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1 Supplementary Online Content Sciurba FC, Criner GJ, Strange C, et al; RENEW Study Research Group. Effect of endobronchial coils vs usual care on exercise tolerance in patients with severe emphysema: the RENEW randomized clinical trial. JAMA. doi: /jama eappendix. Additional Methods efigure 1. Typical Sagittal CT Slice Demonstrating Homogeneous vs. Heterogeneous Disease Distribution efigure 2. Elevair Endobronchial Coils of Different Coil Lengths efigure 3. Chest Radiograph Post Bilateral Coil Treatment etable 1. Definition of Major Complications etable 2. Criteria for Diagnosis and Treatment of Serious Coil Associated Opacity Events efigure 4. Local Tissue Reaction Characteristic of Coil Associated Opacity etable 3. Baseline Non-Respiratory Comorbidities-of-Interest efigure 5. Distribution of Non-Respiratory Comorbidity Frequency etable 4. Procedure and Device Results etable 5a. Primary Efficacy Analysis: Rank-Transformed 6-Minute Walk Distance After MCMC Multiple Imputation - ITT Population etable 5b. Secondary Endpoint Analysis: Rank-Transformed Percent Change in FEV1 After MCMC Multiple Imputation - ITT Population etable 6a. Descriptive Summary of Disease Characteristics by Visit Through 12 Months for Complete Cases (Part 1 of 2) etable 6b. Descriptive Summary of Disease Characteristics by Visit Through 12 Months for Complete Cases (Part 2 of 2) etable 7. Effectiveness Based on Combined Hyperinflation and Emphysema Distribution Subgroups ITT Population efigure 6. Risk Stratification Algorithm Based on Hyperinflation and Emphysema Distribution - ITT Population, Post-Hoc Analysis etable 8a. 6-Minute Walk Distance by Detailed Baseline Residual Volume After MCMC Multiple Imputation - ITT Population etable 8b. St. George s Respiratory Questionnaire After MCMC Multiple Imputation by Detailed Baseline Residual Volume, ITT Population etable 8c. Percent Change in FEV1 by Detailed Baseline Residual Volume After MCMC Multiple Imputation - ITT Population etable 9. Impact of Co-morbidity Prevalence on Efficacy Measures ITT Population etable 10. Impact of Cardiac Co-morbidity Presence on Efficacy Measures ITT Population etable 11. # of Non-respiratory Comorbidities and Proportion With Cardiac Disease by RV% and Treatment Complete Cases etable 12. Listing of Deaths Through 12 Months, All Cause, ITT Population etable 13. Serious Adverse Events Through 12 Months, Safety Population etable 14. Major Complications Through 12 Months by Time Period, Safety Population etable 15. Results of DMC Adjudication of Pneumonia Adverse Events etable 16a. Change in Effectiveness Endpoints at 12 Months From Baseline for Coil participants, with Confirmed Coil Associated Opacities, Confirmed or Unadjudicable Pneumonia, and With Neither Coil Associated Opacity nor Pneumonia (ITT Population) etable 16b. Change in Effectiveness Endpoints at 12 Months From Baseline for Control Participants With or Without Pneumonia (ITT Population) This supplementary material has been provided by the authors to give readers additional information about their work.

2 eappendix. Additional Methods Participants: Inclusion Criteria: years of age. 2. CT scan indicates bilateral emphysema, as determined by the Core Radiology Lab using the criteria presented in the "CT Scoring Plan for Core Radiology Lab". 3. has post-bronchodilator FEV 1 45% predicted. 4. has Total Lung Capacity >100% predicted. 5. has residual volume (RV) 175% predicted. 6. has marked dyspnea scoring 2 on mmrc scale of has stopped smoking for at least 8 weeks prior to entering the study, as confirmed by a Cotinine test or other appropriate diagnostic test. 8. has read, understood and signed the Informed Consent form. 9. has completed a pulmonary rehabilitation program within 6 months prior to treatment and/or is regularly performing maintenance respiratory rehabilitation if initial supervised therapy occurred more than 6 months prior to baseline testing. 10. has received Pneumococcal and Influenza vaccinations consistent with local recommendations and/or policy. 11. If treated in France, Participant must be entitled to French social security. Exclusion Criteria: 1. has severe homogeneous emphysema as determined by the Core Radiology Lab using the criteria presented in the "CT Scoring Plan for Core Radiology Lab." 2. has co-morbidities that may significantly reduce participant s ability to improve exercise capacity (e.g. severe arthritis, planned knee surgery) or baseline limitation on 6-minute-walk distance is not due to dyspnea. 3. has a change in FEV 1 >20% (or, for participants with pre-bronchodilator FEV1 below 1 L, a change of >200 ml) post-bronchodilator unless investigator can confirm by other means that participant does not have asthma. 4. has D L CO <20% of predicted. 5. has severe gas exchange abnormalities as defined by: PaCO 2 >55 mm Hg PaO 2 <45 mm Hg on room air (High altitude criterion: PaO 2 <30 mm Hg) 6. has a history of recurrent clinically significant respiratory infections, defined as 3 hospitalizations for respiratory infection during the year prior to enrollment. 7. has severe pulmonary hypertension defined by right ventricular systolic pressure >50 mm Hg via right heart catheterization and/or echocardiogram. 8. has an inability to walk >140 meters (150 yards) in 6 minutes. 9. has evidence of other severe disease (such as, but not limited to, lung cancer or renal failure), which in the judgment of the investigator may compromise survival of the participant for the duration of the study. 10. is pregnant or lactating, or plans to become pregnant within the study timeframe. 11. has an inability to tolerate bronchoscopy under moderate sedation or general anesthesia. 12. has clinically significant bronchiectasis. 13. has giant bullae >1/3 lung volume. 14. has had previous LVR surgery, lung transplantation, lobectomy, LVR devices or other devices to treat COPD in either lung. 15. has been involved in pulmonary drug or device studies within 30 days prior to this study. 16. is taking >20 mg prednisone (or equivalent dose of a similar steroid) daily. 17. requires high level chronic immunomodulatory therapy to treat a moderate to severe chronic inflammatory autoimmune disorder.

