LungFX™ device

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION Device Generic Name: Ex Vivo Lung Perfusion System Device Trade Name: LungFX™ device Device Procode: PHO Applicant’s Name and Address: Lung Bioengineering Inc., LB1 Building 1015 Spring Street, Silver Spring, MD 20910 Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P240033 Date of FDA Notice of Approval: Priority Review: None ## II. INDICATIONS FOR USE The LungFX™ device (“LungFX”) is indicated for centralized, *ex vivo* (outside the body) evaluation of deceased-donor lungs (single and double) that cannot be placed for transplantation by an Organ Procurement Organization (OPO) with any of the matched candidates if using direct-to-recipient procurement and preservation procedures. LungFX provides normothermic perfusion and ventilation of procured donor lungs initially stored with cold static preservation solution. LungFX is intended to allow for re-assessment, in a controlled environment, of procured donor lungs’ suitability for transplantation into male and female patients aged 18 years or older with end-stage lung disease awaiting first time (double or single) lung transplantation. Lungs accepted for transplantation after LungFX require a second period of storage with cold static preservation solution, and cumulative preservation time of transplanted lungs is not intended to exceed 20 hours. ## III. CONTRAINDICATIONS There are no known contraindications. {1} P240033 Page 2 # IV. WARNINGS AND PRECAUTIONS # A. Warnings - The LungFX device is not intended for the preservation of donor lungs that could be matched and successfully placed by an OPO without utilization of the device. In the CLES Pivotal Study, the observed 12-month survival rate among recipients of LungFX lungs did not meet the pre-specified performance goal (> 95% posterior probability of 1 year survival > 81.2%); rates of 12-month overall mortality and Clinical Events Committee (CEC)-adjudicated lung graft-related mortality were higher in EVLP subjects as compared to non-EVLP contemporaneous control subjects; and two-year survival within several pre-specified subgroups were clinically less favorable among EVLP donor lungs than among non-EVLP control donor lungs. Before deciding to proceed with LungFX organ preservation, a physician should fully consider the risks and benefits of this device and those of other organ preservation modalities. Transplant physicians are advised to carefully review the available clinical data in the LungFX device labeling when considering its use for any donor lungs and recipients. Refer to section G. Safety and Effectiveness Results for a summary. - Only qualified Lung Bioengineering (LBE) personnel can operate the LungFX device. - Only trained physicians can evaluate lung suitability for transplantation after LungFX evaluation. # B. Precautions - Safety and effectiveness of the LungFX device are derived principally (i.) from clinical data collected prospectively in the CLES Pivotal Study within 1 year after organ preservation and transplantation and (ii.) from 2 years of observational, post-transplantation survival data. Therefore, the impact of the LungFX device on clinical outcomes such as longer-term recipient survival and graft function (e.g., chronic lung allograft dysfunction (CLAD)) is uncertain. Other approved devices allow for pre-transplant assessment of procured donor lungs under conditions of ex vivo normothermic perfusion and ventilation, and there are various approaches available for isolated cold static storage preservation of procured donor lungs. Each alternative has its own advantages and disadvantages. A physician should fully discuss these alternatives with transplant candidates to identify the type of donor organ and preservation method that best meet patient expectations. {2} P240033 Page 3 - Safety and effectiveness of the LungFX device has not been studied in: ○ Patients under the age of 18 years. ○ Patients listed for same-side lung re-transplantation. ○ Patients listed for multiple organ transplantation including lung and any other organ. ○ Patients listed for live donor lobar lung transplant. ○ Patients positive for human immunodeficiency virus (HIV) or Burkholderia cenocepacia infection. - Safety and effectiveness of the LungFX device has not been studied for donors or donor lungs with the following: ○ Confirmed pneumonia and/or persistent purulent secretions identified via bronchoscopy prior to donor lung excision. ○ Confirmed evidence of aspiration. ○ Significant mechanical lung injury or trauma. ○ HIV or active hepatitis C. • A device malfunction or User error could lead to a potential loss of a donor lung. Additional warnings and precautions can be found in the LungFX™ device labeling. ## V. DEVICE DESCRIPTION The LungFX is an ex vivo lung perfusion (EVLP) device that uses an acellular perfusate to perfuse the lung to simulate normothermic (37°C) in situ lung function in an ex vivo controlled environment for the purpose of extended preservation and evaluation of potential donor lungs that would not otherwise be used for transplant. LungFX is an assembly of device components comprising a combination of off-the-shelf medical equipment and single-use disposables. The device components fall into 2 classifications: 1) Hardware and 2) EVLP Circuit Single-Use Disposables. A photograph of the device is provided in Figure 1 below. - The Hardware includes an extracorporeal heater-cooler unit (HCU), intensive care unit (ICU) ventilator, arterial blood gas (ABG) analyzer, and a modular perfusion system comprised of the following: a central workstation with the user interface, a pump console module (inclusive of metal frame, power supply, roller pump, and console/control module), a centrifugal pump driver, and diagnostic module that works with accessory components (flow sensor and temperature probe) and ancillary component (pressure transducers) to {3} P240033 Page 4 measure and monitor flow, temperature, and pressure. Table 1 below provides a list of operational use parameters for the hardware. - The EVLP Circuit Single-Use Disposables include an organ chamber, cannula set, perfusate solution, heat exchanger, centrifugal pump head and a perfusion circuit kit consisting of tubing lines, a sample manifold, waste/drain bags, hardshell reservoir, oxygenator, and leukocyte reduction filter. The organ chamber, cannula set, heat exchanger, centrifugal pump head, and perfusion circuit kit are assembled together to form the perfusate loop of the LungFX EVLP circuit. The LungFX EVLP circuit includes the perfusate loop, HCU, perfusion system, and ICU ventilator. The lung in the organ chamber is directly connected to the ICU ventilator and cannula set. The ABG analyzer is a stand-alone component used to analyze perfusate samples taken during an EVLP procedure. A schematic of the EVLP circuit is provided in Figure 1. The LungFX Hardware and EVLP Circuit Single-Use Disposables are either 510(k)-cleared or PMA-approved by the FDA for human use. These device components are manufactured by their respective firms and intended to be used off-the-shelf. The PMA-approved single-use disposable components are specifically intended for use to perform EVLP. The 510(k)-cleared hardware and single-use disposables were originally intended for use to support extracorporeal bypass perfusion and oxygenation of blood for a living patient during cardiopulmonary surgery. The inclusion of these device components as part of the LungFX device involves no manipulation of the original device components for the LungFX device design or the manufacturing process. Their function in the LungFX device is essentially the same, except acellular perfusate is being circulated instead of blood, the perfusate is deoxygenated to allow oxygenation by the organ, and the devices are being used ex vivo with isolated lungs instead of direct contact with a patient. Where the use of the LungFX Hardware and EVLP Circuit Single-Use Disposable device components to perform EVLP differs from the original intended use (eg, use with perfusate instead of blood), the qualification for use of the hardware and/or single-use disposable component has been performed. LungFX is intended to be operated/used exclusively by the company, Lung Bioengineering Inc. (LBE), in company-controlled facilities by specifically trained and qualified personnel. LungFX is not to be sold to any other entity nor operated/used by an entity that is not a company-controlled facility. Table 1: LungFX Preset Limit or Alarm Ranges and Operational Use Parameters | Equipment | Parameter/ Use | Operational Use Parameters | Limit or Alarm Ranges | | --- | --- | --- | --- | | HCU Ventilator: Volume Control | Temperature (°C) | 4 to 40 | | | | Peak (cmH₂O) | 0 to 25 | Upper limit 25 | | | Respiratory Rate (b/min) | 7 and 10 | | | | End Expiratory Pressure (cmH₂O) | 2 to 10 | | | | VT (mL) | 100 to 2,000* | | | | PEEP (cmH₂O) | 5 | | | | FiO2 (%) | 21 and 100 | | {4} P240033 Page 5 | Equipment | Parameter/ Use | Operational Use Parameters | Limit or Alarm Ranges | | --- | --- | --- | --- | | | I:E ratio | 1:2 | | | | Tpause Time (%): | 0 | | | | Inspiratory Rise Time (%) | 5 | | | | Trigger Pressure | -2 | | | Perfusion System | Roller Pump Speed (RPM) | 0 to 250 | | | | LA/PA Pressure Monitoring (mmHg) | -10 to 50 | 2 to 6 | | | Perfusate Temperature Monitoring (°C) | 9 to 39 | 9.8 to 37.4 | | | Centrifugal Pump Speed (RPM) | 0 to 3,500 | | | | Flow Rate (LPM) | 0 to 10 | | | ABG Analyzer | Measures PO₂, PCO₂, PH, glucose and lactate | Samples in acellular perfusate | | Abbreviations: EVLP, ex vivo lung perfusion; FiO₂, fraction of inspired oxygen; HCU, Heater-Cooler Unit; IBW, Ideal Body Weight; ICU, Intensive Care Unit; I:E, inspiratory :expiratory; LAP, left atrial pressure; LPM, liters per minute; PA, pulmonary artery; Ppeak, Peak Airway Pressure; PEEP, Positive End-Expiratory Pressure; RPM, revolutions per minute; VT, Tidal Volume *A low and max VT is listed, but during EVLP, the calculation for VT is based on the following: Double Lung VT Maintenance is seven (7) mL/kg x IBW, Double Lung VT O₂ Challenge is 10 mL/kg x IBW; Single Right Lung VT is 60% of Double VT; Single Left Lung VT is 40% of Double VT. {5} P240033 Page 6  Abbreviations: EVLP, ex-vivo lung perfusion; HCU, heater-cooler unit; ICU, intensive care unit; LAP, left atrial pressure; PAP, pulmonary artery pressure Figure 1: Schematic of the LungFX Device with EVLP Circuit Flow The LungFX Device EVLP circuit flow (corresponding to 1-5 as shown in Figure 1 above) is summarized as follows: 1. The perfusate is added into the EVLP circuit through a standard aseptic interface on the hardshell reservoir. The height of the reservoir is adjusted as needed during the EVLP procedure to maintain left atrial (LA) pressure (LAP). 