cohort. Considerations for patient selection include use of TYRX to hold a CIED securely in order to provide a stable environment. for the wrap-it study population and patients with highest risk of cied infection 1 1 Blomström -Lundqvist C, Traykov V, Erba PA, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace . 2020;22(4):515-549. 2 Tarakji KG, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019;380(20):1895-1905.

30. 30 TYRX WRAP-IT Study Overview | December 2020 Better outcomes, better value. It’s achievable, together. TYRX ™ Envelope Medtronic actively supports program education and rollout Coordinate activation to drive program awareness Reimbursement information designed to assist customer in identifying Qualifying Events Discuss program performance throughout the contract term TYRX Outcomes Protection Program* 1 2 3 4 5 PARTICIPATING FACILITY Contracted facility where patient is admitted for qualifying event QUALIFYING EVENT Patient with a Medtronic CIED + TYRX Envelope admitted for CIED pocket infection within 12 months of implant REBATE AMOUNT $10,000 rebate payment per qualifying event REBATE CAP Up to 50% of CRM purchases, not to exceed $50,000 over 12-month rebate period CONTRACT TERM The contract will continue for two years + * Participation in the TYRX Outcomes Protection Program requires a fully executed agreement and is subject to those terms. See your contract documents or ask your Medtronic representative for complete terms and details.

31. 31 TYRX WRAP-IT Study Overview | December 2020 The chain of evidence is complete for the tyrx ™️ envelope demonstrated by wrap-it study results The Consequence of CIED Infection 1 > 3x mortality risk at 1 year $56–83k range of average cost to treat an infection $6k–31k range of average margin loss to treat an infection 1 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280. 2 Tarakji KG, et al. N Engl J Med . 2019;380(20):1895-1905. 3 Blomström -Lundqvist C, et al. Europace . 2020;22(4):515-549. 4 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13(10):e008503. TYRX Technology Proven Outcomes 2 40% reduction of major CIED infections 61% reduction of pocket infections No increased risk of complications Recommended by International Consensus 3 ‘Green Heart” for WRAP-IT population and for high risk factors Is Cost-effective 4 For the WRAP-IT population Aligned with ACC/AHA practice guidelines

32. Appendix

33. 33 TYRX WRAP-IT Study Overview | December 2020 Baseline Characteristics Between Groups 1 TYRX ™ WRAP-IT STUDY Characteristic Envelope (N = 3,495) Control (N = 3,488) Age, (years) [Mean ± SD] 70.0 ± 12.6 70.1 ± 12.4 Female (%) 997 (28.6%) 976 (28.0%) BMI (%) [Mean ± SD] 29.1 ± 6.1 29.2 ± 6.3 Diabetes 1,080 (30.9%) 1,085 (31.1%) Renal dysfunction 585 (16.8%) 554 (15.9%) Baseline Medications     Antiplatelets 2,007 (57.5%) 1,972 (56.6%) Anticoagulants 1,377 (39.5%) 1,390 (39.9%) Antibiotics 36 (1.0%) 37 (1.1%) Immunosuppressive * 48 (1.4%) 85 (2.4%) Insulin 348 (10.0%) 375 (10.8%) Oral antidiabetic 615 (17.6%) 620 (17.8%) *No significant differences between groups except for the use of immunosuppressive agents (p=0.001); standardized difference does not suggest imbalance. 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med . 2019;380(20):1895-1905.