3 18. is on an antiplatelet agent (such as Plavix) or anticoagulant therapy (such as heparin or Coumadin) which cannot be stopped for seven (7) days prior to procedure. 19. has a sensitivity or allergy to nitinol (nickel titanium) or its constituent metals. 20. has a known sensitivity to drugs required to perform bronchoscopy. 21. has been diagnosed with alpha-1 antitrypsin deficiency (AATD). 22. has any other disease, condition(s) or habit(s) that would interfere with completion of study and follow-up assessments, would increase risks of bronchoscopy or assessments, or in the judgment of the investigator would potentially interfere with compliance to this study or would adversely affect study outcomes. 23. If treated in France, participant is a "personne vulnerable" as defined by French regulation. Adjudication of Pneumonia Events for Coil Associated Opacity Background: During the course of the RENEW Study, PneumRx and study investigators became aware of a localized tissue response that occurred post-coil implantation, which we have termed Coil Associated Opacity. Coil Associated Opacity sometimes presented with symptoms similar to infectious pneumonia and this made it difficult to distinguish between them. The Data Monitoring Committee (DMC) recommended investigating Coil Associated Opacity further with the help of an advisory committee of experienced RENEW investigators. An advisory committee developed a methodology for distinguishing between Coil Associated Opacity and infectious pneumonia and recommendations for diagnosis and treatment for these events which was reviewed and approved by the DMC. It was noted that while some degree of Coil Associated Opacity can occur up to 2 months following the Coil procedure, most of these events were asymptomatic or symptomatically mild, resolve with limited intervention, and do not develop into SAEs. However, on occasion, these events do become serious and in that case, Coil Associated Opacity can be difficult to differentiate from pneumonia. The DMC and advisory committee identified a number of distinguishing characteristics between the 2 events which were summarized in etable 1 below. Statistical Methods (Detailed Summary) Effectiveness analyses were performed for both the ITT and PP populations, with the primary analysis based on the ITT population. The intent-to-treat (ITT) population was defined as all participants randomized. The PP population was defined as all participants who completed the study without noteworthy protocol violations. The hypothesis testing for superiority of the primary effectiveness endpoint was one-sided at α = significance level. The hypothesis testing for superiority of the secondary endpoints was one-sided with adjustments on family wise type I error at α = 0.025, using the Hochberg step-up procedure. All missing 12-month values for primary and secondary effectiveness endpoints were estimated by multiple imputation. Missing values were imputed 50 times using the Markov Chain Monte Carlo method. Analysis of the imputed datasets was conducted according to the statistical methods described below. Multiple imputation analysis results were combined using the standard methods described by Rubin and available in statistical packages (eg, SAS PROC MIANALYZE) for means and confidence intervals or as the median of percentiles for median and IQR. For additional detail, see the statistical analysis plan. Baseline comparability between treatment groups was assessed for demographics, baseline disease characteristics and comorbidities using analysis of variance (ANOVA) with factors for treatment and investigational site or Cochran-Mantel-Haenszel (CMH) test stratified by investigational site; unless Cochran s rule was not satisfied, where Fisher s exact test was used.

4 Comparison of endobronchial coils versus Control in the primary effectiveness endpoint, change from baseline to 12 months in 6-minute-walk Distance, was tested using rank ANCOVA controlling for the covariates of baseline 6-minute-walk Distance, analysis center and emphysema status. Graphical examination and Shapiro-Wilk test of the residuals from parametric ANCOVA revealed significant skewness. (CI) between treatment differences were calculated using the Hodges-Lehman estimator after covariate adjustment for baseline 6-minute-walk distance. Additional sensitivity analyses of the primary endpoint were conducted to assess poolability across analysis centers and robustness of results to missing data handling methods and protocol deviations. The secondary endpoint of percent change in FEV1 was compared between treatments using the same methods as for the primary endpoint, also due to non-normality of residuals. Responders in 6-minute-walk Distance were defined as improving at least 25 meters. Response rates were compared between treatments using a logistic regression model controlling for the covariates of baseline 6-minute-walk Distance, analysis center and emphysema status. The full logistic regression model resulted in an incomplete convergence due to a quasi-complete separation with one analysis center. Therefore, results of 6-minute-walk Distance responder rates using a logistic regression model with factors of baseline 6-minute-walk Distance and emphysema status and treatment group were reported, including the odds ratio (CI), within group proportions (CI) and frequency (n) estimated from multiple imputation. Comparison of coils versus Control in the secondary effectiveness endpoint of change in Saint George s Respiratory Questionnaire was tested using ANCOVA controlling for the covariates of baseline Saint George s Respiratory Questionnaire, analysis center and emphysema status. Mean (CI) between treatment differences adjusted for covariates from ANCOVA were reported. Other effectiveness endpoints included Saint George s Respiratory Questionnaire responder analysis (responders were defined as a decreased of at least 4 points in Saint George s Respiratory Questionnaire) which was analyzed using logistic regression and the absolute differences in RV and RV/TLC, which was analyzed using ANCOVA, with factors for baseline covariates, emphysema status, analysis center and treatment group. Analyses of other effectiveness endpoints were not adjusted for multiple comparisons. Post-hoc analyses compared effectiveness between Coil and Control separately by pre-specified subgroups for type of emphysema and baseline RV% (<225% or 225%), by high ( 4) and low (0-3) number of non-respiratory comorbidities, by presence or absence of cardiac comorbidity and by presence or absence of Coil Associated Opacity or pneumonia. Post hoc analyses used the same methods as described above for the primary and secondary effectiveness analyses with the exclusion of the factor of analysis center. Two data values of change in RV were determined to be a result of data collection errors and excluded from post hoc analyses of that endpoint. The frequency (n), proportion (%) and 95% confidence intervals of participants experiencing major complication, SAEs and AEs were compared between treatments using two-sided Fisher s Exact Test. All analyses were conducted using SAS version 9.3. For additional detailed information about statistical methods, see the statistical analysis plan.

5 efigure 1. Typical Sagittal CT Slice Demonstrating Homogeneous (Left Panel) vs. Heterogeneous (Right Panel) Disease Distribution Procedure Details: Two dedicated team members from each site implanted the coils under fluoroscopic guidance via bronchoscopy. The choice of moderate sedation or general anesthesia depended on site practice and was determined by the investigator. The bronchoscopist advanced the bronchoscope to the ostium of the target sub-segmental airway and then advanced a catheter with guide wire into the bronchial segment of the treatment lobe to within 30 mm of the pleural surface. The implanter selected the most appropriate coil length (100, 125 or 150mm) based on subsegmental airway length. Once loaded into the dedicated deployment device, the implanter advanced the coil into the target airway. The endobronchial coil reverted to its original shape once fully deployed, thus coiling up the surrounding airway and tensioning the adjacent parenchyma. The goal was to place a minimum of 10 endobronchial coils in the most affected lobe of each lung to achieve an optimal effect of lung tissue compression throughout the diseased area.

6 efigure 1. Typical Sagittal CT Slice Demonstrating Homogeneous (Left Panel) vs. Heterogeneous (Right Panel) Disease Distribution (continued) Procedure Details: Two dedicated team members from each site implanted the coils under fluoroscopic guidance via bronchoscopy. The choice of moderate sedation or general anesthesia depended on site practice and was determined by the investigator. The bronchoscopist advanced the bronchoscope to the ostium of the target sub-segmental airway and then advanced a catheter with guide wire into the bronchial segment of the treatment lobe to within 30 mm of the pleural surface. The implanter selected the most appropriate coil length (100, 125 or 150mm) based on subsegmental airway length. Once loaded into the dedicated deployment device, the implanter advanced the coil into the target airway. The endobronchial coil reverted to its original shape once fully deployed, thus coiling up the surrounding airway and tensioning the adjacent parenchyma. The goal was to place a minimum of 10 endobronchial coils in the most affected lobe of each lung to achieve an optimal effect of lung tissue compression throughout the diseased area.

7 efigure 2. Elevair Endobronchial Coils of Different Coil Lengths (100mm, 125mm, 150mm) Coil length was selected based on airway length assessed prior to insertion using a guidewire scored with radiopaque markers.

8 efigure 3. Chest Radiograph Post Bilateral Coil Treatment A posteroanterior chest radiograph in a patient with severe centrilobular emphysema who participated in the RENEW study. She underwent sequential procedures starting with the placement of 10 coils in the RUL followed by 10 placed in the LUL 118 days later. The procedure times were 30 minutes and 21 minutes respectively.