2. The centrifugal pump draws perfusate from the reservoir through the pump head and circulates it through a heat exchanger where the temperature is controlled via the extracorporeal Heater-Cooler Unit. {6} P240033 Page 7 a. At the start of an EVLP procedure, perfusate is gradually heated to warm the donor lung from cold storage temperatures to normothermic temperatures of ~37°C. During the procedure, the temperature of the perfusate and lung is monitored and maintained at normothermic temperature. b. At the completion of an EVLP procedure, the perfusate is rapidly cooled to ~10°C prior to repackaging for cold storage and transportation to a medical facility for transplant. 3. From the heat exchanger, the perfusate goes through the membrane, oxygenator, which is connected to a deoxygenation gas mix (86% N₂, 8% CO₂, 6% O₂) where the dissolved O₂ in the circuit diffuses out of the perfusate to produce a lower physiologic level representative of venous blood prior to re-entering the lungs. a. A (non-fluid contacting) temperature probe is attached to the oxygenator outlet line to monitor the temperature of perfusate entering the lung. The temperature is measured and displayed by the perfusion system. 4. From the membrane oxygenator, the perfusate passes through a leukocyte filter just before it enters the lung via the pulmonary artery (PA) lung cannula. a. The leukocyte filter functions to reduce the number of microaggregates, microemboli, and activated leukocytes circulating back through the donor lung. b. A (non-fluid contacting) flow sensor is attached to the tubing connected to the PA cannula and monitors the flow rate (LPM) of the deoxygenated perfusate going into the lung. c. A pressure line in the PA lung cannula that is connected to the pressure Monitor via a pressure transducer at the point of interface between the cannula and lung to measure the PA pressure (PAP). 5. The oxygenated perfusate exits the lung through the LA lung cannula. a. A pressure line in the LA lung cannula is connected to the perfusion system via a pressure transducer to measure and monitor the LA pressure (LAP). b. A (non-fluid contacting) temperature probe is attached at the reservoir inlet to monitor the temperature of perfusate exiting the lung. 6. Any perfusate leaking from the lung drains into the organ chamber and is directed back into the hardshell reservoir via a roller pump (not shown in Figure 1 above). 7. Samples from the LA and PA lines via the sample manifold are taken for testing of pH, PCO₂, PO₂, lactate, and glucose, using the ABG analyzer (not shown in Figure 1 above). {7} P240033 Page 8 8. The cycle repeats during the EVLP procedure until a determination is made by the prescribing physician to either accept or decline the lung for transplant (not shown in Figure 1 above). a. Every hour throughout the procedure, the EVLP circuit is drained of a prescribed volume of perfusate via the leukocyte filter drain line and replenished with an equal volume of fresh perfusate added to the hardshell reservoir. Several ancillary components are used to support the assembly and set-up for use, and use of the LungFX to perform the EVLP procedure. Please refer to the LungFX Users Guide for a list of the ancillary components. Please refer to the LungFX Users guide for a complete description of each device component and properties relevant for the Intended Use. ## VI. ALTERNATIVE PRACTICES AND PROCEDURES Standard of care processes for evaluation of donor lung function typically take place within the donor patient's body prior to surgical procurement of the organ. These evaluation techniques and methods are similar to those used ex vivo with the LungFX device. If a decision is made to transplant the organ, then the organ will be placed in cold static storage consisting of a cold solution indicated for lung preservation and transported in a container to the recipient's transplant center. During the standard of care process the organ experiences one cold ischemic time (amount of time the organ is kept cold without oxygen or nutrients) after organ harvesting but prior to transplantation into the recipient. The longer the cold ischemic time the greater the ischemic injury which can lead to tissue damage and worse transplant outcomes. There are 2 other marketed devices for ex vivo perfusion of donor lungs, the TransMedics® Organ Care System™ (OCS) Lung System (P160013) and the XVIVO Perfusion System™ (XPS) with STEEN Solution Perfusate (P180014). The OCS is a portable, normothermic organ perfusion, ventilation, and monitoring medical device indicated for preservation of standard criteria donor lung pairs and for preservation of donor lung pairs initially deemed unacceptable for procurement and transplantation based on limitations of cold static preservation. The XPS is indicated for use in flushing and temporary continuous normothermic machine perfusion of initially unacceptable excised donor lungs during which time the ex vivo function of the lungs can be reassessed for transplantation. Each of these devices allow for ex vivo assessment of donor lungs prior to transplantation. ## VII. MARKETING HISTORY The LungFX has not been marketed in the United States or any foreign country. {8} P240033 Page 9 ### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH LungFX is indicated for use with explanted donor lungs that cannot be placed for transplant by an Organ Procurement Organization with any of the matched candidates when using direct-to-recipient procurement and preservation procedures. While there is no direct patient contact with this device when it is used as labeled, the device has direct contact with the lungs that are subsequently transplanted into the recipients. Therefore, donor lung quality after assessment and preservation may have a potential effect on allograft function and survival. The potential for contamination and mechanical trauma due to the manipulation and cannulation of the lung airway and vascular structures may lead to complications after transplantation. Patients receiving a lung evaluated with LungFX may experience adverse events (AEs) including those experienced with any lung transplant. Below is a list of some of the AEs observed during clinical studies of the device. - Death - Primary graft dysfunction (PGD) - Chronic lung allograft dysfunction (CLAD) - Respiratory failure - Lung transplant rejection - Pulmonary embolism - Pneumonia - Bronchostenosis - Hypoxia - Dysphagia These AEs were also observed in transplant recipients whose lungs did not undergo evaluation with the LungFX device prior to transplantation. For the specific AEs that occurred in the clinical studies, please see Section X below. ### IX. SUMMARY OF NON-CLINICAL STUDIES Non-clinical studies performed included electromagnetic compatibility testing, design verification and validation activities, and human factors/usability validation, which collectively evaluated the system's conformity to design requirements, intended use, and user needs. Testing was conducted using production-equivalent configurations under representative and worst-case conditions, in accordance with applicable regulatory standards and recognized consensus guidelines. The results demonstrate that LungFX meets predefined acceptance criteria for essential performance, safety, and usability, and supports its use in the intended operating environments. Summaries of these studies are detailed below. {9} P240033 Page 10 In addition to non-clinical studies performed by the Sponsor, the LungFX device utilizes off-the-shelf components that are the subject of existing 510(k) clearances. Those pre-market notifications include information regarding biocompatibility, shelf-life, and instructions for reprocessing. LungFX labeling incorporates relevant instructions for use, storage and shelf-life, and cleaning/reprocessing instructions provided by the manufacturers of the LungFX components. ### A. Laboratory Studies #### Electromagnetic Compatibility (EMC) Testing The Sponsor conducted a gap assessment evaluating compliance with IEC 60601-1 General requirements for basic safety and essential performance, specifically comparing Amendment 1 (2012) of the standard with Amendment 2 (2021). The gap assessment confirmed that, with respect to Part 1 of the standard, each device component is certified to its applicable particular and collateral standard. With respect to Part 2 of the standard, the Sponsor performed electromagnetic compatibility (EMC) testing on LungFX in