34. 34 TYRX WRAP-IT Study Overview | December 2020 Balanced Procedure Characteristics Between Groups 1 TYRX ™ WRAP-IT STUDY Characteristic Envelope (N = 3,495) Control (N = 3,488) Infection Management Strategy *     Peri-procedure antibiotic 3,402 (98.6%) 3,413 (98.7%) Post-procedure antibiotic 987 (28.6%) 1,058 (30.6%) Pocket wash 2,539 (73.6%) 2,610 (75.5%) CIED Low Power †     Pacemaker 723 (20.7%) 709 (20.3%) CRT-P 133 (3.8%) 157 (4.5%) CIED High Power †     ICD 964 (27.6%) 909 (26.1%) CRT-D 1,675 (47.9%) 1,713 (49.1%) Procedure attempted, no CIED 2 (0.1%) 3 (0.1%) No procedure attempted 44 (1.3%) 31 (0.9%) *Counts and percentages reflect subjects with procedure attempts. † Device type planned at randomization. **Envelope group patients with successful CIED procedure and TYRX implant attempt by 646 implanters. Very low cross-over rate (0.7% Control; 2.3% Envelope) 99.7% implant procedure success rate with TYRX** 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med . 2019;380(20):1895-1905.

35. 35 TYRX WRAP-IT Study Overview | December 2020 effect sustained with tyrx ™ Envelope through follow-up 1 TYRX ™ WRAP-IT STUDY † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. Title Antibacterial Envelope to Prevent Infections of Cardiac Implantable Devices Objective To evaluate the safety and effectiveness of the TYRX Envelope in reducing the risk of CIED (Cardiac Implantable Electronic Device) infection. Study Design Randomized 1:1 (TYRX vs. no TYRX) clinical trial (RCT) of CIEDs N = 6,983 patients at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection . N Engl J Med . 2019;380(20):1895-1905. Major CIED Infection Rate (%) Secondary Endpoint: Major CIED Infections All Follow-up. P-value shown was not adjusted for multiple comparisons. After the prespecified adjustment for multiple comparison was done, the adjusted p-value was not significant. Patients were followed for an average of 20.7±8.5 months. Months from Procedure

36. 36 Impaired Quality of life through 6 months for patients with a major CIED infection 1 TYRX ™ WRAP-IT STUDY 1 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280. Mean EQ-5D Utility EQ-5D Assessment Time Baseline Infection Diagnosis 1 Month Post-infection 3 Months Post-infection 6 Months Post-infection 0.90 0.85 0.80 0.75 0.70 0.65 P = 0.004 P = 0.001 P = .020 P = 0.423 All P-values compared to baseline Dots represent the mean and error bars represent the 95% CI. Title Impact of CIED Infection: A Clinical and Economic Analysis of the WRAP-IT Study Objective To evaluate the clinical and economic impact of CIED infection from prospectively collected, longitudinal data. Study Design Pre-specified analysis of WRAP-IT Study patients with major CIED infections N = 6,903 patients * at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters * Analysis included only patients with successful CIED procedures. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. TYRX WRAP-IT Study Overview | December 2020

37. 37 $56k u.s. hospital cost to treat major cied infection, substantial margin loss 1 TYRX ™ WRAP-IT STUDY Costs (U.S. Dollars) Hospital Admission Cost -$200,000 -$100,000 $0 $100,000 $200,000 Margin Medicare FFS Margin Medicare Advantage Mean = $55,547 Median = $45,206 Mean = ( $30,828) Median =-($18,664) Mean = ( $6,055) Median =$6,392 Box-and-whisker plots represent distribution of data as follows: solid line = median; dashed line = mean; box = interquartile range; whiskers = minimum and maximum within 1.5 times interquartile range; dots = outliers (outside of 1.5 times interquartile range). TYRX WRAP-IT Study Overview | December 2020 Title Impact of CIED Infection: A Clinical and Economic Analysis of the WRAP-IT Study Objective To evaluate the clinical and economic impact of CIED infection from prospectively collected, longitudinal data. Study Design Pre-specified analysis of WRAP-IT Study patients with major CIED infections N = 6,903 patients * at an increased risk for pocket infection † Patients received standard-of-care pre-op antibiotic prophylaxis 25 countries 181 centers 776 implanters * Analysis included only patients with successful CIED procedures. † Included patients for CIED revision, generator replacement, upgrade, or de novo CRT-D. 1 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280.

