Pulmonx LIBERATE Study Clinical Investigational Plan #630-0012-H ECO# 4000 Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema (LIBERATE STUDY) U.S. Investigational Device Exemption (IDE) Clinical Investigational Plan #630-0012_H Version: June 23, 2017 CONFIDENTIAL Page 1 of 71 The contents of this document are propriety and confidential. This protocol contains valuable engineering, clinical and commercial information that must not be disclosed to persons not directly involved with the study. Duplication and distribution of this document require prior written approval from Pulmonx Pulmonx LIBERATE Study Clinical Investigational Plan #630-0012-H Table of Contents CLINICAL INVESTIGATION PLAN AGREEMENT FORM .......................................................10 1.0 Background ......................................................................................................11 1.1 Pathophysiology of Emphysema ........................................................................11 1.2 Management of Emphysema: Lung Volume Reduction Surgery (LVRS) ...........11 1.3 Bronchoscopic Lung Volume Reduction (BLVR) ................................................11 1.4 BLVR with the Pulmonx Endobronchial Valve (EBV) ..........................................12 1.5 Pivotal Investigation of the EBV: The VENT Study (IDE#G020230) ..................12 1.6 Learnings from the VENT Study .........................................................................12 1.7 Collateral Ventilation Impacts Lung Volume Reduction ......................................12 1.8 Measurement of Collateral Ventilation ................................................................13 1.9 Conclusion from the Prior Studies ......................................................................14 2.0 Study device and intended use .......................................................................14 3.0 Study device / technology description ...........................................................14 3.1 Endobronchial Valve ..........................................................................................14 3.2 Delivery Catheter ...............................................................................................14 4.0 Study purpose ..................................................................................................14 5.0 Study Design ....................................................................................................15 6.0 Study population ..............................................................................................15 6.1 Optimal Medical Therapy ...................................................................................15 7.0 Study Objective ................................................................................................15 7.1 Primary Effectiveness Endpoint .........................................................................15 7.2 Safety Endpoint .................................................................................................16 7.3 Secondary Effectiveness Measures ...................................................................16 7.4 Additional Measures ..........................................................................................16 7.5 Crossover of Control Study Participants .............................................................17 7.6 Interim Analysis .................................................................................................17 7.7 Long-Term Follow-Up ........................................................................................18 8.0 Study participant management .......................................................................18 8.1 Clinical Site Study Team ....................................................................................18 8.2 Clinical Study Site Training ................................................................................18 8.3 Study Candidate Recruiting ...............................................................................18 8.4 Study Candidate Selection .................................................................................18 8.5 Screening Eligibility Criteria ...............................................................................19 8.6 Baseline Eligibility Criteria ..................................................................................22 8.7 Bronchoscopy Plan for CV Assessment and Determining Study Eligibility .........22 8.8 Study Procedure Eligibility Criteria .....................................................................22 8.9 Study Participant Enrollment ..............................................................................23 8.10 Follow-Up Visits .................................................................................................23 8.11 Retention of Study Participants ..........................................................................24 9.0 Pharmacologic treatments for study participants .........................................25 9.1 Optimization of Medications ...............................................................................25 9.2 Bronchodilators ..................................................................................................25 9.3 Corticosteroids ...................................................................................................25 9.4 Other Pharmacologic Agents .............................................................................25 10.0 Post-bronchoscopy PULMONARY REHABILITATION ...................................25 10.1 Pulmonary Rehabilitation Program .....................................................................26 Version: June 23, 2017 CONFIDENTIAL Page 2 of 71 The contents of this document are propriety and confidential. This protocol contains valuable engineering, clinical and commercial information that must not be disclosed to persons not directly involved with the study. Duplication and distribution of this document require prior written approval from Pulmonx Pulmonx LIBERATE Study Clinical Investigational Plan #630-0012-H 11.0 Bronchoscopy Procedure ...............................................................................26 11.1 Procedure Medications ......................................................................................27 11.2 Assessment of Study Procedure Eligibility Criteria .............................................28 11.3 Assignment to Control Arm ................................................................................28 11.4 Assignment to Study Treatment Arm..................................................................28 11.5 Execution of the Study Procedure ......................................................................29 11.6 Post-Bronchoscopy Recovery Period Procedures for Study Treatment Arm ......29 11.7 Procedures Prior to Discharge ...........................................................................31 12.0 Secondary Valve Procedures ..........................................................................32 12.1 Valve Removal ...................................................................................................32 12.2 Valve Replacement ............................................................................................32 12.3 Valve Adjustment ...............................................................................................32 13.0 Clinical Effectiveness Outcomes ....................................................................33 13.1 Spirometry .........................................................................................................33 13.2 Patient-Reported Health Status Measures .........................................................33 13.3 Body Plethysmography Testing ..........................................................................35 13.4 Diffusing Capacity Testing .................................................................................35 13.5 Medication Use ..................................................................................................36 13.6 Daily Diary .........................................................................................................36 13.7 Six-Minute Walk Distance (6MWD) Test ............................................................37 13.8 Blood Work ........................................................................................................37 13.9 Chest X-Ray ......................................................................................................38 13.10 Physical Exam ...................................................................................................38 13.11 High Resolution Computed Tomography ...........................................................38 13.12 BODE Index .......................................................................................................38 14.0 Sequence for Testing.......................................................................................39 14.1 Screening Assessment – within 6 months prior to randomization .......................39 14.2 Baseline Assessment - Conduct ≤ 120 days following screening eligibility .........40 14.3 Bronchoscopy Procedure – Should occur ≤ 60 days after baseline assessment visit ....................................................................................................................40 14.4 Post Procedure