accordance with IEC 60601-1-2 and related IEC 61000 standards to evaluate basic safety and essential performance under electromagnetic disturbances. The objective of testing was to confirm that the system maintains essential performance, including perfusion, ventilation, temperature control, monitoring, and alarm functionality, in the intended operating environment. Testing was conducted on four representative production-equivalent component systems: the perfusion system, heater-cooler unit, ventilator, and ABG analyzer. Testing included electrostatic discharge, radiated and conducted immunity, electrical fast transient/burst, surge, magnetic field immunity, voltage dips, and emissions. Predefined acceptance criteria required maintenance of essential performance (e.g., flow accuracy, temperature stability, ventilation delivery, and alarm capability). All tests met applicable criteria and were reported as passing. Minor transient anomalies were observed during early testing but were either self-resolving or mitigated through corrective actions and successful retesting. Overall, LungFX demonstrated compliance with EMC requirements and maintained safe and effective performance under expected electromagnetic conditions. #### Human Factors / Usability Engineering Validation Human factors validation testing was conducted to evaluate safe and effective use of LungFX under representative conditions. A simulated-use study was performed with 15 trained users working in teams of 3, representing intended operators. The objective was to assess performance of critical tasks including setup, operation, monitoring, and completion of EVLP procedures. Predefined success criteria evaluated correct task execution and absence of critical use errors. {10} P240033 Page 11 All participants successfully completed simulated procedures and all critical tasks. Minor use events were observed but were either self-corrected or did not impact safety or effectiveness. Root cause analyses indicated normal user variability, and residual risks were determined to be acceptable. No deviations impacted study validity. Results demonstrate that the device supports safe and effective use by intended users. ## Design Verification and Validation Design verification and validation (DV&V) activities for LungFX were conducted to confirm that the final device configuration meets established design requirements, user needs, and intended use under representative conditions. Verification activities evaluated conformity of design outputs to design inputs through bench testing, analysis, inspection, and subsystem qualification, while validation activities assessed system performance and usability under simulated use conditions. All testing was performed using production-equivalent configurations and in accordance with applicable regulatory requirements, recognized consensus standards, and internal quality procedures. The following sections summarize the key domains of DV&V testing, including verification, EMC and electrical safety, system validation, human factors integration, and risk management, along with their respective results and conclusions. ### 1. Verification Testing Design verification activities were performed to confirm that the LungFX configuration meets defined design requirements. Methods included bench testing, inspection, and subsystem qualification using production-equivalent units for the perfusion system, heater-cooler unit, ventilator, and ABG analyzer. Acceptance criteria were predefined based on system performance specifications such as flow, pressure, temperature, and analytical accuracy. All verification activities met acceptance criteria with no outstanding nonconformances. ### 2. EMC and Electrical Safety Verification Verification included EMC and electrical safety testing in accordance with IEC 60601-1-2 and recognized safety standards. The system demonstrated immunity to electromagnetic disturbances including ESD, surge, and RF exposure. All acceptance criteria were met, and transient anomalies observed during initial testing were resolved without impact to final system performance. ### 3. System Validation Design validation was conducted using simulated-use EVLP procedures to demonstrate that the device meets user needs and intended use. Testing included multiple EVLP runs with representative donor lungs. Results confirmed stable {11} P240033 Page 12 perfusion, controlled temperature (37°C ± 1°C), proper ventilation, and integration of monitoring and alarms. All predefined performance criteria were achieved. # 4. Human Factors Integration Human factors validation confirmed that trained users can complete all critical tasks safely and effectively. Simulated-use testing demonstrated successful completion of setup, operation, monitoring, and shutdown tasks. Observed use events were minor and did not result in unacceptable risk, confirming adequacy of usability controls. # 5. Risk and Traceability Risk management activities confirmed that all identified risks were mitigated to acceptable levels. Complete traceability from user needs through design inputs, verification, validation, and risk controls was established. Overall, DV&V activities demonstrate that LungFX meets design and performance requirements and is suitable for intended use. Below is a table summarizing the non-clinical testing performed by the Sponsor discussed in more detail above. Table 2: Summary of Non-Clinical Testing | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Electromagnetic Compatibility | To evaluate basic safety and essential performance under electromagnetic disturbances | Maintain essential performance using IEC 60601-1-2 test methods (4 samples) | All tests passed | | Human Factors / Usability Engineering Validation | To evaluate representative users' ability to safely and effectively use LungFX under representative conditions | Successful task completion in a simulated-use study (15 users) | All critical tasks completed | | Device Verification and Validation | To confirm that the final device configuration meets established design requirements, user needs, and intended use under representative conditions | Bench, validation, and subsystem testing meet design requirements and user needs (minimum of 3 data points collected for each test) | All tests passed | {12} P240033 Page 13 ## X. SUMMARY OF CLINICAL STUDIES Three clinical studies were used to establish a reasonable assurance of safety and effectiveness of EVLP with the LungFX device for centralized, *ex vivo* (outside the body) evaluation of deceased-donor lungs (single and double) that cannot be placed for transplantation by an Organ Procurement Organization (OPO) with any of the matched candidates if using direct-to-recipient procurement and preservation procedures. LungFX provides normothermic perfusion and ventilation of procured donor lungs initially stored with cold static preservation solution. LungFX is intended to allow for re-assessment, in a controlled environment, of procured donor lungs' suitability for transplantation into male and female patients aged 18 years or older with end-stage lung disease awaiting first time (double or single) lung transplantation. Lungs accepted for transplantation after LungFX require a second period of storage with cold static preservation solution, and cumulative preservation time of transplanted lungs is not intended to exceed 20 hours. The first study was conducted in Canada and the other two were conducted in the United States (US) under IDEs, G140021 and G170312. G140021 was a feasibility study and data obtained from this trial was used to inform study design and support approval for the pivotal study conducted under G170312. Data from the pivotal clinical study were the basis for the PMA approval decision. A summary of the clinical studies is presented below. ### Canadian HELP Study (Single-Center) The Canadian HELP study (NCT01190059) was a prospective, non-randomized, single-center study that reviewed clinical outcomes in study subjects receiving initially declined donor lungs treated with 4 hours of EVLP using STEEN Solution delivered using off-the-shelf cardiopulmonary bypass equipment. The equipment and STEEN Solution became known as the Toronto EVLP System (TES) and this device was licensed for use in LBE's clinical studies, being renamed the Centralized Lung Evaluation System (CLES) (Brand Name: LungFX) for the subsequent pivotal study. The primary endpoint of the HELP study was the incidence of ISHLT-defined primary graft dysfunction (PGD) Grades 2 and 3 at 72 hours after transplantation. The results were compared to those in a control arm consisting of all available standard-of-care transplant recipients at the same institution transplanted during the study period (2008-2010). PGD Grade 2 at 72 hours was 11% and 23%, and PGD Grade 3 at 72 hours was 3% and 11% for the EVLP and Control Groups, respectively. Following a compassionate use extension of the study, Health Canada approved STEEN Solution for use with off-the-shelf medical equipment to perform EVLP in 2012. One year survival in the EVLP arm (n=49) of the study was 83.7% compared to 85.1% in the control arm (n=262). {13} P240033 Page 14 # Traditional Feasibility Study- PXUS 14-001 After the Canadian HELP study, FDA approved a US feasibility study (PXUS 14-001, IDE G140021), referred to as the Traditional Feasibility Study, which was intended to establish preliminary safety and collect exploratory data. The device and EVLP procedure used in this study were identical to the TES device used for the HELP study. This study also provided a longer-term cohort of recipients followed for 5 years after transplant