38. 38 TYRX WRAP-IT Study Overview | December 2020 Participating centers TYRX ™ WRAP-IT Study 1. Edward Schloss, MD, The Lindner Research Center, US 2. Jose Gallastegui , MD, Clearwater Cardiovascular & Interventional Consultants, US 3. Robert A. Pickett, MD, Saint Thomas Research Institute LLC, US 4. Rudolph Evonich , MD, Upper Michigan Cardiovascular Associates, US 5. Francois Philippon, MD, IUCPQ - Institut Universitaire de Cardiologie et de Pneumologie, Canada 6. Janet McComb , MD, The Newcastle upon Tyne Hospitals, UK 7. Steven Roark, MD, Cardiology Associates of Gainesville, US 8. Denise Sorrentino, MD, Iowa Heart Center, P.C. (West Des Moines), US 9. Darius Sholevar , MD, Lourdes Cardiology Services, US 10. Khaldoun Tarakji, MD MPH, Cleveland Clinic, US 11. Edmond Cronin, MD, Hartford Hospital, US 12. Brett Berman, MD, Chula Vista Cardiac Center, US 13. David Riggio, MD, AZ Arrhythmia Consultants, US 14. Mauro Biffi, MD / Igor Diemberger , MD, Policlinico Sant' Orsola , Malpighi, Italy 15. Hafiza Khan, MD, Baylor Research Institute, US 16. Marc Silver, MD, WakeMed Heart and Vascular, US 17. Jack Collier, MD, Oklahoma Heart Hospital, US 18. Zayd Eldadah , MD, MedStar Heart and Vascular Institute, US 19. David Justin Wright, MD, Liverpool Heart and Chest Hospital, UK 20. JoEllyn Moore, MD, Minneapolis Heart Institute, US 21. Kamel Addo, MD, Mount Carmel East, US 22. R. Chris Jones, MD, Centennial Heart Cardiovascular Consultants, US 23. Robert Schaller, MD, University of Pennsylvania, US 24. Joaquin Martinez- Arraras , MD / Ismaile Abdalla, MD, Amarillo Heart Group, US 25. Ziad Issa, MD, Prairie Education & Research Cooperative, US 26. Calum Redpath, MD, Ottawa Heart Institute, Canada 27. Jean Moubarak , MD, Hamot Medical Center / Medicor Associates, US 28. Surinder Kaur Khelea , MD, Institute Jantung Negara, Malaysia 29. Berit Thornvig Philbert , MD, Rigshospitalet , Denmark 30. Timothy A.Simmers , MD, Catharina Ziekenhuis , Netherlands 31. Lucas V.A. Boersma, MD, St. Antonius Ziekenhuis , Netherlands 32. Panagiotis Korantzopoulos , MD, University Hospital of Ioannina, Greece 33. John Love, MD, Maine Medical Center, US 34. Ralph Augostini , MD, The Ohio State University, US 35. Havard Keilegavlen , MD / Svein Faerestrand , MD, Haukeland Universitetssjukehus , Norway 36. Suneet Mittal, MD, The Valley Hospital, US 37. Scott Wiggins, MD, Ark-La-Tex Cardiology, US 38. Jeff Healey, MD, Hamilton General Hospital, Canada 39. Brian Ramza , MD, Mid America Heart Institute, US 40. Riple Hansalia , MD, Jersey Shore University Medical Center, US 41. Chad Brodt, MD / Paul Wang, MD, Stanford Hospital & Clinics, US 42. Attila Mihalcz , MD, Universitatsklinikum Krems , Austria 43. Daniel Gras, MD, Nouvelles Cliniques Nantaises , France 44. Ulrika Maria Birgersdotter -Green, MD, University of California San Diego, US 45. Ethan Fruechte , MD / Douglas Hodgkin, MD, North Memorial Health Heart & Vascular Center, US 46. Daniel Lustgarten , MD, Fletcher Allen Health Care, US 47. Gery Tomassoni , MD, Lexington Cardiac Research Foundation, US 48. Fozia Ahmed, MD, Central Manchester University Hospital NHS, UK 49. Cecilia Rorsman , MD, Sjukhuset i Varberg , Sweden 50. Pugazhendhi Vijayaraman , MD, Geisinger Clinic, US 51. Judith Mackall, MD / Harish Manyam , MD, University Hospitals Case Medical Center, US 52. Allan Nichols, MD, Ohio Health Corporation, US 53. Serge David Bar-Lev, MD, Sheba Medical Center Tel Hashomer , Israel 54. James Merrill, MD, Wellmont CVA Heart Institute, US 55. Wayne Adkisson , MD, University of Minnesota, US 56. Juan José Olalla, MD, Hospital Marques de Valdecilla , Spain 57. Nagib Chalfoun , MD, Spectrum Health, US 58. Eric Johnson, MD, The Stern Cardiovascular Center, US 59. Jorge Massare , MD, Longview Regional Medical Center, US 60. Camille-Frazier Mills, MD, Duke University Medical Center, US 61. John Chenarides , MD, Allegheny General Hospital, US 62. Mohammad Jazayeri , MD, Bellin Health, US 63. Kevin Boran , MD, Cardiovascular Consultants Heart Center, US 64. John Schoenhard , MD / Simon Milstein, MD, CentraCare Heart & Vascular Center, US 65. John Bailey, MD / Mark Kremers, MD, Novant Health Heart and Vascular Institute, US 66. Thomas Burkart, MD, University of Florida Health Sciences Center Gainesville, US 67. Wilfried Mullens, MD, ZOL, Belgium 68. Jay Franklin, MD, Baylor Research Institute, US 69. Frederick Ehlert, MD, New York Presbyterian Hospital, US 70. Charles Henrikson , MD, Oregon Health & Science University (OHSU), US 71. Ilana Kutinsky , MD, William Beaumont Hospital, US 72. Ignasi Anguera , MD, Hospital Universitari Bellvitge , Spain 73. Michael Springer, MD, Norton Cardiovascular Associates 74. Grant Simons, MD, Englewood Hospital & Medical Center, US 75. Frederic Anselme , MD, Hopital Charles Nicolle - CHU Rouen, France 76. David Sandler, MD, Oklahoma Heart Institute, US 77. Luca Bontempi , MD Azienda Ospedaliera Spedali Civili di Brescia, Italy 78. Laurence Marie-Pierre Guedon -Moreau, MD, CHRU de Lille, France 79. Sei Iwai, MD, Westchester Medical Center, US 80. John McAnulty, MD / Eric Putz, MD, Legacy Medical Group, US 81. Gregory Golovchiner , MD, Rabin Medical Center - Beilinson Hospital, Israel 82. David Juang , MD, University of Rochester Medical Center, US 83. Peter Ammann, MD, Kantonsspital St.Gallen , Switzerland 84. Randy Jones, MD, Providence Health & Services, US 85. Allan Katz, MD, Saint Elizabeth Health Center, US 86. Malini Madhavan , MD, Mayo Clinic, US 87. Martin Emert , MD, The University Kansas Medical Center Research Institute, US 88. António Cãndido de Freitas Fernandes Hipólito Reis, MD, Centro Hospitalar do Porto, Portugal 89. Tina Salo , MD, Sisataudit TYKS, Finland, 90. Christopher Cole, MD, Penrose Hospital, US 91. Stephen Keim , MD, Delmarva Heart, LLC, US 92. George Thomas, MD, Cornell University, US 93. Chanta Chakrabarti, MD, Saint Paul’s