Ultralow Temperature Cryoablation of Ventricular Tachycardia: Interim Analysis of Acute Outcomes of the FULCRUM-VT Trial Travis D. Richardson, MD Assistant Professor of Medicine Clinical Cardiac Electrophysiology on behalf of FULCRUM-VT Investigators

DISCLOSURES • Consultant/honoraria for Medtronic Inc, Johnson & Johnson, Boston Scientific, and Abbott.

DISCLAIMER This presentation describes a preliminary assessment;subject to study database lock, source data monitoring, and final analysis. Final data will be finalized for US FDA submission to support a pre-market approval (PMA) of this Investigational Device. US FDA has not reviewed these data.

MOTIVATION • Continuing search for new ablation technology to improve both effectiveness and safety of VT ablations • Traditional (N20-base, Tb=- 88.50C) cryoablation technology is useful in certain clinical scenarios but lacks power and lesion depth advantage over RF. Guandalini GS, Liang JJ, Marchlinski FE. Ventricular Tachycardia Ablation: Past, Present, and Future Perspectives. J Am Coll Cardiol EP 2019;5:1363–83 ADJUNCTS AND ALTERNATIVES TO RF ABLATION VT = Ventricular Tachycardia;RF= Radiofrequency

ULTRA-LOW TEMPERATURE CRYOABLATION VanderbiltHeart.com OPERATING POINT NEAR-CRITICAL (NC)-N2: combination of pressure and temperature suppresses liquid-gas phase transition • Viscosity of a gas • Density and heat capacity of a liquid • “Vapor lock” – free flow OPERATING PRINCIPLE1 PHYSIOLOGY OF CRYOABLATION2,3,4,5,6 1Adopted with modifications from: Littrup P, Babkin A. Evolving Concepts: Near-Critical Cooling-Based Technologies. In: Cryoablation of Cardiac Arrhythmias. Elsevier Health Sciences 2011. 2 Erinjeri JP, Clark TWI.J Vasc Interv Radiol. 2010;21(8 Suppl): S187–S191 3 Baust JG, Bischof JC, et al. Prostate Cancer and Prostatic Disease (2015)18, 87–95 4 Choi J, Bischof J. Cryobiology 2017;78: 115-118 5 Petrova EV, Brecjt HP, et al. Phys. Med. Biol 2019;63(6):064002 6 Cox JL, Malaisrie SC, Churyla A, et al. Ann Thorac Surg 2021;112:354-62 ULTC TARGET

ULTC SYSTEM DESIGN VanderbiltHeart.com 15 mm • Deep, titratable lesions for endocardial ablation • No apparent attenuation of lesion depth in areas of scar • Catheterstability during energy application • No irrigation N2 LN2 Freeze Duration (sec) Lesion Depth (mm) 30 < 4 60 4-6 120 7-9 180 ≥ 10 240 Safe in tissue ≥10 mm, but therapeutic 300 benefit has not been established Tb=-1960C 9 Fr ~ F-curve 8 electrodes CONSOLE AND DEFLECTABLE CATHETER LESION DEPTH TITRATION (Freeze-Thaw-Freeze protocol)1 PRE-CLINICAL 2-MIN LESION DEPTH ASSESSMENT2 1CS-300 protocol. Adagio Medica, Inc. Data on File 2T. Dewland et al. Ultra-low temperature cryoablation versus ultra-low temperature cryoablation combined with pulsed field ablation in a swine ventricular infarct model. JaCC EP 2025, in press.

PRIOR CLINICAL DATA: CRYOCURE-VT STUDY A. Verma et al. Cryocure-VT: the safety and effectiveness of ultra-low-temperature cryoablation of monomorphic ventricular VanderbiltHeart.com tachycardia in patients with ischaemic and non-ischaemic cardiomyopathies Europace 2024, MAE = Major Adverse Event LVEF= Left Ventricular Ejection Fraction

STUDY DESIGN • Protocol-defined Major Adverse Events (MAEs) 0-7 days • Acute non-inducibility of VTs targeted for ablation • Freedom from sustained VT or ICD intervention wo AAD escalation – 12-mo health outcomes endpoints • Cardiac and overall mortality • Reduction in shock and VT hospitalizations • Patient Population – 20% ≤ LVEF ≤ 50% , clinical indication for VT ablation – ICM – NICM • Including : ARVC • Excluding : sarcoidosis, active myocarditis, HCM, drug or alcohol CM, and isolated epicardialscar – ≤ 1 prior VT ablation in last 2 years EARLY FEASIBILITY PHASE (EFS) PIVOTAL ENROLLMENT PHASE 20 PATIENTS 4 CENTERS COMPLETED IN ‘24 +187 PATIENTS +15 CENTERS • 207 PATIENT SAFETY COHORT • 155 PATIENT TREATMENT EFFECTIVENESS COHORT • INDEPENDENT CEC AND DSMB COMMITTEES • INDEPENDENT VT EVENTS COMMITTEE Feasibility of Ultra-Low Temperature Cryoablation for Recurring Monomorphic VT • Study Design – Single arm; 206+ patients at 20 sites – Primary endpoints FULCRUM-VT PROGRAM AAD= Antiarrhythmic Drugs; ICD = Implantable Cardioverter-Defibrillator; ICM = Ischemic Cardiomyopathy; NICM = NonIschemic Cardiomyopathy ARVC = Arrhythmogenic Right Ventricular Cardiomyopathy; HCM = Hypertrophic Cardiomyopathy; CM = Cardiomyopathy; RV= Right Ventricle