under a Data Use Agreement with United Network for Organ Sharing (UNOS) that provided access to the federal Organ Procurement and Transplantation Network (OPTN) database. # A. Study Design PXUS 14-001 was an unblinded, non-randomized, feasibility study. EVLP with TES (later redesignated as the “CLES” which was changed to “LungFX”) was performed exclusively by the Sponsor at the Sponsor’s facility with the same EVLP device used in the subsequent pivotal study. The study included male and female lung transplant recipients, requiring first-time SLT or DLT, who were at least 18 years of age, and were not receiving mechanical ventilation, ECMO, or other extracorporeal life support (ECLS) at the time of initial lung offer. Patients received a transplant with either lungs preserved and assessed on the EVLP device (EVLP group) or a conventional lung transplant (non-EVLP group) preserved using static cold storage only. Patients who received a non-EVLP lung transplant were matched to the EVLP group with respect to transplant center, Single or Double Lung transplant (SLT or DLT, respectively), and Lung Allocation Score Disease Diagnosis Group. The primary safety endpoints were PGD 3 at 72 hours after transplant and 30-day mortality. Patients were treated between July 2015 and October 2018. The database for this study reflected data collected through January 13, 2020 and included 118 patients (66 EVLP and 52 non-EVLP). There were 8 investigational sites with 7 that transplanted at least 1 lung following evaluation with the TES. The EVLP group consisted of 31 SLT subjects and 35 DLT subjects and the non-EVLP group consisted of 21 SLT subjects and 31 DLT subjects. The study database was locked for analyses of endpoints after the last subject completed their last visit at 12 months, on November 07, 2019, and all ongoing AEs were followed until resolution or for 30 days after the subject’s last Study Center visit, whichever occurred first. # B. Feasibility Study Results The incidence of PGD 3 at 72 hours was substantially higher in the EVLP group (24.2%) compared to the non-EVLP group (3.8%), primarily as a consequence of more post-transplant ECMO use in the EVLP group. {14} P240033 Page 15 All subjects that received a lung transplant in this study survived to Day 30. At 1 year post-transplant, survival was 89.4% in the EVLP group and 92.3% in the non-EVLP group. Subjects in the study were followed for 5 years post-transplant via the OPTN database, and survival status for all subjects was complete. Survival for years 2 through 5 post-transplant are presented in Table 3. At 5 years, the survival rates in both arms were similar.: Table 3: Feasibility study (PXUS-14-001) Patient Survival Results | Follow up | Subject Status | EVLP | | | Control | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | SLT (N=31) | DLT (N=35) | Overall (N=66) | SLT (N=21) | DLT (N=31) | Overall (N=52) | | <= 1 Year Post-Transplant | Living | 29 (93.5%) | 30 (85.7%) | 59 (89.4%) | 20 (95.2%) | 28 (90.3%) | 48 (92.3%) | | | Dead | 2 (6.5%) | 5 (14.3%) | 7 (10.6%) | 1 (4.8%) | 3 (9.7%) | 4 (7.7%) | | | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | | 2 Year Post-Transplant | Living | 28 (90.3%) | 29 (82.9%) | 57 (86.4%) | 15 (71.4%) | 25 (80.6%) | 40 (76.9%) | | | Dead | 3 (9.7%) | 6 (17.1%) | 9 (13.6%) | 6 (28.6%) | 6 (19.4%) | 12 (23.1%) | | | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | | 3 Year Post-Transplant | Living | 24 (77.4%) | 26 (74.3%) | 50 (75.8%) | 14 (66.7%) | 25 (80.6%) | 39 (75.0%) | | | Dead | 7 (22.6%) | 9 (25.7%) | 16 (24.2%) | 7 (33.3%) | 6 (19.4%) | 13 (25.0%) | | | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | | 4 Year Post-Transplant | Living | 16 (51.6%) | 24 (68.6%) | 40 (60.6%) | 10 (47.6%) | 22 (71.0%) | 32 (61.5%) | | | Dead | 15 (48.4%) | 11 (31.4%) | 26 (39.4%) | 11 (52.4%) | 9 (29.0%) | 20 (38.5%) | | | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | | 5 Year Post-Transplant | Living | 12 (38.7%) | 21 (60.0%) | 33 (50.0%) | 9 (42.9%) | 19 (61.3%) | 28 (53.8%) | | | Dead | 19 (61.3%) | 14 (40.0%) | 33 (50.0%) | 12 (57.1%) | 12 (38.7%) | 24 (46.2%) | | | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | ### CLES Pivotal Study A pivotal clinical study, EVP-DEV-LTX-301 (referred to as the CLES Pivotal Study) was conducted to establish reasonable assurance of safety and effectiveness of the CLES (Brand Name: LungFX) device under IDE G170312. Data from the CLES Pivotal Study are the principal basis for the PMA approval decision. A summary of the CLES Pivotal Study is presented below. Clinical results from the HELP and Traditional Feasibility Studies were used to inform the pivotal study's study design and statistical analysis plan. The primary objective of the CLES Pivotal Study was to establish the safety and effectiveness of LungFX to evaluate lungs that would not otherwise be used for transplantation. #### A. Study Design The CLES Pivotal Study, was a prospective, multicenter, open-label, non-randomized study that tracked post-transplant patient management, survival, and reported AEs among {15} P240033 Page 16 recipients of lungs that underwent EVLP with the LungFX device (the EVLP group) and among contemporaneous recipients of lungs that did not undergo EVLP with the LungFX device (non-EVLP group); the contemporaneous non-EVLP recipients were prospectively matched based on pre-specified characteristics (see below), and EVLP recipients were also compared to aggregate contemporaneous results from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) The Primary Endpoint was twelve-month survival within the EVLP group, with a comparison of the EVLP group's twelve-month survival against a pre-specified performance goal; the US Food and Drug Administration (FDA) had indicated that powered hypothesis-testing of the primary endpoint would be necessary to appropriately inform a benefit-risk assessment of the device. The target sample size for the study was 93 subjects in the EVLP group. Safety and effectiveness measures were further assessed by comparing matched cohorts from the EVLP and non-EVLP groups; 75 EVLP subjects were to be matched 1:1 on the following characteristics to the non-EVLP subjects: - Transplant Center - Transplant Type (SLT or DLT) - Lung Allocation Score Disease Diagnosis Group (A, B, C, or D) - Pre-operative use of ECMO Unlike the feasibility study, the pivotal study's protocol explicitly allowed for inclusion of donor lungs conventionally classified as "extended criteria" or "standard criteria" (see below), but this parameter was not a component of the matching process. There was a total of 18 investigational sites, 12 of which transplanted at least 1 lung following evaluation with the LungFX device. Patients were transplanted between April 2019 and December 2022. The database for the CLES Pivotal Study reflects data collected through 29 March 2024 and included 174 patients (94 EVLP, 80 non-EVLP). The study database was locked for analyses of endpoints after the last subject completed their last visit at 12 months, and all ongoing AEs were followed until resolution or for 30 days after the subject's last Study Center visit, whichever occurred first. FDA had indicated that longer-term recipient survival data would be informative and recommended their collection; these data were obtained from an OPTN/SRTR database query as of 31 March 2025. A Data Monitoring Committee (DMC), independent of the Sponsor, was established to monitor subject safety, as well as advise the Sponsor on potential decisions for stopping the study prematurely concerning either EVLP futility or effectiveness as observed in this study. Over the course of the study, when reviewing the safety data, the DMC identified no safety concerns that warranted Sponsor action. A separate Clinical Events Committee (CEC), independent of both the Sponsor and DMC, was charged with adjudicating the relatedness of investigator-reported serious adverse events (SAEs) to EVLP, lung transplantation, and ECMO usage, as well as all deaths reported for a determination of lung graft-related mortality. Adjudication was blinded to transplant group to the extent possible for an open-label study. {16} P240033 Page 17 # 1. Clinical Inclusion and Exclusion Criteria Enrollment in the CLES Pivotal Study was limited to the donor lungs and transplant recipients that met the following criteria. # Donor Lung Inclusion and Exclusion Criteria (Pre-EVLP) Eligible donor lungs included both “standard criteria” and “extended criteria” donor organs. Extended criteria donor lungs were defined as either donation after circulatory death (DCD) or as having two or more of the following: - Final PaO₂/FiO₂ <300 mmHg - Age at death >55 years - Greater than or equal to 20 pack-year smoking history - Diabetes mellitus diagnosis - Evidence of blood infection - Abnormal chest x-ray or computed tomography - Evidence of pulmonary edema Donor lungs that did not meet extended criteria were considered “standard” for the purposes of subgroup analysis. The donor lung and referral process is described in Figure 2 below. Donor lungs were eligible for EVLP evaluation if an Organ Procurement Organization (OPO) verified that those lungs would not otherwise be used for transplantation. Donor lungs could be referred to LBE for EVLP by either a study center investigator or the participating OPO. The protocol did not limit the reasons why donor lungs were determined to be otherwise unusable. However, in all cases OPOs were asked to provide the reason(s) why the lungs would not otherwise be used; common reasons included one or more of the following: - Allocation ended: attempts to place the