Hospital, Vancouver, BC, Canada 94. Christina Murray, MD, Oklahoma University Health Science Center, US 95. Pierce Vatterott, MD, United Heart and Vascular Clinic, US 96. Robert Sangrigoli , MD, Doylestown Cardiology Associates – VIAA, US 97. Theofanie Mela, MD, Massachusetts General Hospital, US 98. Mark John Mason, MD, Royal Brompton & Harefield NHS Foundation Trust, UK 99. Robert Winslow, MD, Danbury Hospital, US 100. Shang- Chiun Lee, MD, Mercy Hospital Springfield, US 101. Przemyslaw Mitkowski , MD, Szpital Kliniczny Przemienienia Panskiego , Poland 102. Antoine Da Costa, MD, Cen Hosp Univ Saint Etienne - Hopital Nord, France 103. Girish Nair, MD, Saint Vincent Heart Center of Indiana, US 104. Westby Fisher, MD, NorthShore University Health System, US 105. Jean-Claude Deharo , MD, Hopital de la Timone - CHU de Marseille, France 106. Mark Castellani, MD / David Rhine, MD, Sparrow Clinical Research Institute, US 107. Hamid Ghanbari , MD, University of Michigan Cardiovascular Center, US 108. Gautham Kalahasty , MD, Virginia Commonwealth University Medical Center, US 109. Daniel Anderson, MD, University of Nebraska, US 110. Daniel Frisch, MD, Thomas Jefferson University , US 111. Larry Chinitz , MD / Charles Love, MD, NYU – Langone Medical Center, US 112. Andrew Rubin, MD, Eisenhower Medical Center, US 113. Timothy Lessmeier , MD, Heart Clinics Northwest, P.S., US 114. Steven Compton, MD, Alaska Heart Institute, US 115. Mark Mitchell, MD, Forsyth Medical Center, US 116. Katherine Fan, MD, Grantham Hospital, Hong Kong 117. Saeed Bandar Al Ghamdi , MD, King Faisal Specialist Hospital, Saudi Arabia 118. Gabriela Kaliska , MD, Stredoslovensky Ustav srdcovych a cievnych chorob (SUSCCH), Slovakia 119. Peter Margitfalvi , MD, NUSCH a.s. Bratislava, Slovakia 120. Glenn Meininger , MD, MedStar Health Research Institute, US 121. Aamir Cheema, MD, Saint Mary's Medical Center, US 122. Maria Grazia Bongiorni , MD, Azienda Ospedaliero Univ Pisana - Stabilimento di Cisanello , Italy 123. Jeffrey Luebbert , MD, Pennsylvania Hospital, US 124. Michael Pelini, MD, Northeast Ohio Cardiovascular Specialists, US 125. Silvia Misikova , MD, VUSCH, Slovakia 126. Jerome Kuhnlein , MD, Great Lakes Heart & Vascular Institute, PC, US 127. Robert Schweikert , MD, Akron General Medical Center, US 128. Jean-Manuel Herzet , MD, CHR La Citadelle , Belgium 129. Stefano Pedretti , MD, Presidio Ospedaliero Sant Anna, Italy 130. Byron Lee, MD, University of California San Francisco, US 131. Peter Santucci, MD, Loyola University Medical Center, US 132. Jonas Hörnsten , MD, Karolinska Universitetssjukhuset , Sweden 133. Samir Saba, MD / Evan Adelstein, MD / Stuart Mendenhall, MD, University of Pittsburgh Medical Center 134. Ngai-Yin Chan, MD, Princess Margaret Hospital, Hong Kong 135. Shabbar Jamaly , MD, Sahlgrenska Universitetssjukhuset , Sweden 136. Javier Moreno, MD, Hospital Universitario Ramon y Cajal, Spain 137. Tiziano Moccetti , MD, Cardio Centro Ticino, Switzerland 138. Paresh Shah, MD, Sinai Hospital of Baltimore, US 139. John Douglas Pappas, MD, Cardiology Associates of Corpus Christi, US 140. Thomas Blum, MD, Universitaets-Herzzentrum Freiburg Bad Krotzingen , Germany 141. Etienne Pruvot , MD, CHUV - University Hospital, Switzerland 142. Anthony Chu, MD, The Miriam Hospital, US 143. Chetan Gangireddy , MD / Joshua Cooper, MD, Temple University Hospital, US 144. Walter Chien , MD, Saint Joseph’s Medical Center, US 145. Ali Al- Mugamgha , MD, Saint Joseph's Hospital Health Center, US 146. Matthew Smelley , MD, Asheville Cardiology Associates, PA, US 147. Heath Saltzman, MD, Drexel University College of Medicine, US 148. Arun Kolli , MD, Tri-City Cardiology Consultants, US 149. William Kostis, MD / Sluja Amardeep , MD, Robert Wood Johnson Medical School, US 150. Charles Kennergren, MD, Sahlgrenska University Hospital, Sweden 151. Rajiv Handa , MD, Saint Anthony’s Medical Center, US 152. Emmanuel Simantirakis , MD, University Hospital of Heraklion, Greece 153. Tony Simmons, MD, Wake Forest University Health System, US 154. Randel Smith, MD, Hattiesburg Clinic/Forrest General, US 155. Marye Gleve , MD, Washington University School of Medicine, US 156. George N. Theodorakis, MD, Onassis Cardiac Surgery Center, Greece 157. Emad Aziz, MD, Mount Sinai Saint Luke’s Hospital, US 158. Scott Burke, MD, St. Mary’s Medical Center, US 159. Kah Leng Ho, MD, National Heart Center, Singapore 160. Carlo De Asmundis , MD, Heart Rhythm Management Centre, UZ Brussels VUB Brussel, Belgium 161. Kenneth Civello , MD, Our Lady of the Lake, US 162. Tan Vern Hsen , MD, Changi General Hospital, Singapore 163. Darryl Wells, MD, Swedish Medical Center Cherry Hill, US 164. Hüseyin Ince, MD, Universitatsklinikum Rostock, Germany 165. Sami Pakarinen , MD, Helsingin Seudun Yliopistollinen Keskussairaala , Finland 166. Jodie Hurwitz, MD, North Texas Heart Center, US 167. Vinay Mehta, MD, Aurora BayCare Medical Center, US 168. Imra Zainal Abidin , MD, Universiti Malaya Medical Centre, Malaysia 169. Michael Osayamen , MD, Jackson Clinic, US 170. Javier Banchs , MD, Scott & White Hospital, US 171. Kelly Kim, MD, SCL Physicians Heart Institute of Colo, US 172. Andrzej Kutarski , MD, Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie , Poland 173. João Manuel Frazão Rodrigues de Sousa, MD, Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, EPE, Portugal 174. Senthil Tambidorai , MD, Plaza Medical Center of Fort Worth, US 175. James Sandberg, MD, Lehigh Valley Hospital, US 176. Rubén Aguayo, MD, Hospital San Juan de Dios, Chile 177. Darren Traub, MD, St. Lukes Hospital and Health Network, US 178. Siddarth Mukerji, MD / Rajesh Venaktaraman , MD / Ramesh Hariharan, MD, EP Heart LLC, US 179. Saravanan Krishinan , MD, Hospital Sultanah Bahiyah , Malaysia 180. Jorge Silvestre, MD, Hospital Universitario La Paz, Spain 181. Vladimir Rankovic , MD, Florida Electrophysiology Associates, US

