An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients with Severe Emphysema

Inclusion Criteria:

1. Subject is willing and able to provide informed consent and to participate in thestudy.

2. Subject is aged ≥ 40 and ≤ 80 years at the time of the ICF signature date.

3. Subject has completed a documented pulmonary rehabilitation (in clinic orhome-based) program within 12 months prior to Baseline.

4. Subject has stopped smoking for at least 8 weeks prior to the ICF signature date asconfirmed by carboxyhemoglobin or cotinine levels.

5. Subject has a recent HRCT meeting the scan parameter requirements and performedwithin 3 months of the ICF signature date with the following findings at -910Hounsfield Units:

6. At least one (1) lobe with segmental emphysema destruction score ≥ 50%.

7. Subject has heterogenous emphysema, defined as difference in emphysemadestruction score of ≥ 15 between the density scores of the target lobe and theipsilateral non-target lobe(s) per QCT report with % voxel density of < -910HU. For non-target lobes that include the RML, calculate the combination ofnon-target lobes as a single density score using volume-weighted percent.

8. LUL, LLL, RUL, RLL, or RUL+RML are targets for valve intervention.

9. Subject has a gap in the interlobar fissure that corresponds to one or moresegments and the fissure(s) contacting the target lobe is ≥ 80% complete perQCT report.

10. Subject has 98% of the fissure gap confined to a maximum of 3 segments withinthe target lobe per Fissure Targeting Report (FTR).

11. Subject has 6MWD ≥ 150 m and ≤ 450 m.

12. Subject has clinically significant dyspnea with an mMRC score of ≥ 2.

13. Subject has post-bronchodilation FEV1 ≥ 15% predicted and ≤ 45% predicted.

14. Subject has an FEV1/FVC ratio of < 0.7.

15. Subject has post-bronchodilation TLC, measured by body plethysmography, ≥ 100%predicted.

16. Subject has post-bronchodilation RV ≥ 175% predicted, measured by bodyplethysmography.

17. Subject has post-bronchodilation DLCO ≥ 20% predicted.

18. Subject has received preventative vaccinations against potential respiratoryinfections, including COVID-19, consistent with local recommendation or policy.

19. Subject is on optimal medical management for more than one month prior to the ICFsignature date.

20. Subject has collateral ventilation (CV+) as confirmed per the Chartis assessmentprior to the AeriSeal Index Procedure.

Exclusion Criteria:

1. Subject has prior lung volume reduction surgery, lobectomy or pneumonectomy, lungtransplantation, airway stent placement, pleurodesis, or BLVR of any type, exceptBLVR using Zephyr Valve with < 50% TLVR at 6 months, followed by valve removal > 6months prior to ICF signature date.

2. Subject has visible radiological abnormality on HRCT scan such as pulmonary nodulegreater than 0.8 cm in diameter (does not apply, if present for 2 years or morewithout increase in size or if deemed benign by biopsy) or active pulmonaryinfection (e.g., unexplained parenchymal infiltrate, significant interstitial lungdisease or significant pleural disease).

3. Post-COVID-19 pathology on CT, including ground glass opacities with or withoutconsolidation, adjacent pleura thickening, interlobular septal thickening, or airbronchograms.

4. Large bullae encompassing greater than 1/3 of the total lung.

5. Subject had 3 or more COPD exacerbations requiring hospitalization within 12 monthspreceding the ICF signature date or a COPD exacerbation requiring hospitalizationwithin 8 weeks of the ICF signature date. Subjects may be re-considered for futureenrollment.

6. Subject has asthma as their primary diagnosis.

7. Subject has chronic bronchitis (defined as greater than 4 tablespoons of sputumproduction per day) as their primary diagnosis.

8. Subject has clinically significant bronchiectasis.

9. Subjects with evidence of active respiratory infection should be considered forenrollment only after satisfactory resolution.

10. Subject requires invasive ventilatory support. Note: The use of Continuous PositiveAirway Pressure (CPAP) or BiPAP devices for sleep apnea is permitted.

11. Subject has severe gas exchange abnormalities as defined by any one of the followingtests, conducted at rest, on room air, as tolerated.

• PaCO2 ≥ 50 mm Hg (6.7 kPa)

• PaO2 < 45 mm Hg (6.0 kPa)

12. Subject has pulmonary hypertension, defined as mean pulmonary systolic pressure > 45mm Hg.

13. Subject has known documented alpha-1 antitrypsin deficiency.

14. Subject has clinically significant hematological disorder.

15. Subject has recent significant unplanned or unexplained weight loss or otherrelevant comorbidities considered by the investigator to be potentially confoundingor limiting to the subject's participation in the study.

16. Subject has non-atrial arrhythmias or conduction abnormalities on EKG.

17. Subject has high cardiac risk after undergoing cardiac risk assessment in accordancewith published guidelines (Fleisher 2007) or has ischemic heart disease, congestiveheart failure, cerebrovascular disease (stroke or TIA within 6 months of the ICFsignature date), serum creatinine > 2.0 mg/dL (177 μmol/L), or left ventricularejection fraction (LVEF) < 45% on echocardiogram.

18. Subject has uncontrolled exercise induced syncope.

19. Subject has evidence of severe disease which in the judgment of the investigator maycompromise the anticipated treatment effect or the subject's survival for theduration of at least 12 months.

20. Subject has any other condition that the investigator believes would interfere withthe intent of the study or would make participation not in the best interest of thesubject including but not limited to alcoholism, high risk for drug abuse, ornoncompliance in returning for follow-up visits.

21. Subject cannot tolerate corticosteroids or relevant antibiotics.

22. Subject use of systemic corticosteroids > 20 mg/day prednisolone or equivalentwithin four (4) weeks of the ICF signature date. Subjects may be re-considered forfuture enrollment.

23. Subject use of immunosuppressive agents within four (4) weeks of the ICF signaturedate. Subjects may be re-considered for future enrollment.

24. Subject is unable to temporarily discontinue heparins and oral anticoagulants (e.g.,warfarin, dicumarol) according to local pre-procedural protocols. Note: Antiplateletdrugs including aspirin, thienopyridines and ticagrelor are permitted.

25. Subject has allergy or sensitivity to medications required to safely performbronchoscopy under conscious sedation or general anesthesia.

26. Subject has known allergy to the following device components: Polyether block amide (PEBAX), Polyvinyl Alcohol or Glutaraldehyde, Nitinol (nickel-titanium) or itsconstituent metals (nickel or titanium) or Silicone.

27. Subject is a female who is pregnant (positive βHCG Pregnancy test), breast-feeding,or planning to be pregnant in the next 12 months.

28. Subject has Body Mass Index < 18 kg/m2 or > 35 kg/m2.

29. Subject participated in an investigational study of a drug, biologic, or device notcurrently approved for marketing within 30 days prior to the ICF signature date.Note: Subjects being followed as part of a long-term surveillance of a non-pulmonarystudy that has reached its primary endpoint are eligible for participation in thisstudy.