lungs via match run sequence yielded refusal responses to standard (non-EVLP) offers and the OPO concluded that the lack of remaining allocation time supported the decision for EVLP - Logistics: the OPO did not have time to perform/complete a lung-specific match run. For example, the overall organ donation process may have been accelerated due to donor deterioration, limited operating room availability, donor family request, procurement teams with recipient urgency for other organs, other competing issues requiring donor surgery to be scheduled prior to lung placement, or another procurement team recovering the lungs for an accepting center - DCD - Operating room decline: an unexpected suitability issue was identified at the time of procurement resulting in a decision that the previously designated recipient was no longer appropriate, which also severely limited time for the OPO to reallocate the lungs {17} P240033 Page 18 - Recipient availability: after procurement started, the original intended recipient was unable to receive the transplant, creating a critical timing challenge for the OPO to reallocate the lungs - Other: the OPO determined the lungs would not otherwise be used for transplant for reasons not listed above; in these cases, additional details were provided to verify the lungs met study criteria before proceeding to EVLP Donor lungs were ineligible for EVLP evaluation if 1 or more of the following criteria were met: - Confirmed pneumonia and/or persistent purulent secretions identified via bronchoscopy prior to donor lung excision - Confirmed evidence of aspiration - Significant mechanical lung injury or trauma - HIV or active Hepatitis C - The initial cold ischemic time (CIT-1, the time period spanning donor aortic cross-clamp/initial flush to start of EVLP), which includes organ shipment from the donor site to the Sponsor, estimated to be >10 hours ### Donor Lung Inclusion Criteria (Post-EVLP) To be eligible for transplantation, the donor lung(s) had to complete EVLP, be accepted by the Investigator, and meet the following 3 criteria: - At least 1 of the following 2 standard clinical criteria for transplantation were met at final assessment on the LungFX device: a. Partial pressure of oxygen in arterial blood (PaO₂)/FiO₂ ≥300 mmHg at the end of EVLP; or b. PAP, pulmonary vascular resistance (PVR), and peak airway pressure measurements defined as stable or no more than 20% worse than the Hour 1 assessment (baseline) compared to measurements at the end of EVLP; - The transplant physician was clinically satisfied with the lung evaluation; and - Purulent secretions identified via bronchoscopy prior to donor lung excision, but not considered persistent (i.e., were clear by the Hour 3 assessment). Donor lungs were evaluated for transplant suitability by the Investigator, in consultation with the EVLP team, but ultimately it was the responsibility of the Investigator to accept or decline lungs for the intended recipient. {18} P240033 Page 19  Figure 2: Donor Lung Referral and Evaluation Process For SLT and the first lung of DLT, the maximum allowed total preservation time was 22 hours. The maximum allowed preservation time for the second lung of DLT was 26 hours. ### Clinical Subject (Recipient) Inclusion and Exclusion Criteria Enrollment in the study was limited to patients who met the following inclusion criteria: - 18 years of age or older - Male or female - Actively awaiting a SLT or DLT - Provided informed consent for participation in the study prior to participating in any study-related assessments or procedures - Matched with and underwent transplantation of a donor lung Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: {19} P240033 Page 20 - Listed for same-side lung re-transplantation - Listed for multiple organ transplantation (lung + any other organ) - Listed for live donor lobar lung transplant - Positive for HIV or Burkholderia cenocepacia infection - Received a standard-of-care (non-EVLP) lung transplant, but did not match to an EVLP subject per matching characteristics above - Transplanted with a lung that used another EVLP technology - Current participation in another respiratory or cardiovascular clinical study # 2. Screening and Follow-up Schedule Potential study subjects were screened at any time up to 1 year prior to the day of the lung transplant procedure. The Post-Intervention Period was defined as 12 months or until the initial hospital discharge post-transplant, whichever occurred last. During this period, there were 7 formal study visits that occurred at 24, 48, and 72 hours, as well as Day 30, Day 90, and at Months 6 and 12, post-transplant. During each visit, subject-specific data were collected to inform aggregate safety and effectiveness analyses. Data for longer-term survival was obtained from the OPTN/SRTR registry. # 3. Clinical Endpoints # I. Primary Endpoint The primary endpoint was the 12-month survival rate post-transplant. The Primary Endpoint's statistical analysis was calculation of the posterior probability of EVLP 12-month survival being greater than a pre-specified performance goal, which LBE set at \(81.2\%\). The Primary Endpoint's statistical hypothesis would be met if the posterior probability was greater than 0.95. # II. Secondary Endpoints The secondary endpoints for both the EVLP and non-EVLP groups included: - Adjudicated lung graft-related mortality, measured as the percentage of subject deaths determined to be directly or indirectly related to the transplanted organ - 2016 International Society for Heart and Lung Transplantation (ISHLT) primary graft dysfunction (PGD) score (Grades 0 to 3) at Hours 0 (ICU admission), 24, 48, and 72 post-transplant - Subject survival at Days 30 and 90 and at Months 6 and 12 post-transplant - Rate of CLAD within one year post-transplant, measured as the percentage of subjects diagnosed with CLAD at Day 90, 6 months and 12 months - Duration of ventilator support, measured as the total number of hours where subject required ventilator support prior to the initial hospital discharge post-transplant {20} P240033 Page 21 - Rate of ECMO use, measured as the proportion of subjects that required ECMO support for any reason, at any time prior to the initial hospital discharge post-transplant - ICU length of stay (LOS), measured as total number of days in the ICU until the initial hospital discharge post-transplant, inclusive of ICU readmissions during initial hospitalization - Hospital LOS, measured as the total number of days in the hospital until initial discharge post-transplant - Extended evaluation and preservation time, defined as the elapsed time between donor aortic cross-clamp at procurement and placement of the first stitch in the anastomosis at transplant (recorded separately for each lung in a DLT) - Rate of respiratory failure - Forced expiratory volume in 1 second (FEV₁) The following secondary endpoints were evaluated for the EVLP group only: - Assessment of reported AEs of LungFX lung transplants during subject participation in the study - Utilization rate of EVLP lungs, measured as the number of EVLP procedures resulting in lungs accepted for transplant divided by the number of EVLP procedures performed on lungs referred for EVLP - Increase in use of donor lungs, measured by the number of lungs referred for EVLP and accepted for transplantation at a study center without the use of EVLP Although not a Secondary endpoint, Adverse Events were captured and compared between the EVLP and non-EVLP groups. ### Subgroup Analyses Supplemental analyses of all primary and secondary endpoints were pre-specified for the following subgroups: - Donor lung criteria (extended or standard) Extended criteria donor lungs were defined as meeting the following: - Donation after circulatory death (DCD); or - Two or more of the following: - Final PaO₂/FiO₂ <300 mmHg - Age at death >55 years - Greater than or equal to 20 pack-year smoking history - Diabetes mellitus diagnosis - Evidence of blood infection {21} P240033 Page 22 • Abnormal chest x-ray or computed tomography • Evidence of pulmonary edema Donor lungs that did not meet extended criteria were considered standard criteria. • SLT or DLT • CIT-1: first (pre-EVLP) cold ischemia time (first lung and second lung) • CIT-2: second (post-EVLP) cold ischemia time (first lung and second lung) • Total preservation time (TPT): CIT-1 + EVLP preservation + CIT-2 (first lung and second lung) • Recipient pre-operative ECMO (use or non-use) • Donor lung EVLP referral source (OPO or transplant clinician) • Study center enrollment numbers (high-enrollment or low-enrollment) ### B. Accountability of the CLES Pivotal Study Cohorts There were 642 wait-listed lung transplant candidates screened for enrollment; with enrollment defined as having provided informed consent (up to one year before transplantation) and having undergone a transplantation procedure. At the time of database lock, 174 (27%) were enrolled into the study and 153 (87.9%) patients were available for analysis at the completion of the study, the 12 month post-operative visit on December 22, 2023. There were no subjects lost to follow-up. All subjects who did not complete the study through the 12-month Post-Intervention Period did not complete the study due to death. #### 1. Full Analysis Set The Full Analysis Set (FAS) included all subjects in the EVLP group regardless of subject outcome or subsequent re-transplant. This population was used for the primary analysis and secondary endpoints and safety analyses. There were 94 subjects enrolled in the CLES Pivotal Study who received lungs after EVLP. Data on vital status of all 94 (100.0%) subjects