39. 39 TYRX WRAP-IT Study Overview | December 2020 Study committees TYRX ™ WRAP-IT Study Steering Committee Clinical Events Data Monitoring Bruce Wilkoff, M.D. (Chair) Cleveland Clinic Ralph Corey, M.D. Duke Clinical Research Institute Charles Kennergren, M.D. Sahlgrenska University Hospital Suneet Mittal, M.D. Valley Health System Jeanne Poole, M.D. University of Washington Khaldoun Tarakji, M.D. Cleveland Clinic Ken Ellenbogen , M.D. (Chair) Medical College of Virginia Frank Bracke , M.D. Catharina Hospital Antonio Curnis , M.D. University of Brescia Arnold Greenspon , M.D. Jefferson University Rizwan Sohail , M.D. Mayo Clinic Charles Swerdlow , M.D. UCLA Andrew Krahn , M.D. (Chair) University of British Columbia Helen Boucher, M.D. Tufts Medical Center Anne Curtis, M.D. Buffalo General Medical Center Thomas Heywood, M.D. Scripps Clinic Kerry Lee, Ph.D. Duke Clinical Research Institute

40. 40 TYRX WRAP-IT Study Overview | December 2020 Study Limitations TYRX ™ WRAP-IT STUDY Study limitations included 1 : Medtronic devices only, not sequential patients Commercial availability of TYRX Envelope allowed for possible selection bias Immunosuppressive use was not balanced between cohorts Did not collect antibiotic susceptibility data Did not control for peri- and post-procedure infection prevention strategies TYRX ™ Envelope 1 Tarakji KG, Mittal S, Kennergren C, et al. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med . 2019;380(20):1895-1905.