9 etable 1. Definition of Major Complications Major Complications: Death; Pneumothorax that requires a chest drainage tube for more than 7 days (from time of chest drainage tube insertion to the time of chest drainage tube removal); Hemoptysis requiring blood transfusion(s), arterial embolization, or surgical/endoscopic procedure; COPD exacerbation that becomes life-threatening or disabling as a result of an increase in respiratory symptoms requiring in-patient hospitalization of >7 days with or without mechanical ventilation; Lower Respiratory Infections (including pneumonia) defined by new or increased clinical symptoms such as fever, chills, productive cough, chest pain, dyspnea and an infiltrate on plain chest x-ray and hospitalization for administration of intravenous antibiotics and/or steroids; Respiratory failure defined as a requirement for mechanical ventilatory support (whether via endotracheal tube or mask) for >24 hours; and An unanticipated bronchoscopy in order to remove one or more Coils due to a device-related AE. (Note: This definition does not include re-positioning, replacement or removal of the Coil(s) during the initial placement procedure.)

10 etable 2. Criteria for Diagnosis and Treatment of Serious Coil Associated Opacity Events Diagnosis Pneumonia Likely Purulent sputum Fever >100.5 F Positive blood culture Pneumonia Suspected CXR Opacity is central/lobar, segmental Positive sputum culture WBC > 12K with >5% bands, shifts Coil Associated Opacity Likely CXR Opacity is peripheral, localized to area around Coils, horse-shoe shaped Fever <100.5 F WBC < 12K without shifts Negative blood or sputum culture No change from baseline sputum Antibiotics Suggested Treatment Course Corticosteroids at discretion of investigator Suggest no antibiotics* Corticosteroids 30 mg x 5 days Ibuprofen at investigator discretion Suggest follow-up with CXR in 7d to confirm DX *If high clinical suspicion of infectious process, start antibiotic therapy These recommendations became available more than 2 months after all endobronchial coil procedures had been completed in the RENEW Study, which likely led to misclassification of some Coil Associated Opacity events as pneumonia because these recommendations were not yet available. Approach: The DMC asked PneumRx to conduct a retrospective analysis of the reported pneumonia events in light of the above recommendations to determine the most appropriate diagnosis. This included evidence of infection (pneumonia) versus inflammation (Coil Associated Opacity) and the response to antibiotics (positive effect on pneumonia) and steroids (positive effect on Coil Associated Opacity). PneumRx also reviewed ecrfs and source documentation loaded into EDC for additional information including fever, blood and sputum culture results, sputum characteristics, white blood cell (WBC) counts and Imaging reports to assist in diagnosis. On February 6, 2016, the Clinical Event Committee met to retrospectively analyze 75 investigator reported pneumonia serious adverse events. A total of 58 events from the Treatment Group and 17 events from the Control Group were reviewed. The DMC followed the guidelines in etable 1 to adjudicate events. The DMC was blinded to the treatment group (coil vs. usual care) and imaging was excluded from this review to ensure the blind was maintained. Events were classified events into the following categories: Coil Associated Opacity Likely Pneumonia Likely Pneumonia Suspected Unadjudicable (not enough source evidence to classify event) Other (sufficient evidence to rule out both Pneumonia and Coil Associated Opacity) The DMC classification resulted in 26 unadjudicable events. Results of the adjudicable cases were presented in etable 15.

11 efigure 4. Local Tissue Reaction Characteristic of Coil Associated Opacity Serial posteroanterior chest radiographs in a RENEW patient with severe bilateral centrilobular emphysema demonstrating the development and resolution of the local tissue reaction characteristic of Coil Associated Opacities in the Right Lung. Panel A. The pre-procedural baseline radiograph. Panel B. The radiograph obtained at the onset of chest discomfort 3 weeks following the placement of 10 coils in the right upper lobe. Panel C. This radiograph obtained 6 weeks following treatment demonstrates the typical opacities in the periphery of the treated lobe (Red circle). Panel D. This radiograph, obtained 14 weeks post first treatment and 2 weeks post second treatment of 10 coils in the left upper lobe, demonstrates the eventual resolution associated with lobar retraction. The red arrow depicts the migration of the minor fissure inferior to the now retracted right upper lobe. A B C D

12 etable 3. Baseline Non-Respiratory Comorbidities-of-Interest Comorbidity of Interest Coil (N=158) (N=157) ARTHRITIS 28 (17.7% ) 24 (15.3% ) CACHEXIA 8 (5.1% ) 13 (8.3% ) CARDIAC DISEASE 41 (25.9% ) 28 (17.8% ) DEPRESSION 44 (27.8% ) 37 (23.6% ) DIABETES 11 (7.0% ) 13 (8.3% ) EDEMA 17 (10.8% ) 18 (11.5% ) GERD 47 (29.7% ) 36 (22.9% ) HYPERLIPIDEMIA 50 (31.6% ) 48 (30.6% ) HYPERTENSION 76 (48.1% ) 66 (42.0% ) OBESITY 24 (15.2% ) 23 (14.6% ) OSTEOPOROSIS 26 (16.5% ) 27 (17.2% ) PERIPHERAL VASCULAR DISEASE 10 (6.3% ) 6 (3.8% ) RENAL DYSFUNCTION 4 (2.5% ) 7 (4.5% ) SLEEP APNEA 20 (12.7% ) 15 (9.6% ) STROKE 4 (2.5% ) 4 (2.5% )

13 efigure 5. Distribution of Non-Respiratory Comorbidity Frequency Percent of Participants Coil (N=158) Control (N=157) n Baseline Comorbidities of Interest

14 etable 4. Procedure and Device Results Procedure duration (minutes) 1 st Procedure (N^ = 155) (M^ = 1613) 2 nd Procedure (N^ = 144) (M^ = 1518) Overall (N^ = 299) (M^ = 3131) Mean ± SD (n) Range (min, max) 43.2 ± (155) 41.0 (5, 102) 40.9 ± (144) 37.0 (15, 100) 42.1 ± 16.3 (299) 39.0 (5, 102) Fluoroscopy time (minutes) Mean ± SD (n) Range (min, max) 13.5 ± 8.62 (152) 12.5 (2, 49) 12.9 ± 8.27 (144) 11.0 (1, 41) 13.2 ± 8.4 (296) 12.0 (1, 49) Post-procedure hospital overnight stay (nights) * Mean ± SD (n) Range (min, max) 1.0 ± 0.53 (154) 1.0 (0, 5) 1.1 ± 1.36 (144) 1.0 (0, 15) 1.1 ± 1.02 (298) 1.0 (0, 15) Implant locations Left Lower Lobe 1.9% (3/155 ) 15.3% (22/144 ) 8.4% (25/299) Left Upper Lobe 12.3% (19/155 ) 70.1% (101/144 ) 40.1% (120/299) Right Lower Lobe 12.3% (19/155 ) 2.1% (3/144 ) 7.4% (22/299) Right Upper Lobe 73.5% (114/155 ) 12.5% (18/144 ) 44.1% (132/299 ) Number of Coils implanted by sizes 100 mm 46.7% (754/1613) 41.2% (626/1518) 44.1% (1380/3131) 125 mm 46.9% (757/1613) 52.0% (789/1518) 49.4% (1546/3131) 150 mm 6.3% (102/1613) 6.8% (103/1518) 6.5% (205/3131) Number of Coils implanted by location Right Upper Mean ± SD (n) 10.0 ± 0.9 (114) 10.2 ± 0.5 (18) 10.0 ± 0.9 (132) Range (min, max) (2.0, 12.0) (10.0, 12.0) (2.0, 12.0) Left Upper Mean ± SD (n) 10.0 ± 0.3 (19) 10.1 ± 0.9 (101) 10.1 ± 0.8 (120)

15 etable 4. Procedure and Device Results Range (min, max) (9.0, 11.0) (3.0, 12.0) (3.0, 12.0) Right Lower Mean ± SD (n) 12.8 ± 2.2 (19) 10.3 ± 2.9 (3) 12.5 ± 2.4 (22) Range (min, max) (10.0, 20.0) (7.0, 12.0) (7.0, 20.0) Left Lower Mean ± SD (n) 13.0 ± 1.0 (3) 13.0 ± 1.2 (22) 13.0 ± 1.2 (25) Range (min, max) (12.0, 14.0) (10.0, 14.0) (10.0, 14.0) Number of Coils per procedure Mean ± SD (n) 10.4 ± 1.5 (155) 10.5 ± 1.4 (144) 10.5 ± 1.4 (299) Range (min, max) (2.0, 20.0) (3.0, 14.0) (2.0, 20.0) ^ N represents the total number of procedures; M represents the total number of Coils implanted. * Post-procedural hospital overnight stay (nights) calculated as discharge date admission date.