were available for analysis at the completion of the study, Month 12 (Visit 7). No subjects were re-transplanted or lost to follow-up. Note: the FAS is the subset of EVLP subjects within the Ancillary Population Set (below). #### 2. Ancillary Population Set The Ancillary Population Set (APS) included all subjects who received either a transplant by EVLP or standard-of-care (i.e., the “non-EVLP group”). This population was used for the safety analyses and as supportive for the primary and secondary endpoints. There were 174 subjects enrolled in the CLES Pivotal Study (94 EVLP, 80 non-EVLP). Data on vital status of all 174 (100.0%) APS subjects were available for analysis at the completion of the study, Month 12 (Visit 7). There were no subjects lost to follow-up. Note: the FAS (above) is the subset of EVLP subjects within the APS. {22} P240033 Page 23 ### 3. Matched Analysis Set The Matched Analysis Set (MAS) included all subjects in the APS who received either a transplant by EVLP or standard-of-care and were matched 1:1 across study groups by the criteria previously described. This population was added post hoc due to intended 1:1 matching for APS being incomplete at the time of enrollment closure. This population was used as supportive for the primary and secondary endpoints and safety analyses. There were 158 matched subjects enrolled in the CLES Pivotal Study (79 EVLP and 79 non-EVLP). Data on vital status of all 158 (100.0%) MAS subjects were available for analysis at the completion of the study, Month 12 (Visit 7). ### 4. Study Center Enrollment Numbers A total of 12 sites enrolled subjects as shown in Table 4 (APS) and Table 5 (MAS) below. The 3 highest enrolling sites collectively enrolled over half of the study's subjects (56% of APS subjects and 57% of MAS subjects). Table 4: Ancillary Population Set Enrollment | Site Number | Institution Name | EVLP Count | Non-EVLP Count | | --- | --- | --- | --- | | 102 | Cleveland Clinic | 6 | 3 | | 103 | Mayo Clinic Jacksonville | 15 | 14 | | 105 | New York University | 6 | 6 | | 106 | Vanderbilt University | 18 | 16 | | 108 | Duke University | 1 | 1 | | 109 | University of Maryland | 11 | 11 | | 110 | INOVA Fairfax | 20 | 15 | | 111 | Johns Hopkins University | 7 | 7 | | 112 | Newark Beth Israel | 2 | 1 | | 114 | University of Michigan | 1 | 1 | | 116 | Emory University | 2 | 1 | | 117 | Spectrum Health | 5 | 4 | Table 5: Matched Analysis Set Population Enrollment | Site Number | Institution Name | EVLP Count | Non-EVLP Count | | --- | --- | --- | --- | | 102 | Cleveland Clinic | 3 | 3 | | 103 | Mayo Clinic Jacksonville | 14 | 14 | | 105 | New York University | 5 | 5 | | 106 | Vanderbilt University | 16 | 16 | | 108 | Duke University | 1 | 1 | | 109 | University of Maryland | 11 | 11 | | 110 | INOVA Fairfax | 15 | 15 | | 111 | Johns Hopkins University | 7 | 7 | | 112 | Newark Beth Israel | 1 | 1 | | 114 | University of Michigan | 1 | 1 | | 116 | Emory University | 1 | 1 | | 117 | Spectrum Health | 4 | 4 | {23} P240033 Page 24 Abbreviations: DLT, double lung transplant; EVLP, ex vivo lung perfusion; SLT, single lung transplant Source: CLES A full consort diagram of the study is provided in Figure 3, and Table 6 (APS) and Table 7 (MAS) below.  Abbreviations: DLT, double lung transplant; EVLP, ex vivo lung perfusion; SLT, single lung transplant Source: CLES Figure 3: Summary of Subject Cohort Disposition - Ancillary Population Set Table 6: Summary of Subject Cohort Disposition - Ancillary Population Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLTN=25 | DLTN=69 | OverallN=94 | SLTN=23 | DLTN=57 | OverallN=80 | | Completed Study Month 12, n (%) | | | | | | | | Yes | 20 (80.0) | 59 (85.5) | 79 (84.0) | 23 (100) | 51 (89.5) | 74 (92.5) | | No | 5 (20.0) | 10 (14.5) | 15 (16.0) | 0 (0.0) | 6 (10.5) | 6 (7.5) | | Did Not Complete Study Month 12, n (%) | | | | | | | | Death | 5 (20.0) | 10 (14.5) | 15 (16.0) | 0 (0.0) | 6 (10.5) | 6 (7.5) | Abbreviations: DLT, double lung transplant; EVLP, ex vivo lung perfusion; SLT, single lung transplant Note: Ancillary Population Set included subjects who received either EVLP or standard (non-EVLP) transplant. Note: Percentages were based on the total number (N) of subjects in the Ancillary Population Set per group. {24} P240033 Page 25 Table 7: Summary of Subject Cohort Disposition – Matched Analysis Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=22) | DLT(N=57) | Overall(N=79) | SLT(N=22) | DLT(N=57) | Overall(N=79) | | Completed Study Month 12, n (%) | | | | | | | | Yes | 19 (86.4) | 49 (86.0) | 68 (86.1) | 22 (100) | 51 (89.5) | 73 (92.4) | | No | 3 (13.6) | 8 (14.0) | 11 (13.9) | 0 (0.0) | 6 (10.5) | 6 (7.6) | | Did Not Complete Study Month 12, n (%) | | | | | | | | Death | 3 (13.6) | 8 (14.0) | 11 (13.9) | 0 (0.0) | 6 (10.5) | 6 (7.6) | Abbreviations: DLT, double lung transplant; EVLP, ex vivo lung perfusion; SLT, single lung transplant Note: Matched Analysis Set included subjects who received either EVLP or standard (non-EVLP) transplant. Note: Percentages were based on the total number (N) of subjects in the Matched Analysis Set per group. ### C. Study Population Demographics and Baseline Parameters #### Recipients Eighty five of the 94 (90%) EVLP recipients had been on the waiting list for less than one year, while 74 of the 80 (93%) non-EVLP recipients had been on the waiting list for less than 1 year. Medians, means, and ranges of Lung Allocation Scores (LAS) were very similar for EVLP and non-EVLP groups, both at the time of initial listing and at the time of lung matching. The demographics of the study population are shown in Table 8 (APS) and (MAS) below. Of the 174 lung transplant recipients in this study, the median age at enrollment was 60 years (range: 23 to 75) in the EVLP group and 64 years (range: 24 to 74) in the non-EVLP group. Subjects undergoing SLT tended to be older than subjects who underwent DLT. In the APS, the majority of subjects enrolled were male, 62/94 (66.0%) subjects in the EVLP group and 48/80 (60.0%) in the non-EVLP group. There were 9/94 (9.6%) subjects in the EVLP group using ECMO at the time of initial lung allocation, whereas 3/80 (3.8%) in the non-EVLP group were on ECMO. In both groups, most recipients were Lung Allocation Score Disease Diagnosis Group (LASDDG) D (Restrictive Lung Disease), consistent with the representation of LASDDGs on the OPTN waiting list. Table 8: Summary of Subject (Recipient) Demographics and Baseline Characteristics – Ancillary Population Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=25) | DLT(N=69) | Overall(N=94) | SLT(N=23) | DLT(N=57) | Overall(N=80) | | Age at Transplantation (Years) | | | | | | | | Mean | 64.6 | 55.7 | 58.0 | 67.3 | 59.3 | 61.6 | | SD | 6.45 | 10.48 | 10.33 | 3.75 | 10.70 | 9.92 | | Median | 65.0 | 58.0 | 60.0 | 67.0 | 61.0 | 64.0 | | Min – Max | 55 - 75 | 23 - 73 | 23 - 75 | 59 - 72 | 24 - 74 | 24 - 74 | | Sex, n (%) | | | | | | | {25} P240033 Page 26 | Male | 21 (84.0) | 41 (59.4) | 62 (66.0) | 14 (60.9) | 34 (59.6) | 48 (60.0) | | --- | --- | --- | --- | --- | --- | --- | | Female | 4 (16.0) | 28 (40.6) | 32 (34.0) | 9 (39.1) | 23 (40.4) | 32 (40.0) | | Race, n (%) | | | | | | | | Asian | 0 (0.0) | 2 (2.9) | 2 (2.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Black or African American | 2 (8.0) | 15 (21.7) | 17 (18.1) | 1 (4.3) | 13 (22.8) | 14 (17.5) | | White | 21 (84.0) | 49 (71.0) | 70 (74.5) | 18 (78.3) | 43 (75.4) | 61 (76.3) | | Unknown | 1 (4.0) | 3 (4.3) | 4 (4.3) | 2 (8.7) | 0 (0.0) | 2 (2.5) | | Other | 1 (4.0) | 0 (0.0) | 1 (1.1) | 2 (8.7) | 1 (1.8) | 3 (3.8) | | Ethnicity, n (%) | | | | | | | | Hispanic or Latino | 2 (8.0) | 2 (2.9) | 4 (4.3) | 4 (17.4) | 2 (3.5) | 6 (7.5) | | Not Hispanic or Latino | 23 (92.0) | 67 (97.1) | 90 (95.7) | 19 (82.6) | 55 (96.5) | 74 (92.5) | | Unknown | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Height (cm)^{a} | | | | | | | | Mean | 173.25 | 170.08 | 170.92 | 167.86 | 172.12 | 170.89 | | SD | 9.781 | 10.849 | 10.617 | 10.131 | 9.226 | 9.627 | | Median | 173.00 | 170.20 | 172.00 | 170.20 | 175.00 | 172.50 | | Min - Max | 148.6 - 194.0 | 117.8 - 190.5 | 117.8 - 194.0 | 147.3 - 182.9 | 152.4 - 190.5 | 147.3 - 190.5 | | Weight (kg)^{a} | | | | | | | | Mean | 83.49 | 78.71 | 79.98 | 74.51 | 79.02 | 77.72 | | SD | 14.446 | 15.103 | 15.005 | 14.262 | 14.877 | 14.757 | | Median | 79.00 | 79.20 | 79.10 | 68.30 | 81.60 | 80.10 | | Min - Max | 62.6 - 121.4 | 48.5 - 116.0 | 48.5 - 121.4 | 56.1 - 100.1 | 41.5 - 103.4 | 41.5 - 103.4 | | Category | EVLP | | | Non-EVLP | | | | | SLT (N=25) | DLT (N=69) | Overall (N=94) | SLT (N=23) | DLT (N=57) | Overall (N=80) | | BMI (kg/m^{2}) | | | | | | | | Mean | 27.73 | 27.35 | 27.45 | 26.31 | 26.58 | 26.50 | | SD | 3.424 | 6.033 | 5.447 | 3.481 | 4.217 | 4.000 | | Median | 26.29 | 26.93 | 26.91 | 26.51 | 27.24 | 26.86 | | Min - Max | 21.6 - 34.1 | 16.0 - 62.9 | 16.0 - 62.9 | 19.8 - 32.4 | 16.4 - 37.3 | 16.4 - 37.3 | | ECMO Use Status at Time of Initial Lung Allocation, n (%) | | | | | | | | Yes | 0 (0.0) | 9 (13.0) | 9 (9.6) | 0 (0.0) | 3 (5.3) | 3 (3.8) | | No | 25 (100) | 60 (87.0) | 85 (90.4) | 23 (100) | 54 (94.7) | 77 (96.3) | | Lung Allocation Score Disease Diagnosis Group, n (%) | | | | | | | | Group A: Obstructive Lung Disease | 2 (8.0) | 16 (23.2) | 18 (19.1) | 1 (4.3) | 14 (24.6) | 15 (18.8) | | Group B: Pulmonary Vascular Disease | 0 (0.0) | 1 (1.4) | 1 (1.1) | 1 (4.3) | 0 (0.0) | 1 (1.3) | | Group C: Cystic Fibrosis/Immunodeficient Disorders | 0 (0.0) | 5 (7.2) | 5 (5.3) | 0 (0.0) | 3 (5.3) | 3 (3.8) | | Group D: Restrictive Lung Disease | 23 (92.0) | 47 (68.1) | 70 (74.5) | 21 (91.3) | 40 (70.2) | 61 (76.3) | | Lung Allocation Score at