41. COMPREHENSIVE DATA ON OVER 14,000 PATIENTS TYRX ™ ENVELOPE CLINICAL EVIDENCE SUMMARY REAL-WORLD, CLINICAL EVIDENCE 8 original research peer-reviewed, published manuscripts: 1-8 > 7,500 patients > 70 centers High implant success (99.5%) 1 Reduced rate of “re-twiddling” with TYRX, 8 no evidence of increased complications 1-8 Very low rate of CIED infections with TYRX (0.44%): 6 70–100% relative reduction in infection vs. without TYRX 2-6 Meta-analysis: 69% relative reduction in infection vs. without TYRX ( P = 0.0002) 9 86% relative reduction in infection after Propensity Score Matching ( P = 0.003) 9 No performance difference between TYRX Absorbable and non-absorbable Envelopes 5 TYRX was cost-effective with all CIEDs 10 : When used at a baseline probability of infection exceeding 1.95% RANDOMIZED, CONTROLLED CLINICAL EVIDENCE 11 The largest randomized, controlled, global CIED trial 6,983 patients randomized 25 countries 181 centers 776 implanters 40% reduction of major CIED infections, meeting the primary objective 61% reduction of pocket infections No increased risk of complications through 12 months, meeting the safety objective No difference in procedure time 99.7% implant procedure success rate with TYRX 1 Bloom, et al. (COMMAND) Pacing Clin Electrophysiol . 2011;34:133-142. 2 Kolek , et al. Pacing Clin Electrophysiol . 2013;36:354-361. 3 Mittal, et al. Heart Rhythm . 2014;11:595-601. 4 Shariff, et al. J Cardiovasc Electrophysiol . 2015;26:783-789. 5 Kolek , et al. J Cardiovasc Electrophysiol . 2015;26:1111-1116. 6 Henrikson , et al. (Citadel, Centurian ). JACC: CEP . 2017;3:1158-67. 7 Hassoun , et al. J Hosp Infect . 2017;95:286-291. 8 Osoro , et al. Pacing Clin Electrophysiol . 2018;41:136-142. 9 Koerber , et al. J Cardiov Elect . 2018;29:609-615. 10 Kay, et al. J Med Econ . 2018;21:294-300. 11 Tarakji KG, et al. N Engl J Med . 2019;380(20):1895-1905. 41 TYRX WRAP-IT Study Overview | December 2020