16 etable 5a. Primary Efficacy Analysis: Rank-Transformed 6-Minute Walk Distance After MCMC Multiple Imputation - ITT Population Treatment Group (N) Baseline 6-minute-walk distance Mean (95% CI) Mean Rank Absolute Change in 6-minutewalk distance at 12 Months from Baseline Mean (95% CI) Adjusted Mean Rank Absolute Change in 6- minute-walk distance at 12 Months from Baseline Mean (95% CI) Difference (Coil vs. ) [95% CI] 1 P-value 1 (One-sided) (N=157) (290.2, 315.2) (133.9, 162.2) (129.6, 162.0) Coil (N=158) (299.5, 324.6) (153.2, 182.6) (152.4, 184.7) 22.8 [2.1, 43.4] ¹ Based on difference in least squares means from MCMC multiple imputation results of ANCOVA with factors of treatment and analysis center and baseline 6- minute-walk distance and emphysema heterogeneity as covariates. P-value was from one-sided test.

17 etable 5b. Secondary Endpoint Analysis: Rank-Transformed Percent Change in FEV1 After MCMC Multiple Imputation - ITT Population Treatment Group (N) Baseline FEV 1 Mean (95% CI) Mean Rank Percent Change in FEV1 at 12 Months from Baseline Mean (95% CI) Adjusted Mean Rank Percent Change in FEV1 at 12 Months from Baseline Mean (95% CI) Difference (Coil vs. Usual Care) [95% CI] 1 P-value 1 (One-sided) Hochberg Adjustment 2 (N=157) Coil (N=158) 0.7 (0.7, 0.8) 0.7 (0.7, 0.7) (124.2, 150.7) (163.0, 193.8) (126.7, 158.6) [21.1, 62.7] (168.4, 200.7) <.001 Significant ¹ Based on difference in least squares mean from Markov Chain Monte Carlo multiple imputation results of rank ANCOVA with factors of treatment and analysis center and baseline FEV 1 and emphysema heterogeneity as covariates. P-value was based on one-sided test. FEV 1 = Forced Expiratory Volume in 1 Second. ² Testing results after adjustment made on family-wise type I error using Hochberg method.

18 etable 6a. Descriptive Summary of Disease Characteristics by Visit Through 12 Months for Complete Cases (Part 1 of 2) Efficacy and Lung Function Measurements 6-minute-walk distance (meters) Mean ± SD (n) Range (min, max) Coil (N=158) 312.0±79.9(158) (149.4, 540.0) Visit 1 Visit 4 Visit 7 Baseline 1 Month after Treatment 1 1 Months after Treatment 2 Coil Coil (N=157) (N=154) (N=155) (N=136) (N=146) 302.7±79.3 (157) (141.1, 670.6) 322.2±85.9(153) (61.0, 542.0) 307.8±85.2 (155) (91.4, 655.0) 319.4±101.6 (136) (22.9, 537.0) 299.7±86.1 (146) (120.0, 623.6) FEV 1 (liters) Mean ± SD (n) Range (min, max) 0.71±0.20 (158) 0.66 (0.38, 1.23) 0.72±0.21 (157) 0.68 (0.35, 1.66) 0.77±0.22 (154) 0.73 (0.43, 1.43) 0.72±0.21 (155) 0.69 (0.39, 1.64) 0.79±0.25 (136) 0.76 (0.40, 1.89) 0.71±0.20 (146) 0.69 (0.33, 1.67) FEV 1 Predicted (%) Mean ± SD (n) Range (min, max) Saint George s Respiratory Questionnaire Total Score Mean ± SD (n) Range (min, max) 25.7±6.3 (158) 24.9 (12.9, 43.6) 60.0±12.8 (158) 60.0 (26.7, 94.9) 26.3±6.7 (157) 25.6 (11.2, 44.9) 57.4±14.8 (157) 58.8 (8.2, 96.7) 28.0±6.8 (154) 27.4 (14.6, 45.8) 51.2±14.7 (154) 51.7 (18.3, 86.9) 26.5±6.8 (155) 26.0 (11.9, 44.9) 57.5±14.8 (153) 58.7 (22.3, 95.5) 28.3±7.5 (136) 27.5 (15.6, 60.5) 49.61±16.0 (136) 49.4 (6.8, 88.9) 26.0±6.7 (146) 25.4 (9.1, 43.8) 57.8±15.3 (146) 59.1 (16.3, 90.5)

19 etable 6b. Descriptive Summary of Disease Characteristics by Visit Through 12 Months for Complete Cases (Part 2 of 2) Efficacy and Lung Function Measurements 6-minute-walk distance (meters) Mean ± SD (n) Range (min, max) Visit 8 Visit 10 9 Months after Treatment 1 12 Months after Treatment 1 Coil Coil (N=133) (N=140) (N=138) (N=140) 319.8±103.0 (131) (60.7, 589.0) 296.5±83.0 (141) (121.9, 523.0) 318.5±100.7 (137) (61.0, 584.0) 299.5±87.8 (140) (80.0, 548.6) FEV 1 (liters) Mean ± SD (n) Range (min, max) 0.77±0.27 (133) 0.71 (0.35, 2.00) 0.69±0.21 (140) 0.67 (0.30, 1.46) 0.76±0.25 (137) 0.72 (0.36, 2.00) 0.70±0.19 (140) 0.68 (0.31, 1.29) FEV 1 Predicted (%) Mean ± SD (n) Range (min, max) Saint George s Respiratory Questionnaire Total Score Mean ± SD (n) Range (min, max) 28.7±12.5 (133) 25.7 (13.7, 136.3) 50.5±16.8 (131) 51.5 (4.8, 91.4) 26.0±8.5 (140) 25.0 (9.6, 81.8) 57.0±16.4 (141) 58.3 (9.0, 97.2) 27.2±7.7 (137) 26.1 (11.7, 56.3) 51.2±15.0 (138) 50.9 (13.9, 89.5) 25.7±6.5 (140) 25.4 (13.8, 47.6) 58.1±15.5 (139) 59.3 (22.2, 92.2)