Time of Waitlist Addition | | | | | | | | Mean | 41.303 | 46.942 | 45.442 | 43.212 | 43.723 | 43.576 | | SD | 11.2566 | 18.1469 | 16.7260 | 12.6566 | 15.6120 | 14.7457 | | Median | 37.110 | 38.870 | 38.135 | 39.300 | 36.900 | 37.995 | | Min - Max | 33.00 - 85.91 | 30.22 - 90.08 | 30.22 - 90.08 | 32.70 - 87.90 | 32.20 - 89.58 | 32.20 - 89.58 | | Lung Allocation Score at Time of Lung Match | | | | | | | | Mean | 45.589 | 54.887 | 52.414 | 47.445 | 52.986 | 51.393 | {26} P240033 Page 27 | SD | 15.9064 | 22.8604 | 21.5516 | 17.2602 | 21.9369 | 20.7474 | | --- | --- | --- | --- | --- | --- | --- | | Median | 41.000 | 43.170 | 41.400 | 40.830 | 41.380 | 41.105 | | Min - Max | 33.59 - 89.14 | 32.60 - 90.30 | 32.60 - 90.30 | 33.30 - 87.90 | 32.20 - 91.77 | 32.20 - 91.77 | Abbreviations: BMI, body mass index; DLT, double lung transplant; ECMO, extracorporeal membrane oxygenation; EVLP, ex vivo lung perfusion; SLT, single lung transplant a Height is reported from Screening and weight is reported from the Baseline/Admission Visit. Note: Percentages were based on the total number (N) of subjects in the Ancillary Population Set per transplant group. {27} P240033 Page 28 Table 9: Summary of Subject (Recipient) Demographics and Baseline Characteristics – Matched Analysis Set | | EVLP | | | Control | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT (N=22) | DLT (N=57) | Overall (N=79) | SLT (N=22) | DLT (N=57) | Overall (N=79) | | **Age at transplantation (years)** | | | | | | | | Mean | 64.2 | 57.2 | 59.1 | 67.2 | 59.3 | 61.5 | | SD | 6.30 | 9.63 | 9.34 | 3.79 | 10.70 | 9.94 | | Median | 65.0 | 59.0 | 61.0 | 67.0 | 61.0 | 64.0 | | Min - Max | 55–75 | 23–73 | 23–75 | 59–72 | 24–74 | 24–74 | | n | 22 | 57 | 79 | 22 | 57 | 79 | | **Gender** | | | | | | | | Male | 18 (81.8%) | 34 (59.6%) | 52 (65.8%) | 14 (63.6%) | 34 (59.6%) | 48 (60.8%) | | Female | 4(18.2%) | 23(40.4%) | 27 (34.2%) | 8 (36.4%) | 23 (40.4%) | 31 (39.2%) | | **Race** | | | | | | | | American Indian/Alaska Native | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Asian | 0 (0.0%) | 1 (1.8%) | 1 (1.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Black or African American | 2 (9.1%) | 13 (22.8%) | 15 (19.0%) | 1 (4.5%) | 13 (22.8%) | 14 (17.7%) | | Native Hawaiian/Pacific Islander | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | White | 19 (86.4%) | 40 (70.2%) | 59 (74.7%) | 17 (77.3%) | 43 (75.4%) | 60 (75.9%) | | Unknown | 1 (4.5%) | 3 (5.3%) | 4 (5.1%) | 2 (9.1%) | 0 (0.0%) | 2 (2.5%) | | Other | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (9.1%) | 1 (1.8%) | 3 (3.8%) | | **Ethnicity** | | | | | | | | Hispanic or Latino | 1 (4.5%) | 1 (1.8%) | 2 (2.5%) | 4 (18.2%) | 2 (3.5%) | 6 (7.6%) | | Not Hispanic or Latino | 21 (95.5%) | 56 (98.2%) | 77 (97.5%) | 18 (81.8%) | 55 (96.5%) | 73 (92.4%) | | Unknown | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | **Height (cm)^{a}** | | | | | | | | Mean | 173.50 | 169.35 | 170.50 | 168.68 | 172.12 | 171.16 | | SD | 10.407 | 11.270 | 11.129 | 9.555 | 9.226 | 9.386 | | Median | 174.00 | 170.00 | 170.20 | 171.25 | 175.00 | 172.70 | | Min–Max | 148.6–194.0 | 117.0–190.5 | 117.0–194.0 | 147.3–182.9 | 152.4–190.5 | 147.3–190.5 | | n | 22 | 57 | 79 | 22 | 57 | 79 | | **Weight (kg)^{a}** | | | | | | | | Mean | 84.14 | 79.03 | 80.46 | 74.79 | 79.02 | 77.84 | | SD | 14.987 | 15.185 | 15.210 | 14.532 | 14.877 | 14.812 | | Median | 79.20 | 78.10 | 79.00 | 69.90 | 81.60 | 80.70 | | Min–Max | 62.6–121.4 | 48.5–116.0 | 48.5–121.4 | 56.1–100.1 | 41.5–103.4 | 41.5–103.4 | | n | 22 | 57 | 79 | 22 | 57 | 79 | | **BMI (kg/m)** | | | | | | | | Mean | 27.86 | 27.71 | 27.75 | 26.12 | 26.58 | 26.45 | | SD | 3.537 | 6.210 | 5.573 | 3.442 | 4.217 | 4.000 | {28} P240033 Page 29 | Median | 27.19 | 27.61 | 27.61 | 26.49 | 27.24 | 26.64 | | --- | --- | --- | --- | --- | --- | --- | | Min-Max | 21.6-34.1 | 17.3-62.9 | 17.3-62.9 | 19.8-32.4 | 16.4-37.3 | 16.4-37.3 | | n | 22 | 57 | 79 | 22 | 57 | 79 | | ECMO Use Status at time of initial lung allocation | | | | | | | | Yes | 0 (0.0%) | 3 (5.3%) | 3 (3.8%) | 0 (0.0%) | 3 (5.3%) | 3 (3.8%) | | No | 22 (100%) | 54 (94.7%) | 76 (96.2%) | 22 (100%) | 54 (94.7%) | 76 (96.2%) | | Lung Allocation Score Disease Diagnosis Group | | | | | | | | Group A: Obstructive Lung Disease | 1 (4.5%) | 14 (24.6%) | 15 (19.0%) | 1 (4.5%) | 14 (24.6%) | 15 (19.0%) | | Group B: Pulmonary Vascular Disease | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Group C: Cystic Fibrosis of Immunodeficient Disorders | 0 (0.0%) | 3 (5.3%) | 3 (3.8%) | 0 (0.0%) | 3 (5.3%) | 3 (3.8%) | | Group D: Restrictive Lung Disease | 21 (95.5%) | 40 (70.2%) | 61 (77.2%) | 21 (95.5%) | 40 (70.2%) | 61 (77.2%) | | Lung Allocation Score at Time of Waitlist Addition | | | | | | | | Mean | 41.646 | 44.727 | 43.869 | 43.453 | 43.723 | 43.648 | | SD | 11.9592 | 16.4218 | 15.2987 | 12.9003 | 15.6120 | 14.8259 | | Median | 36.845 | 38.140 | 38.080 | 39.860 | 36.900 | 38.080 | | Min-Max | 33.00-85.91 | 30.22-88.58 | 30.22-88.58 | 32.70-87.90 | 32.20-89.58 | 32.20-89.58 | | n | 22 | 57 | 79 | 22 | 57 | 79 | | Lung Allocation Score at Time of Lung Match | | | | | | | | Mean | 46.500 | 52.608 | 50.907 | 47.931 | 52.986 | 51.578 | | SD | 16.7693 | 21.9938 | 20.7508 | 17.5044 | 21.9369 | 20.8132 | | Median | 41.150 | 40.460 | 41.000 | 41.265 | 41.380 | 41.380 | | Min-Max | 33.59-89.14 | 32.60-90.30 | 32.60-90.30 | 33.30-87.90 | 32.20-91.77 | 32.20-91.77 | | n | 22 | 57 | 79 | 22 | 57 | 79 | Abbreviations: BMI, body mass index; DLT, double lung transplant; ECMO, extracorporeal membrane oxygenation; EVLP, ex vivo lung perfusion; SLT, single lung transplant a Height is reported from Screening and weight is reported from the Baseline/Admission Visit. Note: Percentages were based on the total number (N) of subjects in the Ancillary Population Set per transplant group. ### Donors A total of 326 deceased donors were referred to LBE for EVLP during the study. There were 135 of the referred donors (41%) declined for EVLP based on the exclusion criteria listed above, and an additional 40 (12%) were declined for transplantation by any investigator after EVLP. There were 131 donor lung referrals (40%) accepted for EVLP and 91 were ultimately accepted for transplantation. However, 60 additional referrals were transplanted without having undergone CLES EVLP; 53 (88%) of these 60 donor lungs were implanted into non-study patients conventionally after in-situ assessments made by investigators. {29} P240033 Page 30 Of the 326 lung referrals 91 donor lungs (28%); underwent EVLP followed by post-EVLP transplantation, into 94 recipients (3 of the bilateral lungs donated were split between 6 transplant recipients). Overall, 26/91 EVLP donors (29%) were DCD; only 2 non-EVLP donors were DCD. Importantly, commercial use of normothermic machine perfusion of “non-EVLP” group donor lungs was not included in this study, but the Scientific Registry of Transplant Recipients reports that in 2024 18% of all US lung donations were DCD. DCD was in fact the most frequently cited criterion (Table 10) for EVLP referral among FAS subjects (26/94 (28%), with 3 EVLP donors yielding SLT for 6 recipients), followed by intra-operative decline of provisionally accepted non-EVLP donor lungs. One quarter of the referrals were for non-specific “logistical challenges.” Of the 94 EVLP transplantations, 8 (9%) came from lung referrals made to LBE by the OPO, as opposed to by an investigator. Table 10: Summary of Reasons for EVLP Referral (Full Analysis Set) | Reason for Referral\( ^{a} \) | n/N(%) | | --- | --- | | Donation after Circulatory Death | 26/94 (27.7%) | | OR Decline | 25/94 (26.6%) | | Logistical Challenges | 23/94 (24.5%) | | Allocation Ended | 9/94 (9.6%) | | Recipient Availability | 4/94 (4.3%) | | Other (verbatim reasons provided below) | 11/94 (11.7%) | | Aggressive placement due to low \( PaO_{2} \) | 1/11 (0.9%) | | Declining Donor \( PaO_{2} \) w/ susp pulm edema +/- atl | 1/11 (0.9%) | | Donor instability prior to the OR | 1/11 (0.9%) | | Low \( PaO_{2} \) | 1/11 (0.9%) | | NA-NYUC accepted right lung from OR | 1/11 (0.9%) | | Requesting LungBio due to Medical quality – low \( PaO_{2} \) | 1/11 (0.9%) | | Study Center Investigator requires assessment | 1/11 (0.9%) | | Surgeon believes lungs have marginal oxygenation | 1/11 (0.9%) | | VAFH to place on EVLP due to decline in \( PaO_{2} \) | 1/11 (0.9%) | | X-ray, CT and gases showing marginal lung | 1/11 (0.9%) | | No reason provided | 1/11 (0.9%) | \( ^{a} \) Subjects may have more than one reason for referral. List of multiple referral reasons include: 103-0033: Logistical Challenges/Recipient Availability 106-0002: Donation after Circulatory Death/OR Decline 110-0007: Logistical Challenges/Recipient Availability 112-0023: Allocation Ended/Recipient Availability A total of 168 donors provided lungs in this study to 94 recipients in the EVLP group and 80 recipients in the non-EVLP group. Median donor age at death was 41 years (range: 14 to 61) in the EVLP group and 33 years (range: 15 to 59) in the non-EVLP group (Table 11). Three EVLP donors provided SLT to 6 recipients, and 1 non-EVLP provided SLT to 2 recipients; donor information for 2 non-EVLP recipients was not available because authorization for research was not documented in the donor records. Extended criteria lungs, as defined above, accounted for approximately half (37/77 (48%)) of the donors for the non-EVLP group's APS population. Conversely, the majority of donors in the EVLP group's FAS and APS (68/91 (75%)) were extended criteria. {30} P240033 Page 31 Among extended criteria donors, 26 of the 68 EVLP (38%) were classified as such on the basis of DCD, whereas