20 32 155 All patients Treatment Cohort Number of Patients 207 155 Age 68 ± 11 y.o. 69 ± 10 y.o. Male Sex 92.4% 95.5% BMI 30 ± 6 30 ± 6 Cardiomyopathy 93.6% 91.4% ICM 60.8% 61.8% NICM 27.5% 23.7% both ICM and NICM 5.4% 5.9% LVEF 35% ± 10% 35% ± 10% ≤ 30% 38.2% 36.6% 31-40% 33.3% 35.8% 41-50% 23.7% 24.6% >50% 4.8% 3.0% CAD 72.4% 74.3% Prior MI 55.7% 60.3% Diabetes Mellitus 37.8% 40.3% Congestive Heart Failure 74.9% 78.3% Hypertension 84.1% 83.9% Class I AADs 2.0% 2.1% Class III AADs 82.8% 82.0% Amiodarone 64.1% 64.4% PATIENT POPULATION PATIENT COHORT DETAILS EFS Cohort Roll-In Patients Treatment Cohort Roll-in patients (one per operator) are counted towards safety but not effectiveness endpoints.

110 53 46 54 17 0 50 100 150 200 206 250 Procedure Time Catheter Dwell Time Ablation Time Freeze Time Mapping Time Fluoroscopy Time Minutes PROCEDURAL DETAILS Number of Patients n=143 Substrate Mapping 94% Activation Mapping 73% Pace Mapping 65% Entrainment Mapping 15% Number of Patients n=143 Substrate Homogenization 69% VT Exit 63% Slow Conduction Channel 55% VT Isthmus 39% LAVA Elimination 17% Scar De-channeling 10% Core Isolation 1% Number of Patients n=143 Lesions / patients 12 +/- 6, range [2-34] Freeze time* / lesion, min 4 +/- 1, range [1-8] MAPPING STRATEGIES ABLATION STRATEGIES / TARGETS PROCEDURAL TIMES * includes both primary and secondary freezes LAVA = Local Abnormal Ventricular Activities

LESION DISTRIBUTION • Substantial difference in lesion distribution between patients with NICM vs ICM ISCHEMIC CARDIOMYOPATHY NON- ISCHEMIC CARDIOMYOPATHY RV RV ANTERIOR 2.5% LATERAL LATERAL ANTERIOR 15.0% 15.1% INFERIOR 9.1% INFERIOR 2.4% 3.7% 2.2% 0.0% 3.2% 1.4% 4.0% 8.3% 0.3% 4.4% 3.5% 0.0% 1.2% 0.8% 0.3% 2.3% 6.0% 5.5%

SAFETY: PROCEDURE-RELATED EVENTS All patients Treatment Cohort Number of Patients 207 155 Cardiac Perforation 2 (1.0%)* Pericardial Effusion 3 (1.4%) 3 (1.9%) Shock 5 (2.4%) 2 (1.3%) Air Embolism Stroke 1 (0.5%) Resp Failure/ Hypoxia 3 (1.4%) 2 (1.3%) Access Site Complications 3 (1.0%) 2 (1.3%) Larynx Hematoma 1 (0.5%) 1 (0.6%) TOTAL 18 (8.7%) 10 (6.5%) PRIMARY SERIOUS ADVERSE EVENTS PER CEC ADJUDICATION ALL PATIENTS 207 1 (0.5%) 1 (0.5%) 1 (0.5%) 1 (0.5%) 4 (1.9%) ASSOCIATED MORTALITY * Includes one (1) EFS event adjudicated as “possibly-related” to procedure, and reported earlier - Investigational Device-related event • Primary Safety Endpoint: five (2.5%) of protocol-defined MAEs – Only one (0.5%) MAE definitely investigational device-related • sepsis post-surgery, roll-in patient • hypoxic failure after surgical RV laceration • acute decompensation post-anesthesia • air embolism during sheath exchange, roll-in patient

VT INDUCIBILITY AND ACUTE PROCEDURAL SUCCESS 154 patients 382 VTs 204 Clinical 135 Non-Clinical 43 Undetermined 201 Clinical 105 Non-Clinical 39 Undetermined 178 Clinical 93 Non-Clinical 28 Undetermined 298 Non-reinducible 8 Reinducible 39 No PES Done 5 Clinical 2 Non-Clinical 1 Undetermined 19 Clinical 10 Non-Clinical 10 Undetermined 97.4% Acute Success Number of Patients n=154 VTs per patient 2.8 % Clinical 53.4% % Hemodynamically Stable 34.6% Average CL (ms) 365 +/- 84 345 VTs Targeted for Ablation BASELINE INDUCIBILE VTs STATISTICS

117 2 4 No VTs reinduced in post-ablation PES Non-clinical VTs after post-ablation PES Clinical VTs in post-ablation PES PATIENT-LEVEL DATA: 96.7% CLINICAL SUCCESS 154 patients 17 patients 137 patients 14 patients 117 patients 2 patients 4 patients No VT induction after pre-ablation PES Clinical VTs(5) reinduced Neither clinical nor non-clinical VTs reinduced No clinical VTs, but non-clinical VTs are reinduced Post-ablation PES not performed Post-ablation PES 95.1% 96.7% - Full Success - Clinical Success PES = Programmed Electrical Stimulation

CONCLUSIONS • In large, multi-center cohort of patients with both ischemic and non-ischemic cardiomyopathies the ULTC system demonstrated very promising acute performance for ablation of VT associated with structural heart disease. – Favorable safety profile • Low rate of intra- and peri-procedural complications, consistent with underlying morbidity of the treated population • No signal of incremental risk associated with the specific technology/novel energy source – Excellent acute effectiveness • 97.4% elimination of targeted VTs • 96.7% patient-level clinical success (elimination of clinical VTs) • 6-mo outcome data should be available by HRS’ 26 • Next-generation catheter design (8.5Fr, D/F, more flexible, colder and shorter ablations) is in the works