Study to Assess Safety, Feasibility, and Preliminary Efficacy of the Apreo Implant for Severe Emphysema

Inclusion Criteria:

1. Age ≥ 35 and ≤ 80 years old

2. Computed tomography (CT) scan evidence of homogeneous or heterogeneous emphysema

3. At least one target lobe with > 35% destruction (percent of voxels with < -950Hounsfield units on CT)

4. Post-bronchodilator ratio of FEV1/FVC < 0.7 at screening

5. Post-bronchodilator FEV1 percent predicted ≥15% and ≤50% of predicted at screening

6. Post-bronchodilator RV > 180% predicted

7. Post-bronchodilator RV/TLC ≥ 0.55 at screening

8. Marked dyspnea, scoring ≥ 2 on the modified Medical Research Council scale of 0-4

9. Cotinine testing or carboxyhemoglobin at screening indicates nonsmoker and stoppedsmoking at least 8 weeks before entering the trial and agrees to refrain fromsmoking for duration of study participation

10. Participation in a pulmonary rehabilitation program and/or confirmed to have beenengaged or attempted regular physical activity in the 12 months prior to the firstApreo Procedure and agrees to continue or restart regular physical activity for theduration of the study

11. Fully vaccinated for Covid-19 (up to date per local government guidelines) and hascurrent pneumococcus and influenza vaccination (or documented clinical intolerance)

12. Cognitively and physically able to provide written informed consent and completeparticipant questionnaires

Exclusion Criteria:

1. Arterial blood on room air: PaCO2 > 50 mmHg (8 kPa) or PaO2 ≤ 45 mmHg (6 kPa)

2. DLCO <20% at screening

3. Steroid therapy of 10 mg prednisolone (prednisone) or more per day

4. Two or more hospitalizations for acute exacerbations of COPD or respiratoryinfections in the past year before enrollment

5. Any acute exacerbation of COPD or respiratory infection less than 4 weeks before thefirst Apreo Procedure

6. Previous lung volume reduction surgery or lobectomy, segmentectomy or bullectomy,vapor, glue, or other pulmonary device implant

7. Known or suspected history of pulmonary arterial hypertension with a PASP > 50 mmHgon echocardiogram or mPAP > 25 mmHg on a right heart catheterization

8. Presence of a giant bulla (≥ 30% of hemithorax)

9. History of adult asthma or chronic bronchitis

10. Presence of suspicious pulmonary nodule/infiltrate that requires additionalfollow-up, diagnostics or treatment

11. Unequivocal and symptomatic bronchiectasis

12. Unequivocal lung cancer or other current cancer diagnosis except non-metastasizedbasal cell skin cancer

13. Uncontrolled hypertension (blood pressure that is inadequately treated or resistantto treatment) with a systolic > 200 mmHg or diastolic > 110 mmHg at screening orprior to first Apreo Procedure

14. Uncorrectable coagulopathy or other condition likely to increase risk of peri- orpost- Apreo Procedure bleeding

15. On anticoagulant or antiplatelet therapy and unable or unwilling to hold for ApreoProcedure

16. History of myocardial infarction or unstable angina within past 6 months

17. History of a stroke less than 1 year before the first Apreo Procedure

18. Clinical history of heart failure with documented LVEF ≤ 40%

19. Clinical history of diabetes with a HbA1c > 9.0%

20. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (CKD-EPI) ORparticipant with kidney failure (Stage 5 kidney disease)

21. Mechanical ventilator dependence except participants using nocturnal bi-levelpositive airway pressure (biPAP) or continuous positive airway pressure (CPAP) areallowed if it would not preclude safe implantation of the study device

22. Pregnant, lactating, or women of childbearing potential who plan to become pregnantwithin the study duration

23. Known hypersensitivity to nitinol

24. Significantly immunocompromised, such as organ transplant recipients, those withcongenital immune deficiencies, AIDS, or severe rheumatoid arthritis

25. Any disease or condition likely to limit survival to less than one year

26. Concomitant illnesses or medications that may pose a significant increased risk forcomplications following an Apreo Procedure

27. Currently enrolled in another trial and actively receiving experimental treatment

28. Any condition in the opinion of the investigator that would interfere with safe andcomplete collection of study data including the safe conduction of bronchoscopyprocedures