42. SIGNIFICANT REDUCTION OF CIED INFECTIONS TYRX ™ ENVELOPE CLINICAL EVIDENCE SUMMARY 1-7 1 Henrikson CA, et al. JACC Clin Electrophysiol . 2017;3:1158-1167. 2 Bloom HL, et al. Pacing Clin Electrophysiol . 2011;34:133-142. 3 Mittal S, et al. Heart Rhythm . 2014;11:595-601. 4 Kolek MJ, et al. Pacing Clin Electrophysiol . 2013;36:354-361. RANDOMIZED CONTROL TRIAL (EXCLUDED HIGHEST RISK PATIENTS) REAL WORLD (INCLUDED HIGHEST RISK PATIENTS) * The COMMAND, C&C (Citadel & Centurion), Valley, Vanderbilt (Non-absorbable) and UPMC Studies were performed utilizing the TYRX ™ Non-absorbable Antibacterial Envelope. † The Vanderbilt (Absorbable) Study was performed utilizing the Absorbable TYRX Absorbable Antibacterial Envelope. 5 Kolek MJ, et al. J Cardiovasc Electrophysiol . 2015;26:1111-1116. 6 Shariff N, et al. J Cardiovasc Electrophysiol . 2015;26:783-789. 7 Tarakji KG, et al. N Engl J Med . 2019;380(20):1895-1905. 42 TYRX WRAP-IT Study Overview | December 2020 (Absorbable)