20 etable 7. Effectiveness Based on Combined Hyperinflation and Emphysema Distribution Subgroups ITT Population* RV 225% RV <225% Heterogeneous Homogeneous Heterogeneous Homogeneous Change at 12 Months from Baseline Saint George s Respiratory 6-minute-walk distance Change FEV1 % Change (L) Questionnaire Change (meters) (points) RV Change (L) Coil Coil Coil Coil (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) N Mean (95% CI) (-22.6, 38.2) (-40.1, 14.1) (5.2, 22.9) (-7.2, 8.1) (-14.0, -4.5) (-3.3, 4.9) (-1.05, -0.38) (-0.65, -0.03) (IQR) (-13.0, 66.0) (-52.0, 43.5) (-3.2, 21.4) (-8.9, 11.3) (-19.7, -1.9) (-5.0, 7.3) (-1.40, 0.14) (-0.88, 0.05) Difference^ (95% CI) (-8.8, 66.7) (1.6, 22.1) (-16.3, -3.9) (-0.83, 0.08) N Mean (95% CI) ( -8.7, 19.3) (-27.6, 0.6) (3.6, 10.9) (-6.1, 1.2) (-10.1, -5.6) (-0.2, 4.4 ) (-0.47, -0.12) (-0.23, 0.13) (IQR) (-32.0, 45.0) (-42.4, 20.1) ( -5.5, 18.8) (-8.8, 2.8) (-17.5, 0.7) (-3.2, 9.5) (-0.75, 0.21) (-0.42, 0.39) Difference^ (95% CI) (2.5, 38.9) (3.5, 12.9) (-13.3, -6.7) (-0.50, 0.00) N Mean (95% CI) (-75.6, 33.1) (-92.0, 62.6) (-10.7, 7.1) (-14.4, 10.2) (-17.8, 1.9) (-11.8, 15.7) (-0.53, 0.39) (-0.29, 1.01) (IQR) (-36.0, 43.6) (-39.0, 0.6) (-5.9, 5.4) (-2.9, 1.5) (-18.4, 5.6) (2.9, 11.2) (-0.23, 0.35) (0.06, 0.50) Difference^ (95% CI) (-102.5, 84.1) (-19.0, 16.6) (-26.8, 7.1) (-1.29, 0.44) N Mean (95% CI) (-29.4, 11.4) (-11.9, 29.0) (-3.6, 8.4) (-8.7, 3.0) (-10.6, -2.7) (-7.4, 0.6) (-0.42, -0.00) (-0.06, 0.34) (IQR) (-33.2, 24.7) (-35.5, 64.0) (-9.6, 9.2) (-13.4, 6.2) (-14.3, 0.5 ) (-11.8, 2.9) (-0.71, 0.14) (-0.13, 0.31) Difference^ (95% CI) (-48.1, 16.1) (-4.0, 11.1) (-8.9, 2.4) (-0.64, -0.06) *All analyses conducted on full ITT analysis set with multiple imputation. Mean (CI) from ANCOVA adjusted for covariates. ^ Between treatment difference in mean (CI) based on ANCOVA for Saint George s Respiratory Questionnaire and RV, between treatment difference in median (CI) based on Hodges Lehmann estimator adjusted for baseline for 6-minute-walk distance and FEV1.

21 etable 8a. 6-Minute-Walk Distance by Detailed Baseline Residual Volume After MCMC Multiple Imputation - ITT Population Residual Volume RV>=250% RV>=225% and <250% RV>=200% and <225% 2 RV>=175% and <200% Treatment Group N Baseline 6-minutewalk distance (meters) Mean Absolute Change in 6-minute-walk distance (meters) at 12 Months from Baseline Adjusted Mean Absolute Change in 6- minute-walk distance (meters) at 12 Months from Baseline Mean (95%CI)) Mean (95%CI)) Mean (95%CI)) (282.4,330.0 ) (-41.0,-0.7 ) (-41.2,0.9 ) Difference (meters) (Coil vs. Usual Care) (95% CI) 1 p-value 1 (Onesided) Coil (284.2,328.6 ) 5.1 (-14.2,24.4 ) 5.9 (-14.7,26.4 ) 26.1 (-1.4, 53.5) (290.1,329.3 ) -5.8 (-19.4,7.8 ) -6.5 (-23.8,10.7 ) Coil (305.1,345.3 ) 6.2 (-13.7,26.2 ) 7.4 (-12.4,27.1 ) 13.9 (-9.5, 37.3) (281.2,343.3 ) 11.5 (-19.9, 42.9 ) (-54.0,27.0 ) Coil (251.2,317.7 ) (-42.2,18.8 ) (-71.9,3.8 ) (-63.7, 22.6) (238.1,287.4 ) 1.4 (-21.6,24.5 ) 2.0 (-33.3,37.3 ) Coil (295.4,358.3 ) (-40.3,15.1) -8.6 (-37.5,20.4 ) (-55.4, 34.4) ¹ Based on difference in least squares means from MCMC multiple imputation results of ANCOVA with factors of treatment and baseline 6-minute-walk distance and emphysema heterogeneity as covariates. P-value was based on one-sided test. 2 Due to no missing values in this subgroup for subjects, multiple imputation was not utilized.

22 etable 8b. Saint George's Respiratory Questionnaire After MCMC Multiple Imputation by Detailed Baseline Residual Volume, ITT Population Residual Volume RV>=250% RV>=225% and <250% RV>=200% and <225% 2 RV>=175% and <200% Treatment Group N Baseline Saint George s Respiratory Questionnaire Mean Absolute Change in Saint George s Respiratory Questionnaire at 12 Months from Baseline Adjusted Mean Absolute Change in Saint George s Respiratory Questionnaire at 12 Months from Baseline Mean (95%CI)) Mean (95%CI)) Mean (95%CI)) (54.3,62.3 ) 3.1 (0.3,6.0 ) 2.8 (-0.4,6.1 ) Coil (58.3,65.0 ) -9.5 (-12.6,-6.5 ) -9.3 (-12.4,-6.1 ) (53.5,60.8 ) 1.0 (-1.5,3.4 ) 0.6 (-2.3,3.5 ) Difference (Coil vs. Usual Care) (95% CI) (-16.2, - 7.9) p-value 1 (Onesided) Coil (55.2,62.1 ) -7.1 (-10.6,-3.6 ) -7.2 (-10.7,-3.6 ) -7.8 (-11.9, -3.6) (54.1,66.1 ) -0.9 (-5.9, 4.1 ) -2.0 (-8.7,4.6 ) Coil (54.2,64.6 ) -8.1 (-13.6,-2.6 ) -9.4 (-15.8,-3.1 ) -7.4 (-14.4, -0.4) (45.8,61.5 ) -3.5 (-8.8,1.7 ) -3.0 (-10.0,4.0 ) Coil (53.1,65.0 ) -6.2 (-12.6,0.2 ) -4.8 (-11.0,1.3 ) -1.8 (-10.3, 6.6) <.0001 ¹ Based on difference in least squares mean from MCMC multiple imputation results of ANCOVA with factors of treatment and baseline Saint George s Respiratory Questionnaire and emphysema heterogeneity as covariates. P-value was based on one-sided test. 2 Due to no missing values in this subgroup for subjects, multiple imputation was not utilized.