only 2 of the 37 (5%) non-EVLP extended criteria donors were DCD. Table 11: Summary of Donor Demographics and Baseline Characteristics – Ancillary Population Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT (N=22) | DLT (N=69) | Overall (N=91) | SLT (N=22) | DLT (N=55) | Overall (N=77) | | **Donor Lung Criteria, n (%)** | | | | | | | | Standard | 1 (4.5) | 22 (31.9) | 23 (25.3) | 11 (50.0) | 29 (52.7) | 40 (51.9) | | Extended | 21 (95.5) | 47 (68.1) | 68 (74.7) | 11 (50.0) | 26 (47.3) | 37 (48.1) | | **Donation After Circulatory Death, n (%)** | | | | | | | | Yes | 6 (27.3) | 20 (29.0) | 26 (28.6) | 0 (0.0) | 2 (3.6) | 2 (2.6) | | No | 16 (72.7) | 49 (71.0) | 65 (71.4) | 22 (100) | 53 (96.4) | 75 (97.4) | | **Age at Death (Years)** | | | | | | | | Mean | 41.3 | 37.7 | 38.6 | 36.6 | 34.1 | 34.8 | | SD | 14.08 | 12.48 | 12.89 | 13.69 | 11.97 | 12.45 | | Median | 42.5 | 39.0 | 41.0 | 36.5 | 33.0 | 33.0 | | Min - Max | 15 - 61 | 14 - 58 | 14 - 61 | 17 - 59 | 15 - 59 | 15 - 59 | | **Sex, n (%)** | | | | | | | | Male | 17 (77.3) | 37 (53.6) | 54 (59.3) | 14 (63.6) | 37 (67.3) | 51 (66.2) | | Female | 5 (22.7) | 32 (46.4) | 37 (40.7) | 8 (36.4) | 18 (32.7) | 26 (33.8) | | **Race, n (%)** | | | | | | | | Asian | 1 (4.5) | 0 (0.0) | 1 (1.1) | 0 (0.0) | 1 (1.8) | 1 (1.3) | | Black or African American | 5 (22.7) | 20 (29.0) | 25 (27.5) | 3 (13.6) | 16 (29.1) | 19 (24.7) | | White | 14 (63.6) | 43 (62.3) | 57 (62.6) | 16 (72.7) | 32 (58.2) | 48 (62.3) | | Unknown | 2 (9.1) | 6 (8.7) | 8 (8.8) | 2 (9.1) | 6 (10.9) | 8 (10.4) | | Other | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (4.5) | 0 (0.0) | 1 (1.3) | | **Height (cm)** | | | | | | | | Mean | 175.87 | 170.70 | 171.95 | 171.46 | 172.55 | 172.24 | | SD | 8.161 | 9.601 | 9.494 | 9.925 | 9.994 | 9.921 | | Median | 175.13 | 170.18 | 173.00 | 170.00 | 173.00 | 173.00 | | Min - Max | 163.0 - 188.0 | 140.0 - 185.0 | 140.0 - 188.0 | 157.5 - 191.0 | 147.0 - 193.0 | 147.0 - 193.0 | {31} P240033 Page 32 | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=22) | DLT(N=69) | Overall(N=91) | SLT(N=22) | DLT(N=55) | Overall(N=77) | | Weight (kg) | | | | | | | | Mean | 86.17 | 85.96 | 86.01 | 74.62 | 77.35 | 76.57 | | SD | 26.121 | 21.179 | 22.318 | 16.983 | 17.705 | 17.435 | | Median | 80.55 | 83.00 | 81.60 | 73.10 | 77.00 | 76.20 | | Min - Max | 56.1 - 174.0 | 53.6 - 171.0 | 53.6 - 174.0 | 45.9 - 113.6 | 42.6 - 141.0 | 42.6 - 141.0 | | Primary Cause of Death, n (%) | | | | | | | | Anoxia/Cardiac Arrest | 8 (36.4) | 29 (42.0) | 37 (40.7) | 6 (27.3) | 18 (32.7) | 24 (31.2) | | Head Trauma | 7 (31.8) | 18 (26.1) | 25 (27.5) | 9 (40.9) | 23 (41.8) | 32 (41.6) | | Cerebrovascular/Stroke | 5 (22.7) | 20 (29.0) | 25 (27.5) | 7 (31.8) | 12 (21.8) | 19 (24.7) | | CNS Tumor | 1 (4.5) | 0 (0.0) | 1 (1.1) | 0 (0.0) | 1 (1.8) | 1 (1.3) | | Other | 1 (4.5) | 2 (2.9) | 3 (3.3) | 0 (0.0) | 1 (1.8) | 1 (1.3) | | Age of Death Over 55 Years, n (%) | | | | | | | | Yes | 7 (31.8) | 6 (8.7) | 13 (14.3) | 3 (13.6) | 4 (7.3) | 7 (9.1) | | No | 15 (68.2) | 63 (91.3) | 78 (85.7) | 19 (86.4) | 51 (92.7) | 70 (90.9) | | Diabetes Diagnosis Status, n (%) | | | | | | | | Yes | 4 (18.2) | 12 (17.4) | 16 (17.6) | 0 (0.0) | 3 (5.5) | 3 (3.9) | | No | 18 (81.8) | 57 (82.6) | 75 (82.4) | 20 (90.9) | 47 (85.5) | 67 (87.0) | | Unknown | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (9.1) | 3 (5.5) | 5 (6.5) | | Does the Donor Have a History of Smoking Less Than 20 Pack-Years, n (%) | | | | | | | | Yes | 15 (68.2) | 47 (68.1) | 62 (68.1) | 18 (81.8) | 32 (58.2) | 50 (64.9) | | No | 4 (18.2) | 9 (13.0) | 13 (14.3) | 0 (0.0) | 3 (5.5) | 3 (3.9) | | Unknown | 3 (13.6) | 13 (18.8) | 16 (17.6) | 4 (18.2) | 20 (36.4) | 24 (31.2) | | Chest X-ray Normal Without Infiltrate, n (%) | | | | | | | | Yes | 3 (13.6) | 14 (20.3) | 17 (18.7) | 2 (9.1) | 18 (32.7) | 20 (26.0) | | No | 19 (86.4) | 55 (79.7) | 74 (81.3) | 19 (86.4) | 34 (61.8) | 53 (68.8) | | Unknown | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (4.5) | 3 (5.5) | 4 (5.2) | | Bronchoscopy Normal Without Significant Secretions, n (%) | | | | | | | | Yes | 8 (36.4) | 37 (53.6) | 45 (49.5) | 12 (54.5) | 25 (45.5) | 37 (48.1) | | No | 10 (45.5) | 19 (27.5) | 29 (31.9) | 9 (40.9) | 27 (49.1) | 36 (46.8) | | Unknown | 1 (4.5) | 2 (2.9) | 3 (3.3) | 1 (4.5) | 3 (5.5) | 4 (5.2) | | Not Done | 3 (13.6) | 11 (15.9) | 14 (15.4) | 0 (0.0) | 0 (0.0) | 0 (0.0) | {32} P240033 Page 33 | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=22) | DLT(N=69) | Overall(N=91) | SLT(N=22) | DLT(N=55) | Overall(N=77) | | Sputum Gram Stain Absent of Organisms, n (%) | | | | | | | | Yes | 4 (18.2) | 15(21.7) | 19(20.9) | 5 (22.7) | 10(18.2) | 15(19.5) | | No | 4 (18.2) | 20(29.0) | 24(26.4) | 7 (31.8) | 23(41.8) | 30(39.0) | | Unknown | 6 (27.3) | 16(23.2) | 22(24.2) | 1 (4.5) | 11(20.0) | 12(15.6) | | Not Done | 8 (36.4) | 18(26.1) | 26(28.6) | 9 (40.9) | 11(20.0) | 20(26.0) | | Final \( PaO_2/FiO_2 \) Ratio Less Than 300 mmHg, n (%) | | | | | | | | Yes | 2 (9.1) | 9 (13.0) | 11(12.1) | 1 (4.5) | 1 (1.8) | 2 (2.6) | | No | 20 (90.9) | 60(87.0) | 80(87.9) | 21(95.5) | 54(98.2) | 75(97.4) | ### Organ Preservation Times For non-EVLP recipients, total preservation time (TPT) of each transplanted lung was comprised of a single cold ischemic time period (CIT-1) that spanned the period from donor aortic cross-clamping until initiation of an anastomosis within the recipient's chest cavity; SLT accordingly had one CIT-1, and DLT had two CIT-1s. For EVLP recipients, TPT of each transplanted lung was comprised of three distinct time periods: CIT-1 (time between donor aortic cross-clamping and initiation of device EVLP); a normothermic EVLP time (time between EVLP initiation and cessation); and a second cold ischemic time (CIT-2) that spanned the time from EVLP cessation until initiation of an anastomosis within the recipient's chest cavity after organ transport with cold static storage preservation. EVLP SLT had one CIT-1, one EVLP time, and one CIT-2, while EVLP DLT had one CIT-1, one EVLP time, and two CIT-2s. The protocol stipulated that TPT for SLT and first lung of DLT be \( \leq \) 22 hours; and that TPT for second lung of DLT be \( \leq \) 26 hours. The breakdown of TPT is below • EVLP time ≥3 hours but ≤6 hours • CIT-1 ≤10 hours • First lung CIT-2 ≤6 hours • Second lung CIT-2 be 10 hours Table 12 and Table 13 show the preservation times for recipients' allografts in the Ancillary Population Set and the Matched Analysis Set, respectively. For APS, in the EVLP group, overall median TPT for first lung was 13.11 hours (range: 7.8 to 18.4), and overall median TPT for second lung was 15 hours (range: 8.1 to 20.1). In the non-EVLP group, overall median TPT for first lung was 3.08 hours (range: 1.0 to 7.6), and overall median TPT for second lung was 4.90 hours (range: 1.0 to 9.3). As expected, TPT was markedly longer (mean and median ~10 hours longer) for EVLP than for non-EVLP, which had mean and median cold ischemic times of approximately 3.5 hours (first lung) and 5 hours (second lung). Most of the increased preservation time with EVLP as {33} P240033 Page 34 compared to non-EVLP was secondary to the need for two separate periods of cold static preservation; EVLP perfusion time was fairly consistent, at approximately 4 hours. Scatter plots of EVLP and non-EVLP subjects' key preservation times are shown in Figure 4 and Figure 5. Ancillary analyses of endpoints stratified by preservation times were performed (see below). Table 12 Summary of Total Preservation Time - Ancillary Population Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=25) | DLT(N=69) | Overall(N=94) | SLT(N=23) | DLT(N=57) | Overall(N=80) | | TPT First Lung (Hours) | | | | | | | | Mean | 13.16 | 13.12 | 13.13 | 3.35 | 3.36 | 3.36 | | SD | 1.807 | 2.447 | 2.285 | 1.208 | 1.208 | 1.200 | | Median | 13.13 | 13.08 | 13.11 | 3.10 | 3.05 | 3.08 | | Min - Max | 10.6 - 18.2 | 7.8 - 18.4 | 7.8 - 18.4 | 1.1 - 5.9 | 1.0 - 7.6 | 1.0 - 7.6 | | n | 25 | 69 | 94 | 23 | 55 | 78 | | TPT Second Lung (Hours) | | | | | | | | Mean | | 14.55 | 14.55 | | 4.89 | 4.89 | | SD | | 2.896 | 2.896 | | 1.591 | 1.591 | | Median | | 15.00 | 15.00 | | 4.90 | 4.90 | | Min - Max | | 8.1 - 20.1 | 8.1 - 20.1 | | 1.0 - 9.3 | 1.0 - 9.3 | | n | | 69 | 69 | | 55 | 55 | | CIT-1 (Hours) | | | | | | | | Mean | 5.39 | 5.51 | 5.48 | | | | | SD | 1.226 | 1.601 | 1.505 | | | | | Median | 5.17 | 5.37 | 5.30 | | | | | Min - Max | 3.7 - 8.8 | 2.4 - 9.7 | 2.4 - 9.7 | | | | | n | 25 | 69 | 94 | | | | | EVLP Time (Hours) | | | | | | | | Mean | 3.89 | 3.86 | 3.87 | | | | | SD | 0.520 | 0.350 | 0.400 | | | | | Median | 3.68 | 3.80 | 3.79 | | | | | Min - Max | 3.4 - 5.4 | 3.4 - 5.4 | 3.4 - 5.4 | | | | | n | 25 | 69 | 94 | | | | {34} P240033 Page 35 | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=25) | DLT(N=69) | Overall(N=94) | SLT(N=23) | DLT(N=57) | Overall(N=80) | | CIT-2 First Lung (Hours) | | | | | | | | Mean | 3.89 | 3.75 | 3.78 | | | | | SD | 1.649 | 1.328 | 1.413 | | | | | Median | 3.90 | 3.92 | 3.92 | | | | | Min - Max | 1.3 - 9.3 | 1.2 - 6.1 | 1.2 - 9.3 | | | | | n | 25 | 69 | 94 | | | | | CIT-2 Second Lung (Hours) | | | | | | | | Mean | | 5.17 | 5.17 | | | | | SD | | 1.919 | 1.919 | | | | | Median | | 5.65 | 5.65 | | | | | Min - Max | | 1.4 - 8.3 | 1.4 - 8.3 | | | | | n | | 69 | 69 | | | | Table 13: Summary of Total Preservation Time – Matched Analysis Set | Category | EVLP | | | Non-EVLP | | | | --- | --- | --- | --- | --- | --- | --- | | | SLT(N=22) | DLT(N=57) | Overall(N=79) | SLT(N=22) | DLT(N=57) | Overall(N=79) | | TPT First Lung (Hours) | | | | | | | | Mean | 13.18 | 13.33 | 13.29 | 3.25 | 3.36 | 3.33 | | SD | 1.859 | 2.307 | 2.181 | 1.127 | 1.208 | 1.179 |…