43. 43 Average cied infection cost summary CIED infections are costly to the healthcare system 1 Greenspon AJ, et al. Treatment Patterns and Resource Utilization among Medicare Beneficiaries with Cardiac Implantable Electronic Device Infection. Pacing and Clinical Electrophysiology. 2018. DOI: 10.1111/pace.13300 2 Medicare Provider Analysis and Review (MEDPAR) File, FY 2012, on file with Medtronic, plc. 3 Sohail MR, et al. The Incidence, Treatment Intensity and Incremental Annual Expenditures for Patients Experiencing a Cardiac Implantable Electronic Device Infection: Evidence from a Large US Payer Database One-Year Post Implantation. http://dx.doi.org/10.1161/CIRCEP.116.003929. Circulation: Arrhythmia and Electrophysiology. 2016;9:e003929. Originally published August 9, 2016. 4 Sohail et al. Mortality and Cost Associated With Cardiovascular Implantable Electronic Device Infections. Arch Intern Med. 2011;171(20):1821-1828. 5 Eby EL et al. J Med Econ . 2020 Apr 22;1-8.  doi : 10.1080/13696998.2020.1751649. 6 Shariff et al. Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as a Standard of Care for Cardiac Implantable Electronic Device Implantation. 7 2012 Premier Healthcare Database. Data on file with Medtronic plc. 8 Lopatto , et al. Antibacterial Envelope is Associated with Medical Cost Savings in Patients at High Risk for Cardiovascular Implantable Electronic Device Infection. Poster presented at ACC 2017 Scientific Sessions. Data on file with Medtronic plc 9 Wilkoff BL, et al. Circ Arrhythm Electrophysiol . 2020;13:e008280 . Hospital Costs Medicare FFS Costs Medicare FFS 100% SAF 2010-2013 1 MedPar 2012 2 * Citadel and Centurion studies include only ICD and CRT-D devices. MA = Medicare Advantage FFS = Fee for Service Medicare Advantage Costs TYRX WRAP-IT Study Overview | December 2020

44. 44 TYRX WRAP-IT Study Overview | December 2020 Medtronic 710 Medtronic Parkway Minneapolis, MN 55432-5604 USA Toll-free in USA: 800.633.8766 Worldwide: +763.514.4000 UC201910733d EN ©2020 Medtronic. Minneapolis, MN. All Rights Reserved. 10/2020 medtronic.com Brief Statement The TYRX ™ Absorbable Antibacterial Envelope is intended to hold a pacemaker pulse generator or defibrillator securely in order to provide a stable environment when implanted in the body. The TYRX Absorbable Antibacterial Envelope contains the antimicrobial agents minocycline and rifampin, which have been shown to reduce infection in an in vivo model of bacterial challenge following surgical implantation of the generator or defibrillator. The TYRX Absorbable Antibacterial Envelope is NOT indicated for use in patients who have an allergy or history of allergies to tetracyclines, rifampin, or absorbable sutures. The TYRX Absorbable Antibacterial Envelope is also NOT indicated for use in patients with contaminated or infected wounds, or Systemic Lupus Erythematosus (SLE). The use of this product in patients with compromised hepatic and renal function, or in the presence of hepatotoxic or renal toxic medications, should be considered carefully, because minocycline and rifampin can cause additional stress on the hepatic and renal systems. Patients who receive the TYRX Absorbable Antibacterial Envelope and who are also taking methoxyflurane should be monitored carefully for signs of renal toxicity.