23 etable 8c. Percent Change in FEV 1 by Detailed Baseline Residual Volume After MCMC Multiple Imputation - ITT Population Residual Volume RV>=250% RV>=225% and <250% RV>=200% and <225% 2 RV>=175% and <200% Treatment Group N Baseline FEV 1, L Mean (95%CI)) Mean Percent Change in FEV 1 at 12 Months from Baseline Mean (95%CI)) Adjusted Mean Percent Change in FEV 1 at 12 Months from Baseline Mean Change (95%CI)) (0.6,0.7 ) -2.3 (-6.3,1.7 ) -1.2 (-6.4,3.9 ) Difference in FEV 1 Percent Change (Coil vs. Usual Care) (95% CI)1 p-value 1 (Onesided) Coil (0.6,0.7 ) 10.3 (4.7,15.9 ) 10.9 (5.6,16.2 ) 12.1 (5.2, 19.0) (0.7,0.8 ) -1.4 (-4.7,1.9 ) 0.6 (-4.4,5.6 ) Coil (0.7,0.8 ) 7.4 (1.0,13.9 ) 9.6 (3.9,15.2 ) 9.0 (2.2, 15.8) (0.6,0.8 ) -2.9 (-9.6, 3.7 ) -1.7 (-12.1,8.6 ) Coil (0.6,0.9 ) 2.5 (-6.1,11.0 ) 4.6 (-5.1,14.2 ) 6.3 (-4.7, 17.3) (0.6,0.9 ) -1.7 (-8.5,5.1 ) -3.9 (-12.4,4.6 ) Coil (0.7,0.9 ) -0.3 (-7.7,7.1 ) -1.5 (-9.0,6.0 ) 2.3 (-8.1, 12.8) ¹ Based on difference in least squares means from MCMC multiple imputation results of ANCOVA with factors of treatment and baseline FEV1 and emphysema heterogeneity as covariates. P-value was based on one-sided test. 2 Due to no missing values in this subgroup for subjects, multiple imputation was not utilized.

24 etable 9. Impact of Co-morbidity Prevalence on Efficacy Measures ITT Population* Change at 12 Months from Baseline 6-minute-walk distance Change Saint George s Respiratory FEV1 % Change RV Change (L) (meters) Questionnaire Change (points) Coil Coil Coil Coil (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) N High: 4+ Mean (95% CI) (IQRs) (-43.4, 2.7) -8.8 (-65.5, 40.0) -7.5 (-34.4, 19.5) -9.0 (-33.0, 15.2) 5.7 (-0.5, 11.9) 4.1 (-5.3, 14.3) 2.8 (-4.4, 9.9) 0.0 (-7.5, 8.4) -7.7 (-11.8, -3.6) -9.3 (-17.7, 1.1) -0.1 (-4.8, 4.6) 0.1 (-5.9, 9.9) (-0.77, -0.26) (-0.79, 0.12) (-0.42, 0.18) (-0.27, 0.45) Difference^ (95% CI) -1.1 (-28.8, 25.0) 3.0 (-4.9, 10.6) -7.6 (-13.1, -2.1) (-0.73, -0.06) N Low: 0-3 Mean (95% CI) (IQRs) 9.4 (-4.6, 23.4) 15.2 (-28.0, 52.0) (-24.4, 1.6) -4.5 (-44.0, 32.0) 8.8 (4.9, 12.7) 3.6 (-6.3, 16.5) -2.0 (-5.4, 1.5) -3.2 (-9.1, 3.4) -7.8 (-10.2, -5.4) -7.1 (-17.7, 0.4) 1.1 (-1.1, 3.3) 1.5 (-5.1, 8.4) (-0.53, -0.19) (-0.81, 0.22) (-0.29, 0.03) (-0.47, 0.33) Difference^ (95% CI) 21.0 (4.4, 37.9) 8.2 (4.1, 12.6) -8.9 (-11.9, -6.0) (-0.44, -0.02) See etable 3 for list of comorbidities included in analyses *All analyses conducted on full ITT analysis set with multiple imputation. Mean (CI) from ANCOVA adjusted for covariates. ^ Between treatment difference in mean (CI) based on ANCOVA for Saint George s Respiratory Questionnaire and RV, between treatment difference in median (CI) based on Hodges Lehmann estimator adjusted for baseline for 6-minute-walk distance and FEV1.

25 etable 10. Impact of Cardiac Co-morbidity Presence on Efficacy Measures ITT Population* Cardiac Co-morbidity Change at 12 Months from Baseline 6-minute-walk distance Saint George s Respiratory FEV1 % Change RV Change (L) Change (meters) Questionnaire Change (points) Coil Coil Coil Coil (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) (N=158) (N=157) N Yes Mean (95% CI) (IQRs) (-45.9, 1.6) 0.0 (-47.0, 26.8) (-44.5, 11.1) (-39.2, 13.3) 8.2 (0.7, 15.6) 0.0 (-0.0, 0.1) 1.3 (-7.5, 10.2) -0.0 ( -0.1, 0.0) -7.7 (-12.1, -3.3) -9.5 (-19.1, -1.9) -1.3 (-6.5, 3.9) -0.5 (-11.7, 10.2) (-0.82, -0.23) (-1.01, 0.13) 0.09 (-0.29, 0.46) 0.06 (-0.22, 0.38) Difference^ (95% CI) 3.1 (-28.0,34.0) 4.7 (-2.9,12.7) -6.4 (-12.5, -0.2) (-1.01, -0.20) N No Mean (95% CI) (IQRs) 8.3 (-5.7, 22.3) 15.0 (-28.0, 52.0) -9.3 (-22.2, 3.6) -2.4 (-40.0, 28.3) 7.7 (4.0, 11.4) 0.0 (-0.0, 0.1) -1.4 (-4.7, 1.9) -0.0 (-0.1, 0.0) -7.7 (-10.1, -5.4) -7.1 (-17.3, 0.5) 1.2 (-0.9, 3.3) 1.5 (-4.9, 7.9) (-0.52, -0.20) (-0.76, 0.22) (-0.31, -0.01) (-0.45, 0.33) Difference^ (95% CI) 19.7 (3.5,36.1) 7.8 (3.7,11.9) -8.9 (-11.8, -6.1) (-0.39, 0.00) *All analyses conducted on full ITT analysis set with multiple imputation. Mean (CI) from ANCOVA adjusted for covariates. ^ Between treatment difference in mean (CI) based on ANCOVA for Saint George s Respiratory Questionnaire and RV, between treatment difference in median (CI) based on Hodges Lehmann estimator adjusted for baseline for 6-minute-walk distance and FEV1.

26 etable 11. # of Non-Respiratory Comorbidities and Proportion With Cardiac Disease by RV% and Treatment Complete Cases Mean ± SD Treatment Group RV% N # of comorbidities/ participant N (%) with Cardiac Disease Control Group <225% ± (27.0%) Group >=225% ± (15.0%) Coil Group <225% ± (37.2%) Group >=225% ± (21.7%)

27 etable 12. Listing of Deaths Through 12 Months, All Cause, ITT Population Coil Group (N = 158) Coil Participants Cause of Death # Days post initial treatment # Days post second treatment * Participant 1 Pulmonary hemorrhage and oxygen desaturation leading to cardiac arrest Intra-procedural NA Participant 2 Respiratory failure 73 NA Participant 3 Respiratory failure Participant 4 Bilobar Pneumonia and Aspergillosis 148 NA Participant 5 Respiratory failure Participant 6 Respiratory failure Participant 7 Acute worsening of chronic renal failure Participant 8 COPD exacerbation 254 NA Participant 9 COPD exacerbation Participant 10 Bone cancer Participants Cause of Death Group (N = 157) # Days post randomization Participant 1 Respiratory arrest 50 Participant 2 COPD exacerbation leading to respiratory insufficiency 92 Participant 3 Cardiopulmonary arrest 100 Participant 4 End-stage COPD 115 Participant 5 Participant 6 Participant 7 Pseudomonas pneumonia, sepsis resulting in an acute MI and acute Exacerbation of COPD Complications from intestinal cancer surgery leading to septic shock COPD exacerbation leading to hospitalization and transfer to hospice care Participant 8 COPD exacerbation leading to respiratory insufficiency 261 *Days post second treatment was NA (not applicable) for Coil Group participants who did not have a second treatment.

