The REDUCE EU Study - Endobronchial Thermal Liquid Ablation (ETLA) for the Treatment of Emphysema

Inclusion Criteria:

• Age ≥ 40 years old

• Diagnosis of COPD with FEV1/FVC less than 0.7 post-bronchodilation

• Post-bronchodilator Forced Expiratory Volume (FEV1) ≥ 20% and ≤ 49% of predictedvalue

• Total lung capacity (TLC) ≥ 100% predicted

• Residual volume (RV) ≥ 175% predicted

• 6 Minute Walk Distance (6MWD) ≥ 140 meters

• Dyspnea scoring ≥ 1 on the modified Medical Research Council scale (mMRC)

• Blood gas values of PCO2 ≤ 55 mmHg; PO2 ≥ 45 mmHg on room air

• Optimized medical management (consistent with GOLD guidelines) as confirmed by theInvestigator

• Non-smoking for 3 months prior to study enrollment, as confirmed by lab testing

• Participant must engages in physical exercise beyond activities of daily living (i.e., a walking program, pulmonary rehabilitation) on n a regular basis for morethan 6 weeks prior to enrollment and agree to continue the activity throughout studyparticipation

• Participant must live within approximately 1 hour of the study hospital, or livewithin 1 hour of adequate regional care, or be willing to remain in the hospital forat least five days post-procedure

• Vaccinated for COVID-19, pneumococcus, and influenza (per European Union and MemberState guidelines) or documented clinical intolerance or documented patient refusal

• Cognitively able to provide written informed consent and willing to comply withstudy requirements

• Severe emphysematous lung subsegments eligible for ETLA treatment

Exclusion Criteria:

• Body mass index (BMI) < 16 kg/m^2 or ≥ 33 kg/m^2

• DLCO < 20% predicted

• Chronic bronchitis as defined by cough and sputum production for at least 3 monthsper year for two consecutive years, in the absence of other conditions that canexplain these symptoms

• 75ml or greater sputum production per day most days of the week

• Greater than two hospitalizations for COPD exacerbations and/or pneumonia in the 12months prior to enrollment

• Diagnosis of asthma that is confirmed according to the Global Initiative for Asthma (GINA) guidelines

• Prior lung volume reduction via endobronchial valves(s), coil(s), vapor and/orpolymer. Patients whose valves have been removed > 3 months previously can betreated if a baseline bronchoscopy reveals no airway obstruction or obvious tissuegranulation and the reason for valve removal was not for complications e.g.,Pneumonia, severe exacerbation, or pneumothorax.

• Pulmonary hypertension

• Alpha-1 antitrypsin deficiency

• Uncontrolled diabetes mellitus

• Prior heart or lung transplant

• Myocardial infarction or stroke within the 12 months of enrollment

• Diagnosis of heart failure

• Heart failure requiring hospitalization, within 6 months prior to enrollment

• History of bleeding disorders or enhanced predisposition to bleeding

• History of severe/massive hemoptysis defined as >200ml of blood loss in < 24 hours

• Unable to discontinue anti-coagulants or platelet inhibitors (acetylsalicylic acid [ASA]and non-ASA, including low dose) for at least 7 days prior to each procedure (or as per physician discretion based on the specific agent) and for at least 6weeks after each procedure

• Daily systemic steroids equivalent to > 15mg prednisolone

• Immunosuppressive drugs, such as for the treatment of cancer, autoimmune disease, orprevention of tissue/organ rejection

• Pregnant, lactating, or women of childbearing potential that plan to become pregnantwithin the study duration

• Currently enrolled in another trial studying an experimental treatment

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

• Concomitant illnesses or medications that may pose a significant increased risk forcomplications following treatment with ETLA

• Any condition that would interfere with evaluation or completion of the studyincluding study assessments and procedures, including bronchoscopy.

• Active aspergillus infection

• Clinically significant bronchiectasis as determined by the Investigator

• Radiological evidence of bronchiectasis in target region(s) and/or cysticradiological bronchiectasis in any region of the lungs

• Clinically significant pulmonary fibrosis

• Lung nodule not proven stable unless proven to have benign pathology

• Large bulla (defined as > 1/3 volume of a lung)

• Prior Lung Volume Reduction Surgery (LVRS), bullectomy, or lobectomy

• The remaining lung tissue NOT targeted for ETLA treatment is too highly diseased

• Active respiratory infection or recent respiratory infection with resolution < 4weeks prior to screening or procedure

• Recent COPD exacerbation within < 6 weeks prior to screening or procedure