28 etable 13. Serious Adverse Events Through 12 Months, Safety Population* MedDRA SOC Term Preferred Term Participant Counts n (%) Coil Treatment (N = 155) (N = 157) P- value 1 Cardiac disorders 8 (5.2%) 4 (2.5%) 0.26 Acute myocardial infarction 2 (1.3%) 0 (0.0%) N/A Angina pectoris 2 (1.3%) 0 (0.0%) N/A Atrial fibrillation 2 (1.3%) 0 (0.0%) N/A Cardiac Failure 1 (0.6%) 0 (0.0%) N/A Cardio-respiratory arrest 0 (0.0%) 1 (0.6%) N/A Cardiomyopathy 0 (0.0%) 1 (0.6%) N/A Sinus tachycardia 1 (0.6%) 0 (0.0%) N/A Supraventricular tachycardia 0 (0.0%) 1 (0.6%) N/A Tachycardia 0 (0.0%) 1 (0.6%) N/A Gastrointestinal disorders 7 (4.5%) 2 (1.3%) N/A Abdominal pain 1 (0.6%) 0 (0.0%) N/A Colitis 1 (0.6%) 0 (0.0%) N/A Diverticulum 1 (0.6%) 0 (0.0%) N/A Food poisoning 0 (0.0%) 1 (0.6%) N/A Intestinal obstruction 1 (0.6%) 0 (0.0%) N/A Pneumoperitoneum 1 (0.6%) 0 (0.0%) N/A Small intestinal obstruction 1 (0.6%) 1 (0.6%) N/A Upper gastrointestinal haemorrhage 1 (0.6%) 1 (0.6%) N/A General disorders and administration site conditions 7 (4.5%) 1 (0.6%) N/A Adverse drug reaction 1 (0.6%) 0 (0.0%) N/A Asthenia 1 (0.6%) 0 (0.0%) N/A Chest pain 0 (0.0%) 1 (0.6%) N/A Medical device complication 5 (3.2%) 0 (0.0%) N/A Hepatobiliary disorders 1 (0.6%) 0 (0.0%) N/A Cholecystitis 1 (0.6%) 0 (0.0%) N/A Immune system disorders 2 (1.3%) 0 (0.0%) N/A Allergy to metals 1 (0.6%) 0 (0.0%) N/A Latex allergy 1 (0.6%) 0 (0.0%) N/A

29 MedDRA SOC Term Preferred Term Participant Counts n (%) Coil Treatment (N = 155) (N = 157) P- value 1 Infections and infestations 44 (28.4%) 13 (8.3%) < Abdominal sepsis 1 (0.6%) 0 (0.0%) N/A Bronchitis 5 (3.2%) 2 (1.3%) N/A Bronchitis bacterial 1 (0.6%) 0 (0.0%) N/A Bronchopulmonary aspergillosis 3 (1.9%) 0 (0.0%) N/A Diverticulitis 1 (0.6%) 0 (0.0%) N/A Gastrointestinal infection 0 (0.0%) 1 (0.6%) N/A Influenza 2 (1.3%) 1 (0.6%) N/A Lung infection 2 (1.3%) 1 (0.6%) N/A Lung infection pseudomonal 1 (0.6%) 0 (0.0%) N/A Pneumonia 31 (20.0%) 7 (4.5%) < Pneumonia staphylococcal 1 (0.6%) 0 (0.0%) N/A Pseudomonas infection 1 (0.6%) 0 (0.0%) N/A Sepsis 1 (0.6%) 0 (0.0%) N/A Septic shock 0 (0.0%) 1 (0.6%) N/A Subacute endocarditis 1 (0.6%) 0 (0.0%) N/A Tracheobronchitis 1 (0.6%) 0 (0.0%) N/A Upper respiratory tract infection 0 (0.0%) 1 (0.6%) N/A Wound infection 0 (0.0%) 1 (0.6%) N/A Injury, poisoning and procedural complications 2 (1.3%) 2 (1.3%) N/A Anastomotic leak 0 (0.0%) 1 (0.6%) N/A Pneumothorax traumatic 0 (0.0%) 1 (0.6%) N/A Rib fracture 1 (0.6%) 0 (0.0%) N/A Spinal compression fracture 1 (0.6%) 0 (0.0%) N/A Investigations 0 (0.0%) 1 (0.6%) N/A Influenza A virus test positive 0 (0.0%) 1 (0.6%) N/A Metabolism and nutrition disorders 1 (0.6%) 1 (0.6%) N/A Dehydration 1 (0.6%) 0 (0.0%) N/A Malnutrition 0 (0.0%) 1 (0.6%) N/A Musculoskeletal and connective tissue disorders 3 (1.9%) 1 (0.6%) N/A Arthritis 1 (0.6%) 0 (0.0%) N/A

30 MedDRA SOC Term Preferred Term Participant Counts n (%) Coil Treatment (N = 155) (N = 157) P- value 1 Musculoskeletal chest pain 1 (0.6%) 1 (0.6%) N/A Myalgia 1 (0.6%) 0 (0.0%) N/A Neoplasms benign, malignant and unspecified (incl cysts and polyps) 3 (1.9%) 1 (0.6%) N/A Bone neoplasm malignant 1 (0.6%) 0 (0.0%) N/A Colon cancer 0 (0.0%) 1 (0.6%) N/A Lung neoplasm 1 (0.6%) 0 (0.0%) N/A Thyroid neoplasm 1 (0.6%) 0 (0.0%) N/A Nervous system disorders 1 (0.6%) 5 (3.2%) N/A Cerebrovascular accident 0 (0.0%) 1 (0.6%) N/A Ischaemic stroke 0 (0.0%) 1 (0.6%) N/A Sciatica 0 (0.0%) 1 (0.6%) N/A Syncope 1 (0.6%) 0 (0.0%) N/A Transient ischaemic attack 0 (0.0%) 2 (1.3%) N/A Renal and urinary disorders 2 (1.3%) 0 (0.0%) N/A Nephrolithiasis 1 (0.6%) 0 (0.0%) N/A Renal failure acute 1 (0.6%) 0 (0.0%) N/A Respiratory, thoracic and mediastinal disorders 61 (39.4%) 38 (24.2%) Acute respiratory failure 3 (1.9%) 1 (0.6%) N/A Bronchial secretion retention 1 (0.6%) 0 (0.0%) N/A Chronic obstructive pulmonary disease 43 (27.7%) 32 (20.4%) 0.15 Dyspnoea 5 (3.2%) 1 (0.6%) N/A Emphysema 1 (0.6%) 1 (0.6%) N/A Haemoptysis 4 (2.6%) 0 (0.0%) N/A Pleural effusion 1 (0.6%) 0 (0.0%) N/A Pneumothorax 15 (9.7%) 1 (0.6%) Pulmonary embolism 1 (0.6%) 0 (0.0%) N/A Pulmonary haemorrhage 2 (1.3%) 0 (0.0%) N/A Pulmonary venous thrombosis 1 (0.6%) 0 (0.0%) N/A Respiratory arrest 0 (0.0%) 1 (0.6%) N/A Respiratory failure 5 (3.2%) 1 (0.6%) N/A Sleep apnoea syndrome 0 (0.0%) 1 (0.6%) N/A

31 MedDRA SOC Term Preferred Term Participant Counts n (%) Coil Treatment (N = 155) (N = 157) P- value 1 Vascular disorders 5 (3.2%) 1 (0.6%) N/A Aortic aneurysm 0 (0.0%) 1 (0.6%) N/A Coeliac artery occlusion 1 (0.6%) 0 (0.0%) N/A Deep vein thrombosis 2 (1.3%) 0 (0.0%) N/A Haematoma 1 (0.6%) 0 (0.0%) N/A Hypotension 1 (0.6%) 0 (0.0%) N/A 1 By Fisher s exact test Note: P-value was provided only for events with participant counts > 5% in either treatment group. Participants were counted at most once for each preferred term and each SOC term * Three (3) participants randomized to the Coil Treatment who did not receive Coils were excluded from the Safety population.

32 etable 14. Major Complications Through 12 Months by Time Period, Safety Population* Major complication Coil Group (N=155) Participants, n (%) Events (n) Peri-procedure Group (N=157) p-value ** Participants, n (%) Events (n) (% participants) Total 25 (16.1%) 31 5 (3.2%) 5 < Death 2 (1.3%) 2 0 (0.0%) Pneumothorax 0 (0.0%) 0 0 (0.0%) 0 N/A Hemoptysis 1 (0.6%) 1 0 (0.0%) COPD Exacerbation 8 (5.2%) 8 1 (0.6%) Lower respiratory infection 15 (9.7%) 17 4 (2.5%) Respiratory failure 3 (1.9%) 3 0 (0.0%) Days Post-Treatment through 9 Months post Visit 2^ Total 32 (20.6%) (13.4%) Death 7 (4.5%) 7 8 (5.1%) 8 >0.99 Pneumothorax 1 (0.6%) 1 1 (0.6%) 1 >0.99 Hemoptysis 1 (0.6%) 1 0 (0.0%) COPD Exacerbation 7 (4.5%) 8 9 (5.7%) Lower respiratory infection 17 (11.0%) 19 2 (1.3%) Respiratory failure 3 (1.9%) 3 5 (3.2%) > 9 months through 12 months post Visit 2^ Total 9 (5.8%) 10 7 (4.5%) Death 1 (0.6%) 1 0 (0.0%) Pneumothorax 0 (0.0%) 0 0 (0.0%) 0 N/A Hemoptysis 0 (0.0%) 0 0 (0.0%) 0 N/A COPD Exacerbation 5 (3.2%) 5 4 (2.5%) Lower respiratory infection 4 (2.6%) 4 2 (1.3%) Respiratory failure 0 (0.0%) 0 1 (0.6%) 1 >0.99 * Three (3) participants randomized to the Coil Treatment who did not receive Coils were excluded from the Safety population. ** By Fisher s exact test. Peri-procedural period was defined as 0-30 days following either Visit 2 or Visit 5, where Visit 2 was the first post-randomization office visit for Control participants and the initial Coil treatment for Coil participants; Visit 5 was an office visit for participants and the second Coil treatment for Coil participants to occur 4 months after Visit 2 (-2 weeks/+4 weeks). ^ Visit 2 was defined in the study protocol as the first post-randomization visit for Control participants and the initial coil treatment for Coil participants.

33 etable 15. Results of DMC Adjudication of Pneumonia Adverse Events Coil Associated Opacity Likely Coil Group (# Events)* 14 0 Group (# Events)* Other 2 0 Pneumonia Likely 17 5 Pneumonia Suspected 7 4 Unadjudicable 18 8 Total *A single participant could have experienced more than one pneumonia/cao event. Of the adjudicable events for participants in the Coil Treatment group (n=40), approximately one-third (35%, 14/40) were determined to likely be Coil Associated Opacity by the DMC based on their review of the source records.

34 etable 16a. Change in Effectiveness Endpoints at 12 Months From Baseline for Coil Participants, With Confirmed Coil Associated Opacities, Confirmed or Unadjudicable Pneumonia, and With Neither Coil Associated Opacity nor Pneumonia (ITT Population)* END POINTS Coil Participants with Confirmed Coil Associated Opacities Coil Participants with Confirmed or Unadjudicable Pneumonia Events Coil Participants without Coil Associated Opacities nor Pneumonia (N=14) (N=31) (N=113) Primary Endpoint Change in 6-minute-walk Distance (meters) Mean (95% CI) 12.5 ( -26.4, 51.5) 3.3 (-23.8, 30.4) -2.2 (-18.7, 14.4) (IQRs) 20.9 (-23.0, 70.0) 11.6 (-25.2, 57.0) 9.0 (-35.4, 41.0) Secondary Endpoints 6-minute-walk Distance Responder Rate, % (95% CI) ( 25m increase) 47.8% (20.1, 75.6) 45.3% (26.1, 64.5) 38.9% (27.6, 50.2) Percent Change in FEV1 (%) Mean (95% CI) 17.5 (6.1, 28.9) 13.3 (5.5, 21.0) 4.7 (-0.2, 9.5) (IQRs) 10.8 (3.5, 22.7) 7.0 (-6.0, 23.1) 2.2 (-7.8, 14.5) Change in Saint George s Respiratory Questionnaire Mean (95% CI) (-17.8, -4.6) -6.7 ( -11.2, -2.1) -8.4 (-11.3, -5.5) (IQRs) (-19.1, -4.6) -7.4 (-15.9, -1.1) -6.7 (-17.3, 0.9) Other Endpoints Saint George s Respiratory Questionnaire Responder Rate, % (95% CI) 75.6 % (51.3, 99.9) 64.4% (45.2, 83.6) 60.0% (47.9, 72.0) ( 4 point decrease) Change in RV (L) Mean (95% CI) (-1.15, -0.28) (-0.77, -0.15) (-0.52, -0.15) (IQRs) (-1.69, 0.14) (-0.92, 0.20) (-0.71, 0.19) Change in RV/TLC (%) Mean (95% CI) -5.9 (-9.2, -2.6) -4.9 (-7.2, -2.6) -3.4 (-4.8, -2.0) (IQRs) -4.3 (-13.0, -1.0) -3.5 (-10.2, 1.0) -2.5 (-5.3, 0.4) * All analyses conducted on the full ITT analysis set with multiple imputation. Mean (CI) from ANCOVA adjusted for covariates. Responder rate (CI) from logistic regression adjusted for covariates.

35 etable 16b. Change in Effectiveness Endpoints at 12 Months From Baseline for Participants With or Without Pneumonia (ITT Population)* END POINTS Primary Endpoint Change in 6-minute-walk Distance (meters) Participants with Pneumonia (N=13) Participants without Pneumonia (N=-144) Mean (95% CI) ( -70.9, 0.8 ) -6.2 ( -16.6, 4.3 ) (IQRs) ( -66.0, -0.6 ) -5.1 ( -39.3, 33.5 ) Secondary Endpoints 6-minute-walk Distance Responder Rate, n (%), [95% CI] ( 25m increase) Percent Change in FEV1 (%) 1 (7.8) [0.0, 28.0] 40 (27.8) [20.3, 35.4] Mean (95% CI) -3.5 ( -11.1, 4.2 ) -1.8 ( -4.1, 0.5 ) (IQRs) -2.9 ( -11.5, 1.6 ) -2.5 ( -8.9, 4.8 ) Change in Saint George s Respiratory Questionnaire Mean (95% CI) 2.0 ( -4.0, 7.9 ) 0.9 ( -0.8, 2.6 ) (IQRs) 3.5 ( -1.5, 6.1 ) 0.9 ( -5.3, 9.2 ) * Mean (CI) for the full ITT analysis set with multiple imputation.